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Pesticides

Friends of the Earth has recently launched a new 'Real Food' campaign, which includes a campaign for zero pesticide residues - more details on the Real Food web site.

A large number of pesticides have been identified as possible or definite endocrine disrupters, many of the pesticides implicated are described below.

DDT

The insecticide DDT has been banned in the developed world for many years, though is in widespread use in the developing world. Various DDT metabolites have endocrine effects, including blocking the action of male hormones. More details...

Lindane

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].

Vinclozolin

Vinclozolin is a fungicide and is a proven endocrine disrupter, causing anti-androgenic ('anti-maleness') effects. Exposure of male rats in the womb and shortly after birth to low doses of vinclozolin leads a range of sex organ changes, including retained nipples, reduced ejaculated sperm numbers and reduced ventral prostate weight [1]. Young male rats exposed to vinclozolin showed delayed puberty [2]. These anti-androgenic effects are due to two of its metabolites (breakdown products), which are able to bind the androgen receptor (including the human androgen receptor), blocking its activity [3, 4].


Carbendazim

Carbendazim is a fungicide. It disrupts the production of sperm and damages testicular development in adult rats, probably partly through disrupting the assembling of cells in tissues ­ which is the same way as carbendazim works as a fungicide [5, 6]. In addition, carbendazim is also a teratogen ­ damaging development of mammals in the womb. Experiments have shown that exposure of developing rats in the womb leads to deformities such as lack of eyes and hydrocephalus ("water on the brain") [7].


Benomyl

Benomyl is a fungicide, that is metbolised into carbendazim, see above.


Procymidone

Procymidone is an anti-androgen, with anti-maleness properties similar to vinclozolin. It is able to block androgen binding to the human androgen receptor, and male offspring of rats exposed to procymidone during pregnancy and early lactation showed a range of reproductive deformities, such as permanent nipples and malformed penises [8].


Chlorpyrifos

Chlorpyrifos is a organophosphate insecticide, and has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it is linked to male and female genital deformities [14]. Chlorpyrifos is a neurotoxin, and exposure to low concentrations can affect brain development in rats [9,10]. Chlorpyrifos has also been shown to affect the thyroid system in ewes, reducing blood thyroxine concentrations [18].


Deltamethrin

Deltamethrin is a pyrethroid insecticide and has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it can affect sperm and the placenta [14]. Research has shown that chronic exposure of adult rats to deltamethrin causes the death of some testicular cells [11].


Dimethoate

Dimethoate is an organophosphate insecticide and has been listed as a potential endocrine disrupter by the German Federal Environment Agency [14]. Dimethoate caused testicular damage, damage to sperm production and reduction in testosterone levels when fed to adult male rats [12]. Dimethoate also resulted in decreased thyroxine concentrations in ewes [18], and affected thyroid metabolism in mice [13].


Carbofuran

Carbofuran is a carbamate insecticide and has been listed as a potential endocrine disrupter by the German Federal Environment Agency [14]. Carbofuran caused sperm and reproductive system damage when fed to either adult male rats or to developing male rats exposed in the womb [15,16]. Damage to sperm production was also seen when adult rabbits were exposed to carbofuran [17]. Carbofuran has also been shown to affect the thyroid system in ewes, resulting in increased thyroxine concentrations [18].


Amitraz

The insecticide Amitraz has been shown to disrupt oestrus in rats, due to amitraz binding the a-noradrenergic receptors and blocking the action of norepinephrine [19].


Trichlorfon

The organophosphate insecticide Trichlorfon has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it can cause mammary tumours and affect sperm and egg production [14].
A cluster of Down's syndrome children in Hungary was associated with consumption of fish from a local fish farm after the fish had become excessively contaminated by trichlorfon [20]. A degradation product of trichlorfon, dichlorvos, has been shown to damage immune system function in humans; trichlorfon itself damages immune function in Carp [21].


Penconazole

The fungicide Penconazole has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it can affect thyroid, prostate and testes weight [14].


Prochloraz

The conazole fungicide Prochloraz has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it can affect pituitary weight [14].


Propiconazole

The conazole fungicide Propiconazole has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it can affects steroid metabolism [14].


Tridemorph

The morpholine fungicide Tridemorph has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it is linked to cystic ovaries [14]. Tridemorph is a potent inhibitor of the human sterol isomerase enzyme, which is part of the cholesterol biosynthesis pathway [22].


Epoxyconazole

Epoxyconazole is a fungicide that has been listed as a confirmed endocrine disrupter by the German Federal Environment Agency, who report that it can have effects on sex hormone balance and cause ovarian tumours [14].


Metiram

The dithiocarbamate pesticide Metiram has been listed as a confirmed endocrine disrupter by the German Federal Environment Agency, who report that it can reduce levels of thyroid hormones [14].


Oxydemeton-methyl

Oxydemeton-methyl has been listed as a potential endocrine disrupter by the German Federal Environment Agency, who report that it can affect egg production and testis and ovary size [14].


Atrazine

The herbicide atrazine has been shown to affect reproductive system development in rats. Mothers were dosed with atrazine and their offspring showed a delay in vaginal opening in the females and a higher incidence of prostate inflammation in the males [23]. Atrazine has also been shown to affect hormone metabolism in women, which may have possible implications for breast cancer - see DDT for more details.


Linuron

Linuron is a urea-based herbicide which has been shown to have a weak affinity for the androgen receptor. A multi-generation study with rats dosed with Linuron led to a range of male reproductive tissue problems in offspring, including testicular malformations and reduced size of androgen-dependant tissues [24].


Other pyrethroids

Research using the MCF-7 human breast carcinoma cells line has found that the pyrethroid insecticides sumithrin, fenvalerate are oestrogens, permethrin is a weak oestrogen and d-trans allethrin may be an anti-oestrogen [25].


This page was last updated in July 2000
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References

1. Gray, L. E., Ostby, J., Monosson, E. and Kelce, W. R. 1999. Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicology and Industrial Health 15: 48-64.

2. Monosson, E., Kelce, W. R., Lambright, C., Ostby, J. and Gray, L. E. J. 1999. Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat. Toxicology and Industrial Health 15: 65-79.

3. Gray, L. E. 1998. Xenoendocrine disrupters: laboratory studies on male reproductive effects. Toxicology Letters 102-103: 331-5.

4. Vinggaard, A. M., Joergensen, E. C. and Larsen, J. C. 1999. Rapid and sensitive reporter gene assays for detection of antiandrogenic and estrogenic effects of environmental chemicals. Toxicology and Applied Pharmacology 155: 150-60.

5. Lim, J. and Miller, M. G. 1997. The role of the benomyl metabolite carbendazim in benomyl-induced testicular toxicity. Toxicology and Applied Pharmacology 142: 401-10.

6. Nakai, M., Toshimori, K., Yoshinaga, K., Nasu, T. and Hess, R. A. 1998. Carbendazim-induced abnormal development of the acrosome during early phases of spermiogenesis in rat testes. Cell and Tissue Research 294: 145-152.

7. Mantovani, A., Maranghi, F., Ricciardi, C., Macrì, C., Stazi, A. V., Attias, L. and Zapponi, G. A. 1998. Developmental toxicity of carbendazim: Comparison of no-observed-adverse-effect level and benchmark dose approach. Food and Chemical Toxicology 36: 37-45.

8. Ostby, J., Kelce, W. R., Lambright, C., Wolf, C. J., Mann, P. and Gray, L. E. J. 1999. The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicology and Industrial Health 15: 80-93.

9. Johnson, D. E., Seidler, F. J. and Slotkin, T. A. 1998. Early biochemical detection of delayed neurotoxicity resulting from developmental exposure to chlorpyrifos. Brain Research Bulletin 45: 143-147.

10. Roy, T. S., Andrews, J. E., Seidler, F. J. and Slotkin, T. A. 1998. Chlorpyrifos elicits mitotic abnormalities and apoptosis in neuroepithelium of cultured rat embryos. Teratology 58: 62-68.

11. El-Gohary, M., Awara, W. M., Nassar, S. and Hawas, S. 1999. Deltamethrin-induced testicular apoptosis in rats: the protective effect of nitric oxide synthase inhibitor. Toxicology 132: 1-8.

12. Afifi, N. A., Ramadan, A., Abd-El-Aziz, M. I. and Saki, E. E. 1991. Influence of dimethoate on testicular and epididymal organs, testosterone plasma level and their tissue residues in rats. Deutsche Tieraerztliche Wochenschrift 98: 419-420.

13 Maiti, P. K. and Kar, A. 1997. Dimethoate inhibits extrathyroidal 5'-monodeiodination of thyroxine to 3,3',5-triiodothyronine in mice: the possible involvement of the lipid peroxidative process. Toxicological Letters 91: 1-6.

14. ENDS 1999. Industry glimpses new challenges as endocrine science advances. ENDS Report 290: 26-30.

15. Pant, N., Prasad, A. K., Srivatava, S. C., Shankar, R. and Srivastava, S. P. 1995. Effect of oral administration of carbofuran on male reproductive system of rat. Human & Experimental Toxicology 14: 889-894.

16. Pant, N., Shankar, R. and Srivastava, S. P. 1997. In utero and lactational exposure of carbofuran to rats: Effect on testes and sperm. Human & Experimental Toxicology 16: 267-272.

17. Yousef, M. I., Salem, M. H., Ibrahim, H. Z., Helmi, S., Seehy, M. A. and Bertheussen, K. 1995. Toxic effects of carbofuran and glyphosate on semen characteristics in rabbits. Journal of Environmental Science and Health B30: 513-534.

18. Rawlings, N. C., Cook, S. J. and Waldbillig, D. 1998. Effects of the pesticides carbofuran, chlorpyrifos, dimethoate, lindane, triallate, trifluralin, 2,4-D, and pentachlorophenol on the metabolic endocrine and reproductive endocrine system in ewes. Journal of Toxicology and Environmental Health 54: 21-36.

19. Cooper, R. L., Goldman, J. M. and Stoker, T. E. 1999. Neuroendocrine and reproductive effects of contemporary-use pesticides. Toxicology and Industrial Health 15: 26-36.

20. Czeizel, A. E. 1996. Human germinal mutagenic effects in relation to intentional and accidental exposure to toxic agents. Environmental Health Perspectives 104 Suppl. 3: 615-617.

21. Voccia, I., Blakley, B., Brousseau, P. and Fournier, M. 1999. Immunotoxicity of pesticides: a review. Toxicology and Industrial Health 15: 119-132.

22. Paul, R., Silve, S., De Nys, N., Dupuy, P. H., Bouteiller, C. L., Rosenfeld, J., Ferrara, P., Le Fur, G., Casellas, P. and Loison, G. 1998. Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. Journal of Pharmacology and Experimental Therapeutics 285: 1296-302.

23. Cooper, R. L., Goldman, J. M. and Stoker, T. E. 1999. Neuroendocrine and reproductive effects of contemporary-use pesticides. Toxicology and Industrial Health 15, p26-36.

24. Gray, L. E., Wolf, C., Lambright, C., Mann, P., Price, M., Cooper, R. L. and Ostby, J. 1999. Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p, p'-DDE, and ketonazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicology and Industrial Health 15, p94-118.

25. Go, V., Garey, J., Wolff, M. S. and Pogo, B. G. T. 1999. Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line. Environmental Health Perspectives 107, p173-177.

26. EU to ban lindane use in agriculture. ENDS Daily 17th July 2000. The Pesticides Action Network-UK has a range of information about lindane at their site.

27. Lyons, G (for WWF) 1999. Chemicals Tresspass: A Toxic Legacy. WWF, July 1999. [Press release][Executive Summary]

28. Celius, T., Haugen, T. B., Grotmol, T. and Walther, B. T. 1999. A sensitive zonagenetic assay for rapid in vitro assessment of estrogenic potency of xenobiotics and mycotoxins. Environmental Health Perspectives 107, p63-68.

29. Silvestroni, L. and Palleschi, S. 1999. Effects of organochlorine xenobiotics on human spermatozoa. Chemosphere 39, p1249-1252.


URL: http://website.lineone.net/~mwarhurst/pesticides.html