FORMALDEHYDE
CASRN: 50-00-0 For other data, click on the Table of Contents
Human Health Effects:
Evidence for Carcinogenicity:
CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION:
Based on limited evidence in humans, and sufficient evidence in animals. Human
data include nine studies that show statistically significant associations
between site-specific respiratory neoplasms and exposure to formaldehyde
or formaldehyde-containing products. An increased incidence of
nasal squamous cell carcinomas was observed in long-term inhalation studies in
rats and in mice. The classification is supported by in vitro genotoxicity data
and formaldehyde's structural relationships to other
carcinogenic aldehydes such as acetaldehyde. HUMAN CARCINOGENICITY DATA:
Limited. ANIMAL CARCINOGENICITY DATA: Sufficient.
A2. A2= Suspected human carcinogen.
Evaluation: There is limited evidence in humans for the carcinogenicity of formaldehyde.
There is sufficient evidence in experimental animals for the carcinogenicity of formaldehyde.
Overall evaluation: Formaldehyde is probably carcinogenic to
humans (Group 2A).
Human Toxicity Excerpts:
IF SOLN IS INGESTED, MUCOUS MEMBRANES OF MOUTH, THROAT, & INTESTINAL
TRACT ARE IRRITATED, & SEVERE PAIN, VOMITING, & DIARRHEA RESULT. AFTER
ABSORPTION, FORMALDEHYDE DEPRESSES CNS & SYMPTOMS NOT
UNLIKE THOSE OF ALC INTOXICATION ARE NOTED. THEY CONSIST OF VERTIGO, DEPRESSION,
& COMA. RARELY CONVULSIONS ARE OBSERVED.
ALTERATION OF TISSUE PROTEINS BY FORMALDEHYDE CAUSES LOCAL
TOXICITY & PROMOTES ALLERGIC REACTIONS. REPEATED CONTACT WITH SOLN ... MAY
CAUSE ECZEMATOID DERMATITIS. DERMATITIS FROM CLOTHING TREATED WITH FORMALDEHYDE
... HAS OCCURRED.
AQ SOLN ... SPLASHED OR DROPPED ON HUMAN EYES HAVE CAUSED INJURIES RANGING
FROM SEVERE PERMANENT CORNEAL OPACIFICATION & LOSS OF VISION TO MINOR
TRANSIENT INJURY OR DISCOMFORT, DEPENDING UPON WHETHER SOLN WERE OF HIGH OR LOW
CONCN.
INHALATION OF HIGH CONCN ... CAUSED SEVERE IRRITATION OF RESP TRACT, LEADING
IN 2 INSTANCES TO DEATH. ... PULMONARY EDEMA, WITH RESIDUAL CARDIAC IMPAIRMENT
IN 1 CASE, WAS REPORTEDLY CAUSED BY SINGLE ACUTE INHALATIONS ... .
IN SENSITIZED SUBJECTS SPECIFIC LATE ASTHMATIC REACTIONS MAY BE PROVOKED BY
BRIEF EXPOSURES AT APPROX 3 PPM.
Ingestion of formaldehyde can cause a reduction in body
temperature.
Symptoms related to ingestion of formaldehyde include:
jaundice, acidosis, & hematuria. Symptoms related to inhalation include:
rhinitis, anosmia, laryngospasm, tracheitis, & gastroenteritis.
In a survey of 57 embalmers who were exposed to atmospheric concn below 2 ppm,
there was a high incidence of symptoms of irritant effects on the eyes (81%)
nose & throat (75%). Other respiratory effects included cough (33%), chest
tightness (23%), wheezing (12%), & shortness of breath (11%). On the basis
of the results, 10% were acute bronchitics, & 30% were chronic bronchitics.
No control group was used & cigarette smoking was not taken into account.
Eyes: concn 1-10 ppm may produce appreciable eye irritation on initial
exposure; lacrimation occurs at about 4 ppm.
CULTURED BRONCHIAL & FIBROBLASTIC CELLS FROM HUMANS WERE USED TO STUDY
DNA DAMAGE & TOXICITY. FORMATION OF CROSSLINKS BETWEEN DNA & PROTEINS,
CAUSED SINGLE-STRAND BREAKS IN DNA, & INHIBITED RESEALING OF SINGLE-STRAND
BREAKS PRODUCED BY IONIZING RADIATION.
Formaldehyde induced a 1.5-3 fold increase in sister
chromatid exchanges in ... human lymphocytes in culture.
Formaldehyde was mutagenic for diploid human lymphoblasts in
culture ... /inducing an incr number of mutations at/ 130 uM or 4 ppm by weight.
OUTBREAK OF HEMOLYTIC ANEMIA, ATTRIBUTED TO ACCIDENTAL EXPOSURE ... OCCURRED
AMONG PATIENTS ON HEMODIALYSIS. 41 YR OLD WOMAN DIED 28 HR AFTER INGESTING 120
ML OF ... SOLN (37% WT/VOL FORMALDEHYDE, 12.5% VOL/VOL
METHANOL, CONTAINING NO FORMIC ACID).
EFFECTS IN WOMEN ATTRIBUTED TO EXPOSURE ... INCL MENSTRUAL DISORDERS &
SECONDARY STERILITY.
SYMPTOMATOLOGY: A. Inhalation: 1. Irritation of mucous membranes, especially
of eyes, nose & upper respiratory tract. 2. With higher concn, cough,
dysphagia, bronchitis, pneumonia, edema or spasm of the larynx. Pulmonary edema
is uncommon. B. Ingestion. 1. Immediate intense pain in mouth, pharynx &
stomach. 2. Nausea, vomiting, hematemesis, abdominal pain & occasionally
diarrhea (which may be bloody). 3. Pale, clammy skin & other signs of shock.
4. Difficult micturition, hematuria, anuria. 5. Vertigo, convulsions, stupor,
& coma. 6. Death due to respiratory failure. C. Skin contact: 1. Irritation
& hardening of skin. Strong solutions produce coagulation necrosis. 2.
Dermatitis & hypersensitivity from prolonged or repeated exposure.
INVESTIGATIONS OF CILIOSTATIC EFFECT OF ALDEHYDES ARE OF SPECIAL INTEREST
SINCE MANY HAVE IRRITATING EFFECT ON TRACHEAL MUCOSA. COMPARISON OF CILIOSTATIC
EFFECT SHOWED FORMALDEHYDE TO BE MOST TOXIC FOLLOWED BY
ACETALDEHYDE & ACROLEIN. CROTONALDEHYDE & METHACROLEIN SHOWED WEAKEST
EFFECT. TECHNIQUE USED FOR OBSERVING TRACHEAL CILIARY ACTIVITY WAS THE IN VITRO
TECHNIQUE.
One hundred nine workers & 254 control subjects were studied to evaluate
the effects of formaldehyde on the mucous membranes &
lungs. A modified, respiratory symptom questionnaire & spirometry were admin
to all study participants before & after their work shift, & formaldehyde
levels were determined for each test subject. Over the course of the monitored
work shift, test subjects demonstrated a dose-dependent excess of irritant
symptoms & a statistically significant decline in certain lung function
parameters. Baseline spirometry values were not significantly different between
test & control groups, & formaldehyde-exposed workers
did not report an excess of respiratory symptoms. Formaldehyde
is a dose-dependent irritant of the eyes & mucous membranes at low-level
exposures. It can exert a small, across-shift effect on airways but after a mean
exposure of 10 yr does not appear to cause permanent respiratory impairment.
The effect of formaldehyde exposure on medical students
conducting dissections in the gross anatomy laboratory course /was evaluated
using/ self-administered questionnaires designed to assess the frequency of
occurrence of various symptoms indicating the acute effects of formaldehyde
exposure. The questionnaires were given to a cohort of 1st-yr medical students
on completion of the gross anatomy lab course. Air sampling of formaldehyde
levels in the anatomy labs was carried out on one day during the time in which
these students were conducting dissections. ... Although the results of the air
sampling showed formaldehyde levels to be well below current
occupational standards, significant numbers of students reported experiencing
symptoms associated with formaldehyde exposure. Estimates of
the relative risk of experiencing formaldehyde-related symptoms
in the anatomy laboratories compared to the control laboratories ranged from
2.0-19.0, depending on the particular symptom. In addn, it was found that female
students were 3 times more likely to report formaldehyde-related
symptoms than male students.
A population based case control study was undertaken in 13 counties of
western Washington to determine if occupational formaldehyde
exposure was related to cancer of the oropharynx & hypopharynx (OHPC,
N=205), nasopharynx (NPC, N=27) or sinus & nasal cavity (SNC, N=53).
Controls were selected by random digit dialing (N= 552). A telephone interview
inquired about lifetime occupational history as well as a number of potential
confounding factors, including smoking & drinking. Approximately half
(N=143) of the case interviews were with next of kin. ... Logistic regression
was used to estimate exposure odds ratios STET while taking into account
multiple risk factors for each site. No significant associations were found
between occupational formaldehyde exposure & any of the
cancer sites under study. However, relative risk estimates associated with the
highest exposure score categories were evaluated for oropharynx &
hypopharynx (OR=1.3, 95% Confidence Interval= 0.6-3.1) & nasopharynx
(OR=2.1, 95% Cl=0.4-10.0). When an induction period was accounted for only
oropharynx & hypopharynx & nasopharynx increased to 1.7 & 3.1,
respectively. Several limitations in the study tend to conservatively bias the
results. ...
Because of the paucity of scientific data concerning the inhalation toxicity
of formaldehyde in humans, determinations of the symptoms &
alterations in pulmonary function resulting from inhalation for 1 hr of 3 ppm formaldehyde
were studied. The protocol consisted of randomized exposure of each subject to
clean air or 3.0 ppm formaldehyde on 2 separate days.
Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE=
65/min) & 16 asthmatic subjects performed intermittent moderate exercise (VE=
37/min). Symptoms & pulmonary functions were assessed during the time course
of exposure; nonspecific airway reactivity was assessed after exposure. Both
groups exhibited similar, significant (p<0.01) increases in perceived odor,
nose/throat irritation, & eye irritation throughout the exposure. The
non-asthmatic group had the following slight but statistically significant
(p<0.02) lower pulmonary functions after 55 min of exposure to formaldehyde
as compared to clean air: 3.8% in FEV1, 2.6% in FVC, & 2.8% in FEV3. The
asthmatic group showed no statistically significant decrements in pulmonary
function.
A retrospective mortality analysis was conducted in a cohort of 9,365
individuals employed as of 1940 in two chrome leather tanneries in the United
States and followed to the end of 1982. Vital status as of the closing date was
determined for over 95% of the cohort. Potential hazardous workplace exposures
varied with department and included ... formaldehyde. ...
Mortality from all causes combined was lower than expected for each tannery. ...
Deaths from cancer of each site, including the lung, were also lower than
expected compared to those of either the population of the United States or of
local state rates. A significant excess of deaths was observed, however, due to
accidental causes in one tannery and cirrhosis of the liver, suicide, and
alcoholism in the other. These excesses did not appear to be casually associated
with occupational exposures.
Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was ...
efficiently inactivated by formalin ... .
Eight symptomatic individuals chronically exposed to indoor formaldehyde
at low concentrations (0.07-0.55 ppm) were compared to 8 nonexposed subjects
with respect to: (1) presence of IgG and IgE antibodies to formaldehyde
conjugated to human serum albumin (F-HSA); (2) the percentage of venous blood T-
and B-cells by E- and EAC-rosetting; and (3) the ability of T- and B-cells to
undergo mitogen (phytohemagglutin and pokeweed) stimulated blastogenesis as
measured by the incorporation of tritiated thymidine. Anti-F-HSA IgG, but not
IgE, antibodies were detected in the sera of the 8 exposed subjects; none were
found in 7 of the controls. T-lymphocytes were decreased in the exposed (48%)
compared to the control (65.9%) subjects (p< 0.01). B-cells were 12.6%
(exposed group) and 14.75% (controls) (p< 0.05). The incorporation of labeled
thymidine by T-cells (phytohemagglutin) was decreased: 17,882 cpm (exposed
group) and 28,576 cpm (p< 0.01). T- and B-cell blastogenesis (pokeweed) was
9,698 cpm (exposed group) and 11,279 (controls) (p< 0.1).
Both death and survival from 4-oz formalin ingestions have
been reported in adults. The probable mean lethal adult dose is 1 to 2 oz. Death
may occur within 3 hours; survival past 48 hours usually means recovery.
An environmental survey of 2 wood products (plywood, particle-board)
companies revealed mean concns in the plywood forming areas of 0.8 ppm &, in
2 particle-board forming areas, of 1.1 to 1.4 ppm /formaldehyde/.
Ophthalmologic evaluations were conducted & eye irritation self-reports were
collected from 84 subject workers, including unexposed controls, from various
areas in the plants. Results from both were unremarkable, as were tests mapping
their visual fields. However, there were subjective reports of at least
occasional eye irritation in 67% of the exposed subjects, with more such reports
coming from workers in areas of the plant with the higher concns. An explosion
at the factory closed a major product line & resulted in laying off many of
the volunteer subjects prior to performance testing; the remaining 49 workers
were tested before & after their workshift (& 13 of them were tested on
2 days) in order to assess acute effects of formaldehyde on
visual acuity, depth perception, peripheral vision, accommodation, eye movement
& fixation, divided attention, & color vision. Subjective reports of eye
irritation on the day of testing did not correlate, or correlated negatively,
with formaldehyde concns on the test day, which averaged 0.4
ppm. Average visual test scores were better at the end of the day than at the
beginning, & there was a trend for those with higher formaldehyde
levels to demonstrate greater improvement. Some of the changes reached
traditional levels of statistical significance. The results from this
investigation, while relevant to the neurotoxicity of formaldehyde,
suffer from the small sample size & the possibility that the comparison
subjects had also experienced formaldehyde exposure. With these
caveats, this study suggests that mean formaldehyde exposures
at 0.4 ppm produce no deleterious acute effects on visual performance, but
chronic exposures between 0.8 & 1.4 ppm may produce an increased incidence
of self reported symptoms of eye irritation in persons who do not have clinical
ophthalmologic defects.
Symptoms: Local: Conjunctivitis, corneal burns; brownish discoloration of
skin; dermatitis, urticaria (hives), pustulovesicular eruption. Inhalation:
rhinitis & anosmia (loss of sense of smell); pharyngitis, laryngospasm;
tracheitis & bronchitis; pulmonary edema, cough, constriction in chest;
dypsnea (difficult breathing), headache, weakness, palpitation (rapid heart
beat), gastro enteritis (inflammation of the stomach & intestines).
Ingestion: Burning in mouth & esophagus; nausea & vomiting; abdominal
pain, diarrhea, vertigo (dizziness), unconsciousness, jaundice, albuminuria,
hematuria, anuria, acidosis, convulsions.
Aldehydes increase airflow at concentrations below those that decrease
respiratory frequency. /Aldehydes/
Data on concentration of formaldehyde and 15 organic
solvents in Finnish furniture factories from 1975 to 1984 were presented.
Workers often complained of severe eye, nose, and upper respiratory tract
irritation. Formaldehyde was collected in a 1% sodium bisulfite
solution and analyzed by the chromatropic method. The solvents were adsorbed in
a charcoal tube, desorbed with carbon-disulfide or dimethylformamide, and
analyzed by gas chromatography. All highly exposed workers were monitored. The
widest range of formaldehyde concentration was recorded in the
operation of the curtain painting furniture receiving operation, which was
between 0.2 and 5.4 ppm. The mean concentrations of most organic solvents
studied ranged from 4 to 66 ppm. Formaldehyde levels were high
and the 1 ppm exposure limit, defined as the 15 minute time weighted average by
the Finnish Board of Labor Protection, was exceeded about 40% of the time.
A study of 759 histologically verified cancers of the nasal cavity (287
cases), paranasal sinuses (179 cases), and nasopharynx (293 cases) and 2465
cancer controls diagnosed in Denmark between 1970 and 1982 was conducted to
investigate the importance of occupational exposure to formaldehyde.
Information on job history for cases and controls was derived from a national
data linkage system and exposure to formaldehyde and wood dust
was assessed by industrial hygienists unaware of the case control status of the
patients. The exposure rates for formaldehyde among male and
female controls were 4.2% and 0.1% respectively. After proper adjustment for
contemporary wood dust exposure, relative risk of 2.3 (95% CI= 0.9-5.8) for
squamous cell carcinoma and 2.2 (95% CI= 7-7.2) for adenocarcinoma of the nasal
cavity and paranasal sinuses were detected among men who have been exposed to formaldehyde
in their job compared with those never exposed.
The National Cancer Institute study on the relationship between exposure to formaldehyde
& mortality from nasophryngeal cancer was evaluated. The study had indicated
little evidence of a link between formaldehyde at concns
normally encountered in the workplace & risk of nasopharyngeal cancer.
Although the overall standardized mortality ration was significantly elevated in
subjects exposed to formaldehyde, the overall risk did not incr
with increasing intensity of exposure. A reanalysis, however, suggested that
simultaneous exposure to particulates & formaldehyde could
be a risk factor. A further review of the National Cancer Institute findings
showed that the significant excess mortality was based on deaths occurring in a
single factory (factory-A) & occurred primarily in short term employees.
When the data were analyzed in terms of cumulative exposures that were known to
include both formaldehyde & particulates, only the highest
exposure group had a significantly increased excess nasopharyngeal cancer
mortality. This excess was clearly located in factory-A. A follow-up study of
factory-A that added 5 more years of follow-up was initiated. It showed no
additional deaths from nasopharyngeal cancer even among workers with the highest
formaldehyde & particulate exposures. The four deaths from
nasopharyngeal cancer in this factory occurred in workers employed in the same
department & hired between 1949 & 1955. Although these workers were
exposed to formaldehyde & particulates, they were not among
the most highly exposed.
This study evaluates the histological changes, especially the presence of
possible precancerous lesions, in the nasal mucosa of workers exposed to formaldehyde.
Nasal biopsies of 37 workers occupationally exposed to formaldehyde
for more than five years and 37 age matched referents showed a higher degree of
metaplastic alterations in the former group. In addition, three cases of
epithelial dysplasia were observed among the exposed. These results indicate
that formaldehyde may be potentially carcinogenic in man.
Combination of this finding with the inconclusive epidemiological studies
suggests that formaldehyde is a weak carcinogen and that
occupational exposure to formaldehyde alone is insufficient to
induce nasal cancer.
Clinical & animal studies suggest that formaldehyde
adsorbed on respirable particles may elicit a greater pulmonary physiologic
& inflammatory effect than gaseous formaldehyde alone. This
study was to determine if respirable carbon particles have a synergistic effect
on the acute symptomatic & pulmonary physiologic response to formaldehyde
inhalation. Normal, nonsmoking, methacholine-nonreactive subjects were exposed
to 2 hr each of clean air, 3 ppm formaldehyde, 0.5 mg/cu m
respirable activated carbon aerosol, & the combination of 3 ppm formaldehyde
plus activated carbon aerosol. The subjects engaged in intermittent heavy
exercise (VE= 57 1/min) for 15 min each half hour. Formaldehyde
exposure was associated with significant increases in reported eye irritation,
nasal irritation, throat irritation, headache, chest discomfort, & odor.
Synergistic increases in cough, but not in other irritant respiratory tract
symptoms, were observed with inhalation of formaldehyde &
carbon. Small (<5%) synergistic decreases in FVC & FEV3 were also seen.
No formaldehyde effect was observed on FEV1; however, we did
observe small (<10%) significant decreases in FEF25-75%, which may be
indicative of increased airway tone. Overall, results demonstrated synergism,
but the effect is small & its clinical significance is uncertain.
To study the cytotoxic effect of formaldehyde on the human
nasal mucosa 75 men with occupational exposure to formaldehyde
or to formaldehyde & wood dust, were examined, looking
particularly at early signs of irritative effects & histopathological
changes in the nasal mucosa. A nasal biopsy specimen was graded from 0-8
according to the morphological changes. A high frequency of nasal symptoms,
mostly a running nose & crusting, was related to exposure to formaldehyde.
Only three men had a normal mucosa; the remainder has loss of cilia & goblet
cell hyperplasia (11%) & squamous metapolasia (78%); in 6 cases (8%) there
was a mild dysplasia. The histological grading showed a significantly higher
score when compared with unexposed controls (2.9 v 1.8). There was no dose
response relation, no malignancies, & no difference in the histological
score between those exposed to formaldehyde or to formaldehyde
& wood dust.
A study of respiratory symptoms and pathophysiological effects associated
with occupational exposure to formaldehyde and wood dust was
conducted. The cohort consisted of 70 Swedish workers exposed to formaldehyde
during the production of formaldehyde and formaldehyde
based products (formaldehyde group) and 100 furniture workers
exposed to formaldehyde and wood dust (formaldehyde/wood
dust group). The comparisons consisted of 36 local government clerks. The formaldehyde
group was exposed to 0.05 to 0.5 mg/cu m formaldehyde and the
furniture workers to 0.2 to 0.3 mg/cu m formaldehyde and 1 to 2
mg/cu m wood dust. Annual formaldehyde exposures of the
comparisons averaged 0.09 mg/cu m. Sixty four percent of the formaldehyde
group, 53% of the formaldehyde/wood dust group, and 25% of the
comparisons reported nasal discomfort. Symptoms from the lower airways were
reported by 44% of the formaldehyde group, 39% of the formaldehyde/wood
dust group, and 14 % of the comparisons. Symptoms of nasal obstruction and
watery discharges were more frequent in the exposed subjects than in the
comparisons. More pronounced nasal swelling was found in the cohort than in the
comparisons. 20% of the formaldehyde and 15% of the formaldehyde/wood
dust group had impaired mucociliary clearance versus only 3% of the comparisons.
Both exposed groups had a reduced sense of smell. Forced vital capacity was
significantly decreased in the exposed groups.
A study was conducted to determine if pathologists with exposure to formaldehyde
demonstrate an excess risk of cancer, particularly cancers of the nasopharyngeal
and pharyngeal areas. A population of 6411 physicians with occupational formaldehyde
exposure participated in the study. The occurrence of these types of cancers was
4.7 times higher in these persons than in a comparable sized group of
psychiatrists, but even so it is difficult to determine the importance of this
increased risk as being directly tied to formaldehyde exposure.
Pathologists and other members of the study group were exposed to other
chemicals and infectious agents as well as formaldehyde. There
was an apparent excess of mortality from pancreatic cancer and brain cancers as
well as leukemia.
The relation of chronic respiratory symptoms & pulmonary function to formaldehyde
in homes was studied in a sample of 298 children (6-15 yr of age) & 613
adults. Formaldehyde measurements were made with passive
samplers during two 1 wk periods. Significantly greater prevalence rates of
asthma & chronic bronchitis were found in children from houses with formaldehyde
levels 60-120 ppb than in those less exposed, especially in children also
exposed to environmental tobacco smoke. In children, levels of peak expiratory
flow rates decreased linearly with formaldehyde exposure, with
the estimated decr due to 60 ppb of formaldehyde equivalent to
22% of peak expiratory flow rates level in nonexposed children. The effects in
asthmatic children exposed to formaldehyde below 50 ppb were
greater than in healthy ones. The effects in adults were less evident:
decrements in peak expiratory flow rates due to formaldehyde
over 40 ppb were seen only in the morning, & mainly in smokers.
The long term effects of formaldehyde on the respiratory
tract have been investigated in a group of 164 workers exposed daily to the
chemical during the production of urea formaldehyde resin,
together with 129 workers not exposed to free formaldehyde.
Exposure was classified as high (corresponding to an 8 hr time weighted exposure
of >2.0 ppm), medium (0.6-2.0 ppm), or low (0.1-0.5 ppm). 25% of workers had
high exposure at some time & 17% moderate exposure. Both exposed &
unexposed groups had an annual assessment that included lung function. The
proportion with self reported respiratory symptoms was similar in the two
groups, 12% & 16% reporting breathlessness on hurrying & 26% & 20%
wheezing. The initial forced expiratory volume in 1 sec was within 0.5 l (approx
on standard deviation) of the predicted value (by age & height) in 65% of
the exposed & 59% of unexposed workers & >0.5 l below the predicted
value in 9% of exposed & 11% unexposed workers. The mean decline in forced
expiratory volume in 1 sec was 42 ml/yr (standard deviation 45) in the exposed
& 41 ml/yr in the unexposed group (standard deviation 40 ml/yr). The rate of
decline showed the expected association with smoking in the unexposed group, but
in the exposed group the mean rate of decline in the never smokers was similar
to that in current smokers. There were, however, relatively few never smokers
& considerable variation in the rates of decline. In the exposed group no
association was found between the rate of decline & indices of exposure to formaldehyde.
Thus there is no evidence from this study of an excess of respiratory symptoms
or decline in lung function in the workers exposed to formaldehyde.
The similar rate of decline of forced expiratory volume in 1 sec however in
never smokers & smokers of the exposed group is consistent with finding of
other studies for workers exposed to formaldehyde.
A prospective evaluation of pulmonary function & respiratory symptoms was
conducted among 103 medical students exposed to formaldehyde
over a 7 month period to determine the incidence of bronchoconstriction &
respiratory symptoms in response to exposure. Time-weighted average formaldehyde
exposures were generally <1 ppm & peak exposures were <5 ppm. Acute
symptoms of eye & upper respiratory irritation were significantly associated
with exposure. There was no pattern of bronchoconstriction in response to
exposure after either 2 wks or 7 months. Twelve subjects had a history of
asthma; they were likely to have symptoms of respiratory irritation or changes
in pulmonary function than those without such a history. These findings are
consistent with previous case reports that indicate exposure to formaldehyde
vapor at levels that are commonly encountered in occupational & residential
seetings do not commonly cause significant bronchonconstriction, even among
subjects with preexisting asthma.
A case of anaphylactoid reaction to a patch test with formaldehyde
was described. The 40 year old woman developed bronchospasm and laryngospasm
following the inhalation of formaldehyde vapor. A year later
she accidentally entered a hospital room relatively soon after it had been
disinfected, and was hospitalized with dyspnea, cyanosis, bronchospasm, and
laryngospasm. Days later she did react to a patch test with a 1% solution of formaldehyde
in water. Pulmonary function tests 20 min after the patch test revealed a 50%
reduction in FEV1 and a 63% reduction in MEF 25.
Four groups of patients with long-term inhalation exposure to formaldehyde
were compared with controls who had short-term periodic exposure to formaldehyde.
The following were determined for all groups: total white cell, lymphocyte, and
T cell counts; T helper/suppressor ratios; total Ta1+, IL2+, and B cell counts;
antibodies to formaldehyde-human serum albumin conjugate and
autoantibodies. When compared with the controls, the patients had significantly
higer antibody titers to formaldehyde-human serum albumin. In
addition, significant increases in Ta1+, IL2+, and B cells and autoantibodies
were observed. Immune activation, autoantibodies, and anti formaldehyde-human
serum albumin antibodies are associated with long-term formaldehyde
inhalation.
The incidence of spontaneous abortions among hospital staff who used ethylene
oxide, glutaral (glutaraldehyde) & formaldehyde for the
chemical sterilization of instruments was studied using data from a
questionnaire & a hospital discharge register. ... When the staff were
concerned in sterilizing during their pregnancy the frequency was 16.7% compared
with 5.6% for the nonexposed pregnancies. The incr frequency ... correlated with
exposure to ethylene oxide but not with exposure to glutaral or formaldehyde.
Employees exposed to formaldehyde in the woodworking
industry and nonexposed control subjects were examined by spirometry and the
nitrogen washout technique. A dose-response relationship was found between
exposure to formaldehyde and decrease in lung function.
Industrial exposure to formaldehyde causes transient lung
function impairment over a work shift, with a cumulative effect over the years.
The impairment, however, can be reversed with 4 wk of no exposure.
The mortality of 1,332 male workers employed at least 30 days in 1959-1980 in
a resins-manufacturing plant was examined. Ambient measurements taken in the
plant between 1974 and 1979 documented a potential for exposure to levels of formaldehyde
as high or greater than 3.0 mg/cu m. Vital status was ascertained for 98.6% of
the cohort members, and their mortality was compared with expected deaths drawn
from the national and local population rates. A statistically significant
increase in lung cancer was observed, based on 18 deaths, which was not fully
accounted for by possible confounding factors linked to personal habits or
sociocultural characteristics. This elevated risk, however, could not be
attributed specifically to exposure to formaldehyde. Mortality
from digestive cancer (14 deaths observed) and hematologic neoplasms (5 deaths
observed) was not substantially higher than expected.
Formaldehyde has been found to cause bronchial asthma-like
symptoms in humans. A young male neurology resident who spent 2 hr in autopsy of
formaldehyde-preserved human brains experienced both
conjunctival & nasal irritation while working; however, over the next 15 hr
after cessation of exposure, he developed progressive dyspnea & tightness in
the chest. Early edema indicative of pneumonitis was visible on Xray, &
after treatment with aminophyline, hydrocortisone, & oxygen (nasal prong at
4 l/min), he gradually improved over the following 2 days. He continued to need
prednisone (20 mg every other day for 2 wk), & he had fully recovered 5 wk
after the onset of his hypersensitivity reaction to inhaled formaldehyde.
In cultured human bronchial fibroblasts exposed to the carcinogen N-methyl-N-nitrosourea
(NMU) in combination with formaldehyde, formaldehyde
was observed to inhibit repair of alkylation of DNA at the O6 guanine position
induced by NMU. Whether formaldehyde enhances the effects of
other DNA-damaging agents has not yet been evaluated.
Hemodialysis patients are exposed chronically to trace levels of formaldehyde
(by formalin sterilization of their dialyzers to permit reuse).
Erythrocytes can be characterized in terms of MN phenotypes, analogous to the
AB-O system. The normal distribution of MM, NN, an MN phenotypes is about 25,
25, and 50%, respectively. Only 25% of the population would be expected to have
anti-N antibodies. Formaldehyde exposure may be followed by the
development of anti-N-like antibodies probably as a result of reaction with the
dissolved form of formaldehyde, methylene glycol. The
anti-N-like antibodies are also found following exposure to sodium hypochlorite.
The use of formaldehyde as a nail hardener, on the other
hand, is accompanied by a significant number of serious injuries to sensitive
nail and adnexal tissues. This type of exposure may contribute substantially to
that portion of the 4% sensitization index seen in clinical patients which is
cosmetic-related.
In a study ..., a group of 33 observers judged the perceived irritation &
odor of formaldehyde during 29-min chamber esposures to concns
ranging from 0.3-2.4 mg/cu m. The sensory irritation increased with time for the
lower concns & decreased with time for the highest. This effect was true for
irritation of eyes, nose, & throat & the sensitivity proved to be
roughly equal for all three sites. The sensory irritant effect of formaldehyde
at 1.2 mg/cu m was shown to decr when the chemical pyridine was injected into
the chanber; such sensory interactions occur in environmentally realistic
situations.
... Healthy volunteers (24 men, 9 women) /were exposed/ to formaldehyde
concns ranging between 0.036 & 4.8 mg/cu m air (33 volunteers for 35 min, 48
volunteers for 1.5 min. Eye blinking rates as well as subjective irritation
effects were determined. The irritation threshold was found to range between 1.2
& 2.4 mg formaldehyde/cu m. A similar threshold (1 mg/cu m)
was found in other studies. ... /It was/ noted that 9 out of 53 medical student
volunteers exposed to formaldehyde concns of between 0.39 &
0.60 mg/cu m for 8 hr/wk, complained of headaches, a burning sensation in the
eyes, sore throat, & annoyance because of the smell.
A 60-yr old man swallowed 60-90 mg of a 40% formaldehyde
soln. Thirty hr after death, the mucosa of the lowere part of the esophagus,
stomach, & first portion of duodenum were dark chocolate brown in color
& of the consistency of leather. All organs & tissues in contact with
the stomach were "hardened" to a depth of about 8 mm.
Workers exposed to 0.35-1.0 ppm (0.43-1.2 mg/cu m) for 6 minutes had a
significant irritation response at 1.0 ppm; nonsignificant responses were
reported at 0.7 and 0.9 ppm(0.9 and 1.1 mg/cu m).
Formaldehyde vapor is very irritating to the mucous
membranes and toxic to animals, including man.
... examined smears of nasal respiratory mucosa cells sampled from the inner
turbinate of 15 nonsmokers who were exposed to formaldehyde
released from a urea-formaldehyde glue used in a plywood
factory and 15 age- and sex-matched nonexposed clerks from outside of the
factory. Estimates of formaldehyde air conc ranged from : 0.21
to 0.60 (mean 0.39 + or - 0.20 ppm) in the warehouse where seven subject worked,
0.08 to 0.14 ppm (mean 0.1 + or - 0.02 ppm) in the shearing press where six
subjects worked, and 0.09 ppm (only one sample taken) in the sawmill area where
two subjects worked. Mean wood dust concn for the three areas were 0.23 + or -
0.1 mg/m3, 0.41 + or - 0.21 mg/m3, and 0.73 mg/m3, respectively. Exposed
subjects worked at the factory for 2-19 yr (mean 6.8 + or - 5.0 yr). Nasal
mucosal slides were scored as follows: normal cellularity, 1; number of
mucus-secreting cells greater than ciliated cells, 1.5; hyperplasia, 2; squamous
metaplasia, 2.5; mild dysplasia, 3; moderate dysplasia, 4; severe dysplasia, 5;
and malignant cells, 6. In the exposed group, all subjects had a greater number
of nonciliated than ciliated cells, 40% had hyperplasia, 67% had squamous
metaplasia, and 6% slight dysplasia. In controls, 26% had normal cytology, 67%
had more ciliated than nonciliated cells, 33% had hyperplasia, and 6% had
squamous metaplasia. The mean cytology score for the exposed group (2.3 + or -
0.5) was reported to be statistically significantly greater than the control
score (1.6 + or - 0.5). Also found in this study was a statistically
significantly higher percentage of micronucleated mucosal cells in the exposed
group compared with the control group (0.91% + or - 0.47 versus 0.25% + or -
0.22).
Mean baseline PEFR /(peak expiratory flow rate)/ declined by about 2% over a
10-wk period in a group of 24 physical therapy students who dissected cadavers
for 3-hr periods/wk ... . Estimates of breathing zone formaldehyde
concn ranged from 0.49-0.93 ppm (geometric mean 0.72 + or - 1.22 ppm). PEFR, the
only pulmonary function variable measured in this study, was measured before
& after each exposure period. Postexposure PEFR means were 1-3% lower than
preexposure PEFR means during the first 4 wk, but this difference was not
apparent during the last 6 wk. Fourteen wk after the end of the 10-wk period,
the mean PEFR for the group returned to the preexposure baseline value.
... evaluated the immunologic response of asthmatic subjects exposed to urea-formaldehyde
foam insulation (UFFI) off-gas products. Subjects consisted of 23 individuals
with a history of asthmatic symptoms attributed to UFFI & 4 individuals
(controls) with asthma unrelated to UFFI by-products. Subjects were exposed to
one of the following: room air (placebo) for 30 min; 1 ppm formaldehyde
gas for 3 hr; UFFI particles (4 um, 0.5 particles/ml) for 3 hr, commencing 48 hr
after formaldehyde gas exposure; & UFFI off-gas products
for 3 hr, commencing 48 hr after UFFI particle exposure. There were no
significant alterations in any of the white blood cell populations ... .
However, there was a significant incr in the % & absolute number of
eosinophils & basophils in the subject (who also lived in UFFI-homes) after
exposure to UFFI in the exposure chamber when compared to the white blood cell
values obtained before chamber exposure to UFFI.
Occupational exposures to formaldehyde have been assoc with
dermal irritation and the diagnosis of allergic contact dermatitis by patch
testing. Reported historical percentages of subjects with skin problems showing
positive responses to formaldehyde in patch tests performed by
dermatologists using aqueous soln with 1 or 2% formaldehyde
incl 7.8% in North America between 1992 and 1994 ... 1.6% in a 1983-1984 Swedish
study ... 2.6% in a 1988-1989 European study ... and 3.7% in a 1990-1994 Polish
study ... . Lack of case-specific exposure info for these patients precludes the
determination of the degree to which sensitization may have been caused by
direct dermal contact to formaldehyde in liquids or by contact
with formaldehyde gas in air, but the widespread use of formaldehyde
or formaldehyde-releasing chemicals in cosmetics and cleaning
agents ... suggest that the dermal route of exposure may be the more important
sensitizing route.
... measured elevated levels of formaldehyde-specific IgE in
24/62 8-yr old children who were students in three particle board-paneled
classrooms with est formaldehyde air concn of 0.075, 0.069, and
0.043 ppm. In a health survey, the children reported headaches (29/62), fatigue
(21/62), dry nasal mucosa (9/62), rhinitis (23/62) cough (15/62), and nosebleeds
(14/62). Sums of numbers of children with each of nine symptoms for each
classroom decr with decr formaldehyde conc (49, 47, and 24,
respectively for the 0.075-, 0.069-, and 0.043-ppm classrooms), but the
investigators reported that elevated levels of specific IgE did not correlate
with the number and severity of symptoms. The children were moved to a new
school without particle board paneling and were evaluated again, 3 mo after
moving. Est formaldehyde concn in the new classrooms were
0.029, 0.023, and 0.026 ppm. The numbers of children reporting symptoms decr
significantly compared with premoving reporting figures, and mean serum levels
of formaldehyde-specific IgE, measured in 20 of the children,
declined significantly compared with premoving mean levels.
... investigated the correlation between formaldehyde-induced
contact dermatitis and granulocyte chemiluminescence resulting from free-radical
release in healthy and formaldehyde-sensitive patients.
Thirteen patients with contact dermatitis who were occupationally exposed to formaldehyde
and five healthy volunteers participated in the study. All subjects underwent
skin-prick tests for common allergens as well as a histamine inhalation
provocation test. Subjects were exposed to 0.5 mg/m3 (0.41 ppm) formaldehyde
for 2 hr, and peak expiratory flow was measured immediately before exposure, at
60 and 120 min of exposure, and at 6 and 21 hr after completion of exposure. In formaldehyde-sensitive
patients, skin-prick tests and total serum IgE were normal; no antiformaldehyde
IgE was detected. In formaldehyde-sensitive patients,
peripheral blood granulocyte chemiluminescence significantly incr within 30 min
of exposure commencement, and remained elevated 24 hr later, compared to initial
values. Granulocyte chemiluminescence did not incr in healthy patients.
... measured the formation of DNA-protein cross links in peripheral white
blood cells of occupationally exposed workers (n=12) & unexposed controls
(n=8). The avg length of ... exposure was 13 yr. ... Venous blood samples were
collected ... . Personal & room concn of formaldehyde were
collected at various periods during the working day among the exposed subjects,
with formaldehyde room concn ranging from 1.38-1.6 ppm.
Personal monitoring devices indicated formaldehyde concn of
2.8-3.1 ppm during peak work & an avg concn of 1.46 ppm at times when work
was usually completed. Exposure to formaldehyde resulted in a
significant incr in the incidence of DNA-protein cross links. Mean ...
incidences in exposed & nonexposed workers were 28 + or - 6 & 22 + or -
6%, respectively. Within the exposed workers group, technicians had
significantly greater levels of DNA-protein cross links than physicians (32.3 +
or - 4.3 & 26.3 + or - 4.4%, respectively). A linear relationship between yr
of exposure & DNA-protein cross links formation was also detected. When the
data were analyzed considering worker smoking habits, DNA-protein cross links
was consistently elevated among formaldehyde-exposed versus
corresponding controls (p=0.03).
The finding of nasal tumors in rodents exposed to high levels of airborne formaldehyde
in the early 1980s ... led to a concern for cancer effect in occupationally
exposed workers. There are now more than 40 epidemiology studies examining the
potential for occupational formaldehyde exposure to cause
cancer in humans. The studies include cohort mortality studies of formaldehyde-exposed
industrial workers, cohort mortality studies of formaldehyde-exposed
professionals or medical specialists, & case-control studies that looked for
assoc between occupational exposure to formaldehyde &
cancers of the nose, pharynx, or lung. ... Although some of the epidemiological
studies have found some scattered evidence for extra-respiratory site cancers in
groups of formaldehyde-exposed workers, the data are not
consistent across studies & adjustment for potential confounding cancer risk
factors has not often been possible. Most, if not all reviewers, have agreed
that cancer of the respiratory tract, particularly the upper respiratory tract,
is more biologically plausible than formaldehyde-induced cancer
at distant sites given the reactivity of formaldehyde, the
capacity of tissues to metabolize formaldehyde, & the
results from chronic rodent inhalation studies showing that formaldehyde-induced
nonneoplastic & neoplastic effects are restricted to the upper respiratory
tract with exposures to concn below 5-10 ppm. Accordingly, the meta-analyses of
the human data have focused on the findings for respiratory cancer deaths in
occupationally exposed humans.
... describe the case of a 58-yr old man who swallowed 4 ounces of formalin
(517 mg formaldehyde/kg) in a suicide attempt. The man was
found unconscious by a co-worker about 1 hr after his shift began. In the
emergency room, the subject regained consciousness but was lethargic. Lab
results indicated significant acidosis. Approx 3 hr after ingesting the formalin,
the patient complained of abdominal pain & began retching without emesis; he
was admitted for observation & treated with ethanol. The patient's abdominal
pains became more severe & he had difficulty breathing. At 5.5 hr after
ingestion, the patient became obtund, & both his respiratory rate &
blood pressure fell significantly; he was intubated & placed on 100% oxygen.
Shortly thereafter, the patient began to experience seizures; treatment with
diazepam & phenytoin was unproductive, but pancuronium was effective in
treating the seizures. IV bicarbonate & ethanol therapies were begun after
the seizures started. The patient was transported for dialysis, but on arrival,
had clinical signs of intravascular coagulopathy. He subsequently sustained a
cardiac arrest from which he could not be revived. At autopsy, the patient's
stomach was hard, white, & leathery; the esophagus & intestines appeared
to be normal.
A 55-yr old woman and a 34-yr old man ingested, with suicidal intent, an
unknown amt of what was reported to have been formalin ... .
The female patient was found in a coma and admitted to the hospital with shock
(systolic blood pressure 50 mm Hg), respiratory insufficiency, and metabolic
acidosis. The male patient, who had a history of alcohol abuse, was also
hospitalized with shock (systolic blood pressure 60 mm Hg), respiratory
insufficiency, and metabolic acidosis. Both patients underwent hemodialysis and
hemofiltration treatment. Analysis of the formaldehyde samples
ingested by both patients showed no evidence that these products contained
methanol, although it was expected to have been detected. A
chemical-toxicological screening /of blood samples/ indicated that no drugs
other than formaldehyde had been ingested ... . Three wk after
ingestion of formaldehyde, the female patient died of cardiac
failure refractory to catecholamine therapy. The male patient developed adult
respiratory distress syndrome and died 8 wk after formaldehyde
ingestion with signs of cardiac failure.
Human lymphoblast mutants at the X-linked hprt locus have been examined by
Southern blot, Northern blot & DNA sequence analysis. A previous study had
shown that approx a third of the spontaneously arising mutants & half those
induced by formaldehyde showed no alteration in restriction
fragment pattern & thus were classified as point mutation. In this report,
these point mutants fall into 4 catagories: normal size & amount of RNA,
normal size but reduced amounts, reduced size RNA or no RNA. Sequence analyses
of cDNAs prepared from hprt mRNAs were performed on 1 spontaneous & 7 formaldehyde
induced mutants were base substitutions, all of which occurred at AT base-pairs.
There was an apparent hot spot, in that 4/6 independent mutants were AT----CG
transversions at one specific site. The remaining mutant had lost exon 8.
Human Toxicity Values:
The probable mean lethal adult dose is 1-2 oz.
Skin, Eye and Respiratory Irritations:
Contact with the skin causes irritation, tanning effect, and allergic
sensitization. Contact with eyes causes irritation, itching, & lacrimation.
...
Formaldehyde vapor is very irritating to the mucous
membranes and toxic to animals, including man.
Medical Surveillance:
Consider the skin, eyes, & resp tract in any placement or periodic
examination, esp if the patient has a history of allergies.
PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is
indicated, in particular when exposure to a carcinogen has occurred, ad hoc
decisions should be taken concerning ... /cytogenetic and/or other/ tests that
might become useful or mandatory. /Chemical Carcinogens/
... No biologic monitoring techniques exist at present, either for the
reliable determineation of formaldehyde levels in tissue or for
the determination of formaldehyde adducts formed with
macromolecules. Techniques are under development for nonspecific monitoring of
exposure through periodic assessment of chromosome damage (micronucleus
formation or sister chromatid exchange frequency) in workers exposed to formaldehyde.
Preemployment baseline data should be recorded for the respiratory tract,
liver, and skin condition of any worker who will be exposed to formaldehyde.
Thereafter, periodic monitoring should be conducted to detect symptoms of
pulmonary or skin sensitization or effects on the liver.
The assessment of formaldehyde exposure can be accomplished
through measurement of the metabolite formic acid. Formic acid is also an
endogenously produced substance formed by the degradation of glycine. There was
no information in the literature that showed a correlation between urinary
formic acid levels & formaldehyde exposure levels. This
measurement is also a poor indicator of the extent of formaldehyde
absorption, due to the high endogenous levels of formic acid. Urine Reference
Ranges: Normal- normal population level: 21 mg/l (endogenously produced formic
acid); Exposed- not established; Toxic- not established.
Respiratory Symptom Questionnaires: Questionnaires published by the American
Thoracic Society (ATS) & the British Medical Research Council have proven
useful for identifying people with chronic bronchitis. Certain pulmonary
function tests such as the FEV1 have been found to be better predictors of
chronic airflow obstruction.
Chest Radiography: Chest radiographs are widely used to assess pulmonary
disease. They are useful for detecting early lung cancer in asymptomatic people,
& especially for detecting peripheral tumors such as adenocarcinomas.
However, even though OSHA mandates this test for exposure to some toxicants such
asbestos, experts' views on the risk-to-benefit ratio in detection of pulmonary
disease conflict, so routine annual chest x-rays are not recommended for all
people.
Pulmonary Function Tests: The tests that have been found to be practical for
population monitoring include: Spirometry & expiratory flow-volume curves;
Determination of lung volumes; Diffusing capacity for carbon monoxide;
Single-breath nitrogen washout; Inhalation challenge tests; Serial measurements
of peak expiratory flow; Exercise testing.
Urine Albumin: Albuminuria has been shown to be a specific marker of
glomerular dysfunction. Tubular damage, however, can also result in increased
levels of albumin in the urine.
Urinary Beta-2-Microglobulin &/or Retinal Binding Protein: Measurements
for the presence of either of these low molecular weight proteins are useful in
detection of early impairment of proximal tubular function. However,
beta-2-microglobulin is unstable at urinary pH <6, & may degrade in the
bladder prior to collection & subsequent neutralization of the urine sample.
Measurement of retinal binding protein appears to be a better marker for early
tubular dysfunction due to its stability in the urine subsequent to collection
& analysis. However, retinal binding protein is produced in the liver &
not a constitutive protein of the kidney, so that its presence in the kidney
provides only indirect evidence of tubular damage.
Urinary Enzyme N-Acetylglucosaminidase: This lysosomal enzyme has shown
promise in assessment of subclinical nephrotoxic injury. This enzyme is not
normally filtered at the glomerulus due to its high molecular weight. In the
absence of glomerular injury, this enzyme will be detected in the urine as a
result of leakage or exocytosis from damaged, stimulated, or exfoliated renal
cells. The sensitivity of measurement for this enzyme has not been thoroughly
studied, but it's usefulness has shown some promise. However, this enzyme is
unstable at urinary pH >8, which could diminish the sensitivity of the
measurement due to enzyme degradation.
DNA-Protein Crosslinks: Measurement of DNA-protein crosslinks in white blood
cells may be a useful test for assessing formaldehyde exposure.
In addition, measurement of these crosslinks in other formaldehyde
sensitive tissues, such as the upper respiratory tract, may be a useful
indicator of formaldehyde exposure. However, other toxicants
may cause similar crosslinks, so that the specificity of this test for assessing
only formaldehyde exposure is questionable.
Routine Urinalysis: Performing a routine urinalysis including parameters such
as specific gravity, glucose, & microscopic exam may be useful for assessing
renal toxicity.
Urinary Alpha & Pi Isoenzymes of Glutathione S-Transferase:
Radio-immunological & Elisa techniques have been developed for quantitation
of /alpha/ & /pi/ isoenzymes of glutathione S-transferase, which are
constitutive proteins in the kidney. The /alpha/ isoenzyme is located only in
the proximal tubule, while the /pi/ isoenzyme is located in the distal
convoluted tubule, the loop of Henle, & the collecting ducts of the kidney.
Damage to epithelial cell membranes can result in the increased excretion of
these isoenzymes in the urine. This test for assessing renal tubular damage
appears to have many advantages over other available tests, such as: (1) the
/alpha/ & /pi/ isoenzymes are constitutive proteins in the kidney; (2) these
isoenzymes are stable in the urine; (3) the test is simple & reproducible;
& (4) due to selective localization of the isoenzymes, differential
diagnosis of specific tubular damage is possible. In addition, increased levels
of these isoenzymes were seen in patients previously exposed to nephrotoxicants
where conventional tests for kidney function were normal, indicating a high
degree of sensitivity.
Populations at Special Risk:
Mean formaldehyde levels are highest in hospital autopsy
rooms compared with other commercial settings. /Hospital autopsy workers are
possibly exposed/.
Release of /formaldehyde/ vapors in mobile homes has been
associated with headache & pulmonary & dermal irritation. /Occupants of
mobile homes are possibly exposed/.
Two populations of humans have received considerable attention in the
literature as being particularly sensitive to formaldehyde
exposure following inhalation and/or dermal routes. The first population is
asthmatics, and concern focuses on the changes in lung function parameters that formaldehyde
may produce ... . Most of these studies concluded that there is no evidence of
incr airway reactivity as a result of formaldehyde exposure in
either normal or asthmatic individuals. ... The second population of potential
concern is people with dermal sensitization ... Formaldehyde
liquid, but neither the gaseous phase nor formalin, is
considered to be a dermal sensitizer ... . Anaphylactic reactions have been
reported ... . Dermal allergic reactions have also been reported in doctors and
nurses exposed to formaldehyde ... as well as in fiberglass
workers ... .
Workers in industries where formaldehyde is used or released
may receive potentially high exposures. Members of the general population who
live in newly constructed homes or homes where pressed wood products have
recently been installed may be exposed to high levels of formaldehyde
by inhalation for short periods of time until the latent formaldehyde
has been released. Exposure in mobile homes are expected to be higher than
conventional homes due to their lower rate of air exchange ... . Members of the
general population that handle large amt of permanent press fabrics treated with
formaldehyde-releasing resins may also receive potentially high
exposures. The use of some cosmetics, such as nail hardeners, may result in high
short-term exposure.
Smokers and persons who live in a home with a cigarette smoker also may be
exposed to higher levels of formaldehyde. Environmental tobacco
smoke, which is a combination of diluted sidestream smoke released form a
cigarette's burning end and mainstream smoke exhaled by an active smoker, can
contribute 10-25% (0.1-1 mg/day) of the total average indoor exposure to
formadehyde ... .
Probable Routes of Human Exposure:
... /VAPORS/ GIVEN OFF DURING HOT MOLDING OF SYNTH RESINS (/IS A/ COMMON
SOURCE OF EXPOSURE) ... A SURVEY OF 6 FUNERAL HOMES ... REVEALED MEAN CONCN, IN
DIFFERENT ESTABLISHMENTS, BETWEEN 0.25 & 1.39 PPM. ... /EXPOSURES ARE
ENCOUNTERED/ IN PHENOL-FORMALDEHYDE RESIN MOULDING PLANT ...
/FROM WHICH/ CHRONIC AIRWAY OBSTRUCTION LOWERED FORCED EXPIRATORY VOL/FORCED VOL
CAPACITY RATIO & EYE, NOSE & THROAT IRRITATION & LOWER RESP TRACT
SYMPTOMS /HAVE BEEN OBSERVED/.
... /EXPOSURES TO/ FORMALDEHYDE VAPOR EMISSIONS IN
PERMANENT-PRESS FABRICS INDUSTRY (8 PLANTS) /HAVE BEEN REPORTED IN WHICH/ CONCN
RANGING ... FROM 0.3 TO 2.7 PPM (IN SEWING AREA) WITH AVG OF 0.68 PPM /WERE
DETECTED/. COMPLAINTS CONSISTED OF ANNOYING ODOR (ODOR THRESHOLD, BELOW 1.0
PPM), CONSTANT PRICKLING IRRITATION OF MUCOUS MEMBRANES & DISTURBED SLEEP.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,329,322
workers (441,902 of these are female) are potentially exposed to formaldehyde
in the US(1). The NOES Survey does not include farm workers(SRC). Occupational
exposure to formaldehyde may occur through inhalation and
dermal contact with this compound at workplaces where formaldehyde
is produced or used(2). Monitoring data indicate that the general population may
be exposed to formaldehyde via inhalation of ambient air,
ingestion of food, and dermal contact with cosmetic and aerosol products
containing formaldehyde(2).
Humans are exposed to formaldehyde from a variety of
sources. The major source of atmospheric discharge is from combustion processes
specifically from auto emissions and also from the photooxidation of
hydrocarbons in auto emissions(1,2). Additional exposure to formaldehyde
emissions comes from its use as an embalming fluid in anatomy labs, morgues, etc
and its use as a fumigant and sterilant(1). Resin treated fabric, rugs, paper,
etc and materials such as particle board and plywood which use resin adhesives
and foam insulation release formaldehyde which may build up in
homes and occupational atmospheres(1,2). Contact with industrial waste water,
especially from lumber related operations where formaldehyde is
used in adhesives, has resulted in the Pacific Northwest, Northeast, parts of
Texas, and lumber areas of the south(1)(SRC). The estimated daily intake of formaldehyde
among exposed Finnish workers is 3000 ug, whereas heavily exposed workers
(particle-board and glue production, foundry work) is 10,000 ug(3).
In a 12-week study of exposure in a gross anatomy lab of a medical school,
44% of breathing room samples and 11% of ambient air samples were >1.0 ppm
the ceiling recommended by ACGIH; Half the breathing zone samples were between
0.6-1.0 ppm and the range was 0.3-2.63 ppm(1). A 1976 report estimates that 8000
US workers were potentially exposed to formaldehyde during its
production(3). A more recent estimate of the number of exposed workers in
industries producing and using formaldehyde and its derivatives
range from 1.4-1.75 million(2). Concentrations of formaldehyde
in occupational areas dating from the 1960's and early 1970's are: textile plant
0-2.7 ppm, 0.68 ppm avg; garment factory 0.9-2.7 ppm; clothing store 0.9-3.3
ppm; laminating plant 0.04-10 ppm; funeral homes 0.09-5.26 ppm, 0.25-1.39 ppm
avg; resin manufacture and paper production 16-30 ppm; paper conditioning
0.9-1.6 ppm; wood processing 31.2 ppm max(2). Concns in occupational settings
dating from the late 70's are: textile plants 0.1-0.5 ppm, 0.2 ppm avg; shoe
factory 0.9-2.7 ppm, 1.9 ppm avg; particle board plant 0.1-4.9 ppm, 1.15 ppm
avg; plywood plant 0.1-1.2 ppm, 0.35 ppm avg; wooden furniture manufacturing
plant 0.1-5.4 ppm, 1.35 ppm avg; adhesive plants 0.8-3.5 ppm, 1.75 ppm avg;
foundries 0.05-2.0 ppm, 0.6 ppm avg; construction sites 0.5-7.0 ppm, 2.8 ppm
avg; hospitals and clinics 0.05-3.5 ppm, 0.7 ppm avg(2). More recent survey
results for occupational environments include: fertilizer production 0.2-1.9
ppm; dyestuffs <0.1-5.8 ppm; textile manufacture <0.1-1.4 ppm; resins
(foundry) <0.1-5.5 ppm; bronze foundry 0.12-0.8 ppm; iron foundry
<0.02-18.3 ppm; treated paper 0.14-0.99 ppm; hospital autopsy room 2.2-7.9
ppm; plywood industry 1.0-2.5 ppm; urea-formaldehyde foam
applicators <0.08-2.4 ppm(4).
Potential occupational exposure to formaldehyde are as
follows: agricultural workers, anatomists, beauticians, biologists, bookbinders,
botanists, chemical production workers, cosmetic formulators, crease-resistant
textile finishers, disinfectant makers, disinfectors, dress-goods shop
personnel, electrical insulation makers, embalmers, embalming fluid makers,
fireproofers, formaldehyde production workers, formaldehyde
resin makers, foundry employees, fumigators, fur processors, furniture makers,
glue and adhesive makers, hide preservers, histology technicians (including
necropsy and autopsy technicians), ink makers, lacquerers and lacquer makers,
medical personnel (including pathologists), mirror manufacturers, paper makers,
particle-board makers, photographic film makers, plastic workers, plywood
makers, rubber makers, taxidermists, textiles mordanters and printers, textiles
waterproofers, varnish workers, wood preservers(1).
The avg concn of formaldehyde in workroom air in formaldehyde
and resin manufacturing plants ranged from 0.1-14.2 mg/cu m(1). The avg concn of
formaldehyde in workroom air of plywood mills, particle-board
mills, furniture factories, other wood product and paper mills ranged from
0.08-7.4 mg/cu m(1). The avg concn of formaldehyde in workroom
air in textile mills and garment factories ranged from 0.1 to 1.9 mg/cu m(1).
The avg concn of formaldehyde in workroom air in foundries and
other industrial facilities ranged from 0.04 to 38.2 mg/cu m(1). The avg concn
of formaldehyde in workroom air in mortuaries, hospitals, and
laboratories ranged from 0.05 to 4.2 mg/cu m(1). The avg concn of formaldehyde
in workroom air in building sites, agriculture, forestry, and misc other
activities ranged from <0.1 to 4.3 mg/cu m(1).
Cigarette smoke and products of combustion contain formaldehyde(1).
Cigarette smoke contains 15 to 20 mg formaldehyde per
cigarette(1). Avg formaldehyde exposure from passive smoking is
between 0.23 to 0.27 ppm(1). A 'pack-a-day' smoker may inhale as much as 0.4-2.0
mg formaldehyde(1).
Several studies have been conducted to determine exposure of students in
laboratories(1). The concn of formaldehyde in the breathing
zone at dissecting tables and in the ambient air in a medical school in the
United States was found to be >1.2 mg/cu m in 44% of the breathing zone
samples and 11 ambient air samples; 50% of the breathing zone samples contained
0.7-1.2 mg/cu m, with a range of 0.4-3.2 mg/cu m(1). During the 1982-82 academic
year, the airborne concn of formaldehyde at a university in the
US was 7-16.5 ppm in the laboratory, 1.97-2.62 ppm in the stockroom, and <1
ppm in the public hallway(1). In another study, of 253 samples of air taken
during laboratory dissection classes at a university in the US, 97 contained
concns above the detection limit of 0.01 mg/cu m; all but four samples had
levels <1.2 mg/cu m(1). The avg concn detected was 0.5 mg/cu m(1).
Average Daily Intake:
AIR INTAKE: Assume 1 to 100 ug/cu m(1), 20 ug to 2,000 ug formaldehyde(SRC).
In Sweden between Dec 1986 to Aug 1987, the mean yearly exposure to formaldehyde
from air pollution was 1.2 ug/cu m(1). The estimated daily exposure of the
Finnish population to formaldehyde from community air is 100 ug
and from the home environment, 1,000 ug(2).
Minimum Fatal Dose Level:
Approximate Minimum Lethal Dose (MLD) (150-lb man): 30 ml
Male single oral ingestion 517 mg/kg
Emergency Medical Treatment:
Emergency Medical Treatment:
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MICROMEDEX, SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF
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strictly prohibited.
The following Overview, *** FORMALDEHYDE ***, is relevant
for this HSDB record chemical.
Life Support:
o This overview assumes that basic life support measures
have been instituted.
Clinical Effects:
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o Formadehyde may be irritating to the eyes, skin, and
mucous membranes. Ingestion may cause corrosive injury
to the gastrointestinal mucosa, with nausea, vomiting,
pain, hematemesis, and perforation. Systemic effects
include CNS depression, seizures, coma, jaundice,
albuminuria, hematuria, anuria, and metabolic acidosis.
o Inhalation can cause respiratory tract irritation,
rhinitis, anosmia, cough, dyspnea, wheezing,
tracheitis, bronchitis, laryngospasm, pulmonary edema,
headache, weakness, dizziness, and palpitations.
o Dermatitis, brownish discoloration of the skin,
urticaria, and pustulovesicular eruptions, may develop
from dermal exposure. Concentrated solutions can
cause coagulation necrosis.
o Irritation, lacrimation, and conjunctivitis may develop
with exposure to vapors. Eye exposure to solutions
with high formaldehyde concentrations may produce
severe corneal opacification and loss of vision.
Solutions containing low formaldehyde concentrations
may produce transient discomfort and irritation.
VITAL SIGNS
0.2.3.1 ACUTE EXPOSURE
o Shock may develop with severe exposures. Tachypnea may
develop in patients with metabolic acidosis. Reduction
in body temperature may be seen.
HEENT
0.2.4.1 ACUTE EXPOSURE
o IRRITATION of the eyes, nose, and throat may occur
following exposure to formaldehyde OR fumes from
urea-formaldehyde foam and adhesive resins.
o Corneal opacification and loss of vision may occur
following direct eye splash exposure to solutions
containing high concentrations of formaldehyde.
Transient discomfort and irritation may result from eye
exposure to solutions containing low concentrations of
formaldehyde.
CARDIOVASCULAR
0.2.5.1 ACUTE EXPOSURE
o Hypotension and cardiovascular collapse may occur with
severe ingestion.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Inhalation of formaldehyde vapors at elevated
concentrations may result in upper respiratory tract
irritation and coughing. Severe exposure may result in
serious lower respiratory effects, such as bronchitis,
pulmonary edema, or pneumonia. Reactive airways may
develop in susceptible individuals.
o Respiratory distress and ARDS has been reported
following ingestion or transdermal absorption of
formaldehyde-containing compounds.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o Lethargy and coma may occur following large ingestions
or marked inhalation exposure.
0.2.7.2 CHRONIC EXPOSURE
o Chronic exposure may result in malaise, headache,
sleeping disturbances and irritability.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting, and severe abdominal pain may occur
following ingestion. Corrosive gastritis, hematemesis,
and edema and ulceration of the esophagus may occur.
Strictures and perforation are possible delayed
complications.
HEPATIC
0.2.9.1 ACUTE EXPOSURE
o Hepatotoxicity has been associated with inhalation
exposure in animals and suggested in humans.
o Hyperbilirubinemia has been reported following
ingestion.
o Biliary sclerosis occurred following formalin
instillation into hydatid cyst.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Nephritis and acute renal failure may occur.
Membranous nephropathy has been associated with
formaldehyde exposure.
ACID-BASE
0.2.11.1 ACUTE EXPOSURE
o Metabolic acidosis and hyperlactacidemia may occur.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Intravascular hemolysis has been reported in dialysis
patients receiving doses of formaldehyde during
treatment.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Allergic dermatitis and rash may occur.
IMMUNOLOGIC
0.2.19.1 ACUTE EXPOSURE
o Antibodies to formaldehyde (Types I and II reactions)
have been measured in exposed persons with clinical
effects ranging from irritation to severe
hypersensitivity reactions. Type IV reactions may
result in allergic contact dermatitis. Immunologic
reactions may be delayed by hours to months.
o Asthma-like signs and symptoms have been reported.
Evidence of formaldehyde sensitization or allergy
causing true asthma is inconclusive. Respiratory
effects do not consistently correlate with the
development of formaldehyde-specific immunoglobulins.
o Membranous nephropathy has been associated with
immunologic reaction to suspected formaldehyde
exposure.
0.2.19.2 CHRONIC EXPOSURE
o Allergic contact dermatitis, eczema and other signs
have been attributed to formaldehyde sensitivity.
REPRODUCTIVE HAZARDS
o Formaldehyde has not been shown definitely to be
teratogenic in animals. Formaldehyde probably presents
little or no risk as a potential human teratogen.
o Menstrual disorders have been reported in women
occupationally exposed to formaldehyde, but these
results are controversial. In experimental animal
studies, some effects on spermatogenesis have been
reported.
o Occupational exposure at recommended limits is not
thought to present a reproductive risk. Formaldehyde
exposure among female hospital workers did not correlate
with an increase in spontaneous abortion in one study,
but did correlate in another.
1. Low-birthweight children have been reported in female
workers exposed to urea-formaldehyde resin, but studies
are inconclusive. Formaldehyde appears to cross the
placental barrier in mice.
CARCINOGENICITY
0.2.21.2 HUMAN OVERVIEW
o Formaldehyde is a probable human nasopharyngeal
carcinogen (IARC 2A Limited evidence in humans and
sufficient evidence in animals).
1. Occupational exposure to formaldehyde has been linked
to the development of buccal and nasopharyngeal
metaplasia/neoplasia, and to a lesser extent cancers
of the nasal cavities.
2. Formaldehyde's role in lower respiratory tract cancer
etiology has not been substantiated. Consensus on
data collection and analysis methods will be necessary
to evaluate the link between formaldehyde and lung
cancer.
3. Formaldehyde reacts with HYDROGEN CHLORIDE to form
BIS-CHLOROMETHYL ETHER, a known human carcinogen.
GENOTOXICITY
o Formaldehyde appears to be mutagenic. The basis for its
genetic activity is its ability to form cross-links in
DNA and proteins.
Laboratory:
o FORMALDEHYDE PLASMA LEVELS are not widely available, but
may help in dialysis monitoring.
o Monitor acid base status in symptomatic patients. Monitor
liver function tests. Monitor hematocrit and hemoglobin
concentration in dialysis patients repeatedly exposed
parenterally to formaldehyde. Monitor blood METHANOL
levels after significant formalin ingestion.
o Pulmonary function testing and nasal and bronchial
provocation tests may be recommended in patients with
signs and symptoms of reactive airways dysfunction
following inhalation of formaldehyde.
Treatment Overview:
ORAL EXPOSURE
o EMESIS: Ipecac-induced emesis is not recommended
because of the potential for cardiovascular instability.
o DILUTION: Following ingestion and/or prior to gastric
evacuation, immediately dilute with 4 to 8 ounces (120
to 240 mL) of milk or water (not to exceed 15 mL/kg in a
child).
o After ingestion of concentrated formaldehyde, gastric
lavage with a soft small-bore NG tube may facilitate
removal. Risk of further mucosal injury should be
weighed against potential benefit. Although no data on
adsorption to activated charcoal could be found, it
should be considered following lavage, although it may
obscure endoscopy findings.
o ACTIVATED CHARCOAL: Administer charcoal as a slurry
(240 mL water/30 g charcoal). Usual dose: 25 to 100 g
in adults/adolescents, 25 to 50 g in children (1 to 12
years), and 1 g/kg in infants less than 1 year old.
o MONITOR ECG AND VITAL SIGNS and acid base status.
Monitor methanol levels.
o ENDOSCOPY: Because acid ingestion may cause severe
gastric burns with relatively few initial signs and
symptoms, endoscopic evaluation is recommended within 24
hours in any patient with a definite history of
ingesting a strong acid, even if asymptomatic. If burns
are found, follow 10 to 20 days later with a barium
swallow.
o PHARMACOLOGIC TREATMENT: Corticosteroids are
controversial. Consider use in second degree burns
within 48 hours of ingestion in patients without
gastrointestinal bleeding or evidence of perforation.
Antibiotics are indicated for suspected perforation or
infection and in patients receiving corticosteroids.
o SURGICAL OPTIONS: Initially, if severe esophageal burns
are found a string may be placed in the stomach to
facilitate later dilation. Insertion of a specialized
nasogastric tube after confirmation of a circumferential
burn may prevent strictures. Dilation is indicated
after 2 to 4 weeks if strictures are confirmed; if
unsuccessful, either colonic intraposition or gastric
tube placement may be performed. Consider early
laparotomy in patients with severe esophageal and/or
gastric burns.
o Administer ethanol or fomepizole in patients with
significant methanol levels. HEMODIALYSIS should be
considered in those patients with severe acid-base
disturbances refractory to conventional therapy, or in
cases with significant methanol levels.
o HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid,
place in Trendelenburg position. If hypotension
persists, administer dopamine (5 to 20 mcg/kg/min) or
norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to
desired response.
INHALATION EXPOSURE
o INHALATION: Move patient to fresh air. Monitor for
respiratory distress. If cough or difficulty breathing
develops, evaluate for respiratory tract irritation,
bronchitis, or pneumonitis. Administer oxygen and
assist ventilation as required. Treat bronchospasm with
beta2 agonist and corticosteroid aerosols.
EYE EXPOSURE
o MEDICAL FACILITY: Irrigate with sterile 0.9% saline for
at least an hour or until the cul-de-sacs are free of
particulate matter and returned to neutrality (confirm
with pH paper).
DERMAL EXPOSURE
o DECONTAMINATION: Remove contaminated clothing and wash
exposed area thoroughly with soap and water. A
physician may need to examine the area if irritation or
pain persists.
Range of Toxicity:
o INGESTION of as little as 30 mL of a 37% solution of
formaldehyde has resulted in death in an adult.
Antidote and Emergency Treatment:
Decontamination: Dilute with milk or water in alert patients as a first aid
measure may reduce corrosive effects at the scene. If ingestion has occurred
within 1 hr before presentation, gentle gastric aspiration with a soft
nasogastric tube may limit systemic absorption. There is little evidence to
support the use of activated charcoal to absorb formate or formaldehyde.
... Elimination enhancement: Severe acidosis & deteriorating vital signs are
indications for considering dialysis, but the literature does not contain
adequate case studies to guide treatment. Aggressive sodium bicarbonate therapy
& frequent monitoring of arterial blood gases may be useful. There are no
antidotes. Supportive care: 1. Monitor electrolytes, fluids, acid-base, &
kidney function closely. 2. Watch for signs of GI hemorrhage & perforation
with serial vital signs, abdominal exams, & complete blood counts. 3. Check
blood methanol levels & treat accordingly in formalin
ingestions. 4. Fibrosis of stomach has required partial gastrectomy in the past.
Irrigate eyes with water. Wash contaminated areas of body with soap and
water. Gastric lavage (stomach wash), if swallowed, using 1% ammonium carbonate
and followed by saline catharsis. Oxygen, if indicated.
Basic Treatment: Skin- Treated as any burn to prevent allergic contact
dermatitis, exposure to formaldehyde or formaldehyde-containing
products should be minimized. Inhalation- Patients should be removed from
exposure. If symptoms persist, hospitalization may be required. Very high levels
(100 ppm) may be lethal. Pulmonary damage may occur. Oral- high concn of formaldehyde
may be irritating to the GI tract. Ingestion can result in metabolic responses
similar to methanol poisoning. Hemodialysis is efficacious just as in methanol
poisoning & should be considered if metabolic acidosis occurs.
Basic treatment: Establish a patent airway. Suction if necessary. Watch for
signs of respiratory insufficiency and assist ventilations if necessary.
Aggressive airway management may be necessary. Administer oxygen by
nonrebreather mask at 10 to 15 L/min. Anticipate seizures and treat if necessary
... . Monitor for shock and treat if necessary ... . Monitor for pulmonary edema
and treat if necessary ... . For eye contamination, flush eyes immediately with
water. Irrigate each eye continuously with normal saline during transport ... .
Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200
ml of water for dilution if the patient can swallow, has a strong gag reflex,
and does not drool. Administer activated charcoal ... . /Aldehydes and related
compounds/
Advanced treatment: Consider orotracheal or nasotracheal intubation for
airway control in the patient who is unconscious or in respiratory arrest.
Intubation should be considered at the first sign of upper airway obstruction
caused by edema. Positive pressure ventilation techniques with a bag-valve-mask
device may be beneficial. Start an IV with D5W /SRP: "To keep open",
minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present.
Watch for signs of fluid overload. Treat seizures with diazepam ... . For
hypotension with signs of hypovolemia, administer fluid cautiously. Consider
vasopressors if patient is hypotensive with a normal fluid volume. Watch for
signs of fluid overload ... . Consider drug therapy for pulmonary edema ... .
Use proparacaine hydrochloride to assist eye irrigation ... . /Aldehydes and
related compounds/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION:
Based on limited evidence in humans, and sufficient evidence in animals. Human
data include nine studies that show statistically significant associations
between site-specific respiratory neoplasms and exposure to formaldehyde
or formaldehyde-containing products. An increased incidence of
nasal squamous cell carcinomas was observed in long-term inhalation studies in
rats and in mice. The classification is supported by in vitro genotoxicity data
and formaldehyde's structural relationships to other
carcinogenic aldehydes such as acetaldehyde. HUMAN CARCINOGENICITY DATA:
Limited. ANIMAL CARCINOGENICITY DATA: Sufficient.
A2. A2= Suspected human carcinogen.
Evaluation: There is limited evidence in humans for the carcinogenicity of formaldehyde.
There is sufficient evidence in experimental animals for the carcinogenicity of formaldehyde.
Overall evaluation: Formaldehyde is probably carcinogenic to
humans (Group 2A).
Non-Human Toxicity Excerpts:
INHALATION ... BY ANIMALS CAUSES PROMPT & SEVERE IRRITATION OF EYES &
RESP TRACT. ... EDEMA & HEMORRHAGES OF ... LUNG, & SIGNS OF HYPEREMIA
& PERIVASCULAR EDEMA IN THE LIVER AND KIDNEYS.
PROLONGED EXPOSURE OF RABBITS TO FORMALDEHYDE CAUSED ACID
PHOSPHATASE, TWEEN-60-ESTERASE, NAPHTHOL-AS-D-ACETATE-ESTERASE, PROLINE-OXIDASE
& HYDROXYPROLINE-2-EPIMERASE ACTIVITIES TO INCREASE &
LEUCYL-AMINOPEPTIDASE & BETA-GLUCURONIDASE TO DECREASE. IT INDUCED BRONCHIAL
CELL HYPERPLASIA WITH HYPERMUCIGENESIS, EXTRUSION OF BRONCHIAL CELLS,
BRONCHIOLAR HYPERMUCIGENESIS, PARCELLARY SQUAMOUS METAPLASIA OR NECROBIOSIS OF
EPITHELIA.
CD-1 MICE WERE GIVEN UP TO 185 MG/KG BODY WT FORMALDEHYDE BY
GAVAGE ON DAYS 6-15 OF GESTATION. HIGHEST DOSE WAS ... TOXIC TO DAMS, BUT NO
EMBRYOTOXICITY OR TERATOGENICITY WAS SEEN WITH ANY DOSE.
ACUTE ... EFFECTS ... IN RATS ... /& OTHER EXPTL ANIMALS/ TO LOW (LESS
THAN 1 PPM) OR MODERATE (10-50 PPM) ... /OF/ VAPOR RESULTED IN INCREASED AIRWAY
RESISTANCE, DECR SENSITIVITY OF NASOPALATINE NERVE, IRRITATION OF EYES & OF
RESP SYSTEM, & CHANGES IN HYPOTHALAMUS. EXPOSURE TO HIGH DOSES (ABOVE 100
PPM) ... CAUSED SALIVATION, ACUTE DYSPNEA, VOMITING, CRAMPS & DEATH ... .
EXPOSURE BY INHALATION FOR UP TO 90 DAYS PRODUCED INTERSTITIAL INFLAMMATION
IN LUNGS OF DOGS, RATS, MONKEYS, RABBITS & GUINEA-PIGS. ... HAIR
DEPIGMENTATION WAS OBSERVED IN BLACK MICE AT SITE OF SC INJECTION OF 100 UG FORMALDEHYDE.
... MICE TREATED WITH FORMALDEHYDE ON SKIN DEVELOPED SEVERE
LIVER DAMAGE.
GROUPS OF 119-120 MALE & 120 FEMALE FISCHER 344 RATS, 7 WK OF AGE WERE
EXPOSED TO 0, 2, 5.6 OR 14.3 PPM (0, 2.5, 6.9, 17.6 MG/CU M) ... GREATER THAN
97.5% PURE VAPOR BY WHOLE-BODY EXPOSURE FOR 6 HR/DAY ON 5 DAYS/WK FOR UP TO 24
MO, FOLLOWED BY 6 MO OBSERVATION PERIOD. ... LIFE-TABLE ANALYSIS OF ... DATA
REVEALED SIGNIFICANT INCR (P< 0.0167) IN INCIDENCES OF SQUAMOUS-CELL
CARCINOMAS IN /NASAL CAVITY OF RATS/ EXPOSED TO 14.3 PPM FORMALDEHYDE
VAPOR; NO OTHER NEOPLASM WAS INCREASED SIGNIFICANTLY. THE INCIDENCE OF A VARIETY
OF NON-NEOPLASTIC LESIONS WERE SIGNIFICANTLY INCREASED IN RATS EXPOSED TO FORMALDEHYDE.
GROUPS OF 6 MALE CYNOMOLGUS MONKEYS ... & 10 MALE & 10 FEMALE SYRIAN
GOLDEN HAMSTERS WERE EXPOSED TO 0, 0.2, 1.0 OR 3 PPM (0, 0.24, 1.2 OR 3.7 MG/CU
M) FORMALDEHYDE VAPOR (98.8% PURE) FOR 22 HR/DAY ON 7 DAYS/WK
FOR 26 WK. SQUAMOUS METAPLASIA OF NASAL TURBINATES WERE EVIDENT IN 6/6 MONKEYS
EXPOSED TO 3 PPM & IN 1/6 EXPOSED TO 1 PPM. ... NO EXPOSURE-RELATED EFFECTS
WERE DEMONSTRATED IN HAMSTERS.
REPEATED INHALATION EXPOSURE TO VAPORS AT 15 PPM IN MALE CHARLES RIVER CD
RATS & MALE C57BL6/F1 MICE WAS STUDIED. RATS WERE RELATIVELY INSENSITIVE TO
IRRITANT ACTION WHILE MICE WERE MORE SENSITIVE, SHOWING COMPARABLE REDUCTION IN
TIDAL VOL, BUT GREATER DECR IN RESPIRATORY RATE & MINUTE VOL. CARBON DIOXIDE
PRODUCTION AS WELL AS BODY TEMP WERE DECR TO GREATER EXTENT IN MICE THAN IN
RATS.
With Salmonella typhimurium, the minimum concn required to induce
8-azaguanine resistance was 170 uM.
15 ppm formaldehyde caused an initial wave of cell
replication in the nasal cavity of mice and rats 18 hr after a 6 hr exposure.
The /percentage/ of replicating cells remained ... elevated for 3-5 days and
then began to decrease. Similar elevations occurred following 3 daily exposures
to 6 ppm formaldehyde in rats, but not mice. ...
... Threshold concn of sensitization effect of /formaldehyde/
in guinea pigs was 0.5 mg/cu m. ... Quantitative changes were seen only in
B-lymphocytes, whereas T-lymphocytes were essentially unchanged. At 3 mg/cu m
the sensitization effect was seen in all the animals. The T-lymphocytes
decreased substantially but B-lymphocytes increased. ...
... Primary hamster embryo cells were treated by exposure to gaseous formaldehyde
or by incorporation into the medium, a dose-related incr in the frequency of SA7
virus transformation was produced. ... Length of chemical treatment and the time
interval before subsequent addition of transforming virus was critical, with 2
hr treatment times being most efficient. ... 2.2 ug/ml produced significantly
enhanced viral transformation. ...
... RATS /EXPOSED/ CONTINUOUSLY DURING PREGNANCY TO ... VAPORS (1 MG/CU M)
... /SHOWED/ NO VISIBLE FETAL MALFORMATIONS. ASCORBIC ACID CONTENT OF TREATED
FETUSES WAS LOWER THAN CONTROLS BUT BODY WT WAS INCR. FETAL DNA CONTENT WAS DECR
& RNA CONTENT WAS INCR.
GROUPS OF 100 MALE SPRAGUE-DAWLEY RATS WERE EXPOSED FROM 9 WK OF AGE TO (A)
14.3 PPM (17.44 MG/CU M) FORMALDEHYDE (PURITY UNSPECIFIED)
& 10 PPM (16.2 MG/CU M) HYDROGEN CHLORIDE GAS BEFORE DILN IN EXPOSURE
CHAMBER TO MAXIMIZE FORMATION OF BIS(CHLOROMETHYL)ETHER; (B) 14.1 PPM (17.2
MG/CU M) FORMALDEHYDE & 9.5 PPM 115.48 MG/CU M) HYDROGEN
CHLORIDE NOT MIXED BEFORE INTRODUCTION INTO ... CHAMBER; (C)14.2 PPM (17.32
MG/CU M) FORMALDEHYDE VAPOR ALONE; (D) HYDROGEN CHLORIDE GAS
ALONE (10.2 PPM); OR (E) AIR (SHAM-EXPOSED CONTROLS). AFTER ... 382 EXPOSURES
OVER ... 588 DAYS (19.4 MO), 10 HISTOLOGICALLY CONFIRMED, GROSSLY VISIBLE NASAL
SQUAMOUS-CELL CARCINOMAS WERE OBSERVED IN RATS EXPOSED TO FORMALDEHYDE
ALONE; NONE WERE SEEN IN CONTROLS OR IN RATS EXPOSED TO HYDROGEN CHLORIDE ALONE
... COMBINED EXPOSURE TO FORMALDEHYDE & HYDROGEN CHLORIDE
DID NOT PRODUCE STATISTICALLY SIGNIFICANT INCR IN INCIDENCE OF NASAL
SQUAMOUS-CELL CARCINOMAS OVER THAT OBTAINED WITH FORMALDEHYDE
ALONE. ...
EXPOSURE OF CULTURED MONKEY KIDNEY CELLS TO 1-16 MMOL ... FOR 15 MIN RESULTED
IN FORMATION OF SHORT RNA CHAINS; CONCN EQUAL TO OR GREATER THAN 2 MMOL PRODUCED
COMPLETE INHIBITION OF THYMIDINE INCORPORATION & CELL GROWTH. ALMOST
COMPLETE REVERSAL OF THESE EFFECTS WERE SEEN WITHIN 24 HR AFTER REMOVAL OF FORMALDEHYDE;
SUCH RECOVERY WAS NOT ACCOMPANIED BY UNSCHEDULED DNA SYNTHESIS.
Addition of aroclor-induced post-mitochondrial supernatant reduced the
mutagenicity of formaldehyde in the bacterial cells.
DNA-protein crosslinks have been formed in the nasal respiratory mucosa of
Fischer-344 rats exposed for 3 hr to selected concentrations of (3)H- and (14)C-formaldehyde.
... In rats depleted of glutathione and exposed to 10 ppm of (3)H-formaldehyde
and (14)C-formaldehyde, the (3)H/(14)C ratio of the fraction of
the DNA that was crosslinked to proteins was significantly (39 + or - 6%) higher
than that of the inhaled gas. This suggests an isotope effect, either on the
formation of DNA-protein crosslinks by labeled formaldehyde or
on the oxidation of labeled formaldehyde catalyzed by formaldehyde
or aldehyde dehydrogenase. These results suggest that the residual (unoxidized) formaldehyde
present in the nasal mucosa of rats exposed to (3)H- and (14)C-formaldehyde
may be "enriched" in 3-formaldehyde relative to
(14)C-formaldehyde which can bind to DNA resulting in an
isotope ratio higher than that of the inhaled gas. The isotope effect on the
oxidation of (3)formaldehyde and (14)C-formaldehyde
suggests that previous estimates of the amount of formaldehyde
covalently bound to nasal mucosal DNA may have been too large.
Glutathione is required for the oxidation of formaldehyde to
formate catalyzed by formaldehyde dehydrogenae. The effects of
glutathione depletion on the mechanisms of labeling of macromolecules in the rat
nasal mucosa and bone marrow by (3)H-formaldehyde and (14)C-formaldehyde
were investigated. Male rats were exposed for 3 hr to atmosphere containing
(3)H-formaldehyde and (14)C-formaldehyde at
concentrations of 0.9, 2,4,6, or 10 ppm, 1 day after a single 3 hr preexposure
to the same concentration of unlabeled formaldehyde. Two hours
prior to the second exposure, the animals were injected either with phorone (300
mg/kg, ip) or with corn oil. The concentration of nonprotein sulfhydryls in the
nasal respiratory mucosa of phorone-injected rats was decreased to 10% of that
of corn oil-injected rats. The metabolic incorporation of (3)H-formaldehyde
and (14)C-formaldehyde into DNA, RNA and proteins in the
respirtory and olfactory mucosa and bone marrow (femur) was significantly
decreased, and DNA-protein crosslinking was significantly increased in the
respiratory mucosa of phorone injected relative to corn oil injected rats at all
formaldehyde concentrations. DNA-protein crosslinks were not
detected in the respiratory mucosa of corn oil injected rats at 0.9 ppm.
Evidence was obtained for the formation of adducts of formaldehyde
with the RNA from the nasal respiratory mucosa of phorone injected rats at
concentrations above 0.9 ppm. Covalent binding of formaldehyde
to macromolecules in the bone marrow was not detected.
Fifty-five chemicals, including /formaldehyde/, were
evaluated in the Charnoffavlock developmental toxicity screen. All chemicals
were administered by gavage to pregnant ICR/SIM mice on gestation day 8-12. The
mice were allowed to deliver, & several neonatal growth & viability
parameters were measured in the offspring. ... Of the 26 cmpds reported in the
literature to be teratogenic or embryotoxic in mice following oral admin, 24
were positive in the developmental toxicity screen. ...
... In a plate assay with Salmonella typhimurium strain TA100 in the absence
and presence of S9 mix, a weak mutagenic response was observed. Using the
pre-incubation method, formaldehyde induced without S9 mix a
1.6-fold and with S9 mix a 2.7-fold increase of revertant numbers over controls.
Poisoning is characterized by severe abdominal pain which may be followed by
collapse and death. In less severe cases, acute nephritis with oliguria may
develop. Formaldehyde poisoning has been recorded in cattle
placed in calving sheds which had been cleaned and disinfected shortly before
with a 35% solution of this material, and after drinking from foot-rot treatment
baths. The addition of formaldehyde as a preservative to milk
has caused intoxiction in calves. The clinical signs recorded included
recumbency, abdominal pain, salivation and diarrhea. Postmortem examination
revealed severe gastrointestinal tract lesions.
The use of formalin for the treatment of foot-rot in sheep
can give rise to keratinization of the interdigital skin if the solution
employed is too concentrated or its application too frequent. In severe cases
this may lead to bacterial infection of the feet and result in serious losses.
Alkaline elution was employed to study DNA damage in Chinese hamster ovary-Kl
cells treated with a series of biotic and xenobiotic aldehydes. DNA
cross-linking was measured in terms of the reduction in the effect of methyl
methanesulphonate on the kinetics of DNA elution and was observed in cells
treated with formaldehyde, acetaldehyde, methylglyoxal and
malonaldehyde. Propionaldehyde, valeraldehyde, hexanal, and 4-hydroxynonenal
produced DNA single strand breaks, or lesions which were converted to breaks in
alkali. Both types of DNA damage occurred in cells exposed to malonaldehyde.
These findings support the hypothesis of a carcinogenic effect of the aldehydic
products (malonaldehyde, methylglyoxal, propionaldehyde, hexanal,
4-hydroxynonenal) released in biomembranes during lipid peroxidation.
Acetaldehyde did not cause DNA breaks.
Two groups of 12 male Wistar rats received either 243 ppm of acetaldehyde or
5.7 ppm of formaldehyde for 8 hr a day, 5 days a week during 5
weeks. These levels represent three times the threshold limit values for these
substances in Brazilian legislation. The animals were evaluated by pulmonary
function tests before and after exposure to the pollutants. The data obtained
from these rats were compared with those of 12 controls, housed in identical
conditions for the same length of time but breathing normal air. The results
showed an increase of the functional residual capacity, residual volume, total
lung capacity and respiratory frequency in the rats exposed to acetaldehyde
atmosphere. The animals exposed to formaldehyde did not present
pulmonary function alterations when compared with the controls. The damage
caused by acetaldehyde to the peripheral regions of the lung parenchyma,
affecting small airways or altering pulmonary elastic properties, is discussed.
A 1 year inhalation toxicity study was performed on male albino rats using
0.1, 1.0, or 10 ppm formaldehyde. The nasal mucosa of half the
rats was damaged bilaterally by electrocoagulation; 20 to 26 hr after which the
rats were subjected to the first 6 hr exposure of formaldehyde.
The schedule for the exposures was 6 hr per day, 5 days a week for up to 52
weeks. Decreases in liver glutathione content were noted in rats with damaged
noses after 13 weeks exposure. Moderate to severe rhinitis was accompanied by
keratinized or nonkeratinized metaplastic respiratory epithelium in rats at the
highest exposure levels with or without nasal damage. Growth retardation was
observed in the animals with or without a damaged nose after 2 weeks exposure at
10 ppm formaldehyde. At lower exposure levels metaplastic
respiratory epithelium occurred only in rats with a damage nasal mucosa,
indicating a higher susceptibility of damage mucosa for the irritating and
cytotoxic actions of formaldehyde. A more severe basal cell
hyperplasia and more severe squamous metaplasia of the respiratory epithelium
was noted in rats exposed to 1 ppm formaldehyde and subjected
to electroagulation, compared to rats with an undamaged nose and 10 ppm exposure
levels. Effects on the olfactory epithelium were exclusively found in animals
treated with 10 ppm formaldehyde effects were more posterior in
rats with damaged noses, perhaps due to an abnormal air flow pattern in the
damaged nose. No adverse effects were seen at 0.1 or 1 ppm in rats with an
intact nasal mucosa. The damaged rat nose is more susceptible than the undamaged
to the cytotoxicity of formaldehyde, and even at a
concentration of 10 ppm formaldehyde has no adverse effects on
organs remote from the site of entry in rats with unchanged mucosa.
The effects of benzo(a)pyrene & formaldehyde, alone
& combined, on cell growth & DNA damage were determined in primary
cultures of rat tracheal epithelial cells dissociated from rat tracheas. Cell
cultures treated with 25 uM benzo(a)pyrene for 24 hr or 200 uM formaldehyde
for 90 min did not have a marked reduction in cell growth. However, their
combined treatment reduced cell growth by 60% of control when cultures were
exposed to benzo(a)pyrene followed by formaldehyde as well as
the reverse order. None of these treatments significantly decreased cell
viability as judged by dye exclusion, nor did they enhance cell terminal
differentiation as measured by cornified envelope formation. Alkaline elution
analysis of DNA damage detected both DNA-protein crosslinks & DNA single
strand breaks as a result of formaldehyde treatment, whereas
BAP treatment caused only single strand breaks. While formaldehyde
induced single strand breaks were repaired within 2 hr, benzo(a)pyrene induced
single strand breaks were detected 3 days after treatment. Combined treatment of
cell cultures with benzo(a)pyrene followed by formaldehyde
resulted in more single strand breaks than was obtained from either agent alone,
but less DNA-protein crosslinks than was detected from formaldehyde
alone. The increased number of single strand breaks obtained from this combined
treatment may be related to the marked enhancement of carcinogenesis observed in
earlier in vivo-in vitro studies.
The effect of formaldehyde inhalation on total cytochrome
p450 in the lungs of Sprague-Dawley rats was assessed after single &
repeated exposure to 0, 0.5, 3, & 15 ppm formaldehyde.
Whole-body exposures were conducted exposure systems for 6 hr/day, 5 days/wk,
for periods of exposure of 1 day, 4 days, 12 wk, or 24 wk. Lung cytochrome p450
were measured 18 hr after the end of exposure at each time point. There were not
detectable levels of total lung p450 in any of the rats that received a single 6
hr exposure to all three formaldehyde doses, while control lung
p450 levels were similar to that found for 4 day & 12 wk control rats. After
4 days of repeated exposures, however, there was a highly significantly,
reproducible, & dose-dependent incr in lung p450 levels relative to
controls, with the 0.5, 3, & 15 ppm groups demonstrating 383, 1026, &
1123% of control values, respectively. Lung p450 levels remained elevated all formaldehyde
concns through 12 & 24 wk of exposure, although the % difference between
exposed & control rats continually dropped throughout the course of
long-term repeated exposures. While formaldehyde exposed rats
did have decreased total body weight relative to controls, lung microsomal
protein & lung weight of nearly all of the formaldehyde
exposed rats was not significantly different from the controls. The initial
inactivation of lung p450 after a single formaldehyde exposure
is apparently a transient phenomenon, with dose-dependent induction of the total
p450 levels in the lung as the pattern of response to repeated exposures to
inhaled formaldehyde.
Male Wistar rats were exposed to 0, 10 or 20 ppm formaldehyde
vapor for 4, 8, or 13 weeks (6 hr/day; 5 days/week), and were then observed for
periods up to 126 weeks. Transient growth retardation occurred in both test
groups. Death rate was not noticably affected by formaldehyde.
Despite recovery periods of at most 126 weeks, the nasal respiratory and
olfactory epithelium of many rats of the 20 ppm group exhibited non-nooplastic
histopathological changes. Similar but much less severe changes of the
respiratory epithelium were seen in a small number of rats of the 10 ppm group;
the olfactory epithelium was not visibly affected in rats of this group. Nasal
tumors considered to be induced by formaldehyde were seen only
in the 20 ppm group and mainly in rats that had been exposed for 13 weeks, the
incidence being 4.5% (6/132). These tumors comprised 3 squamous cell carcinomas,
1 carcinoma in situ and 2 polypoid adenomas, all originating from respiratory
epithelium. Rat nasal respiratory epithelium severely damaged by formaldehyde
vapor ofter does not regenerate and in some cases develops tumors.
Formaldehyde caused nasal squamous cell carcinomas in the
rat following 2 year inhalation exposure. The incidence of this tumor in a
historical data base of 16,794 rats was nil, indicating that it is a rare
spontaneous tumor. Five different mathematical extrapolation models were applied
to the rat nasal tumor data to produce estimates at 10(-4) risk (the size of the
historical data base) of between 3.232 and 0.003 ppm formaldehyde
depending on the model and choice of maximum likelihood estimate or lower
confidence limit values.
The effects of formaldehyde on mammalian respiratory ciliary
function were studied in-vitro. Tracheal rings from New Zealand white rabbits
were incubated with 16, 33, or 66 ug/cu m formaldehyde for up
to 60 minutes. Formaldehyde induced dose & time dependent
decreases in the areas of ciliary activity & ciliary best frequency. The
inhibition of ciliary function was reversible, but the times for recovery
increased with increasing formaldehyde concn. Porcine tracheal
rings were incubated with up to 66 ug/cu m formaldehyde for 60
min followed by up to 65 min recovery. The number of extractable active cilia
(ciliary axonemes) was determined. Formaldehyde decreased the
number of extractable ciliary axonemes & associated ATPase activity in a
dose & time dependent manner. The inhibitory effects were reversible.
The induction of ornithine-decarboxylase activity and DNA synthesis was
studied in the glandular stomach mucosa of rats afer gastric intubation of formaldehyde.
Male Fischer rats were given doses of formaldehyde ranging from
11 to 110 mg/kg body weight by gastric intubation. The maximum increase in
ornithine-decarboxylase activity was a 100 fold increase noted after 16 hours.
The maximum increase in DNA synthesis was a 49 fold increase after 16 hours in
the pyloric mucosa of the stomach. Even doses lower than 75 mg/kg, formaldehyde
induced ornithine-decarboxylase activity and DNA synthesis in the pyloric
mucosa. All the glandular stomach carcinogens and tumor promoters examined have
been found to induce ornithine-decarboxylase activity and stimulate DNA
synthesis in the glandular stomach mucosa. Inductions of ornithine-decarboxylase
activity and DNA synthesis are useful markers of possible tumor promoting
activity in the glandular stomach mucosa.
The relative toxicities of formaldehyde and glutaraldehyde
to the rat nasal epithelium were determined following intra-nasal instillation
of aqueous solutions of these compounds into one nostril of male Fischer 344
(F-344) rats. Lesions identical in appearance to those resulting from acute
inhalation exposure to formaldehyde were induced by both
compounds in a concentration-dependent manner. While sterile saline and 10 mM
glutaraldehyde induced no significant epithelial changes, 20 and 40 mM
glutaraldehyde induced extensive lesions in the treated side of the nose.
Aldehyde induced lesions included inflammation, epithelial hypertrophy, and
squamous metaplasia in association with marked increases (2-8-fold) in labeling
index for both compounds. Formaldehyde induced similar lesions
but required concentrations of 200 mM or more to elicit a toxic response. Thus,
glutaraldehyde is approximately an order of magnitude more toxic to the nasal
epithelium than formaldehyde.
Male and female Sprague-Dawley rats of different ages at the start of the
experiments (12 day embryos, and 7 and 25 weeks old) were administered formaldehyde
in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0
ppm). An increased incidence of leukemias and of gastro-intestinal tumors was
observed in formaldehyde treated rats. Gastro-intestinal tumors
are exceptionally rare in the rats of the colony used.
The effects of formaldehyde on the respiratory tract were
studied in monkeys. Male rhesus monkeys were exposed to 6 ppm formaldehyde
6 hours/day, 5 days/week for 1 or 6 weeks. Histopathological changes induced by formaldehyde
included mild degeneration and early squamous metaplasia in the transitional and
respiratory epithelium of the nasal passages and the respiratory epithelium of
the trachea and bronchi. There was little difference in the severity of the
nasal lesions between animals exposed for 1 or 6 weeks; however, the percentage
of nasal mucosal epithelial area with lesions was significantly larger in
monkeys exposed for 6 weeks. Only minimal histopathological changes occurred in
the lower airways. No treatment related effects were seen in the maxillary
sinuses or nonrespiratory ortans. Thymidine labeling indices were significantly
increased in the respiratory epithelium of the nasal passages at both 1 and 6
weeks. The areas of greatest proliferation corresponded to the areas of the
lesions. Labeling indices in the trachea and carina were significantly elevated
after 1 week of exposure. They were nonsignificantly elevated in the
transitional and olfactory epithelium of the nasasl passages. Formaldehyde
induced nasal lesions are more widespread in the monkey than in the rat, and
monkeys are more sensitive to the acute and subacute effects of formaldehyde.
A 28 month inhalation study was carried out in male SPF reared albino Wistar
rats to determine the significance of electrocoagulation damage for the
induction of nasal tumors by formaldehyde vapor. Male rats with
severely damaged or undamaged noses were exposed 6 hours/day, 5 days/week for 28
months to formaldehyde at concentrations of 0.0, 0.1, 1.0, and
10 ppm. Degenerative, inflammatory and hyperplastic changes were noted in the
nasal respiratory and olfactory mucosa in rats with intact noses at the highest
dose levels. The incidence of formaldehyde induced rhinitis,
hyperplasia and metaplasia of the respiratory epithelium, and degeneration and
hyperplasia and metaplasia of the olfactory epithelium all occurred in increased
numbers in rats exposed to formaldehyde with damage nasal
passages. The incidence of nasal tumors in animals with damage nasal mucosa and
treated with 10 ppm formaldehyde for 28 months was 29% (17 of
58 rats), while in the group of rats with an intact nasal mucosa exposed to 10
ppm formaldehyde for 28 months, only 1 of 26 (4%) developed a
nasal tumor. Increased tumor incidences were not oberved in rats with damaged
nasal mucosa exposed to 0.1 or 1.0 ppm formaldehyde for 28
months or to 0.1, 1.0, or 10 ppm formaldehyde for 3 months. The
condition of the nasal mucosa is an important factor in the development of nasal
tumors among rats exposed to formaldehyde.
Male and female Wistar rats were given formaldehyde solution
in their drinking water at concentrations of 0.50, 0.10, 0.02 and 0% for 24
months. Significant decreases in body weight and food and water intake were
observed in the 0.50% group of both sexes and all rats in this group died by 24
months. Various non-neoplastic lesions were observed in rats, mostly in the
0.50% group. In this group, erosions and/or ulcers were evident in both the
forestomach and glandular stomach. In the forestomach, squamous cell hyperplasia
with or without hyperkeratosis and downward growth of basal cells were observed.
Glandular hyperplasia of the fundic mucosa was noted along the limiting ridge. A
few of such changes of the upper GI tract were seen in the 0.10% group. No
toxicological abnormalities were found in 0.02% group of both sexes. There were
no significant differences in the incidences of any tumors among groups of both
sexes. Based on these findings, the no observable effect level of formaldehyde
was 0.02% in the drinking water (10 mg/kg body wt/day).
The effects of intermittent and continuous inhalation exposure to formaldehyde
were studied in rats. Male Wistar rats were exposed to 0, 1, or 2 ppm formaldehyde
continuously for 8 hours a day, 5 days a week for 13 weeks. Other rats were
exposed to 0, 2, or 4 ppm formaldehyde intermittently, for
eight 30 minute exposures separated by 30 mintue periods of nonexposure, 5 days
a week for 13 weeks. After 13 weeks, the nasal cavity tissues were examined for
histopathological changes. Formaldehyde did not significantly
affect body weight again. A slight nonsignificant increase in cell turnover was
seen after 3 days in rats exposed intermittently to 2 ppm or continuously to 1
ppm formaldehyde. This effect was not seen after 13 weeks.
Treatment related histopathological changes were seen only in nasal tissues from
rats exposed intermittently to 4 ppm formaldehyde. These
consisted of disarrangement, hyperplasia, and squamous metaplasia with or
without keratinization of the respiratory epithelium of the septum and
nasoturbinates. These changes were not seen in rats exposed continuously to 2
ppm formaldehyde, which produced the same total daily dose as
the intermittent 4 ppm exposure group. Under conditions of formaldehyde,
exposure concentration, not total dose, determines the severity of the cytotoxic
effects.
Sprague-Dawley rats were exposed to 0, 5, 10, 20 or 40 ppm formaldehyde
for 6 hr/day from day 6 to 20 of gestation. On day 21 of gestation, no effect on
embryonic or fetal lethality, nor significant alterations in the external,
visceral or skeletal appearance of the fetuses were noted in any of the exposed
groups. Significant concentrations-related reduction of fetal body weight
occurred at 20 & 40 ppm, & at 40 ppm fetal body weights were 20% <
those of the controls. Maternal toxicity, indicated by significant reduction in
body weight & absolute weight gain, was observed at 40 ppm. Formaldehyde
is slightly fetotoxic at 20 ppm. Neither embryolethal nor teratogenic effects
were observed following inhalation exposure at levels up to 40 ppm.
An acute exposure study /was conducted/ using 4 groups of 12 Wistar male rats
each. One of the 4 groups was used as a control; the other 3 were exposed for 6
hr at 10 ppm, 20 ppm, or 30 ppm. In addn to observing behavioral & other
responses during the test period, biochemical & hematologic tests were
performed on the test animals. Responses of the 10 ppm exposed group did not
differ from those of the controls. In the 20 ppm exposed group, a sniffing
motion was observed 1 min after the start of exposure, followed by face-washing
movements 10 min later. The face-washing movements decreased with increased
exposure time. It was observed at the end of the 6 hr exposure that the hair
around the penile area had become yellowed. The movements of the 30 ppm exposed
group were similar to those observed for the animals exposed at 20 ppm
throughout the exposure period except that hair yellowing was seen 2 hr after
the start of exposure. Observations of the 20 ppm & 30 ppm exposed groups
also included irritation of the nasal mucosal membrane & trachea, a decr in
leukocytes & plasma alkaline phosphatase, & an incr in lung alkaline
phosphatase activity. The 10 ppm & 30 ppm groups had a decr in the mean
corpuscualr volume & mean corpuscular hemoglobin. The 30 ppm exposed group
also had a decr in white blood cells.
84 articles relating to adverse health effects in animals & humans from
subchronic exposures to formaldehyde /were reviewed/ &
conclude that animal data revealed a qualitative relationship between formaldehyde
absorption & hepatotoxicity. These data indicate that exposure to formaldehyde
at 3 ppm or less for periods up to 6 months causes adverse effects upon the
liver; higher exposure concns for shorter time periods produce similar effects
upon the liver. The reviewed data appear to establish a relationship between
exposure to formaldehyde & hepatic degeneration, including
decreases in the concn of DNA; mottled, discolored appearance; significant incr
in weight; nuclear polymorphism; a profusion of binuclear cells around the
triads; focal hyperplasia; & dilatation of hepatic veins with some
degeneration of liver cells in the center of the lobules. ... Additional
research is required in order to define formaldehyde as a
potential human hepatotoxin in formaldehyde exposed
populations.
A long-term formaldehyde animal inhalation bioassay in which
groups of about 120 males & 120 female Fischer 344 strain rats & B6C3F1
mice were exposed by inhalation at 0, 2.0, 5.6, or 14.3 ppm of formaldehyde
gas for 6 hr/day, 5 days/wk for 24 months. The exposure period was followed by
up to 6 months of nonexposure. Squamous cell carcinomas were observed in the
nasal cavities of 103 rats (52 females & 51 males) & in 2 male mice; all
had been exposed at 14.3 ppm of formaldehyde. One male &
one female rat exposed at 5.6 ppm of formaldehyde were also
found to have squamous cell carcinomas in their nasal cavities. The two squamous
cell carcinomas found in mice exposed at 14.3 ppm formaldehyde
were not statistically significant in comparison with the incidence in control
mice. However, since this type of nasal lesion is rare in mice, these data can
be considered to have biological importance. Benign tumors, such as polypid
adenomas, were also seen in male rats in /another/ study at all dose levels
& in female rats exposed at 2 ppm formaldehyde. The benign
tumor incidence was not linear in this study; benign tumor incidence was highest
at the 2 ppm exposure & decreased at higher doses. Since benign nasal tumors
are rarely found in rats, the formation in the formaldehyde
exposed animals may be attributed to the formaldehyde
inhalation.
Formaldehyde induces gene mutation in bacteria, fungi,
yeast, & Drosophila larvae as well as in cultured rodent and human cells. In
part, these mutations appear to be the consequence of DNA damage. A second
mechanism by which formaldehyde may damage the genome is
inhibition of DNA repair.
10 rats (strain, age and sex unspecified) were injected subcutaneously once a
week for 15 months with 1 ml of a 0.4% aqueous solution of formaldehyde
and then observed for life. Spindle-cell sarcomas were found in three rats; two
in the skin at the injection site and one in the peritoneal cavity.
In a study to evaluate the effects of formaldehyde on
gastric carcinogenesis induced by oral administration of
N-methyl-N'-nitro-N-nitrosoguanidine, two groups of 10 male Wistar rats, seven
weeks of age, received tap water for the first eight weeks of the study. During
weeks 8-40, one group then received pure water and the other group received 0.5%
formaldehyde in the drinking water. Animals still alive at 40
weeks were killed, rats surviving beyond 30 weeks being considered as effective
animals for the study. Necropsy was performed on most animals that died and all
animals that were killed, and the stomach and other abdominal organs were
examined grossly and histologically. Eight of 10 animals that had received formaldehyde
in drinking water and none of the controls developed forestomach papillomas
(p< 0.01, Fisher's exact test).
Two groups of 16 male and 16 female Oslo hairless mice (age unspecified)
received topical applications of 200 ul of 1 or 10% formaldehyde
in water on the skin of the back twice a week for 60 weeks. All of the animals
treated with 10% formaldehyde were necropsied and the brain,
lungs, nasal cavities and all tumors of the skin and other organs were examined
histologically. Virtually no changes were found in the mice treated with 1% formaldehyde.
The higher dose induced slight epidermal hyperplasia and a few skin ulcers.
There were no benign or malignant skin tumors or tumors in other organs in
either group.
Repeated exposure to formaldehyde vapors at 40 ppm, 6
hr/day, 5 day/wk for up to 13 wk produced 80% mortality in B6C3F1 mice, whereas
mice exposed with the same protocol to 20 ppm showed no mortalities within the
exposure period ... . Deaths occurred predominately in the fifth and sixth wk of
exposure and were assoc with ataxia, severe body weight depression, and
inflammation and metaplasia in the nasal cavity, larynx, trachea, and lungs.
Deaths were attributed to occlusive tracheal lesions and/or prominent
seropurulent rhinitis ... . In other intermediate duration inhalation bioassays,
no exposure-related deaths or early mortalities were found in Wistar rats
exposed to up to 20 ppm, 6 hr/day, 5 days/wk for 13 wk ... in F344 rats,
Cynomolgus monkeys, or Golden Syrian hamsters exposed up to 2.95 ppm, 22 hr/day,
7 days/wk for 26 wk ... or in Wistar rats exposed to up to 20 ppm, 6 hr/day, 5
days/wk for 4, 8, or 13 wk and subsequently observed for 117 wk without exposure
... .
In chronic inhalation bioassays, incr mortality ... was found in
Sprague-Dawley rats exposed to 14.2 ppm formaldehyde, 6 hr/day,
5 days/wk for up to 588 days ... in F344 rats exposed to 5.6 or 14.3 ppm (but
not 2 ppm), 6 hr/day, 5 days/wk for up to 24 mo ... in F344 rats exposed to 15
ppm (but not to 0.7, 2, 6, or 10 ppm) 6 hr/day, 5 days/wk for 24 mo ... and in
F344 rats exposed to 15 ppm (but not to 0.3 or 2 ppm), 6 hr/day, 5 days/wk for
up to 28 mo ... . In general, observations of incr mortality in the rat
bioassays occurred after about one yr of exposure and were assoc with the
development of nasal squamous cell carcinomas. Golden Syrian hamster exposed to
10 ppm formaldehyde, 5 hr/day, 5 days/wk for life showed a
small, but statistically significant, incr in mortality compared with controls,
but no incr incidence of nasal tumors and only a minimal (5% versus zero in
controls) incr incidence of hyperplasia or metaplasia in the nasal epithelium
... . No exposure-related incr motality was found in B6C3F1 mice exposed to up
to 14.3 ppm for 6 hr/day, 5 days/wk for 24 mo ... .
Studies in animals confirm that the upper respiratory tract is a critical
target for inhaled formaldehyde and describe exposure-response
relationships for upper respiratory tract irritation and epithelial damage in
several species. Acute inhalation animal studies show that inhaled formaldehyde,
at appropriate exposure concn, damages epithelial tissue in specific regions of
the upper respiratory tract in rats, mice, and monkeys ... that formaldehyde
is a more potent sensory irritant in mice ... than in rats ... that lung damage
from inhaled formaldehyde occurs at higher concn than those
only affecting the upper respiratory tract ... that mice are less susceptible to
formaldehyde-induced upper respiratory tract epithelial damage
than rats ... that rats and monkeys may be equally susceptible to epithelial
damage ... but display similar epithelial lesions in different regions of the
upper respiratory tract ... and that formaldehyde induces
bronchoconstriction and airway hyperreactivity in guinea pigs ... .
Results from intermediate-duration inhalation studies with rats ... Rhesus
monkeys .. Cynomolgus monkeys ... mice ... and hamsters ... indicate that the
nasal epithelium is the most sensitive target of inhaled formaldehyde.
The studies support the hypothesis that mice and hamsters are less sensitive
than rats and monkeys to formaldehyde-induced nasal damage ...
show that formaldehyde-induced damage to the upper respiratory
tract epithelium (hyperplasia and squamous cell metaplasia) has a wider regional
distribution in Rhesus monkeys than in rats ... show that site-specific nasal
lesions in both monkeys and rats corresponded to regions with high rates of
cellular proliferation ... indicate that damage to the respiratory epithelium is
more concn-dependent than duration-dependent ... and show that concn of
DNA-protein cross links are correlated with regional sites of formaldehyde-induced
epithelial damage in the nose of rats ... .
Chronic-duration exposures in inhaled formaldehyde have also
been studied in rats, mice, and hamsters. In rats exposed to concn < or = 15
ppm, formaldehyde-induced effects were restricted to
nonneoplastic and neoplastic lesions found primarily in anterior regions of the
nasal epithelium, posterior to the vestibule ... . Nonneoplastic damage to rat
nasal epithelium occurred at concn as low as 2 ppm, 6 hr/day, 5 days, wk ...
whereas significantly incr incidences of neoplastic lesions (squamous cell
carcinomas, squamous cell papillomas or polyploid adenomas) were found in rats
generally at concn greater than 6 ppm ... . Nonneoplastic damage to upper
respiratory tract epithelium has also been observed in mice exposed to > or =
5.6 ppm, 6 hr/day, 5 days/wk for 2 yr ... and in hamsters exposed to 10 ppm, 5
hr/day, 5 days/wk for life ... . Nasal tumors similar to those found in mice
exposed to 14.3 ppm for 2 hr ... but were not found in formaldehyde-exposed
hamsters ... .
Studies in laboratory animals have also demonstrated that formaldehyde
can be genotoxic in some cells after inhalation exposure. ... exposed male
Sprague-Dawley rats to formaldehyde concn of 0, 0.5, 3, and 15
ppm, by inhalation for 6 hr/day for 5 days. The rats were sacrificed, and their
pulmonary macrophages and bone marrow cells were harvested and analyzed ... .
... An incr in chromosomal abnormalities in pulmonary macrophages, predominantly
chromatid breaks, was observed in the 15 ppm group (7.5 versus 3.4% for
controls) after 5 days of exposure.
... admin 20, 40 or 90 mg/kg/day formaldehyde 5 days/wk for
4 wk to male Wistar rats by gavage. Incr absolute and relative lymph node
weights were observed beginning at 40 mg/kg/day. Antibody production was assayed
by measurement of total blood IgG and IgM, a hemagglutination assay, a
plaque-forming cell assay, and by measurement of IgM production in spleen cells.
Only the hemagglutination assay showed a significant effect; the combined IgG
and IgM titers were significantly lower than controls at 20 mg/kg/day and above,
although individual IgM and IgG titers were only significantly different from
controls at 40 and 80 mg/kg/day.
Albino guinea pigs (Hartley strain) were treated with 0.1 ml of various
dilutions of formalin (1, 3, and 10% formalin;
approximately equivalent to 0.4, 1.2, and 4% formaldehyde) to
demarcated test sites, and the formalin soln was gently rubbed
into the skin with a cotton-tipped applicator ... . An unexposed control site
and a vehicle control were used in each series. The sites were left unoccluded
and the treatments were repeated once daily immediately after skin-fold
measurements. Each site was examined prior to skin-fold measurements for the
presence of erythema, edema, fissuring, and scaling. From a mean of 10 sites,
erythema appeared on day 2 (4%), day 5 (1.2%), and day 6 (0.4%). Increased
skin-fold thickness was statistically significant on day 3 (4%), day 7 (1.2%),
and day 9 (0.04%) after daily treatment with various concn of formaldehyde.
Increased cell replication occurs as a result of the cytotoxic effects of formaldehyde
on the nasal mucosa. Morphological changes (acute degeneration, swelling,
formation of "dense bodies", & vacuoles in epithelial cells) were
described in the respiratory epithelium of rats after a single 6 hr exposure to
18 mg formaldehyde/cu m. When such exposure was repeated 3-5
times, ulceration was observed in the respiratory epithelium in most
experimental animals. After a 9-day exposure, reparative hyperplasia &
metaplasia were found. At 7.2 mg/cu m, hyperplasia & slight degenerative
changes were still detected. In contrast, morphological changes could not be
proved at 0.6 & 2.5 mg formaldehyde/cu m.
Chronic toxicity and oncogenicity were evaluated in male and female Fischer
344 rats (120/sex/dose level, 240/sex controls) exposed to formaldehyde
by inhalation at 0, 2, 6 or 15 ppm for 6 hrs/day, 5 days/week, for 24 months. A
total of 95 confirmed cases of nasal squamous cell carcinoma were observed in
rats exposed to the highest dose level, 3 cases were observed in rats exposed to
6 ppm, and no cases were observed at the 2 ppm dose level or in controls.
Further results from this study were not reported in this progress report.
Chronic toxicity and oncogenicity were evaluated in male and female B6C3F1
mice (120/sex/dose level, 240/sex controls) exposed to formaldehyde
by inhalation at 0, 2, 6 or 15 ppm for 6 hrs/day, 5 days/week, for 24 months. A
total of 2 confirmed cases of nasal squamous cell carcinoma were observed in
mice exposed to the highest dose level and no cases were observed at the 2 or 6
ppm dose levels or in controls. Further results from this study were not
reported in this progress report.
The effects of acute oral exposure to formaldehyde by gavage
in male Wistar rats (20 in control group (water), 5/treated group, number of
treated groups not reported) were determined. Formaldehyde (100
or 200 mg/kg) was administered in a single dose and the rats were necropsied on
the 11th day following dosing. There were differences between treated and
control animals at the highest does level in the following: increase in sperm
head count, and a highly significant increase in the percentage of abnormal
sperm heads, including straight heads (i.e. no hook), excessive curvature of
heads, folded, coiled, thin or amorphous heads. There were no significant
differences between treated and control animals in the following: clinical
observations, histopathology of the testes, and testes weights.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
RAPID OXIDN OF FORMALDEHYDE INTO FORMATE FOLLOWED BY FURTHER
OXIDN TO CARBON DIOXIDE TAKES PLACE PRINCIPALLY IN ERYTHROCYTES & LIVER.
WHEN FEMALE RATS WERE ADMIN (14)C-FORMALDEHYDE IP AT DOSE
LEVEL OF 70 MG/KG, 82% OF DOSE WAS EXPIRED AS (14)CARBON DIOXIDE & 13-14%
WAS EXCRETED VIA KIDNEYS IN FORM OF METHIONINE, SERINE, & FORMALDEHYDE-CYSTEINE
ADDUCT.
Rats injected ip with 0.26 mg/kg (14)C-labeled formaldehyde
... excreted approx 22% of this dose in the urine over 5 days. Formic acid &
a thiazolidine-4-carboxylic acid derivative were identified in urine as formaldehyde
metabolites.
SHORTLY AFTER IV INJECTION OF 35 MG/KG FORMALDEHYDE, INTO
DOGS, THERE WAS NO INCR IN PLASMA FORMALDEHYDE CONCN, BUT BIG
INCR IN FORMIC ACID CONCN. ... THE RATE OF FORMALDEHYDE OXIDN
IS COMPARABLE IN SEVERAL SPECIES OF MAMMALS ...
A novel modification for urinary formic acid analysis was developed in order
to gain experience in the biological monitoring of farmers exposed to the acid
vapors in silage making. It appeared that the farmers excreted varying amounts
of acid before the actual silage making period, but all showed increased
excretion rates up to 15 hr after the exposures. The data indicated that formic
acid may have a long biological half-life possibly causing an accumulation of
the acid in the body. This might constitute unappreciated toxicological hazard,
as the acid is an inhibitor of oxygen metabolism.
The effect of deuterium substitution on the metab of formaldehyde
& formate to carbon dioxide in vivo was examined. 4 groups of male
Sprague-Dawley rats were injected ip with (14)C labeled formaldehyde,
formaldehyde-d2, sodium formate, or sodium formate-d at doses
of 0.67 mmol/kg. Similar rates of labeled carbon dioxide exhalation were
observed for the 4 groups of animals, the cumulative excretion of (14)Carbon
dioxide in breath reaching 68-71% of the theoretical value 12 hr after injection
in all cases. Plots of amount remaining to be excreted showed that the metab was
biexponential, with half-lives of approx 0.4 & 3 hr for the two phases for
each of the 4 compounds. ...
Homogenates of respiratory & olfactory tissue from the rat nasal cavity
were examined for their capacity to catalyze the NAD(+)-dependant oxidation of formaldehyde
(in the presence & absence of glutathione) & of acetaldehyde. Both
aldehydes were oxidized efficiently by nasal mucosal homogenates, & formaldehyde
dehydrogenase & aldehyde dehydrogenase were tentatively identified in both
tissue samples. At least 2 isoenzymes of aldehyde dehydrogenase differing either
with respect to their apparent Km & max values with acetaldehyde as
substrate, were found in the nasal mucosa, one of which may catalyze the
oxidation of both formaldehyde & acetaldehyde. ... Repeated
exposures of rats to formaldehyde (15 ppm, 6 hr/day, 10 days)
or to acetaldehyde (1500 ppm, 6 hr/day, 5 days) did not substantially affect the
specific activities of formaldehyde dehydrogenase &
aldehyde dehydrogenase in nasal mucosal homogenates. Glutathione is a cofactor
for formaldehyde dehydrogenase; the concn of nonprotein
sulfhydryls in respiratory mucosal homogenates was approx 2.8 uM/g & was not
changed significantly by repeated exposures to formaldehyde (15
ppm, 6 hr/day, 9 days). These data indicate that the rat nasal mucosa, which is
the major target site for both aldehydes in inhalation toxicity studies, can
metabolize both formaldehyde & acetaldehyde, & that the
specific activities of formaldehyde & aldehyde
dehydrogenase in homogenates of the nasal mucosa are essentially unchanged
following repeated exposures to toxic concns of either cmpnd.
The movement of blood formaldehyde in rabbits that were
intoxicated with methanol has been investigated. When methanol alone was admin
to rabbits orally, formaldehyde could not be detected in the
blood. Further, in an experiment on the metab of methanol in vitro, formaldehyde
was not detected in specimen samples but formate was. In contrast, when methanol
was orally admin to rabbits that had been pretreated with
diethyldithiocarbamate, an aldehyde dehydrogenase inhibitor, 17 to 33 microM of formaldehyde
were detected in the blood 4 hr later. However, formaldehyde
was not detected in the blood when methanol was orally admin to rabbits that had
been pretreated with pyrazole, & alcohol dehydrogenase, inhibitor. After
rabbits were given an iv admin of formaldehyde, & on the
addition of formaldehyde to a rabbit liver homogenate &
blood, the formaldehyde in both instances was metabolized
rapidly. Formaldehyde that was not metabolized within 10-15
min, however, bound to the tissue proteins. Formaldehyde was
seen to be rapidly metabolized to formate without accumulating in the blood or
binding to the tissue proteins.
Formaldehyde is a normal metabolite of the body involved in
methylation reactions through the tetrafolate mechanism; normal blood levels of formaldehyde
in humans & animals are approx 2.5 ppm (2.5 mg/l). Formaldehyde
is rapidly metabolized with a half-life in the blood of approx 1.5 min. This
half-life is based primarily on primate data although available human data are
consistent with this observation of a very short half-life. Data from other
species suggest that the half-life of formaldehyde is fairly
similar in many species. Formaldehyde's normal blood levels
& short half-life, as well as the assumption that the levels of water
soluble formaldehyde in the blood are in equilibrium with the
body fluids pool, lead to a calculation that an adult human body normally
produces & metabolizes (detoxify or utilizes) over 50,000 ug of endogenous formaldehyde/day.
Formaldehyde is either converted to carbon dioxide by the
formate pathway & then exhaled or incorporated into the one carbon pool.
Radioactivity following exposure to 14C-formaldehyde is found
throughout the body & supports the concept of rapid incorporation &
metab.
Formaldehyde may be formed endogenously after contact with
xenobiotics; 18 chemicals have been shown to be metabolized by the nasal
microsomes of rats to produce formaldehyde. Formaldehyde
is a normal metabolite in mammalian systems. It is rapidly metabolized to
formate which is partially incorporated via normal metabolic pathways into the
one-carbon pool of the body or further oxidized to carbon dioxide. Formaldehyde
also reacts with proteins & nucleic acids; it reacts with single-strand DNA,
but not with double-strand DNA. This link is reversible. Only formaldehyde
cross-links of DNA & protein are stable. ... The oxidation of absorbed formaldehyde
to formic acid is catalyzed by several enzymes. The most important enzyme is the
NAD-dependent formaldehyde dehydrogenase, which requires
reduced glutathione (GSH) as a cofactor. Thus, exogenous formaldehyde
becomes a source of the so-called one-carbon pool in intermediary metab. ...
There are at least 7 enzymes that catalyze the oxidation of formaldehyde
in animal tissues, namely aldehyde dehydrogenase, xanthinoxidase, catalase,
peroxidase, glycerinaldehyde-3-phosphate dehydrogenase, aldehyde oxidase, &
a specific DPN-dependent formaldehyde dehydrogenase.
Incubation of formaldehyde with human nasal mucus in vitro
resulted in the reversible formation of protein adducts, primarily with albumin,
suggesting that a portion of the inhaled formaldehyde is
retained in the mucous blanket. No adducts were found in high
relative-molecular-mass glycoproteins. Absorbed formaldehyde
may react with nucleophiles (e.g., amino and sulfhydryl groups) at or near the
absorption site, or it can be oxidized to formate and exhaled as carbon dioxide
or incorporated into biological macromolecules via tetrahydrofolate-dependent
one-carbon biosynthetic pathways.
Several of the urinary excretion products of formaldehyde in
rats have been identified after intraperitoneal administration of (14)C-formaldehyde.
After injecting Wistar rats with 0.26 mg/kg body weight, ... formate and a
sulfur-containing metabolite (thought to be a derivative of
thiazolidine-4-carboxylic acid) and products presumed to result from one-carbon
metabolism /were detected/. Thiazolidine-4-carboxylate, which is formed via the
nonenzymatic condensation of formaldehyde with cysteine, was
not detected in urine.
The toxicokinetics of formaldehyde after inhalation, oral,
or dermal exposure has been reported in several species by many investigators.
The toxicokinetics in all of the animals studied is similar across species
lines. Formaldehyde is an essential metabolic intermediate in
all cells. It is produced during the normal metabolism of serine, glycine,
methionine, and choline and also by the demethylation of N-, S-, and O-methyl
compounds. After oxidation of formaldehyde to formate, the
carbon atom is further oxidized to carbon dioxide (CO2) or incorporated into
purines, thymidine, and amino acids via tetra-hydrofolate-dependent one-carbon
biosynthetic pathways. Exogenous formaldehyde appears to be
readily absorbed from the respiratory and GI tracts, but poorly absorbed
following dermal application. Formaldehyde is metabolized to
formate by the enzyme formaldehyde dehydrogenase; this appears
to take place at the initial site of contact. Being normal components of
intermediary metabolism, neither formaldehyde nor formate are
stored to any significant extent in any tissue of the body. Formate is either
excreted in the urine (primarily as formic acid), incorporated into other
cellular molecules, or oxidized to carbon dioxide and exhaled.
Formaldehyde is rapidly metabolized and storage is not a
factor in its toxicity. The metabolism of formaldehyde to
formate ... takes place in all of the tissues of the body as a consequence of
endogenous formation of formaldehyde, and the formate is
quickly removed by the supporting blood supply ... . Formaldehyde
dehydrogenase (FDH) is the major metabolic enzyme involved in the metabolism of formaldehyde
in all of the tissues studies; it is widely distributed in animal tissues,
particularly in the rat nasal mucosa, and is specific for the glutathione adduct
of formaldehyde. If formaldehyde is not
metabolized by FDH, then it can form cross linkages between proteins, between
protein and single-stranded DNA ... or enter the 1 carbon intermediary metabolic
pool by initially binding to tetrahydrofolate ... . Several enzymes can catalyze
the reaction that oxidizes formaldehyde to formic acid ...
however, FDH is the primary enzyme that performs this function and is specific
for formaldehyde ... . Endogenous of exogenous formaldehyde
enters the FDH metabolic pathway and is eliminated from the body as metabolites,
primarily as formate or CO2. Formaldehyde dehydrogenase
activity does not incr ... in response to formaldehyde exposure
... thus no incr in metabolism occurs.
Absorption, Distribution & Excretion:
... ABSORBED FROM ALIMENTARY & RESP TRACTS.
IN RATS & MICE ADMIN (14)C-FORMALDEHYDE
INTRAGASTRICALLY, 40% OF DOSE ... /WAS/ EXPIRED AS CARBON DIOXIDE, 10% /WAS/
EXCRETED IN URINE & 1% IN FECES AFTER 12 HR; CARCASSES CONTAINED 20% AFTER
24 HR & 10% AFTER 4 DAYS. WHEN FEMALE RATS WERE ADMIN (14)C-FORMALDEHYDE
IP AT DOSE LEVEL OF 70 MG/KG, 82% OF DOSE WAS EXPIRED AS (14)CARBON DIOXIDE
& 13-14% WAS EXCRETED VIA KIDNEYS ... .
Less than 1% of the /skin/ applied dose of (14)C /as formaldehyde/
was excreted or concn in the major organs of the monkey. Approx 10 times this
amt was found in the rat and guinea pig excreta and internal organs. ... The
skin of the monkey was much less permeable to formaldehyde than
that of rodents. A significant proportion ... was found after 72 hr at the site
of application, in the skin and fur, and ... for rodents ... in the remaining
carcass.
Airborne (14)C-labeled formaldehyde was primarily absorbed
in the upper respiratory tract of rats, leading to a very high radioactive concn
in the nasal mucosa. ...
The effect of subchronic exposure to formaldehyde on blood formaldehyde
concentrations was studied in monkeys. Young adult Rhesus monkeys were exposed
to 0 or 6.00 ppm formaldehyde vapor 6 hours per day, 5 days per
week for 4 weeks. Blood samples were obtained at 7 minutes and at 45 hours after
the last exposure. The average blood formaldehyde
concentrations obtained 7 minutes and 45 hours after exposure were 1.84 and 2.04
ug/g, respectively. The average blood formaldehyde concentraton
in the controls was 2.42 ug/g. None of the concentrations were statistically
different from each other. Subchronic exposure to a relatively high
concentration of formaldehyde does not significantly increase
the blood formaldehyde concentration of Rhesus monkeys. This
result agrees with those of previous studies in rats and humans. Because formaldehyde
is rapidly metabolized it does not accumulate in the blood or produce toxic
effects at distant sites. The concentration of endogenous formaldehyde
in the blood of Rhesus monkeys is similar to that of humans.
Formaldehyde is readily absorbed from the respiratory &
oral tract, & to a much lesser degree from the skin. Formaldehyde
is the simplest aldehyde & reacts readily with macromolecules such as
proteins & nucleic acids. Inhalation exposure has been reported to result in
almost complete absorption. Dermal absorption due to contact with formaldehyde-containing
materials such as textiles, perma-press clothing, cosmetics, or other materials
is of low order of magnitude. ... Formaldehyde is normally
converted & excreted as carbon dioxide in the air, as formic acid in the
urine, or as one of many breakdown products from one carbon pool metab. Because
of rapid absorption by both the oral & inhalation route & the rapid
metab, little or no formaldehyde is excreted unmetabolized.
Rats exposed to 14C-formaldehyde by inhalation had 40% of the
radiolabel excreted in the air & 20% in the urine & feces; 40% remained
in the carcass.
Formaldehyde is absorbed rapidly and almost completely from
the rodent intestinal tract. In rats, about 40% of an oral dose of (14)C-formaldehyde
(7 mg/kg) was eliminated as (14)C-carbon dioxide within 12 hours, while 10% was
excreted in the urine and 1% in the feces. A substantial portion of the
radioactivity remained in the carcass as products of metabolic incorporation.
Formaldehyde vapors are readily absorbed from the
respiratory tract. Due to rapid metabolism to formate, little, if any, intact formaldehyde
can be found in the blood of humans or animals exposed to formaldehyde.
Formaldehyde is also readily absorbed from the GI tract and
meets with the same metabolic fate as formaldehyde after
inhalation exposure. The studies available in the open literature suggest that
very little formaldehyde is absorbed via the dermal route. In
all cases, absorption appears to be limited to cell layers immediately adjacent
tot eh point of contact. Entry of formaldehyde into the blood
(i.e., systemic absorption) occurs to a very limited extent, if at all.
Biological Half-Life:
... IN SEVERAL SPECIES ... FORMALDEHYDE HAS HALF-LIFE OF
ONLY 1 MIN; BUT THE HALF-LIFE FOR FORMIC ACID IS SPECIES DEPENDENT.
Formaldehyde is rapidly metabolized with a half-life in the
blood of approx 1.5 min. This half-life is based primarily on primate data
although available human data are consistent with this observation of a very
short half-life. Data from other species suggest that the half-life of formaldehyde
is fairly similar in many species.
Mechanism of Action:
The exact mechanism by which formaldehyde exerts its
irritant, corrosive, and cytotoxic effects is not known. Aldehydes as a group
are reactive chemicals with a highly electronegative oxygen atom and less
electronegative atoms of carbon(s), and hence have a substantial dipole moment.
The carbonyl atom is the electrophilic site of these type of molecules, making
it react easily with nucleophilic sites on cell membranes and in body tissues
and fluids such as the amino groups in protein and DNA ... .
... formaldehyde readily combines with free, unprotonated
amino groups of amino acids to yield hydroxymethyl amino acid derivatives and a
proton (H+), which is believed to be related to its germicidal properties.
Higher concn will precipitate protein ... . Either one of these mechanistic
properties or perhaps other unknown properties may be responsible for the
irritation effects seen with formaldehyde exposure. It is
probable that formaldehyde toxicity occurs when intracellular
levels saturate formaldehyde dehydrogenase activity,
overwhelming the natural protection against formaldehyde, and
allowing the unmetabolized intact molecule to exert its effects locally.
Interactions:
MICE EXPOSED TO 11 COMBINATIONS OF ACROLEIN-FORMALDEHYDE;
RESPIRATORY RATE MONITORED & RESULTS INDICATE COMPETITIVE AGONISM BETWEEN
ACROLEIN & FORMALDEHYDE.
/IN GUINEA PIGS/ 1 HR EXPOSURE TO CONCN OF 0.3 PPM & ABOVE PRODUCED INCR
IN PULMONARY FLOW RESISTANCE ACCOMPANIED BY LESSER DECREASE IN COMPLIANCE. ...
THE RESPONSE ... POTENTIATED BY SIMULTANEOUS ADMIN OF ... SODIUM CHLORIDE
AEROSOL OF SUBMICRON PARTICLES. THE VALUES FOR PULMONARY RESISTANCE REMAINED
ABOVE PREEXPOSURE LEVELS FOR 1 HR AFTER THE END OF EXPOSURE WHEN THE GAS-AEROSOL
COMBINATION WAS USED. THIS PROLONGED RESPONSE ... SUGGEST THAT THE POTENTIATION
IS BROUGHT ABOUT BY THE ATTACHMENT OF FORMALDEHYDE TO THE
PARTICLES TO FORM AN IRRITANT AEROSOL. THIS ... IS FURTHER SUPPORTED BY FACT
THAT WHEN 3, 10 & 30 MG/CU M CONCN OF SODIUM CHLORIDE WERE USED, THE
POTENTIATION INCR WITH INCREASING CONCENTRATION OF PARTICLES. THE RESPONSE TO A
GIVEN CONCN OF FORMALDEHYDE PLUS AEROSOL BREATHED BY NOSE WAS
GREATER THAN THE RESPONSE TO THE GAS ALONE BREATHED THROUGH A TREACHEAL CANNULA.
C3H/10T1/2 cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine then
repeatedly exposed to /formaldehyde/ (0.1-2.0 ug/ml). Exposure
of N-methyl-N'-nitro-N-nitrosoguanidine initiated cultures to /formaldehyde/
of 0.5 or 1.0 ug/ml in a variety of treatment regimens resulted in focus
formation in up to 9% of the treated dishes. Transformed foci were observed in
< 2% of the cultures treated N-methyl-N'-nitro-N-nitrosoguanidine or /formaldehyde/
alone. Formaldehyde ... appears to be only a weak tumor
promotor for C3H/10T1/2 cell transformation.
A study was performed on four groups of Sprague-Dawley rats: one exposed to
wood dust (25 mg/cu m), another to formaldehyde (12.4 ppm) and
a third to both wood dust and formaldehyde; the fourth group
served a control group. After 104 weeks of exposure the nose and lungs were
examined histologically. One well differentiated squamous cell carcinoma was
found in the formaldehyde group. Squamous cell metaplasia was
found significantly more often among the formaldehyde exposed
rats. Squamous cell metaplasia with dysplasia was most frequently observed,
however, in the group exposed to both formaldehyde and wood
dust. There were also significantly more rats with pulmonary emphysema in the
groups exposed to wood dust than in the other groups.
The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde
at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats
were exposed by inhalation during 22 hr/day for 3 consecutive days to 0.3, 1.0
or 3.0 ppm formaldehyde or to 0.2, 0.4, or 0.8 ppm ozone, or
they were sham exposed to clean air. Treatment related histopathological nasal
changes, such as dissarrangement, loss of cilia, and hyper/metaplasia of the
epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde.
Simultaneous exposure to both materials did not noticeable affect type, degree,
and size the microscopic nasal lesions.
In cultured human bronchial fibroblasts exposed to the carcinogen
N-methyl-N-nitrosourea (NMU) in combination with formaldehyde, formaldehyde
was observed to inhibit repair of alkylation of DNA at the O6 guanine position
induced by NMU. Whether formaldehyde enhances the effects of
other DNA-damaging agents has not yet been evaluated.
The sensory irritant effect of formaldehyde at 1.2 mg/cu m
was shown to decr when the chemical pyridine was injected into the chanber; such
sensory interactions occur in environmentally realistic situations.
... experiments with mice ... and guinea pigs ... indicate that exposure to
low levels of formaldehyde enhances allergic responses to
intranasal admin of ovalbumin and suggest the possibility of formaldehyde
facilitation of allergic responses to other respiratory allergens.
Pharmacology:
Therapeutic Uses:
Disinfectants; Fixatives
DESENSITIZING TEETH /SOLN, USP/ /FORMER USE/
MEDICATION (VET): FOR VARIOUS SKIN DISEASES OF LARGE ANIMALS & DEMODECTIC
MANGE IN DOG /SOLN, USP/
MEDICATION (VET): ANTISEPTICS, FUMIGANT, HAS BEEN USED IN TYMPANY, DIARRHEA,
MASTITIS, PNEUMONIA, INTERNAL BLEEDING.
MEDICATION (VET): ... In cattle ... foot-rot treatment baths ... Treatment of
foot-rot in sheep ... .
Interactions:
MICE EXPOSED TO 11 COMBINATIONS OF ACROLEIN-FORMALDEHYDE;
RESPIRATORY RATE MONITORED & RESULTS INDICATE COMPETITIVE AGONISM BETWEEN
ACROLEIN & FORMALDEHYDE.
/IN GUINEA PIGS/ 1 HR EXPOSURE TO CONCN OF 0.3 PPM & ABOVE PRODUCED INCR
IN PULMONARY FLOW RESISTANCE ACCOMPANIED BY LESSER DECREASE IN COMPLIANCE. ...
THE RESPONSE ... POTENTIATED BY SIMULTANEOUS ADMIN OF ... SODIUM CHLORIDE
AEROSOL OF SUBMICRON PARTICLES. THE VALUES FOR PULMONARY RESISTANCE REMAINED
ABOVE PREEXPOSURE LEVELS FOR 1 HR AFTER THE END OF EXPOSURE WHEN THE GAS-AEROSOL
COMBINATION WAS USED. THIS PROLONGED RESPONSE ... SUGGEST THAT THE POTENTIATION
IS BROUGHT ABOUT BY THE ATTACHMENT OF FORMALDEHYDE TO THE
PARTICLES TO FORM AN IRRITANT AEROSOL. THIS ... IS FURTHER SUPPORTED BY FACT
THAT WHEN 3, 10 & 30 MG/CU M CONCN OF SODIUM CHLORIDE WERE USED, THE
POTENTIATION INCR WITH INCREASING CONCENTRATION OF PARTICLES. THE RESPONSE TO A
GIVEN CONCN OF FORMALDEHYDE PLUS AEROSOL BREATHED BY NOSE WAS
GREATER THAN THE RESPONSE TO THE GAS ALONE BREATHED THROUGH A TREACHEAL CANNULA.
C3H/10T1/2 cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine then
repeatedly exposed to /formaldehyde/ (0.1-2.0 ug/ml). Exposure
of N-methyl-N'-nitro-N-nitrosoguanidine initiated cultures to /formaldehyde/
of 0.5 or 1.0 ug/ml in a variety of treatment regimens resulted in focus
formation in up to 9% of the treated dishes. Transformed foci were observed in
< 2% of the cultures treated N-methyl-N'-nitro-N-nitrosoguanidine or /formaldehyde/
alone. Formaldehyde ... appears to be only a weak tumor
promotor for C3H/10T1/2 cell transformation.
A study was performed on four groups of Sprague-Dawley rats: one exposed to
wood dust (25 mg/cu m), another to formaldehyde (12.4 ppm) and
a third to both wood dust and formaldehyde; the fourth group
served a control group. After 104 weeks of exposure the nose and lungs were
examined histologically. One well differentiated squamous cell carcinoma was
found in the formaldehyde group. Squamous cell metaplasia was
found significantly more often among the formaldehyde exposed
rats. Squamous cell metaplasia with dysplasia was most frequently observed,
however, in the group exposed to both formaldehyde and wood
dust. There were also significantly more rats with pulmonary emphysema in the
groups exposed to wood dust than in the other groups.
The combined effects on the nasal epithelium of mixtures of ozone and formaldehyde
at cytotoxic and noncytotoxic concentrations were examined. Male Wistar rats
were exposed by inhalation during 22 hr/day for 3 consecutive days to 0.3, 1.0
or 3.0 ppm formaldehyde or to 0.2, 0.4, or 0.8 ppm ozone, or
they were sham exposed to clean air. Treatment related histopathological nasal
changes, such as dissarrangement, loss of cilia, and hyper/metaplasia of the
epithelium were seen at 0.2, 0.4, and 0.8 ppm ozone and at 3 ppm formaldehyde.
Simultaneous exposure to both materials did not noticeable affect type, degree,
and size the microscopic nasal lesions.
In cultured human bronchial fibroblasts exposed to the carcinogen
N-methyl-N-nitrosourea (NMU) in combination with formaldehyde, formaldehyde
was observed to inhibit repair of alkylation of DNA at the O6 guanine position
induced by NMU. Whether formaldehyde enhances the effects of
other DNA-damaging agents has not yet been evaluated.
The sensory irritant effect of formaldehyde at 1.2 mg/cu m
was shown to decr when the chemical pyridine was injected into the chanber; such
sensory interactions occur in environmentally realistic situations.
... experiments with mice ... and guinea pigs ... indicate that exposure to
low levels of formaldehyde enhances allergic responses to
intranasal admin of ovalbumin and suggest the possibility of formaldehyde
facilitation of allergic responses to other respiratory allergens.
Minimum Fatal Dose Level:
Approximate Minimum Lethal Dose (MLD) (150-lb man): 30 ml
Male single oral ingestion 517 mg/kg
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Formaldehyde is ubiquitous in the environment; it is an
important endogenous chemical that occurs in most life forms, including humans.
It is formed naturally in the troposphere during the oxidation of hydrocarbons. Formaldehyde's
production and use in the manufacture of resins, disinfectants, preservatives,
and a variety of other chemicals may result in its release to the environment
through various waste streams. Formaldehyde's production and
use as a fertilizer results in its direct release to the environment. If
released to air, formaldehyde will exist solely as a gas in the
ambient atmosphere. Gas-phase formaldehyde will be degraded in
the atmosphere by reaction with photochemically-produced hydroxyl radicals; the
half-life for this reaction in air is 41 hrs. Formaldehyde
absorbs ultraviolet radiation at wavelengths of >360 nm. Formaldehyde
has a half-life of 6 hrs in simulated sunlight. If released to soil, formaldehyde
is expected to have very high mobility based upon an estimated Koc of 37.
Volatilization from moist soil surfaces is not expected to be an important fate
process based upon a Henry's Law constant of 3.4X10-7 atm-cu m/mole. Formaldehyde
volatilizes from dry soil surfaces because it is a gas. If released into water, formaldehyde
is not expected to adsorb to suspended solids and sediment based upon the
estimated Koc. Formaldehyde readily biodegrades under both
aerobic and anaerobic conditions in the environment. Formaldehyde
in aqueous effluent was degraded by activated sludge and sewage in 48-72 hr. In
a die-away test using water from a stagnant lake, degradation was complete in 30
and 40 hrs under aerobic and anaerobic conditions, respectively. Volatilization
from water surfaces is not expected to be an important fate process based upon
this compound's Henry's Law constant. Experiments performed on a variety of fish
and shrimp show no bioconcentration of formaldehyde. Formaldehyde
is not expected to undergo hydrolysis in the environment because of the lack of
hydrolyzable functional groups. Occupational exposure to formaldehyde
may occur through inhalation and dermal contact with this compound at workplaces
where formaldehyde is produced or used. Monitoring data
indicate that the general population is exposed to formaldehyde
via inhalation of ambient air, ingestion of food, and dermal contact with
cosmetic and aerosol products containing formaldehyde. Concns
of formaldehyde in outdoor and indoor air range from 1 to 20
ug/cu m and 25 to 100 ug/cu m, respectively. (SRC)
Probable Routes of Human Exposure:
... /VAPORS/ GIVEN OFF DURING HOT MOLDING OF SYNTH RESINS (/IS A/ COMMON
SOURCE OF EXPOSURE) ... A SURVEY OF 6 FUNERAL HOMES ... REVEALED MEAN CONCN, IN
DIFFERENT ESTABLISHMENTS, BETWEEN 0.25 & 1.39 PPM. ... /EXPOSURES ARE
ENCOUNTERED/ IN PHENOL-FORMALDEHYDE RESIN MOULDING PLANT ...
/FROM WHICH/ CHRONIC AIRWAY OBSTRUCTION LOWERED FORCED EXPIRATORY VOL/FORCED VOL
CAPACITY RATIO & EYE, NOSE & THROAT IRRITATION & LOWER RESP TRACT
SYMPTOMS /HAVE BEEN OBSERVED/.
... /EXPOSURES TO/ FORMALDEHYDE VAPOR EMISSIONS IN
PERMANENT-PRESS FABRICS INDUSTRY (8 PLANTS) /HAVE BEEN REPORTED IN WHICH/ CONCN
RANGING ... FROM 0.3 TO 2.7 PPM (IN SEWING AREA) WITH AVG OF 0.68 PPM /WERE
DETECTED/. COMPLAINTS CONSISTED OF ANNOYING ODOR (ODOR THRESHOLD, BELOW 1.0
PPM), CONSTANT PRICKLING IRRITATION OF MUCOUS MEMBRANES & DISTURBED SLEEP.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,329,322
workers (441,902 of these are female) are potentially exposed to formaldehyde
in the US(1). The NOES Survey does not include farm workers(SRC). Occupational
exposure to formaldehyde may occur through inhalation and
dermal contact with this compound at workplaces where formaldehyde
is produced or used(2). Monitoring data indicate that the general population may
be exposed to formaldehyde via inhalation of ambient air,
ingestion of food, and dermal contact with cosmetic and aerosol products
containing formaldehyde(2).
Humans are exposed to formaldehyde from a variety of
sources. The major source of atmospheric discharge is from combustion processes
specifically from auto emissions and also from the photooxidation of
hydrocarbons in auto emissions(1,2). Additional exposure to formaldehyde
emissions comes from its use as an embalming fluid in anatomy labs, morgues, etc
and its use as a fumigant and sterilant(1). Resin treated fabric, rugs, paper,
etc and materials such as particle board and plywood which use resin adhesives
and foam insulation release formaldehyde which may build up in
homes and occupational atmospheres(1,2). Contact with industrial waste water,
especially from lumber related operations where formaldehyde is
used in adhesives, has resulted in the Pacific Northwest, Northeast, parts of
Texas, and lumber areas of the south(1)(SRC). The estimated daily intake of formaldehyde
among exposed Finnish workers is 3000 ug, whereas heavily exposed workers
(particle-board and glue production, foundry work) is 10,000 ug(3).
In a 12-week study of exposure in a gross anatomy lab of a medical school,
44% of breathing room samples and 11% of ambient air samples were >1.0 ppm
the ceiling recommended by ACGIH; Half the breathing zone samples were between
0.6-1.0 ppm and the range was 0.3-2.63 ppm(1). A 1976 report estimates that 8000
US workers were potentially exposed to formaldehyde during its
production(3). A more recent estimate of the number of exposed workers in
industries producing and using formaldehyde and its derivatives
range from 1.4-1.75 million(2). Concentrations of formaldehyde
in occupational areas dating from the 1960's and early 1970's are: textile plant
0-2.7 ppm, 0.68 ppm avg; garment factory 0.9-2.7 ppm; clothing store 0.9-3.3
ppm; laminating plant 0.04-10 ppm; funeral homes 0.09-5.26 ppm, 0.25-1.39 ppm
avg; resin manufacture and paper production 16-30 ppm; paper conditioning
0.9-1.6 ppm; wood processing 31.2 ppm max(2). Concns in occupational settings
dating from the late 70's are: textile plants 0.1-0.5 ppm, 0.2 ppm avg; shoe
factory 0.9-2.7 ppm, 1.9 ppm avg; particle board plant 0.1-4.9 ppm, 1.15 ppm
avg; plywood plant 0.1-1.2 ppm, 0.35 ppm avg; wooden furniture manufacturing
plant 0.1-5.4 ppm, 1.35 ppm avg; adhesive plants 0.8-3.5 ppm, 1.75 ppm avg;
foundries 0.05-2.0 ppm, 0.6 ppm avg; construction sites 0.5-7.0 ppm, 2.8 ppm
avg; hospitals and clinics 0.05-3.5 ppm, 0.7 ppm avg(2). More recent survey
results for occupational environments include: fertilizer production 0.2-1.9
ppm; dyestuffs <0.1-5.8 ppm; textile manufacture <0.1-1.4 ppm; resins
(foundry) <0.1-5.5 ppm; bronze foundry 0.12-0.8 ppm; iron foundry
<0.02-18.3 ppm; treated paper 0.14-0.99 ppm; hospital autopsy room 2.2-7.9
ppm; plywood industry 1.0-2.5 ppm; urea-formaldehyde foam
applicators <0.08-2.4 ppm(4).
Potential occupational exposure to formaldehyde are as
follows: agricultural workers, anatomists, beauticians, biologists, bookbinders,
botanists, chemical production workers, cosmetic formulators, crease-resistant
textile finishers, disinfectant makers, disinfectors, dress-goods shop
personnel, electrical insulation makers, embalmers, embalming fluid makers,
fireproofers, formaldehyde production workers, formaldehyde
resin makers, foundry employees, fumigators, fur processors, furniture makers,
glue and adhesive makers, hide preservers, histology technicians (including
necropsy and autopsy technicians), ink makers, lacquerers and lacquer makers,
medical personnel (including pathologists), mirror manufacturers, paper makers,
particle-board makers, photographic film makers, plastic workers, plywood
makers, rubber makers, taxidermists, textiles mordanters and printers, textiles
waterproofers, varnish workers, wood preservers(1).
The avg concn of formaldehyde in workroom air in formaldehyde
and resin manufacturing plants ranged from 0.1-14.2 mg/cu m(1). The avg concn of
formaldehyde in workroom air of plywood mills, particle-board
mills, furniture factories, other wood product and paper mills ranged from
0.08-7.4 mg/cu m(1). The avg concn of formaldehyde in workroom
air in textile mills and garment factories ranged from 0.1 to 1.9 mg/cu m(1).
The avg concn of formaldehyde in workroom air in foundries and
other industrial facilities ranged from 0.04 to 38.2 mg/cu m(1). The avg concn
of formaldehyde in workroom air in mortuaries, hospitals, and
laboratories ranged from 0.05 to 4.2 mg/cu m(1). The avg concn of formaldehyde
in workroom air in building sites, agriculture, forestry, and misc other
activities ranged from <0.1 to 4.3 mg/cu m(1).
Cigarette smoke and products of combustion contain formaldehyde(1).
Cigarette smoke contains 15 to 20 mg formaldehyde per
cigarette(1). Avg formaldehyde exposure from passive smoking is
between 0.23 to 0.27 ppm(1). A 'pack-a-day' smoker may inhale as much as 0.4-2.0
mg formaldehyde(1).
Several studies have been conducted to determine exposure of students in
laboratories(1). The concn of formaldehyde in the breathing
zone at dissecting tables and in the ambient air in a medical school in the
United States was found to be >1.2 mg/cu m in 44% of the breathing zone
samples and 11 ambient air samples; 50% of the breathing zone samples contained
0.7-1.2 mg/cu m, with a range of 0.4-3.2 mg/cu m(1). During the 1982-82 academic
year, the airborne concn of formaldehyde at a university in the
US was 7-16.5 ppm in the laboratory, 1.97-2.62 ppm in the stockroom, and <1
ppm in the public hallway(1). In another study, of 253 samples of air taken
during laboratory dissection classes at a university in the US, 97 contained
concns above the detection limit of 0.01 mg/cu m; all but four samples had
levels <1.2 mg/cu m(1). The avg concn detected was 0.5 mg/cu m(1).
Average Daily Intake:
AIR INTAKE: Assume 1 to 100 ug/cu m(1), 20 ug to 2,000 ug formaldehyde(SRC).
In Sweden between Dec 1986 to Aug 1987, the mean yearly exposure to formaldehyde
from air pollution was 1.2 ug/cu m(1). The estimated daily exposure of the
Finnish population to formaldehyde from community air is 100 ug
and from the home environment, 1,000 ug(2).
Natural Pollution Sources:
Formaldehyde is ubiquitous in the environment; it is an
important endogenous chemical that occurs in most life forms, including
humans(1). It is formed naturally in the troposphere during the oxidation of
hydrocarbons, which react with hydroxyl radicals and ozone to form formaldehyde
and other aldehydes, as intermediates in a series of reactions that ultimately
lead to the formation of carbon monoxide and carbon dioxide, hydrogen and
water(1). Of the hydrocarbons found in the troposphere, methane is the single
most important source of formaldehyde(1). Terpenes and
isoprene, emitted by foliage, react with hydroxyl radicals, forming formaldehyde
as an intermediate product(1). Because of their short half-life, these
potentially important sources of formaldehyde are important
only in the vicinity of vegetation(1). Formaldehyde is one of
the volatile compounds formed in the early stages of decomposition of plant
residues in the soil(1). Formaldehyde occurs naturally in
fruits and other foods(1). Other sources are forest fires, animal wastes,
microbial products of biological systems, and plant volatiles(2,3). Formaldehyde
can also be formed in seawater by photochemical processes(4). However,
calculations of sea-air exchange indicates that this process is probably a minor
source for formaldehyde in the sea(4).
Artificial Pollution Sources:
Formaldehyde's production and use in the manufacture phenol-formaldehyde
resins, urea-formaldehyde resins, acetal resins,
1,4-butanediol, melamine resins, pentaerythritol, hexamethylenetetramine, urea-formaldehyde
concentrates, methylene diisocyanate(1), ethylene glycol, pentaerythritol,
hexamethylenetetramine, and a variety of other chemicals(2), and its use as a
disinfectant, biocide, embalming fluid, preservative, reducing agent (eg, in
recovery of gold and silver), corrosion inhibitor in oil wells, and industrial
sterilant(2) may result in its release to the environment through various waste
streams(SRC). Formaldehyde's production and use as an
fertilizer(2) results in its direct release to the environment(SRC).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value
of 37(SRC), determined from a log Kow of 0.35(2) and a regression-derived
equation(3), indicates that formaldehyde is expected to have
very high mobility in soil(SRC). Volatilization of formaldehyde
from moist soil surfaces is not expected to be an important fate process(SRC)
given a Henry's Law constant of 3.4X10-7 atm-cu m/mole(4). Volatilization of formaldehyde
from dry soil surfaces because it is a gas(5). Formaldehyde
readily biodegrades under both aerobic and anaerobic conditions in the
environment but most of these tests have been conducted under aqueous
conditions(SRC). Formaldehyde in aqueous effluent was degraded
by activated sludge and sewage in 48-72 hr(6-10). In a die-away test using water
from a stagnant lake, degradation was complete in 30 and 40 hrs under aerobic
and anaerobic conditions, respectively(7).
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of
37(SRC), determined from a log Kow of 0.35(2) and a regression-derived
equation(3), indicates that formaldehyde is not expected to
adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces
is not expected(3) based upon a Henry's Law constant of 3.4X10-7 atm-cu
m/mole(4). According to a classification scheme(5), a BCF of 3(SRC), from its
log Kow(2) and a regression-derived equation(6), suggests the potential for
bioconcentration in aquatic organisms is low(SRC). Formaldehyde
readily biodegrades under both aerobic and anaerobic conditions in the
environment(SRC). Formaldehyde in aqueous effluent was degraded
by activated sludge and sewage in 48-72 hr(7-11). In a die-away test using water
from a stagnant lake, degradation was complete in 30 and 40 hrs under aerobic
and anaerobic conditions, respectively(8).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of
semivolatile organic compounds in the atmosphere(1), formaldehyde,
which has a vapor pressure of 3,890 mm Hg at 25 deg C(2), will exist in the gas
phase in the ambient atmosphere(SRC). Gas-phase formaldehyde is
degraded in the atmosphere by reaction with photochemically-produced hydroxyl
radicals(SRC); the half-life for this reaction in air is 41 hrs(SRC), calculated
from its rate constant of 9.4X10-12 cu cm/molecule-sec at 25 deg C(3). The
hydroxy radical initiated oxidation of formaldehyde also occurs
in cloud droplets to form formic acid, a component of acid rain(4). Formaldehyde
absorbs ultraviolet radiation at wavelengths of >360 nm(5); therefore, formaldehyde
may directly photolyze in sunlight(SRC). Formaldehyde has a
half-life of 6 hrs in simulated sunlight(5). The predicted half-life of formaldehyde
due to photolysis in the lower atmosphere is 1.6 hrs at a solar zenith of 40
degrees(5). Formaldehyde reacts with the NO3 radical by H-atom
abstraction with a half-life of 12 days (assuming an average NO3 radical
concentration of 2X10+9/cu cm)(6).
Environmental Biodegradation:
AEROBIC: Formaldehyde, present at 100 mg/l, reached 91% of
its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/l and
the Japanese MITI test(1). Formaldehyde in aqueous effluent was
degraded by activated sludge and sewage in 48-72 hr(2-5). In a die-away test
using water from a stagnant lake, degradation was complete in 30 hours under
aerobic conditions(2). Other biodegradation screening tests gave half-lives
ranging from <1 to 17.3 days(6-11).
ANAEROBIC: In a die-away test using water from a stagnant lake, degradation
was complete in 48 hours under anaerobic conditions(1).
Environmental Abiotic Degradation:
The rate constant for the gas-phase reaction of formaldehyde
with photochemically-produced hydroxyl radicals is 9.4X10-12 cu cm/molecule-sec
at 25 deg C(1). This corresponds to an atmospheric half-life of about 41 hrs at
an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The
hydroxy radical initiated oxidation of formaldehyde also occurs
in cloud droplets to form formic acid, a component of acid rain(2). Formaldehyde
has a photolytic half-life of 6 hrs in simulated sunlight(3). There are two
photolytic pathways, one producing hydrogen gas and carbon monoxide, and the
other producing H and HCO radicals(4,5). The predicted half-life of formaldehyde
due to photolysis in the lower atmosphere is 1.6 hrs at a solar zenith of 40
degrees(4). Formaldehyde reacts with NO3 radicals by H-atom
abstraction with a half-life of 12 days (assuming an average NO3 radical concn
of 2X10+9/cu cm)(6). In water, formaldehyde is hydrated; the
hydrate does not have a chromophore that is capable of absorbing sunlight and
photolytically decomposing(2). Formaldehyde is not expected to
undergo hydrolysis in the environment because of the lack of hydrolyzable
functional groups(7). Solutions containing formaldehyde are
unstable, both oxidizing slowly to form formic acid and polymerizing to form
oligomers(8). In the presence of air and moisture, polymerization readily takes
place in concentrated solutions at room temperatures to form paraformaldehyde, a
solid mixture of linear polyoxymethylene glycols containing 90-99% formaldehyde(9).
In dilute aqueous solution, formaldehyde exists almost
exclusively as the hydrated gem-diol (CH2(OH)2)(10).
Environmental Bioconcentration:
Experiments performed on a variety of fish and shrimp show no
bioconcentration of formaldehyde(1,2).
Soil Adsorption/Mobility:
The Koc of formaldehyde is estimated as 37(SRC), using a log
Kow of 0.35(1) and a regression-derived equation(2). According to a
classification scheme(3), this estimated Koc value suggests that formaldehyde
is expected to have very high mobility in soil(SRC). Formaldehyde
gas adsorbs on clay minerals to a degree at high gas concns which is an
important quality in its use as a soil fumigant(4).
Volatilization from Water/Soil:
The Henry's Law constant for formaldehyde is 3.4X10-7 atm-cu
m/mole(1). This Henry's Law constant indicates that formaldehyde
is expected to be essentially nonvolatile from water surfaces(2). The
volatilization of formaldehyde from dry soil surfaces occurs
because it is a gas under ambient conditions(3).
Environmental Water Concentrations:
DRINKING WATER: Formaldehyde was not detected in National
Organics Reconnaissance Survey of Suspected Carcinogens in Drinking Water(1).
SURFACE WATER: Formaldehyde was detected at 14 heavily
industrialized river basins in the US; 1 of 204 sites were positive at a concn
of 12 ppb(1). Formaldehyde was detected only in hypolimnion of
stagnant lake in Japan(2).
SEAWATER: Formaldehyde was not detected in surface
waters(1).
RAIN/FOG: Formaldehyde levels in rainwater collected in
California were low, ranging from not detected to 0.06 ug/ml(1). The concn of formaldehyde
in rainwater from Mainz and Deuselbach, Germany, and Ireland ranged from 0.111
to 0.174 ppm(2). Formaldehyde was detected in rain water
collected from Enewetek Atoll in the Central Pacific Ocean at range of concns
from 6.2-11.3 ppb(3). Concns of free formaldehyde measured in
fogwater in Corvallis, OR, ranged from 0.4 to 3 mg/l with a volume-weighted mean
of 1.8 mg/l(4). Free formaldehyde concns in fogwater in
Riverside, CA, ranged from 0.12 to 6.8 mg/l, with approximately half of the
samples less than 3 mg/l(5) Status cloud water at Henninger Flats, CA, which is
typically is highly acidic and concentrated in inorganic pollutants, had concns
of free formaldehyde ranging from 1.4 to 1.8 mg/l, comparable
to mid-range Corvallis fogwater concns(5). Formaldehyde concns
ranging from 0.3 to 4.3 mg/l were found in cloud water samples collected in the
Los Angeles Basin(6). Formaldehyde concns in mist samples in
Long Beach and Marina del Ray, CA, were 0.25 and 0.56 mg/l, respectively(1). The
concn of formaldehyde in ice fog from Fairbanks, AK ranged from
0.50 to 1.16 ppm(1). The mean (arithmetic) concn of formaldehyde
in rain water fractions from Mexico City and Rancho Viejo, Mexico ranged from
0.13 to 0.42 mg/l and from 0.18 to 0.21 mg/l, respectively(7). The mean values
of formaldehyde in rain water at 3 locations in Kobe City
(Japan) from Jan 1992 to Dec 1992 were 0.032 mg/l (range, 0.001-0.15 mg/l),
0.035 mg/l (range, 0.001-0.18 mg/l), and 0.016 mg/l (range, 0.001-0.04 mg/l),
respectively(8).
Effluent Concentrations:
The major contributors to indoor formaldehyde are pressed
wood products and foam insulation containing urea-formaldehyde
resins(1). Common indoor combustion sources include gas burners and ovens,
kerosene heaters, and cigarettes(2). The emissions from cigarette smoking are
2,000 ug/cigarette(3). Formaldehyde was detected in 3 effluent
streams, two from chemical plants and one from a sewage treatment plant(4).
Effluent from urea and melamine production contained 4% formaldehyde
and from phenolic resin production contained 0.1% formaldehyde(5).
Emissions from a wastewater treatment plant in Los Angeles, CA (Hyperion) was
391 kg/yr(6).
Formaldehyde is released to outdoor air from both natural
and industrial sources; combustion processes account directly or indirectly for
most of the formaldehyde entering the atmosphere(1). Before
1975, automobiles were found to emit about 2.8X10+8 kg of formaldehyde
each year(2); emissions have been reduced since the introduction of the
catalytic converter in 1975(3). The concn of formaldehyde in
diesel exhaust was 18 ppm(4). The concn of formaldehyde in the
exhaust of a 1970 Ford Maverick gasoline engine ranged from 11 to 15 ppm(4). Formaldehyde
concns in jet engine exhaust have been found to range from 0.761 to 1.14 ppm(5).
Formaldehyde was released from 1982 consumer products, e.g.,
pressed wood products (range, 0.4-21 ug/g product per day); new clothes not
previously washed (range, 0.2-4.9 ug/g product per day); fiberglass insulation
products (range, 0.03-2.3 ug/g product per day); paper plates and cups (range,
0.03-0.36 ug/g product per day), fabrics (range, 0.01-3 ug/g product per day),
and carpets (range, not detected-0.06 ug/g product per day)(4).
Atmospheric Concentrations:
RURAL/REMOTE: Ambient levels of formaldehyde are generally
<1 ug/cu m in remote areas; for example, in the unpopulated Eniwetok Atoll in
the Pacific Ocean, a mean of 0.5 ug/cu m and a max of 1.0 ug/cu m formaldehyde
were measured in outdoor air(1). The avg and range of concns of formaldehyde
in clean marine air are generally <0.5 ppb and <0.03 to 4 ppb,
respectively(2-7).
URBAN/SUBURBAN: Outdoor air concns in urban environments are more variable
and depend on local conditions(1). They are usually 1-20 ug/cu m(1). A major
source of formaldehyde in urban air is incomplete combustion of
hydrocarbon fuels; urban air concn in heavy traffic or during severe inversions
can range up to 100 ug/cu m(1). The concn of formaldehyde was
measured at various sites in US(7); 26% of 749 samples were positive(2); 25% of
samples had concns >2.7 ppb with a max concn of 27 ppb(2). Six cities in US
had avg concns of formaldehyde ranging from 11.3 to 20.6 ppb
with a max concn of 4 ppb(3,4). The daily mean and 1 hr max concn of formaldehyde
at 4 cities in New Jersey ranged from 3.8 to 6.6 ppb and 14 to 20 ppb,
respectively(5). Two cities in Southern California had concns of formaldehyde
ranging from 2 to 48 ppb during photochemical smog episodes(6). From Aug 1979 to
Aug 1980, the mean and range of concns of formaldehyde were
1.28 ppb and 0.11 to 10 ppb (N=174), respectively, at a moderately polluted area
near Julich, Germany(7). The concn of formaldehyde decreases as
one goes up several hundred feet in altitude(8).
URBAN/SUBURBAN: The concn of formaldehyde at the Univ of
Mexico campus between Mar-May 1993 ranged from 9.9 to 110.4 ppb(1). Formaldehyde
was detected in air from San Paulo, Brazil (range, 8.5-19.3 ppb; July 1988)(2),
Athens, Greece (range, 15-25 ppb in Winter 1991; range, 6-20 ppb in Spring
1991)(3), and Grenoble, France (range, 2-18 ppb; May 1995)(4). The concn of formaldehyde
in air from Rome, Italy ranged from 8.8-27.7 ppb between Jun-Jul 1994 and from
8.2-17.6 ppb between Jan-Mar 1995(5). Ambient levels of formaldehyde
from 24 samples were collected every day at 6 Southern California locations
between 9/2/88 and 9/25/89; avg concns in Anaheim, Azusa, Burbank, Hawthorne,
Upland, and W. Los Angeles, CA were 5.3 ppb (max, 25.3 ppb), 5.0 ppb (max, 20.7
ppb), 6.0 ppb (max, 26.0 ppb), 6.0 ppb (max, 29.4 ppb), 5.3 ppb (max, 29.2 ppb),
and 6.1 ppb (max, 25.8 ppb), respectively(6). The avg concn of formaldehyde
in ambient air from Columbus, OH (June-July 1989) was 3.8 ug/cu m(7).
INDOOR AIR: The levels of formaldehyde in indoor air are
often higher than those outside(1). The concn in dwellings depend on the sources
of formaldehyde that are present, the age of the source
materials, ventilation, temperature, and humidity(1). Major sources of formaldehyde
in some dwellings have been reported to be off-gassing of urea-formaldehyde
foam insulation and particle board(1). The mean level in conventional homes with
no urea-formaldehyde foam insulation were 25-60 ug/cu m(1).
Studies conducted in Denmark, Sweden, Germany, and the US frequently found
indoor formaldehyde levels in excess of 0.12 ppm and in several
cases >3.0 ppm(2). In an energy efficient research house, formaldehyde
levels were 65 ppb without furniture, 182 ppb with furniture, 212 ppb occupied
during day, 114 ppb occupied during night(2).
INDOOR AIR: Many studies have been reported since the late 1970s of formaldehyde
levels in mobile homes (caravans)(1). In 3 states, mobile homes (with a filed
complaint) had mean levels of formaldehyde ranging from 0.1 to
0.88 ppm and up to 3.0 ppm(2). Non-complaint mobile homes in Wisconsin which
were <3 yrs old had a mean concn of formaldehyde of 0.54
ppm; mobile homes >3 yr old had a mean concn of 0.19 ppm(3). Homes in
Houston, TX were found to have concns >0.10 ppm in 19% of those tested(4).
The levels of formaldehyde appear to decrease as the mobile
home (and its formaldehyde-based resins) age, with a half-life
of 4 to 5 years(1). In the early 1980s, a mean level of 0.4 ppm and individual
measurements as high as several ppm were measured in new mobile homes. As a
result of new standards set in the mid-1980s for building materials used in
mobile homes and voluntary reductions by the manufacturers, formaldehyde
levels in mobile homes are now typically around 0.1 ppm or less(1).
Food Survey Values:
Formaldehyde occurs naturally in foods, and foods may be
contaminated as a result of fumigation (of e.g. grain), cooking (as a combustion
product) and release from formaldehyde resin-based
tableware(1). It has been used as a bacteriostatic agent in some foods, such as
cheese(1). Fruits and vegetables typically contain 3-60 mg/kg, and meat and
fish, 6-20 mg/kg(1).
Fish/Seafood Concentrations:
Shellfish typically contain 1-100 mg/kg of formaldehyde(1).
Milk Concentrations:
Milk and milk products typically contain about 1 mg/kg of formaldehyde(1).
Other Environmental Concentrations:
LEVEL IN SCHOOL BUILDING WAS 0.3 TO 0.9 PPM DURING SUMMER. SOURCE OF EMISSION
WAS UREA-FORMALDEHYDE RESIN BINDER USED IN FURNITURE &
FLOOR COVERING. AFTER 1 YR, NO FORMALDEHYDE VAPOR WAS RELEASED.
PAPER PLATES & CUPS, LADIES DRESSES, MEN'S SHIRTS, 100% COTTON DRAPERY
FABRIC, GIRLS DRESSES (POLYESTER/COTTON), LATEX-BACKED FABRIC, FOAM-BACKED
CARPET & CHILD'S CLOTHES (65% POLYESTER/35% COTTON) ARE ONLY A FEW OF THE 39
SAMPLE TYPES STUDIED WHICH RELEASED FORMALDEHYDE AT RATE OF 1
TO 34,000 UG/SQ M/DAY.
Free formaldehyde is emitted from formaldehyde
resins used in durable-press cotton when they are heat-cured and stored; in the
US, the concn in 112 fabric samples ranged from 1 to 3517 mg/kg; 18 samples had
a free formaldehyde content greater than 750 mg/kg(1).
Environmental Standards & Regulations:
FIFRA Requirements:
Formaldehyde not more than 1% of pesticide formulation is
exempted from the requirement of a tolerance when used as a preservative for
formulation in accordance with good agricultural practice as inert (or
occasionally active) ingredients in pesticide formulations applied to growing
crops only.
As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive
review of older pesticides to consider their health and environmental effects
and make decisions about their future use. Under this pesticide reregistration
program, EPA examines health and safety data for pesticide active ingredients
initially registered before November 1, 1984, and determines whether they are
eligible for reregistration. In addition, all pesticides must meet the new
safety standard of the Food Quality Protection Act of 1996. Formaldehyde
is found on List A, which contains most food use pesticides and consists of the
194 chemical cases (or 350 individual active ingredients) for which EPA issued
registration standards prior to FIFRA, as amended in 1988. Case No: 0556;
Pesticide type: fungicide, antimicrobial; Registration Standard Date: 05/31/88;
Case Status: OPP is reviewing data from the pesticide's producers regarding its
human health and/or environmental effects, or OPP is determining the pesticide's
eligibility for reregistration and developing the Reregistration Eligibility
Decision (RED) document.; Active ingredient (AI): Formaldehyde;
AI Status: The producers of the pesticide has made commitments to conduct the
studies and pay the fees required for reregistration, and are meeting those
commitments in a timely manner.
CERCLA Reportable Quantities:
Persons in charge of vessels or facilities are required to notify the
National Response Center (NRC) immediately, when there is a release of this
designated hazardous substance, in an amount equal to or greater than its
reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is
(800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The
rule for determining when notification is required is stated in 40 CFR 302.4
(section IV. D.3.b).
Releases of CERCLA hazardous substances are subject to the release reporting
requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to
the requirements of 40 CFR part 355. Formaldehyde is an
extremely hazardous substance (EHS) subject to reporting requirements when
stored in amounts in excess of its threshold planning quantity (TPQ) of 500 lbs.
RCRA Requirements:
U122; As stipulated in 40 CFR 261.33, when formaldehyde, as
a commercial chemical product or manufacturing chemical intermediate or an
off-specification commercial chemical product or a manufacturing chemical
intermediate, becomes a waste, it must be managed according to Federal and/or
State hazardous waste regulations. Also defined as a hazardous waste is any
residue, contaminated soil, water, or other debris resulting from the cleanup of
a spill, into water or on dry land, of this waste. Generators of small
quantities of this waste may qualify for partial exclusion from hazardous waste
regulations (40 CFR 261.5).
Atmospheric Standards:
This action promulgates standards of performance for equipment leaks of
Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing
Industry (SOCMI). The intended effect of these standards is to require all newly
constructed, modified, and reconstructed SOCMI process units to use the best
demonstrated system of continuous emission reduction for equipment leaks of VOC,
considering costs, non air quality health and environmental impact and energy
requirements. Formaldehyde is produced, as an intermediate or a
final product, by process units covered under this subpart.
Listed as a hazardous air pollutant (HAP) generally known or suspected to
cause serious health problems. The Clean Air Act, as amended in 1990, directs
EPA to set standards requiring major sources to sharply reduce routine emissions
of toxic pollutants. EPA is required to establish and phase in specific
performance based standards for all air emission sources that emit one or more
of the listed pollutants. Formaldehyde is included on this
list.
Clean Water Act Requirements:
Formaldehyde is designated as a hazardous substance under
section 311(b)(2)(A) of the Federal Water Pollution Control Act and further
regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations
apply to discharges of this substance. This designation includes any isomers and
hydrates, as well as any solutions and mixtures containing this substance.
Federal Drinking Water Guidelines:
EPA 1000 ug/l
State Drinking Water Standards:
(CA) CALIFORNIA 30 ug/l
State Drinking Water Guidelines:
(CA) CALIFORNIA 30 ug/l
(FL) FLORIDA 600 ug/l
(ME) MAINE 30 ug/l
(MN) MINNESOTA 1000 ug/l
(NJ) NEW JERSEY 100 ug/l
(WI) WISCONSIN 1000 ug/l
FDA Requirements:
Formaldehyde is an indirect food additive for use only as a
component of adhesives.
Formaldehyde is a food additive permitted in feed and
drinking water of animals.
Allowable Tolerances:
Formaldehyde not more than 1% of pesticide formulation is
exempted from the requirement of a tolerance when used as a preservative for
formulation in accordance with good agricultural practice as inert (or
occasionally active) ingredients in pesticide formulations applied to growing
crops only.
Chemical/Physical Properties:
Molecular Formula:
C-H2-O
Molecular Weight:
30.03
Color/Form:
Clear, water-white, very slightly acid, gas or liquid.
Formaldehyde solution is a clear, colorless or nearly
colorless liquid ...
Nearly colorless gas [Note: Often used in an aqueous solution].
Odor:
Pungent, suffocating odor.
Boiling Point:
-19.5 deg C
Melting Point:
-92 deg C
Corrosivity:
Aqueous formaldehyde is corrosive to carbon steel, but formaldehyde
in vapor phase is not.
Critical Temperature & Pressure:
Critical temperature: 137.2-141.2 deg C; critical pressure: 6.784-6.637 MPa
(to convert MPa to atm, divide by 0.101)
Density/Specific Gravity:
1.067 (Air= 1)
Dissociation Constants:
pKa = 13.27 @ 25 deg C
Heat of Combustion:
570.7 kJ/mol (gas)
Heat of Vaporization:
5,917.9 gcal/gmole (to convert to J/g mole, multiply by 4.184)
Index of refraction: 1.3746 at 20 deg C/D /Formaldehyde
soln/
IR: 2538 (Sadtler Research Laboratories Prism Collection)
UV: 3-1 (Organic Electronic Spectral Data, Phillips et al, John Wiley &
Sons, New York)
MS: 37883 (National Institute of Standards and Technology); 74 (Atlas of Mass
Spectral Data, John Wiley and Sons, NY)
Vapor Pressure:
3,890 mm Hg @ 25 deg C
Other Chemical/Physical Properties:
Freezing point: -117 deg C /Formaldehyde, 37% uninhibited/
Formaldehyde solution is a clear, colorless or nearly
colorless liquid having a pungent, irritating odor. /Formaldehyde
soln/
Specified gravity: 0.816 g at 20/20 deg C /Formaldehyde, 37%
uninhibited/
Vapor pressure: 1 mm Hg /Formalin/
In the presence of air and moisture, polymerization readily takes place in
concentrated solutions at room temperatures to form paraformaldehyde, a solid
mixture of linear polyoxymethylene glycols containing 90-99% formaldehyde.
Boiling point: - 19.1 deg C /Formaldehyde 37% uninhibited/
In the presence of air, formaldehyde is oxidized to formic
acid.
Henry's Law constant = 3.37X10-7 atm cu m/mol @ 25 deg C
Hydroxyl radical reaction rate constant = 9.37X10-12 cu cm/molecule-sec @ 25
deg C
Chemical Safety & Handling:
DOT Emergency Guidelines:
Fire or explosion: Flammable/combustible materials. May be ignited by heat,
sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel
to source of ignition and flash back. Most vapors are heavier than air. They
will spread along ground and collect in low or confined areas (sewers,
basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Some
may polymerize (P) explosively when heated or involved in a fire. Runoff to
sewer may create fire or explosion hazard. Containers may explode when heated.
Many liquids are lighter than water. /Formaldehyde, solution,
flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Health: May cause toxic effects if inhaled or ingested/swallowed. Contact
with substance may cause severe burns to skin and eyes. Fire will produce
irritating, corrosive and/or toxic gases. Vapors may cause dizziness or
suffocation. Runoff from fire control or dilution water may cause pollution. /Formaldehyde,
solution, flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Public safety: CALL Emergency Response Telephone Number ... . Isolate spill
or leak area immediately for at least 50 to 100 meters (160 to 330 feet) in all
directions. Keep unauthorized personnel away. Stay upwind. Keep out of low
areas. Ventilate closed spaces before entering. /Formaldehyde,
solution, flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Protective clothing: Wear positive pressure self-contained breathing
apparatus (SCBA). Wear chemical protective clothing which is specifically
recommended by the manufacturer. It may provide little or no thermal protection.
Structural firefighters' protective clothing is recommended for fire situations
only; it is not effective in spill situations. /Formaldehyde,
solution, flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire,
ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial
evacuation for 800 meters (1/2 mile) in all directions. /Formaldehyde,
solution, flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Fire: Some of these materials may react violently with water. Small fires:
Dry chemical, CO2, water spray or alcohol-resistant foam. Large fires: Water
spray, fog or alcohol-resistant foam. Move containers from fire area if you can
do it without risk. Dike fire control water for later disposal; do not scatter
the material. Do not get water inside containers. Fire involving tanks or
car/trailer loads: Fight fire from maximum distance or use unmanned hose holders
or monitor nozzles. Cool containers with flooding quantities of water until well
after fire is out. Withdraw immediately in case of rising sound from venting
safety devices or discoloration of tank. ALWAYS stay away from the ends of
tanks. For massive fire, use unmanned hose holders or monitor nozzles; if this
is impossible, withdraw from area and let fire burn. /Formaldehyde,
solution, flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Spill or Leak: Fully encapsulating, vapor protective clothing should be worn
for spills and leaks with no fire. ELIMINATE all ignition sources (no smoking,
flares, sparks or flames in immediate area). All equipment used when handling
the product must be grounded. Do not touch or walk through spilled material.
Stop leak if you can do it without risk. Prevent entry into waterways, sewers,
basements or confined areas. A vapor suppressing foam may be used to reduce
vapors. Absorb with earth, sand or other non-combustible material and transfer
to containers (except for Hydrazine). Use clean non-sparking tools to collect
absorbed material. Large spills: Dike far ahead of liquid spill for later
disposal. Water spray may reduce vapor; but may not prevent ignition in closed
spaces. /Formaldehyde, solution, flammable; Formaldehyde,
solutions (Formalin); Formaldehyde, solutions,
(Formalin) (corrosive)/
First aid: Move victim to fresh air. Call emergency medical care. Apply
artificial respiration if victim is not breathing. Do not use mouth-to-mouth
method if victim ingested or inhaled the substance; induce artificial
respiration with the aid of a pocket mask equipped with a one-way valve or other
proper respiratory medical device. Administer oxygen if breathing is difficult.
Remove and isolate contaminated clothing and shoes. In case of contact with
substance, immediately flush skin or eyes with running water for at least 20
minutes. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion
or skin contact) to substance may be delayed. Ensure that medical personnel are
aware of the material(s) involved, and take precautions to protect themselves. /Formaldehyde,
solution, flammable; Formaldehyde, solutions (Formalin);
Formaldehyde, solutions, (Formalin)
(corrosive)/
Odor low: 1.4700 mg/cu m; Odor high: 73.5000 mg/cu m
Skin, Eye and Respiratory Irritations:
Contact with the skin causes irritation, tanning effect, and allergic
sensitization. Contact with eyes causes irritation, itching, & lacrimation.
...
Formaldehyde vapor is very irritating to the mucous
membranes and toxic to animals, including man.
Fire Potential:
Flammable
Flammable liquid when exposed to heat or flame; can react vigorously with
oxidizers. ... The gas is a more dangerous fire hazard than the vapor.
NFPA Hazard Classification:
Health: 3. 3= Materials that, on short exposure, could cause serious
temporary or residual injury, including those requiring protection from all
bodily contact. Fire fighters may enter the area only if they are protected from
all contact with the material. Full protective clothing, including
self-contained breathing apparatus, coat, pants, gloves, boots, and bands around
legs, arms, and waist, should be provided. No skin surface should be exposed. /Formaldehyde
gas/
Flammability: 4. 4= This degree includes flammable gases, pyrophoric liquids,
and Class IA flammable liquids. The preferred method of fire attack is to stop
the flow of material or to protect exposures while allowing the fire to burn
itself out. /Formaldehyde gas/
Reactivity: 0. 0= This degree includes materials that are normally stable,
even under fire exposure conditions, and that do not react with water. Normal
fire fighting procedures may be used. /Formaldehyde gas/
Health: 3. 3= Materials that, on short exposure, could cause serious
temporary or residual injury, including those requiring protection from all
bodily contact. Fire fighters may enter the area only if they are protected from
all contact with the material. Full protective clothing, including
self-contained breathing apparatus, coat, pants, gloves, boots, and bands around
legs, arms, and waist, should be provided. No skin surface should be exposed. /Formaldehyde
37% methanol-free/
Flammability: 2. 2= This degree includes materials that must be moderately
heated before ignition will occur and includes Class II and IIIA combustible
liquids and solids and semi-solids that readily give off ignitible vapors. Water
spray may be used to extinguish fires in these materials because the materials
can be cooled below their flash points. /Formaldehyde 37%
methanol-free/
Reactivity: 0. 0= This degree includes materials that are normally stable,
even under fire exposure conditions, and that do not react with water. Normal
fire fighting procedures may be used. /Formaldehyde 37%
methanol-free/
Health: 3. 3= Materials that, on short exposure, could cause serious
temporary or residual injury, including those requiring protection from all
bodily contact. Fire fighters may enter the area only if they are protected from
all contact with the material. Full protective clothing, including
self-contained breathing apparatus, coat, pants, gloves, boots, and bands around
legs, arms, and waist, should be provided. No skin surface should be exposed. /Formaldehyde
37%, 15% methanol/
Flammability: 2. 2= This degree includes materials that must be moderately
heated before ignition will occur and includes Class II and IIIA combustible
liquids and solids and semi-solids that readily give off ignitible vapors. Water
spray may be used to extinguish fires in these materials because the materials
can be cooled below their flash points. /Formaldehyde 37%, 15%
methanol/
Reactivity: 0. 0= This degree includes materials that are normally stable,
even under fire exposure conditions, and that do not react with water. Normal
fire fighting procedures may be used. /Formaldehyde 37%, 15%
methanol/
Flammable Limits:
Lower flammable limit: 7.0% by volume; Upper flammable limit: 73% by volume /Formaldehyde
gas/
Use water spray, dry chemical, alcohol foam, or carbon dioxide. Use water to
keep fire exposed containers cool. If leak or spill has not ignited, use water
spray to disperse vapors, and to protect men attempting to stop leak. Water
spray may be used to flush spills away from exposures and to dilute spills to
nonflammable mixtures.
Approach fire from upwind to avoid hazardous vapors and toxic decomposition
products. Use water spray, dry chemical, "alcohol resistant" foam, or
carbon dioxide.
If material is on fire or involved in a fire: Do not extinguish fire unless
flow can be stopped. Use water in flooding quantities as fog. Solid streams of
water may be ineffective. Cool all affected containers with flooding quantities
of water. Apply water from as far a distance as possible. Use
"alcohol" foam, dry chemical or carbon dioxide.
To fight fire, stop flow of gas (for pure form); alcohol foam for 37%
methanol-free form.
Firefighting Hazards:
Solutions of formaldehyde in water are considered
combustible as the flammable vapors escape and form explosive mixtures with air
over a wide range.
Explosive Limits & Potential:
EXPLOSIVE LIMITS: LOWER 7.0%; UPPER 73.0%
A moderate explosion hazard when exposed to heat or flame. ... When aqueous formaldehyde
solutions are heated above their flash points, a potential for an explosion
hazard exists.
Hazardous Reactivities & Incompatibilities:
(Amines) exothermic reaction, (AZO cmpd) exothermic reaction giving off
nitrogen gas, (caustics) heat generation and violent polymerization,
(dithiocarbamates) formation of flammable gasses and toxic fumes, formation of
carbon disulfide may result, (alkali and alkaline earth metals) heat generation
and formation of flammable hydrogen gas, (nitrides) heat generation, formation
of flammable ammonia gas and violent polymerization, (nitro compd) heat
generation, (unsaturated aliphatics and sulfides) heat generation, (organic
peroxides) violent reaction, (oxidizing agents) heat generation, fire, and
decomposition, (reducing agents) heat generation and formation of flammable
gasses. /From table/
Interaction of nitromethane & formaldehyde in presence
of alkali gives ... 2-nitroethanol, ... di- & tri-condensation products.
After removal of 2-nitroethanol by vacuum distillation, the residue must be
cooled before admitting air into the system to prevent flash explosion or
violent fume-off.
Formaldehyde ... react violently with 90% performic acid.
Formaldehyde and a number of carbonyl cmpd bearing
electronegative substituents in the alpha position add to isocyanic acid at temp
of -70 deg to 0 deg C to form alpha-hydroxy isocyanates. At higher temp, these
isocyanates polymerize and sometimes do so with explosive violence.
Reactions with peroxide, nitrogen dioxide, and performic acid, cause
explosions.
With magnesium carbonate, explosion is due to the pressure of carbon dioxide
formed.
Strong oxidizers, alkalis & acids; phenols; urea [Note: Pure formaldehyde
has a tendency to polymerize. Reacts with HCl to form bis-chloromethyl ether].
Highly chemically reactive. ... Sensitive to light. Powerful reducing agent.
Reacts with sodium hydroxide to yield formic acid and hydrogen. Reacts with
/nitrogen oxides/ at about 180 deg; the reaction becomes explosive.
Hazardous Decomposition:
Uncatalyzed decomposition is very slow below 300 deg C; extrapolation of
kinetic data to 400 deg C indicates that the rate of decomposition is about
0.44%/min at 101 kPa (1 atm). The main products are carbon monoxide and
hydrogen. Metals such as platinium, copper, chromia, and alumina also catalyze
the formation of methanol, methylformate, formic acid, carbon dioxide, and
methane.
Decomposition products: carbon monoxide and carbon dioxide.
When heated to decomposition it emits acrid smoke and fumes.
Hazardous Polymerization:
POLYMERIZES EASILY
Anhydrous, monomeric formaldehyde ... /a dry gas/ is
relatively stable at 80-100 deg C but slowly polymerizes at lower temp. Traces
of polar impurities such as acids, alkalies, and water qreatly accelerate the
polymerization. When liquid formaldehyde is warmed to room temp
in a sealed ampule, it polymerizes rapidly with the evolution of heat (63 kJ/mol
or 15.05 kcal/mol).
... /Polymerization can be/ inhibited by addition of methanol or of
stabilizers such as hydroxypropyl methyl cellulose, methyl and ethyl celluloses
or isophthalobisguanamine.
In the presence of small amts of water, formaldehyde gas may
slowly trimerize to metaformaldehyde.
... Formaldehyde and (AZO cmpd) yield exothermic reaction
giving off nitrogen gas, (caustics) heat generation and violent polymerization.
... Formaldehyde and (Nitrides) cause heat generation,
formation of flammable ammonia gases and violent polymerization. /From table/
Polymerized in aqueous solution to trioxymethylene (retarded by the addition
of methanol).
Immediately Dangerous to Life or Health:
20 ppm; NIOSH considers formaldehyde to be a potential
occupational carcinogen.
Protective Equipment & Clothing:
Respirator selection: (50 ppm) Chemical cartridge respirator with organic
vapor cartridge with full facepiece; Gas mask with organic vapor canister
(chin-style or front- or back-mounted canister); supplied air respirator with
full facepiece, helmet, or hood; self-contained breathing apparatus with full
facepiece; (100 ppm): Type C supplied-air respirator operated in pressure-demand
or other positive pressure or continuous-flow mode; (escape): Gas mask with
organic vapor canister (chin-style or front- or back-mounted canister);
self-contained breathing apparatus.
Wear appropriate eye protection to prevent eye contact.
Recommendations for respirator selection. Condition: At concentrations above
the NIOSH REL, or where there is no REL, at any detectable concentration:
Respirator Class(es): Any self-contained breathing apparatus that has a full
facepiece and is operated in a pressure-demand or other positive pressure mode.
Any supplied-air respirator that has a full facepiece and is operated in
pressure-demand or other positive pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other positive
pressure mode.
Recommendations for respirator selection. Condition: Escape from suddenly
occurring respiratory hazards: Respirator Class(es): Any air-purifying,
full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted
canister providing protection against the compound of concern. Any appropriate
escape-type, self-contained breathing apparatus.
PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent
/should be available./ ... Safety pipettes should be used for all pipetting. ...
In animal laboratory, personnel should ... wear protective suits (preferably
disposable, one-piece & close-fitting at ankles & wrists), gloves, hair
covering & overshoes. ... In chemical laboratory, gloves & gowns should
always be worn ... however, gloves should not be assumed to provide full
protection. Carefully fitted masks or respirators may be necessary when working
with particulates or gases, & disposable plastic aprons might provide addnl
protection. ... Gowns ... /should be/ of distinctive color, this is a reminder
that they are not to be worn outside the laboratory. /Chemical Carcinogens/
Preventive Measures:
Formaldehyde is preferably handled in a closed vessels, and
if this is impossible the vapors should be removed at the level at which they
are evolved. Ventilation must be provided; exposure to concentration above
maximum allowed in factory (escape, splashing of liquid, etc) necessitates the
workmen wearing complete protective equipment (closed-circuit breathing
apparatus, goggles, gloves, etc). Leather and rubber are materials suitable for
protection against vapors liquids containing formaldehyde, and
clothes, and other articles contaminated by formaldehyde should
be copiously washed with water.
PERSONNEL IN CONTACT WITH SOLID MATERIAL CONTAINING FREE FORMALDEHYDE
OR WITH CONCN SOLUTIONS OF FORMALDEHYDE, OR EXPOSED TO FORMALDEHYDE
VAPORS, SHOULD BE PROTECTED BY SUITABLE EXHAUST OR GENERAL VENTILATION & BE
SUPPLIED WITH HAND & ARM PROTECTION & RESP PROTECTIVE EQUIPMENT; BARRIER
CREAMS MAY ALSO PROVIDE VALUABLE SKIN PROTECTION.
Contact lenses should not be worn when working with this chemical.
SRP: The scientific literature for the use of contact lenses in industry is
conflicting. The benefit or detrimental effects of wearing contact lenses depend
not only upon the substance, but also on factors including the form of the
substance, characteristics and duration of the exposure, the uses of other eye
protection equipment, and the hygiene of the lenses. However, there may be
individual substances whose irritating or corrosive properties are such that the
wearing of contact lenses would be harmful to the eye. In those specific cases,
contact lenses should not be worn. In any event, the usual eye protection
equipment should be worn even when contact lenses are in place.
If material is not on fire and not involved in a fire: Keep sparks, flames,
and other sources of ignition away. Keep material out of water sources and
sewers. Build dikes to contain flow as necessary. Use water spray to disperse
vapors and dilute standing pools of liquid.
Personnel protection: Avoid breathing vapors. Keep upwind. ... Do not handle
broken packages unless wearing appropriate personal protective equipment. Wash
away any material which may have contacted the body with copious amounts of
water or soap and water.
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage
of food or of food & beverage containers or utensils, & the application
of cosmetics should be prohibited in any laboratory. All personnel should remove
gloves, if worn, after completion of procedures in which carcinogens have been
used. They should ... wash ... hands, preferably using dispensers of liq
detergent, & rinse ... thoroughly. Consideration should be given to
appropriate methods for cleaning the skin, depending on nature of the
contaminant. No standard procedure can be recommended, but the use of organic
solvents should be avoided. Safety pipettes should be used for all pipetting.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel
should remove their outdoor clothes & wear protective suits (preferably
disposable, one-piece & close-fitting at ankles & wrists), gloves, hair
covering & overshoes. ... clothing should be changed daily but ... discarded
immediately if obvious contamination occurs ... /also,/ workers should shower
immediately. In chemical laboratory, gloves & gowns should always be worn
... however, gloves should not be assumed to provide full protection. Carefully
fitted masks or respirators may be necessary when working with particulates or
gases, & disposable plastic aprons might provide addnl protection. If gowns
are of distinctive color, this is a reminder that they should not be worn
outside of lab. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth
& purification ... should be carried out under well-ventilated hood.
Analytical procedures ... should be carried out with care & vapors evolved
during ... procedures should be removed. ... Expert advice should be obtained
before existing fume cupboards are used ... & when new fume cupboards are
installed. It is desirable that there be means for decreasing the rate of air
extraction, so that carcinogenic powders can be handled without ... powder being
blown around the hood. Glove boxes should be kept under negative air pressure.
Air changes should be adequate, so that concn of vapors of volatile carcinogens
will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological
safety cabinets may be used for containment of in vitro procedures ... provided
that the exhaust air flow is sufficient to provide an inward air flow at the
face opening of the cabinet, & contaminated air plenums that are under
positive pressure are leak-tight. Horizontal laminar-flow hoods or safety
cabinets, where filtered air is blown across the working area towards the
operator, should never be used ... Each cabinet or fume cupboard to be used ...
should be tested before work is begun (eg, with fume bomb) & label fixed to
it, giving date of test & avg air-flow measured. This test should be
repeated periodically & after any structural changes. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or
biochem lab also apply to microbiological & cell-culture labs ... Special
consideration should be given to route of admin. ... Safest method of
administering volatile carcinogen is by injection of a soln. Admin by topical
application, gavage, or intratracheal instillation should be performed under
hood. If chem will be exhaled, animals should be kept under hood during this
period. Inhalation exposure requires special equipment. ... unless specifically
required, routes of admin other than in the diet should be used. Mixing of
carcinogen in diet should be carried out in sealed mixers under fume hood, from
which the exhaust is fitted with an efficient particulate filter. Techniques for
cleaning mixer & hood should be devised before expt begun. When mixing
diets, special protective clothing &, possibly, respirators may be required.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to
skin, animals should be kept in cages with solid bottoms & sides &
fitted with a filter top. When volatile carcinogens are given, filter tops
should not be used. Cages which have been used to house animals that received
carcinogens should be decontaminated. Cage-cleaning facilities should be
installed in area in which carcinogens are being used, to avoid moving of ...
contaminated /cages/. It is difficult to ensure that cages are decontaminated,
& monitoring methods are necessary. Situations may exist in which the use of
disposable cages should be recommended, depending on type & amt of
carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ...
contamination in lab could build up during conduct of expt, periodic checks
should be carried out on lab atmospheres, surfaces, such as walls, floors &
benches, & ... interior of fume hoods & airducts. As well as regular
monitoring, check must be carried out after cleaning-up of spillage. Sensitive
methods are required when testing lab atmospheres. ... Methods ... should ...
where possible, be simple & sensitive. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination
has occurred, such as spillage, should be decontaminated by lab personnel
engaged in expt. Design of expt should ... avoid contamination of permanent
equipment. ... Procedures should ensure that maintenance workers are not exposed
to carcinogens. ... Particular care should be taken to avoid contamination of
drains or ventilation ducts. In cleaning labs, procedures should be used which
do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner
equipped with high-efficiency particulate filter on exhaust, which are avail
commercially, should be used. Sweeping, brushing & use of dry dusters or
mops should be prohibited. Grossly contaminated cleaning materials should not be
re-used ... If gowns or towels are contaminated, they should not be sent to
laundry, but ... decontaminated or burnt, to avoid any hazard to laundry
personnel. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where
carcinogens are used ... should be marked distinctively with appropriate labels.
Access ... limited to persons involved in expt. ... A prominently displayed
notice should give the name of the Scientific Investigator or other person who
can advise in an emergency & who can inform others (such as firemen) on the
handling of carcinogenic substances. /Chemical Carcinogens/
The following engineering controls are recommended to minimize formaldehyde
exposure: 1. Local exhaust ventilation should be installed over work stations
using formalin or specimens preserved in formalin.
2. Small quantities of formaldehyde should be purchased in
plastic containers for ease of handling & safety. 3. Traps should be placed
in floor drains. 4. Spill-absorbent bags should be available for emergencies. 5.
Engineering controls in hemodialysis units should include (a) isolating the main
system from personnel & patients in case of inadvertent spills or (b)
disconnecting the dialyzers before the sterilization process is completed. Also,
formaldehyde vapors should be prevented from entering the room
from the drains serving the main system & the dialysis consoles. The air
should be regularly monitored for formaldehyde, &
in-service education should be conducted periodically on the effects of formaldehyde.
Stability/Shelf Life:
On standing, especially in the cold, may become cloudy, and on exposure to
very low temperature ppt of trioxymethylene formed; in air it slowly oxidizes to
formic acid /40% solution/.
Formaldehyde gas is stable in the absence of water.
Shipment Methods and Regulations:
No person may /transport,/ offer or accept a hazardous material for
transportation in commerce unless that person is registered in conformance ...
and the hazardous material is properly classed, described, packaged, marked,
labeled, and in condition for shipment as required or authorized by ... /the
hazardous materials regulations (49 CFR 171-177)./
The International Air Transport Association (IATA) Dangerous Goods
Regulations are published by the IATA Dangerous Goods Board pursuant to IATA
Resolutions 618 and 619 and constitute a manual of industry carrier regulations
to be followed by all IATA Member airlines when transporting hazardous
materials.
The International Maritime Dangerous Goods Code lays down basic principles
for transporting hazardous chemicals. Detailed recommendations for individual
substances and a number of recommendations for good practice are included in the
classes dealing with such substances. A general index of technical names has
also been compiled. This index should always be consulted when attempting to
locate the appropriate procedures to be used when shipping any substance or
article.
Storage Conditions:
PROTECT AGAINST PHYSICAL DAMAGE. SEPARATE FROM OXIDIZING & ALKALINE
MATERIALS. INDOOR STORAGE SHOULD BE IN AREAS HAVING FLOORS PITCHED TOWARD
TRAPPED DRAIN OR IN CURBED RETENTION AREAS. MINIMUM STORAGE TEMP TO PREVENT
POLYMERIZATION RANGE FROM 83 DEG F FOR 37% FORMALDEHYDE
CONTAINING 0.05% METHYL ALCOHOL TO 29 DEG F FOR FORMALDEHYDE
CONTAINING 15% METHYL ALCOHOL.
Formalin is ... supplied unstabilized or
methanol-stabilized. The latter may be stored at room temp without precipitation
of solid formaldehyde polymers because it contains 5-10% of
methyl alcohol. The uninhibited type must be maintained at a temp of at least 32
deg C to prevent the separation of solid formaldehyde polymers.
Inhibition by methanol decreases the minimum storage temp by about 2.3 deg C
per wt % methanol for unstabilized soln & about 1.3 deg C per wt % methanol
for stabilized solutions. Materials of construction preferred for storage
vessels are 304, 316, and 347-type stainless steels or lined carbon steels.
PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as
practical to lab in which carcinogens are to be used, so that only small
quantities required for ... expt need to be carried. Carcinogens should be kept
in only one section of cupboard, an explosion-proof refrigerator or freezer
(depending on chemicophysical properties ...) that bears appropriate label. An
inventory ... should be kept, showing quantity of carcinogen & date it was
acquired ... Facilities for dispensing ... should be contiguous to storage area.
/Chemical Carcinogens/
Protect containers against physical damage. Separate from oxidizing and
alkaline materials. Indoor storage should be in areas having floors pitched
toward a trapped drain or in curbed retention areas. Store where temperature
range is 16 deg C to 35 deg C. Should not be stored in confined spaces or near
open flames. Indoor storage areas should be equipped with automatic sprinklers.
Storage tanks should be adequately grounded to discharge static electricity and
to reduce other electrical hazard.
Cleanup Methods:
Use fluorocarbon water spray, Cellosize and Hycar to diminish vapors. Sodium
carbonate, ammonium hydroxide, or sodium sulfite can neutralize the spill.
Use universal gel, fly ash, universal sorbent material, or cement powder to
absorb the spill.
Environmental considerations-land spill: Dig a pit, pond, lagoon, holding
area to contain liquid or solid material. /SRP: If time permits, pits, ponds,
lagoons, soak holes, or holding areas should be sealed with an impermeable
flexible membrane liner./ Dike surface flow using soil, sand bags, foamed
polyurethane, or foamed concrete. Absorb bulk liquid with fly ash or cement
powder. Add sodium bisulfite (NaHSO3).
Environmental considerations-air spill: Apply water spray or mist to knock
down vapors. Combustion products include corrosive or toxic vapors.
PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate
arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in
exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms
... Filter housing that is designed so that used filters can be transferred into
plastic bag without contaminating maintenance staff is avail commercially.
Filters should be placed in plastic bags immediately after removal ... The
plastic bag should be sealed immediately ... The sealed bag should be labelled
properly ... Waste liquids ... should be placed or collected in proper
containers for disposal. The lid should be secured & the bottles properly
labelled. Once filled, bottles should be placed in plastic bag, so that outer
surface ... is not contaminated ... The plastic bag should also be sealed &
labelled. ... Broken glassware ... should be decontaminated by solvent
extraction, by chemical destruction, or in specially designed incinerators.
/Chemical Carcinogens/
Environmental considerations: water spill: Use natural barriers or oil spill
control booms to limit spill travel. Use surface active agent (eg detergent,
soaps, alcohols), if approved by USEPA. Inject "universal" gelling
agent to solidify encircled spill and increase effectiveness of booms. Add
sodium bisulfite (NaHSO3). If dissolved, in region of 10 ppm or greater
concentration, apply activated carbon at ten times the spilled amount. Use
mechanical dredges or lifts to remove immobilized masses of pollutants and
precipitates.
Approach release from upwind. use water spray to cool and disperse vapors,
protect personnel, and dilute spills to form nonflammable mixtures. Stop or
control the leak, if this can be done without undue risk. Control runoff and
isolate discharged material for proper disposal.
Disposal Methods:
Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number U122, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Generators of waste (equal to or greater than 100 kg/mo) containing this
contaminant, EPA hazardous waste number U122, must conform with USEPA
regulations in storage, transportation, treatment and disposal of waste.
Formaldehyde is a waste chemical stream constituent which
may be subjected to ultimate disposal by controlled incineration.
A good candidate for rotary kiln incineration at a temperature range of 820
to 1,600 deg C and residence times of seconds for liquids and gases, and hours
for solids. A good candidate for fluidized bed incineration at a temperature
range of 450 to 980 deg C and residence times of seconds for liquids and gases,
and longer for solids.
Dissolve in a combustible solvent, then spray the soln into the furnace with
afterburner. Recommendable methods: Incineration, oxidation, & discharge to
sewer. Not recommendable methods: Evaporation & alkaline hydrolysis.
Peer-review: Dilute formaldehyde waste with a large amt of
water and treat the soln by hypochlorite soln. Concentration of formaldehyde
in the soln should be below 2% in order to avoid excess exothermic reaction
heat. Formaldehyde is a powerful reducing agent and many
oxidants can be used, but may react violently (must be diluted). Alkaline
hydrolysis may be dangerous because of exothermic reaction. (Peer-review
conclusions of an IRPTC expert consultation (May 1985))
PRECAUTIONS FOR "CARCINOGENS": There is no universal method of
disposal that has been proved satisfactory for all carcinogenic compounds &
specific methods of chem destruction ... published have not been tested on all
kinds of carcinogen-containing waste. ... Summary of avail methods &
recommendations ... /given/ must be treated as guide only. /Chemical
Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only
feasible method for disposal of contaminated laboratory waste from biological
expt. However, not all incinerators are suitable for this purpose. The most
efficient type ... is probably the gas-fired type, in which a first-stage
combustion with a less than stoichiometric air:fuel ratio is followed by a
second stage with excess air. Some ... are designed to accept ... aqueous &
organic-solvent solutions, otherwise it is necessary ... to absorb soln onto
suitable combustible material, such as sawdust. Alternatively, chem destruction
may be used, esp when small quantities ... are to be destroyed in laboratory.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate
arrestor) filters ... can be disposed of by incineration. For spent charcoal
filters, the adsorbed material can be stripped off at high temp &
carcinogenic wastes generated by this treatment conducted to & burned in an
incinerator. ... LIQUID WASTE: ... Disposal should be carried out by
incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses
of lab animals, cage litter & misc solid wastes ... should be disposed of by
incineration at temp high enough to ensure destruction of chem carcinogens or
their metabolites. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some
carcinogens can be destroyed using chem reactions ... but no general rules can
be given. ... As a general technique ... treatment with sodium dichromate in
strong sulfuric acid can be used. The time necessary for destruction ... is
seldom known ... but 1-2 days is generally considered sufficient when freshly
prepd reagent is used. ... Carcinogens that are easily oxidizable can be
destroyed with milder oxidative agents, such as saturated soln of potassium
permanganate in acetone, which appears to be a suitable agent for destruction of
hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn
or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating,
arylating or acylating agents per se can be destroyed by reaction with
appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols &
thiosulfate. The reactivity of various alkylating agents varies greatly ...
& is also influenced by sol of agent in the reaction medium. To facilitate
the complete reaction, it is suggested that the agents be dissolved in ethanol
or similar solvents. ... No method should be applied ... until it has been
thoroughly tested for its effectiveness & safety on material to be
inactivated. For example, in case of destruction of alkylating agents, it is
possible to detect residual compounds by reaction with
4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/
The following wastewater treatment technologies have been investigated for formaldehyde:
Biological treatment.
The following wastewater treatment technologies have been investigated for formaldehyde:
Activated carbon.
Recommended Exposure Limit: 15 Min Ceiling Value: 0.1 ppm.
NIOSH considers formaldehyde to be a potential occupational
carcinogen.
NIOSH usually recommends that occupational exposures to carcinogens be
limited to the lowest feasible concentration.
Immediately Dangerous to Life or Health:
20 ppm; NIOSH considers formaldehyde to be a potential
occupational carcinogen.
Other Occupational Permissible Levels:
Australia (1990): 1 ppm TWA. 2 ppm STEL, probable human carcinogen; Federal
Republic of Germany (1991): 0.5 ppm, short-term level 1.0 ppm, 5 min, 8
times/shift; group B, suspected of having carcinogenic potential; danger of
sensitization; Sweden (1989): 0.8 ppm, ceiling 1.0 ppm, sensitizer; United
Kingdom (1991): 2 ppm, 10-minute STEL 2 ppm
Emergency Response Planning Guidelines (ERPG): ERPG(1) 1 ppm (no more than
mild, transient effects) for up to 1 hr exposure; ERPG(2) 10 ppm (without
serious, adverse effects) for up to 1 hr exposure; ERPG(3) 25 ppm (not life
threatening) up to 1 hr exposure.
Manufacturing/Use Information:
Major Uses:
For Formaldehyde (USEPA/OPP Pesticide Code: 043001) ACTIVE
products with label matches. /SRP: Registered for use in the U.S. but approved
pesticide uses may change periodically and so federal, state and local
authorities must be consulted for currently approved uses./
FIXATION OF HISTOLOGICAL SPECIMENS & IN ALTERATION OF BACTERIAL TOXINS TO
TOXOIDS FOR VACCINES. /SOLN, USP/
AS GERMICIDE ... MAINLY USED IN 2-8% CONCN TO DISINFECT INANIMATE OBJECTS ...
.
In the production of fertilizers. As a textile finish, preservative,
stabilizer, disinfectant, and antibacterial food additive.
Polyacetal resins, ethylene glycol, pentaerythritol, hexamethylenetetramine,
biocide, embalming fluids, reducing agent as in recovery of gold and silver,
corrosion inhibitor in oil wells, durable-press treatment of textile fabrics,
industrial sterilant, treatment of grain smut, and a versatile chemical
intermediate.
Used in the manufacture of amino and phenolic resins. Phenol-formaldehyde
resins find use as adhesives for binding wood products (particle board, fiber
board, and plywood), molding compounds (in electrical, automotive, and kitchen
parts), phenolic foam insulation, foundry mold binders, decorative and
industrial laminates, and binders for insulating materials. Urea-formaldehyde
resins find use as molding compounds, adhesives for paper products. Melamine- formaldehyde
resins find use in decorative laminates, thermoset surface coatings, and molding
compounds such as dinnerware.
Use to make 1,4-butanediol, polyols, acetal resins, hexamethylenetetramine,
methylene bis(4-phenyl isocyanate), chelating agents (eg, EDTA and NTA), formaldehyde-alcohol
solutions, paraformaldehyde, trioxane, tetraoxane, and many other chemicals.
Used as a corrosion inhibitor, hydrogen sulfide scavenger, and biocide in oil
production operations such as drilling, waterford, and enhanced oil recovery.
Other uses include fungicides, and silage preservatives.
CHEM INT FOR PHENOLIC, POLYACETAL & MELAMINE RESINS
Soil sterilant in mushroom houses before planting. /Former use/
MEDICATION (VET)
Manufacturers:
Borden Chemical, Inc., 180 East Broad St., Columbus, OH 43215-3799, (614)
225-4000; Production sites: Baytown, TX 77520; Demopolis, AL 36732; Diboll, TX
75941; Fayetteville, NC 28301; Fremont, CA 94538; Geismar, LA 70734; Hope,
AR71801; Kent, WA 98031; La Grande, OR 97850; Louisville, KY 40216; Malvern, AR
72104; Missoula, MT 59801; Sheboygan, WI 53081; South Glen Falls, NY 12803;
Springfield, OR 97477; Vicksburg, MS 39180; Waverly, VA 23890
Borden Chemicals and Plastics, Operating Limited Partnership, Highway 73,
Geismar, LA 70734, (225) 673-6121; Production site: Geismar, LA 70734
Capital Resin Corp., 324 Dering Ave., Columbus, OH 43207-2956, (614)
445-7290; Production site: Columbus, OH 43207
Celanese Ltd., Celanese Chemicals-Americas, 86 Morris Ave., Summit, NJ 07901,
(972) 443-4000; Production sites: Bishop, TX 78343; Rock Hill, SC 29730
D.B. Western, Inc., 1360 Airport Lane, North Bend, OR 97459, (541) 756-0533
Production site: Virginia, MN 55792
Degussa-Huls Corp., 65 Challenger Rd., Ridgefield Park, NJ 07660, (201)
641-6100. Chemical Group; Production site: Theodore, AL 36590
DuPont, 1007 Market St., Wilmington, DE 19898, (800) 441-7515. DuPont
Specialty Chemicals, Dupont Performance, Specialty, and Fine Chemicals;
Production site: La Porte, TX 77571
Georgia-Pacific Resins, Inc., 55 Park Place, 19th floor, Atlanta, GA 30303,
(770) 593-6800; Production sites: Albany, OR 97321; Columbus, OH 43207; Conway,
NC 27820; Crosset, AR 71635; Denton, NC 27239; Grayling, MI 49738; Hampton, SC
29924; Houston, TX 77015; Louisville, MS 39339; Lufkin, TX 75901; Russellville,
SC 29476; Taylorsville, MS 39168; Vienna, GA 31092; White City, OR 97503
Geo Specialty Chemicals, Inc., 28601 Chagrin Blvd., Suite 210, Cleveland, OH
44122, (216) 464-5564. TRIMET Products Group; Production site: Allentown, PA
18104
Hercules Inc., Hercules Plaza, 1313 North Market St., Wilmington, DE 19894-
0001, (302) 594-500. Functional Products Segment, Aqualon Division; Production
site: Louisiana, MO 63353
International Specialty Products, Inc., 1361 Alps Rd., Wayne, NJ 07470-3688,
(973) 628-4000; Production site: Texas City, TX 77590
Neste Resins Corp., 1600 Valley River Drive, Suite 390, Eugene, OR 97401,
(541) 687-8840; Production sites: Andalusia, AL 36420; Moncure, NC 27559;
Springfield, OR 97477; Toledo, OH 43612; Winnfield, LA 71483
New Mexico Adhesives LLC, 780 Airport Route, Las Vegas, NM 87701, (505)
425-5932; Production site: Las Vegas, NM 87701
Praxair, Inc., 39 Old Ridgebury Rd., Danbury, CT 06810-5113, (203) 837-2505;
Production site: Geismar, LA 70734
Solutia, Inc., 575 Maryville Centre Drive, P.O. Box 66760, St. Louis, MO
63166-6760, (314) 674-1000; Production site: Alvin, TX 77511
Wright Chemical Corp., Acme Station, Acme, NC 28446, (910) 251-8952;
Production site: Riegelwood, NC 28456
Methods of Manufacturing:
Historically, formaldehyde has been and continues to be mfr
from methanol. During the decades following World War II ... as much as 20% of formaldehyde
produced in the USA was made by the vapor phase, non-catalytic oxidation of
propane and butanes. ... Today, all of the world's commercial formaldehyde
is mfr from methanol and air by an older process using a metal catalyst and a
newer one using a metal oxide catalyst. ... In early formaldehyde
plants, methanol was oxidized over a copper catalyst, but in recent years this
has been almost completely replaced with silver.
Oxidation of synthetic methanol or low-boiling petroleum gases such as
propane and butane. Silver, copper, or iron-molybdenum oxide are the most common
catalysts.
Methanol (catalytic dehydrogenation)
General Manufacturing Information:
Formaldehyde ... is used in the form of anhydrous monomer,
soln, polymers, and derivatives. Anhydrous, monomeric formaldehyde
is not avail commercially.
U.S. Formaldehyde production capacity in 1989 was 4,310X10+3
tons/yr based on 37% wt formaldehyde (with 2 wt% methanol)
/from Table/
All information on capacity & demand is reported on a 37% wt formaldehyde
basis. Total plant production capacity in the USA in 1978 was 4,086X10+3
tons/year. /From table/
Worldwide production capacity in 1977 was estimated to be over 12.6x10+6
metric tons/yr as 37% by weight formaldehyde.
Formaldehyde, when used as a preservative in shampoos, may
interact unfavorably with both fragrance components and color additives.
Discontinued in 1987 by Chemical Supply Co, Ltd /Formalin/
Worldwide production capacity in 1989 was 15.5X10+6 tons as 37 wt% formaldehyde
solution.
Formulations/Preparations:
Pure formaldehyde is not avail commercially because of its
tendency to polymerize. It is sold as aqueous solutions containing from 37% to
50% formaldehyde by wt & varying amounts of methanol.
Marketed under the trade name Formcel, soln in methanol, n-butanol, and
isobutanol. ...
Aq formaldehyde, known as formalin, is
usually 37% by weight of formaldehyde, though more concn soln
are available. Formalin is the general-purpose formaldehyde
of commerce supplied unstabilized or methanol-stabilized. ... Formaldehyde
may also exist in the form of the cyclic trimer trioxane. This is a fairly
stable cmpd that does not easily release formaldehyde. ...
Grade: Aqueous solutions: 37%, 44%, 50% inhibited (with varying percentages
of methanol) or stabilized or unstabilized (methanol-free), also available in
solution in n-butanol, ethanol, or urea; USP (37% aqueous solution containing
methanol).
Soluble concentrate; hot fogging concentrate
Consumption Patterns:
Worldwide demand for formaldehyde in 1989 was estimated to
be about 85-90% of capacity /about 14X10+6 t as 37 wt% formaldehyde
soln/
CHEM INT FOR UREA-FORMALDEHYDE RESINS, 26.5%; CHEM INT FOR
PHENOLIC RESINS, 19.6%; CHEM INT FOR ACETYLENIC CHEMS, 8.4%; CHEM INT FOR
POLYACETAL RESINS, 7.9%; CHEM INT FOR PENTAERYTHRITOL, 6.7%; CHEM INT FOR
HEXAMETHYLENETETRAMINE, 5.5%; CHEM INT FOR UREA-FORMALDEHYDE
CONCENTRATES, 5.2%; CHEM INT FOR METHYLENE DIANILINE, 3.9%; CHEM INT FOR
MELAMINE RESINS, 3.6%; CHEM INT FOR CHELATING AGENTS, 2.8%; OTHER, 9.9% (1981).
Worldwide demand for formaldehyde in 1976 was estimated to
be about 7.5X10+6 tons or 60% capacity.
During 1985 ... resins going in to adhesives and plastics ... amount to more
than 60% of demand ... most of the rest of formaldehyde demand
is for use as a chemical intermediate.
CHEMICAL PROFILE: Formaldehyde. Demand: 6.73 billion lb;
1989: 6.5 billion lb; 1993 /projected/: 7.6 billion lb. (Includes exports but
not imports, both of which are negligible).
CHEMICAL PROFILE: Formaldehyde. (1989) 11 million lbs
(2002) 140X10+6 lbs (est).
U. S. Exports:
(1978) 1.04X10+10 G (INCL SOLNS)
(1983) 7.80X10+10 G (INCL SOLNS)
(1985) 4.01X10+8 g
CHEMICAL PROFILE: Formaldehyde. (1998) 19 million lbs
(2002) 25X10+6 lbs (est).
Laboratory Methods:
Analytic Laboratory Methods:
... Workplace air samples ... /were/ analyzed by differential pulse
polarography. The method was validated over the range of 5.8 - 17.7 mg/cu m. ...
Average recovery was 103%. The pooled coefficient of variation or relative
standard deviation was 0.08.
Approximately 20 g of soil, accurately weighed, are collected in a glass jar
and dried by the addition of magnesium sulfate. Freon 113
(1,1,2-trichloro-1,2,2-triflouroethane) is used to extract the formaldehyde.
The extracts are combined in a 100 ml volumetric flask and the volume taken to
100 ml with Freon. The sample is scanned on a suitable spectrophotometer from
3200 to 2700 cm-1 using matched 1 cm cells. The sample concentration is
determined from a calibration curve.
Two methods for measuring formaldehyde at ppb levels, the
modified pararosaniline and the modified chromotropic acid, were evaluated in a
laboratory study. A dynamic double dilution system was used to generate
controlled test atmospheres of formaldehyde by the catalytic
depolymerization of trioxane. Impinger samples were collected from the sampling
manifold and /determined/ accordingly. Both methods demonstrated good precision
(3.5% for the pararosaniline and 3.4% for the chromotropic acid) but differed in
accuracy and collection efficiency. Accuracy was 87.7 + or - 7.5% for the
pararosaniline and 92.5 + or - 4.2% for the chromotropic acid, while collection
efficiency was 91.9 + or - 6.9% and 98.7 + or - 4.7%, respectively.
NIOSH Method 2539. Analyte: Formaldehyde. Matrix: Air.
Procedure: Gas chromatography, flame ionization detector and gas
chromatography/mass spectrometry. For formaldehyde this method
has an estimated detection limit of 2 ug aldehyde/sample. The precision/RSD is
not determined. Applicability: This is a screening technique to determine the
presence of aldehydes and should not be used for quantitation. Interferences:
High-boiling naphtha mixtures and mineral spirits may have components with
retention times similar to the formaldehydes and may be interferences in the gas
chromatographic analysis.
NIOSH Method 3500. Analyte: Formaldehyde. Matrix: Air.
Procedure: Visible absorption spectrometry. For formaldehyde
this method has an estimated detection limit of 0.5 ug/sample. The precision/RSD
is 0.03 @ 1 to 20 ug/sample. Applicability: The working range is 0.02 to 4 ppm
(0.025 to 4.6 mg/cu m) for an 80 liter air sample. Interferences: Phenols, in 8
fold excess over formaldehyde produce a -10% to -20% bias.
Little interference is seen from other aldehydes.
NIOSH Method 2541. Analyte: Formaldehyde. Matrix: Air.
Procedure: Gas chromatography hydrogen-air flame ionization detector. For formaldehyde
this method has an estimated detection limit of 1 ug/sample. The precision/RSD
is 0.0052 @ 38 to 194 ug/sample. Applicability: The working range is 0.24 to 16
ppm (0.3 to 20 mg/cu m) for a 10 liter air sample. Interferences: None have been
observed.
NIOSH Method 5700. Determination of Formaldehyde On Dust
(Textile or Wood) by High Performance Liquid Chromatography. This method is
applicable to textile and wood dust. Detection limit = 0.08 ug/cu m.
EPA Method 8015. Direct Injection or Purge-and-Trap Gas Chromatography for
the determination of nonhalogenated volatile organics in solid waste. Under the
prescribed conditions formaldehyde can be detected using this
method. No statistical analysis was determined; specific method performance
information will be provided as it becomes available.
EPA Method 8240. Gas Chromatography/Mass Spectrometry for the determination
of volatile Organics. This method can be used to quantify most volatile organic
compounds including formaldehyde that have boiling points below
200 deg C and are insoluble or slightly soluble in water. The detection limit is
not given. Precision and method accuracy were found to be directly related to
the concentration of the analyte and essentially independent of the sample
matrix.
OSW Method 0011. Sampling of Formaldehyde (and other
aldehydes and ketones) from Stack Emissions by Derivatization with
2,4-Dinitrophenyl-Hydrazine. Formaldehyde, and any other
aldehydes or ketones present, react with DNPH to yield dinitrophenylhydrazones.
These are analyzed by HPLC following extraction and concentration. Detection
limit = 1.8 ppb.
OSW Method 0011A. Analysis for Aldehydes and Ketones by High Performance
Liquid Chromatography. This method is applicable to aqueous samples, leachates
of solid samples (Method 1311), and impinger solutions from Method 0011.
Detection limit = 7.2 ug/l.
OSW Method 8315. Determination of Carbonyl Compounds by High Performance
Liquid Chromatography (HPLC). This method is applicable to various matrices by
derivatization with 2,4-dinitrophenylhydrazine (DNPH). Detection limit = 6.2
ug/l.
OSW Method 8315A-LLE. Determination of Carbonyl Compounds by High Performance
Liquid Chromatography (HPLC) Using Liquid-Liquid Extraction. This method is
applicable to the determination of free carbonyl compounds in various matrices
by derivatization with 2,4-dinitrophenylhydrazine (DNPH). Detection limit = 23
ug/l.
OSW Method 8315A-LSE. Determination of Carbonyl Compounds by High Performance
Liquid Chromatography (HPLC) using Liquid-Solid Extraction. This method is
applicable to the determination of free carbonyl compounds in various matrices
by derivatization with 2,4-dinitrophenylhydrazine (DNPH). Detection limit = 6.2
ug/l.
AOAC Method 897.01. Formaldehyde in Pesticide Formulations
by Cyanide Method. Applicable to diluted solutions only. Detection limit not
specified.
AOAC Method 898.01. Formaldehyde in Pesticide Formulations
by Hydrogen Peroxide Method. Applicable to solutions only. Detection limit not
specified.
AOAC Method 931.03: Formaldehyde in Seed Disinfectants by
Titrimetric Method. Applicable to the detection of formaldehyde
(HCHO) absorbed in inert carrier, e.g., bentonite, talc, charcoal, and sawdust.
Detection limit not specified.
EPA Method 554. Determination of Carbonyl Compounds in Drinking Water by
Dinitrophenylhydrazine Derivatization and High Performance Liquid
Chromatography. This method is used for the determination of selected carbonyl
compounds in finished drinking water or raw source water. Detection limit = 8.1
ug/l.
EPA Method 6. Determination of Carbonyl Compounds in Drinking Water by
Dinitrophenylhydrazine Derivatization and High Performance Liquid
Chromatography. This method is used for the determination of selected carbonyl
compounds in finished drinking water or raw source water. Detection limit = 9
ug/l.
AOAC Method 964.21: Formaldehyde in maple syrup
spectrophotometric method is not suitable for beet or cane sugars. Detection
limit unspecified.
Sampling Procedures:
NIOSH Method 2539. Analyte: Formaldehyde. Matrix: Air.
Sampler: Solid sorbent tube (10% 2-(hydroxy methyl)) pipendine on XAD-2, 20
mg/60 mg. Flow Rate: 0.01 to 0.05 l/min: Sample Size: 5-liters. Shipment: At 25
deg C or lower. Sample Stability: Stable greater or equal to 1 week @ 25 deg C.
NIOSH Method 3500. Analyte: Formaldehyde. Matrix: Air.
Sampler: Filter plus impingers (1 um polytetrafluoroethylene membrane and 2
impingers, each with 20 ml 1% sodium bisulfite solution). Flow Rate: 0.2 to 1
liter/min: Sample Size: 80 liters. Shipment: Transfer samples to flow-density
polyethylene bottles before shipping. Sample Stability: 30 days @ 25 deg C.
NIOSH Method 2541. Analyte: Formaldehyde. Matrix: Air.
Sampler: Solid sorbent tube (10% (2-(hydroxymethyl)) piperidine on XAD-2, 120
mg/60 mg). Flow Rate: 0.01 to 0.10 l/min. Sample Size: 10 liters. Shipment:
Routine. Sample Stability: 3 weeks @ 25 deg C.
OSW Method 0100. Sampling for Formaldehyde and Other
Carbonyl Compounds in Indoor Air. This method provides procedures for the
sampling of various carbonyl compounds in indoor air by derivatization with
2,4-dinitrophenylhydrazine (DNPH) in a silica gel cartridge.
OSW Method 8520. Continuous Measurement of Formaldehyde in
Ambient Air. This method is applicable to the continuous measurement of formaldehyde
in the 6 to 500 ug/m3 range in ambient air. It is used primarily for
nonoccupational exposure monitoring.
Special References:
Special Reports:
Environment Canada; Tech Info for Problem Spills: Formaldehyde
(1985)
Chem Indus Inst of Tox Rpts Conf on Formaldehyde Toxicol
(1983)
TSCA CHIPs present a preliminary assessment of formaldehyde's
potential for injury to human health & the environment (available at EPA's
TSCA Assistance Office: (202) 554-1404 or (800) 424-9065)
WHO; Environmental Health Criteria 89: Formaldehyde (1989)
Ma T, Harris MM; Mutat Res 196: 37-59 (1988). Review of the genotoxicity of formaldehyde.
Schlosser O; Disinfection of operating areas by formaldehyde:
occupational hazards and their prevention. Literature review of the toxicity of formaldehyde
Universit'e Pierre et Marie Curie (Paris VI), Facult'e de m'edecine
Daint-Antoine, Paris, France Medical thesis. The study surveyed the conditions
under which formaldehyde was used as a disinfectant in the
operating theatres of a large hospital in Paris (France), and on the effect this
had on the health of hospital staff. Also included are a literature survey of
the toxicity of formaldehyde and relevant French legislation.
U.S Department of Health & Human Services/National Toxicology Program;
9th Report on Carcinogens. National Institute of Environmental Health Services,
Research Triangle Park, NC. (2000)
Synonyms and Identifiers:
Synonyms:
BFV **PEER REVIEWED**
Dormol **PEER REVIEWED**
Pesticide Code: 043001 **PEER REVIEWED**
FANNOFORM **PEER REVIEWED**
FORMALDEHYDE, GAS **PEER REVIEWED**
FORMALDEHYDE SOLUTION **PEER REVIEWED**
FORMALIN **PEER REVIEWED**
FORMALITH **PEER REVIEWED**
FORMIC ALDEHYDE **PEER REVIEWED**
FORMOL **PEER REVIEWED**
FYDE **PEER REVIEWED**
IVALON **PEER REVIEWED**
LYSOFORM **PEER REVIEWED**
METHANAL **PEER REVIEWED**
METHYL ALDEHYDE **PEER REVIEWED**
METHYLENE OXIDE **PEER REVIEWED**
MORBICID **PEER REVIEWED**
OXOMETHANE **PEER REVIEWED**
OXYMETHYLENE **PEER REVIEWED**
SUPERLYSOFORM **PEER REVIEWED**
Formulations/Preparations:
Pure formaldehyde is not avail commercially because of its
tendency to polymerize. It is sold as aqueous solutions containing from 37% to
50% formaldehyde by wt & varying amounts of methanol.
Marketed under the trade name Formcel, soln in methanol, n-butanol, and
isobutanol. ...
Aq formaldehyde, known as formalin, is
usually 37% by weight of formaldehyde, though more concn soln
are available. Formalin is the general-purpose formaldehyde
of commerce supplied unstabilized or methanol-stabilized. ... Formaldehyde
may also exist in the form of the cyclic trimer trioxane. This is a fairly
stable cmpd that does not easily release formaldehyde. ...
Grade: Aqueous solutions: 37%, 44%, 50% inhibited (with varying percentages
of methanol) or stabilized or unstabilized (methanol-free), also available in
solution in n-butanol, ethanol, or urea; USP (37% aqueous solution containing
methanol).
Soluble concentrate; hot fogging concentrate
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1198; Formaldehyde solutions, flammable
UN 2209; Formaldehyde solutions, with not less than 25% formaldehyde.
IMO 3.3; Formaldehyde solutions, flammable
IMO 8.0; Formaldehyde solutions, with not less than 25% formaldehyde
Standard Transportation Number:
49 131 68; Formaldehyde solution (liquid) or formalin
(flash point more than 141 deg F, in containers over 110 gal)
49 403 64; Formaldehyde solution (liquid) or formalin
(flash point more than 141 deg F, in containers of 110 gal or less)
49 131 69; Formaldehyde solution (paste) or formalin
(flash point more than 141 deg F, in containers over 110 gal)
49 403 65; Formaldehyde solution (paste) or formalin
(flash point more than 141 deg F, in containers of 110 gal or less)
49 131 44; Formaldehyde solution (liquid) or formalin
(flash point not more than 141 deg F, in containers over 110 gal)
49 403 41; Formaldehyde solution (liquid) or formalin
(flash point not more than 141 deg F, in containers of 110 gal or less)
49 131 45; Formaldehyde solution (paste) or formalin
(flash point not more than 141 deg F, in containers over 110 gal)
49 403 42; Formaldehyde solution (paste) or formalin
(flash point not more than 141 deg F, in containers of 110 gal or less)
EPA Hazardous Waste Number:
U122; A toxic waste when a discarded commercial chemical product or
manufacturing chemical intermediate or an off-specification commercial chemical
product or a manufacturing chemical intermediate.
RTECS Number:
NIOSH/LP8925000
Administrative Information:
Hazardous Substances Databank Number: 164
Last Revision Date: 20020531
Last Review Date: Reviewed by SRP on 9/15/2001
Update History:
Complete Update on 05/31/2002, 1 field added/edited/deleted.
Complete Update on 04/19/2002, 92 fields added/edited/deleted.
Field Update on 01/14/2002, 1 field added/edited/deleted.
Field Update on 08/08/2001, 1 field added/edited/deleted.
Field Update on 05/16/2001, 1 field added/edited/deleted.
Complete Update on 09/12/2000, 1 field added/edited/deleted.
Complete Update on 06/12/2000, 1 field added/edited/deleted.
Complete Update on 03/24/2000, 1 field added/edited/deleted.
Complete Update on 03/09/2000, 1 field added/edited/deleted.
Complete Update on 02/11/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 01/11/2000, 6 fields added/edited/deleted.
Field Update on 09/21/1999, 1 field added/edited/deleted.
Field Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 06/03/1999, 3 fields added/edited/deleted.
Field Update on 05/24/1999, 1 field added/edited/deleted.
Field Update on 05/17/1999, 1 field added/edited/deleted.
Complete Update on 03/29/1999, 2 fields added/edited/deleted.
Field Update on 03/18/1999, 1 field added/edited/deleted.
Complete Update on 03/01/1999, 1 field added/edited/deleted.
Complete Update on 02/11/1999, 4 fields added/edited/deleted.
Field Update on 02/01/1999, 1 field added/edited/deleted.
Complete Update on 11/16/1998, 1 field added/edited/deleted.
Complete Update on 11/12/1998, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 10/17/1997, 1 field added/edited/deleted.
Complete Update on 08/13/1997, 1 field added/edited/deleted.
Complete Update on 03/27/1997, 2 fields added/edited/deleted.
Complete Update on 03/11/1997, 3 fields added/edited/deleted.
Complete Update on 02/26/1997, 1 field added/edited/deleted.
Complete Update on 01/09/1997, 1 field added/edited/deleted.
Complete Update on 07/11/1996, 1 field added/edited/deleted.
Complete Update on 05/17/1996, 2 fields added/edited/deleted.
Complete Update on 04/18/1996, 2 fields added/edited/deleted.
Complete Update on 04/09/1996, 7 fields added/edited/deleted.
Field Update on 01/18/1996, 1 field added/edited/deleted.
Complete Update on 09/26/1995, 2 fields added/edited/deleted.
Complete Update on 08/21/1995, 1 field added/edited/deleted.
Complete Update on 05/04/1995, 1 field added/edited/deleted.
Complete Update on 04/20/1995, 1 field added/edited/deleted.
Complete Update on 04/20/1995, 1 field added/edited/deleted.
Complete Update on 02/13/1995, 1 field added/edited/deleted.
Complete Update on 01/20/1995, 1 field added/edited/deleted.
Complete Update on 12/19/1994, 1 field added/edited/deleted.
Complete Update on 09/26/1994, 1 field added/edited/deleted.
Complete Update on 09/26/1994, 1 field added/edited/deleted.
Complete Update on 08/09/1994, 1 field added/edited/deleted.
Complete Update on 06/08/1994, 1 field added/edited/deleted.
Complete Update on 05/05/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 08/07/1993, 1 field added/edited/deleted.
Complete Update on 08/04/1993, 1 field added/edited/deleted.
Complete Update on 04/30/1993, 1 field added/edited/deleted.
Field update on 12/11/1992, 1 field added/edited/deleted.
Complete Update on 11/25/1992, 1 field added/edited/deleted.
Complete Update on 11/20/1992, 3 fields added/edited/deleted.
Field Update on 11/20/1992, 1 field added/edited/deleted.
Complete Update on 07/02/1992, 81 fields added/edited/deleted.
Field Update on 05/29/1992, 1 field added/edited/deleted.
Field Update on 04/16/1992, 1 field added/edited/deleted.
Field Update on 04/01/1992, 1 field added/edited/deleted.
Field Update on 04/01/1992, 1 field added/edited/deleted.
Field Update on 01/13/1992, 1 field added/edited/deleted.
Field update on 11/09/1990, 1 field added/edited/deleted.
Complete Update on 10/10/1990, 2 fields added/edited/deleted.
Field Update on 08/23/1990, 1 field added/edited/deleted.
Complete Update on 05/21/1990, 4 fields added/edited/deleted.
Field update on 05/18/1990, 1 field added/edited/deleted.
Field Update on 05/04/1990, 1 field added/edited/deleted.
Field Update on 01/15/1990, 1 field added/edited/deleted.
Complete Update on 01/11/1990, 2 fields added/edited/deleted.
Complete Update on 04/13/1989, 2 fields added/edited/deleted.
Field Update on 03/01/1989, 1 field added/edited/deleted.
Complete Update on 12/29/1988, 112 fields added/edited/deleted.
Complete Update on 05/02/1985