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Signs and symptoms of exposure
1. Acute exposure: Acute exposure to low levels of chlorine results in eye,
nose, and throat irritation, sneezing, excessive salivation, general excitement,
and restlessness. Higher concentrations causes difficulty in breathing, violent
coughing, nausea, vomiting, cyanosis, dizziness, headache, choking, laryngeal
edema, acute tracheobronchitis, chemical pneumonia. Contact with the liquid can
result in frostbite burns of the skin and eyes [Genium 1992].
2. Chronic exposure: Chronic exposure to low levels of chlorine gas can
result in a dermatitis known as chloracne, tooth enamel corrosion, coughing,
severe chest pain, sore throat, hemoptysis and increased susceptibility to
tuberculosis [Genium 1992].
Exposure to 15 ppm causes throat irritation, exposures to 50 ppm are
dangerous, and exposures to 1000 ppm can be fatal, even if exposure is brief
[Sax and Lewis 1989; Clayton and Clayton 1982]. Earlier literature reported that
exposure to a concentration of about 5 ppm caused respiratory complaints,
corrosion of the teeth, inflammation of the mucous membranes of the nose and
susceptibility to tuberculosis among chronically-exposed workers. The incidence
of fatigue was greater among those exposed above 0.5 ppm [ACGIH 1991]. In 1981,
a study was published involving 29 subjects exposed to chlorine concentrations
up to 2.0 ppm for 4- and 8-hour periods. Exposures of 1.0 ppm for 8 hours
produced statistically significant changes in pulmonary function that were not
observed at a 0.5 ppm exposure concentration. Six of 14 subjects exposed to 1.0
ppm for 8 hours showed increased mucous secretions from the nose and in the
hypopharynx. Responses for sensations of itching or burning of the nose and
eyes, and general discomfort were not severe, but were perceptible, especially
at the 1.0 ppm exposure level [ACGIH 1991]. A 1983 study of pulmonary function
at low concentrations of chlorine exposure also found transient decreases in
pulmonary function at the 1.0 ppm exposure level, but not at the 0.5 ppm level [ACGIH
1991]. Acne (chloracne) is not unusual among persons exposed to low
concentrations of chlorine for long periods of time. Tooth enamel damage may
also occur [Parmeggiani 1983]. There has been one confirmed case of myasthenia
gravis associated with chlorine exposure [NLM 1995].
Effect
of Water Temperature on Dermal Exposure to Chloroform
Chloroform 67-66-3 CHCl3
Synonyms: Trichloromethane; Methyl trichloride; Methane trichloride; methane
chloride
Chloroform is a colorless liquid with a pleasant, nonirritating odor and a
slightly sweet taste. It will burn only when it reaches very high temperatures.
In the past, chloroform was used as an inhaled anesthetic during surgery, but it
isn't used that way today. Today, chloroform is used to make other chemicals and
can also be formed in small amounts when chlorine is added to water.
Overall evaluation
Chloroform is possibly carcinogenic to humans (Group 2B).
CHLOROFORM
(Group 2B)
For definition of Groups, see Preamble
Evaluation.
VOL.: 73 (1999) (p. 131)
CAS No.: 67-66-3
Chem. Abstr. Name: Trichloromethane
5. Summary of Data Reported and Evaluation
5.1 Exposure data
Occupational exposure to chloroform may occur during its production and use
as a solvent and chemical intermediate. The general population may be exposed as
a result of its presence in chlorinated drinking-water, ambient air and some
foods.
5.2 Human carcinogenicity data
Two cohort studies of cancer and drinking-water quality were
carried out in the United States. One conducted in Maryland showed excess
mortality from cancers of the liver and breast in association with water
chlorination, while that conducted in Iowa showed increased risks for cancers of
the colon and lung and skin melanoma associated with chloroform concentrations
in drinking-water.
Eight case–control studies have been reported on bladder
cancer in relation to chlorinated drinking-water in the United States.
Significant results were obtained in five studies, but there was little
consistency in the risk pattern in subgroups defined by sex or surrogate
measures of chloroform intake. Significant increasing trends in the risk for
bladder cancer were seen in two studies. The study in Colorado showed increasing
risk with years of exposure to chlorinated water; the study in Iowa showed
increasing risk with lifetime intake of trihalomethanes (from drinking-water),
but only in men and not in women.
Seven case–control studies addressed the risk for cancers
of the large bowel in association with consumption of chlorinated water. In two
of these studies, lifetime exposure to trihalomethanes was assessed. Two studies
showed significant associations with rectal cancer. Overall, however, the
results were inconsistent with regard to the subsite of the large bowel and sex,
and the quality of the studies varied widely.
Exposure to chloroform in the workplace was addressed in two
case–control studies, both of which had limited statistical power. The study
on brain cancer gave negative results. The other included a number of sites (but
not the brain) and showed associations with cancers of the prostate and lung,
but no association was seen with bladder cancer.
The presence of various water chlorination by-products,
including trihalomethanes, is likely to be highly correlated. Although
chloroform is the most ubiquitous,
the other by-products therefore may act as confounders in studies of
water-mediated exposure. In addition, important sources of chloroform other than
drinking-water were ignored in the majority of the studies.
Although the epidemiological evidence for an association
between consumption of chlorinated drinking-water and the risk for some cancers,
particularly those of the urinary bladder and rectum and possibly of the colon,
seems to favour an interpretation of mild excess, a causal inference cannot be
made with regard to chloroform because of incomplete control for confounding by
other water impurities and other factors and lack of concordance in the results
for men and women. Use of surrogate indicators for exposure to chloroform adds
to the uncertainty.
5.3 Animal carcinogenicity data
Chloroform was tested for carcinogenicity in several
experiments in mice, rats and dogs. In three studies by oral administration and
in one study by inhalation exposure in mice, it produced renal tubule tumours
and, in one study, hepatocellular tumours. In three studies by oral
administration in Osborne-Mendel rats, chloroform produced renal tubule tumours.
No increased incidence of tumours was observed in one study in dogs.
5.4 Other relevant data
Chloroform is metabolized by oxidative and reductive
pathways. Under normal conditions, oxidative metabolism is the major pathway,
and reductive metabolism does not play a significant role. Oxidative metabolism
of chloroform results in the generation of phosgene, which either reacts with
water to give carbon dioxide and hydrogen chloride or binds covalently to tissue
macromolecules. The formation of carbon dioxide as a metabolite of chloroform
has been shown in a number of studies in both rodents and humans in vivo.
The metabolism of chloroform is more rapid in mice than in
rats, and human tissues (liver and kidney) have the lowest activity. CYP2E1 is
the predominant enzyme involved in the metabolism of chloroform in both rodent
and human tissues.
There is a consistent, tissue-, species-, strain- and
sex-specific pattern in the rate of metabolism, cytotoxicity and cell
proliferation produced by chloroform in rodent liver and kidney. Under the
conditions of the high-dose regimens used in cancer bioassays in which tumours
are produced, chloroform induced cytotoxicity and regenerative cell
proliferation in the target organs for cancer. These findings are consistent
with a mode of action for tumorigenesis in the liver and kidney of rodents that
involves cytotoxicity.
Chloroform has been tested for developmental toxicity in mice
and rats by gavage and inhalation. Fetal toxicity in the form of growth
retardation has been observed in several studies, concurrent with evidence of
maternal toxicity. Malformations were observed in one study in rats exposed by
inhalation. In a continuous breeding study, no reproductive effects were noted.
No data were available on the genetic and related effects of
chloroform in humans. There is weak evidence for the genotoxicity of chloroform
in experimental systems in vivo and in mammalian cells, fungi and yeast in
vitro. It was not mutagenic to bacteria.
5.5 Evaluation
There is inadequate evidence in humans for the
carcinogenicity of chloroform.
There is sufficient evidence in experimental animals
for the carcinogenicity of chloroform.
Overall evaluation
Chloroform is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble
Evaluation.
Previous evaluations: Vol.
1 (1972); Vol.
20 (1979); Suppl.
7 (1987)
Synonyms
- HCC 20
- R 20
- R 20 (refrigerant)
- Trichloroform
Last updated: 30 September 1999
http://193.51.164.11/htdocs/monographs/Vol73/73-05.html
PHOSGENE GENERATION FROM CHLOROFORM.
Phosgene # 75-44-5 COCl2 (used as a war gas in WWI) is a
breakdown product of chloroform. Phosgene exposure can cause damage to the
central nervous system in concentrations at only a small fraction of the
permissible exposure limit of chloroform. Chloroform, stabilized with alcohol,
should be purchased in the future whenever possible. If non-stabilized
chloroform is necessary for the work, it needs to be treated like peroxide
forming compounds and be used up in a short amount of time. Amylene is also used
as a stabilizer, but there is evidence that it may not prevent phosgene
generation.
Chlorine fluoride
Chlorine(IV) oxide
Trichlorine nitride
Chlorine trifluoride
Chlorine oxyfluoride
Chlorine fluoride oxide
Chlorine dioxide ion(1-)
Chlorine oxide (ClO3(1-))
Chlorine fluoride (ClF5)
Chlorodiphenyl (42%
chlorine)
Chlorodiphenyl (54%
chlorine)
Chlorinated paraffins (C12,
60% chlorine)
Chlorinated paraffins (C23,
43% chlorine)
Chlorine e6, copper deriv.,
trisodium salt
Chlorine-containing
peptide, from penicillium islandicum
Benzene, chlorine, and
sulfur monochloride reaction products
Hypochlorite solution
containing >7% avaliable chlorine by wt. (UN1791)
Paraffin waxes and
hydrocarbon waxes, chlorinated (C12, 60% chlorine)
Paraffin waxes and
hydrocarbon waxes, chlorinated (C23, 43% chlorine)
4-(Dibenzo(b,e)thiepin-6(11H)-ylidene)-1-methylpiperidine
hydrochlorine
Benzene, reaction products
with chlorine and sulfur chloride (S2Cl2), chlorides
The 1940s saw the beginning of a new era of pesticides and pesticide use. An
array of synthetic organic chemicals were developed, including the notoriously
persistent organochlorines DDT, aldrin, dieldrin, lindane, and chlordane. Long
term persistence and wide-ranging biocidal action were then seen as positive
attributes in the war against pests, but are now seen in a different light.
Rachel Carson's now classic book, Silent Spring (1962) is a recognized starting
point of the debate on pesticide safety, bringing public attention to the hazard
of pesticides. It is now known that the toxicity to diverse species and the
persistence of these chemicals makes them a threat to all living things.
http://www.enviroweb.org/WEN/chlorine/chlorine.html
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