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Endocrine Disrupting Chemicals EDCs

Environmental Estrogens (EEs)
Hormonally Active Agents (HAAs)
Hormone Disrupting Chemicals


EPA recognizes that organochlorine pesticides, such as lindane, may cause endocrine disruption that may be associated with human or ecological risk concerns. The Agency is currently developing a strategy to look at the remaining registered organochlorine pesticides as a group to examine their role as potential endocrine disruptors. Although EPA is closing the Special Review of lindane for kidney effects, the findings from a comprehensive examination of this group of chemicals could lead to further regulatory action on lindane. (For further information see: Lindane - Decision Not to Initiate a Special Review on Kidney Effects, 60 Federal Register 38329, July 26, 1995) [Internet:]

Hormonally Active Agents in the Environment

In humans, results of cognitive and neurobehavioral studies of mother-infant cohorts accidently exposed to high concentrations of PCBs and PCDFs and of mother-infant cohorts eating contaminated fish and other food products containing mixtures of PCBs, dioxin, and pesticides (such as DDE, dieldrin, and lindane) provide evidence that prenatal exposure to these HAAs can affect the developing nervous system. Similarly, monkeys exposed to PCBs in utero and during lactation have deficits in cognitive function when assessed at 14 months post-exposure and rats and mice exposed prenatally to PCBs suffer impaired locomotor ability and learning.

Lindane is an organochlorine pesticide which is under a great deal of regulatory pressure around the world. On the 13th July 2000 an EU regulatory committee voted to ban agricultural uses of Lindane in Europe - though it can still be used in some other products, such as ant killer [26]. It is a persistent pollutant, and is found in human breast milk [27]. The oestrogenic properties of lindane have been demonstrated in several systems, including the production of vitellogenin (egg yolk protein) and zona radiata (egg shell protein) in primary hepatocyctes (liver cells) from Atlantic salmon (Salmo salar L.) [28]. Lindane has also been shown to damage human spermatozoa at concentrations as low as those found in female genital tract secretions [29].

Introduction to Hormone Disrupting Chemicals

Does yo-yo dieting pose cancer threat?

Indeed, contends Davis, the fact that lindane is still used on children to kill head lice "is appalling."

The Effects of estrogenic pesticides on the development of the reproductive tissue in Mammals and Birds

Estrogenic pesticides can have detrimental reproductive effects on adult animals. Chronic exposure of rhesus monkeys to dioxin causes a dosage-dependent increase in the severity and occurrence of endometriosis. (Rier et al., 1995) Endometriosis is characterized by chronic pain, infertility and adhesion formation. Estrogens cause the proliferation of endometrial cells in proestrus and also cause the proliferation and bleeding of ectopic endometrial cells.(Stancel et al., 1995) The pain and ovarian cysts make the monkey incapable to breed. Similar condition can be found in six million woman. In another study, kepone was administered to sexually active rats just before ovulation and after ovulation.(Brown et al., 1991) In both cases, the rats showed a rapid decrease in precopulatory and receptivity behaviours. ovulation was also suppressed. In a study by Bradlow and his colleagues(1995), they found that organochlorine pesticides increase the breakdown of estrogen into 16u-Hydroxyestrone, which cause uncontrolled cell proliferation. This cell proliferation is one the leading cause of pesticide induce breast and endometrial cancers. Adult males also can suffered for the accumulation of pesticides in their diet and bodies. An investigation into the reproductive performance of man exposed to pesticides in the work showed that there was significant decrease frequency of live births and stillbirths, neonatal deaths and congenital defects in the children of exposed man compared to control group.(Rupa et al., 1991) The men also have decreased fertility and increased incidence of abnormal sperm and dead sperm. A study by Leonard Nelson (1990) show that dieldrin and mirex stimulates swimming in sea urchin sperm and lindane inhibits sperm motility. In different study showed that mirex caused testicular atrophy in humans.(Nelson, 1990) In birds, organochlorine accumulation causes eggshell thinning by inhibition of calcium ATPase as well as decreased incubation attentiveness, territorial defence and impairment of chick- rearing behaviours.(Fry, 1995) All this deficiencies cause a reduction in the reproductive fitness of the birds. An number of studies were conducted on adult male rats on the effects of different pesticide on testicular function. The pesticide methoxychlor cause decrease sperm motility, body weight and slight decrease in sperm count.(Linder et al., 1992) The fungicide benomyl produced premature release of germ cells, testicular swelling and occlusion of efferent ductules. Seminiferous tubular atrophy was also observed.(Hess et al., 1991) In one study showed that lindane feed to twenty-one day old male rats resulted in the inhibition of spermatogenesis, proliferation of Leydig cells and degeneration of seminiferous tubule lumens at the highest dosage level.(Chowdhury et al., 1987)

Substances interfering with the endocrine system

A footnote on page 1 of the Wingspread Statement says, "Chemicals known to disrupt the endocrine system include: DDT and its degradation products, DEHP (di(2-ethylhexyl)phthalate), dicofol, HCB (hexachlorobenzene), kelthane, kepone, lindane and other hexachlorocyclohexane congeners, methoxychlor, octachlorostyrene, synthetic pyrethroids, triazine herbicides, EBDC fungicides, certain PCB congeners, 2,3,7,8-TCDD and other dioxins, 2,3,7,8-TCDF and other furans, cadmium, lead, mercury, tributyltin and other organo-tin compounds, alkyl phenols (non-biodegradable detergents and anti-oxidants present in modified polystyrene and PVCs), styrene dimers and trimers, soy products, and laboratory animal and pet food products."

Assessing reproductive toxicity based on zonagenetic assays of xenoestrogens, and new concepts concerning animal gestation

B.Th. Walther

Dept. of Molecular Biology, Univ. of Bergen, N-5020 Bergen, NORWAY

Female sexual maturation proceeds by pivotal hepatic biosynthetic processes under the control of estrogens. In fish, oogenesis involves both zonagenesis and vitellogenesis, forming the bulk of the eggshell (zona) and yolk, respectievely (Walther 1993). Estradiol induces mRNAs for zona radiata proteins (zrp; Oppen-Berntsen et al. 1990) and for vitellogenin (vtg), by interacting with hepatic estrogen receptor, followed by protein synthesis.
Such inductions also occur in primary cultures of hepatocytes from juvenile Atlantic salmon, which secrete zrp and vtg into the culture medium (Oppen-Berntsen et al. 1992). In vivo, zrp and vtg are transported in the blood for specific uptake by the ovaries (Oppen-Berntsen et al. 1994). Recent evidence shows that zonagenesis occurs in response to lower levels of estradiol than are required to initiate vitellogenesis in juvenile Atlantic salmon (Celius & Walther 1998). Zonagenesis may be initiated already at levels approximating those sufficient for induction of hepatic estrogen receptor (ER). Furthermore, at high levels of estradiol, vitellogenesis appears to be somewhat delayed compared to zonagenesis. The finding of zonagenesis induced at putatively constitutive ER-levels, points to initiation of puberty by non-classical steroid signal pathways (Celius & Walther, unpubl.).
In analogy to Sumpter & Jobling (1995), we used in vitro induction of zonagenesis to assess the estrogenic potential by xenobiotics and mycotoxins (Celius et al. 1999). Zonagenesis provides an alternate and supplementary assay for rapid assessment of xenoestrogenicity, as shown in vivo for xenobiotics such as nonylphenol (Arukwe et al. 1997). Nonylphenol, lindane, bisphenol A, and DDT, as well as zearalenone, and both isomers of zearalenol, all induced zonagenesis in vitro, albeit with various potencies. The relative activities of the zearalenol isomers compared to their in vivo activity. Results from this assay may rationalize how various xenobiotics, despite their highly disparate molecular structures (e.g. lindane & DDT), may all exhibit the biological property of estrogenicity.
Finally, the reproductive relevance of zonagenesis is discussed in the context of the evolution of vertebrate gestation, and of sexual reproduction (Walther 1993; 1998). Zonagenesis may protect vertebrate gestation in fish, reptiles and mammals, but zrp-deposition reflects the evolution of the female reproductive tract (Walther 1999). If zonagenesis exists in all vertebrates, it may be a common biomarker for xenoestrogenic action in vertebrates. Since zonagenesis was thought to be more limited than vitellogenesis, this conclusion is surprising.


ENDOCRINE DISRUPTORS: EPIDEMIOLOGIC APPROACHES Release Date: June 12, 2000 RFA: OH-01-001 National Institute for Occupational Safety and Health (NIOSH), Center for Disease Control and Prevention (CDC) National Center for Environmental Research (NCER), U.S. Environmental Protection Agency (EPA) National Cancer Institute (NCI), National Institutes of Health National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health Letter of Intent Receipt Date: August 11, 2000 Application Receipt Date: September 22, 2000 THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.


Paulozzi LJ. International trends in rates of hypospadias and cryptorchidism. Environmental Health Perspectives 1999; 107 (4): 297-302.

Data from the International Clearinghouse for Birth Defects Monitoring Systems on rates of cryptorchidism and hypospadias reveal trends in the diagnosis of these two defects over the past few decades. Marked increases in the diagnosis of hypospadias occurred in two American birth defects registries, and in Scandinavia and Japan, with some evidence of leveling-off after 1985. Increases in hypospadias were not seen in less affluent nations. Increases in cryptorchidism were only seen in two U.S. systems and in South America. It is not clear if these trends reflect increasing diagnosis and reporting of these male genital defects, or if there is a real increase. Both cryptorchidism and hypospadias reflect disruption of the normal maturation process of the male reproductive tract during a specific period of vulnerability during gestation. Estrogenic or anti-androgenic agents, including some environmental chemicals, can cause these defects in laboratory animals.

Hypospadias more common in vegetarian mothers ?

Professor Jean Golding and her colleagues at Bristol's Institute of Child Health, in research commissioned by the BBC in Bristol, has suggested that hypospadias is more common in the male offspring of vegetarian mothers. Hypospadias is the name given to a physical abnormality of the penis which is correctable through surgery. Hypospadias has been linked with an increased risk of testicular cancer (cancer of the "balls") as well as reduced sperm production. It is now thought that the incidence of hypospadias may be increased in the children of mothers who eat a vegetarian diet. Assuming that these results are not due to a statistical error, it is believed that the reason for this increased incidence could caused by the pesticides used to protect fruit and vegetables from pests.

The report, which was broadcast on Newsnight (BBC2 on 25th February 1999) and was reported in the Guardian (26th February 1999, page 8), if corroborated by other studies, would, of course, be very significant. It is already known that exposure to pesticides can increase the risk of physical abnormalities affecting the urogenital area in boys. It is believed that these abnormalities are caused by the artificial oestrogens which some pesticides are thought to produce in the vegetables themselves. In the light of increasing concerns expressed over the pesticide Lindane, which is being associated with breast cancer, this should be a matter is serious concern to us all. Recent research has also linked artificial oestrogens with reduced fertility in men.


According to a recent hypothesis, environmental pollutants such as organochlorines may be contributing to higher rates of structural abnormalities in the male such as hypospadias. This is thought to be related to the influence of such chemicals on steroid hormone function. Increased rates of testicular cancer, and generally reduced male reproductive health have also been noted by Danish observers. This is an intriguing theory, but clarification regarding the contribution of genetics, social, and other environmental factors is necessary.

Lindane has been used for many years in the treatment of lice and scabies. It is an example of an organochlorine pesticide. Lindane is capable of being absorbed into maternal blood and can also cross the placenta. A preferable agent may be a pyrethrin-containing pediculicide which is poorly absorbed through intact skin.

Birth Research Unit General Hospital Kandy, Sri Lanka

Also see:


Tulane University Environmental Estrogens Home Page


Hormonally Active Agents in the Environment (2000)

Child Research



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