Hormone hacking

Under European law, pesticides that disrupt hormones (“endocrine disrupting chemicals” or EDCs) are not allowed to be marketed.¹ Governments recognize the threat posed by endocrine disruption, which are believed to be implicated in serious diseases, such as cancer, reproductive and developmental problems, and birth defects. These effects are thought to result from very low doses over a long period of exposure or from exposures in critical windows of development, such as foetal development in the womb.

The Glyphosate Task Force (GTF) website, which is run by pesticide companies, cites the German government’s view that glyphosate is not an endocrine disruptor.²

But this is seriously misleading. On the contrary, studies from the peer-reviewed independent literature show that both glyphosate and the commercial formulations, such as Roundup, are endocrine disruptors.

The endocrine disrupting effect of glyphosate and its commercial formulations is their most insidious and worrying toxic effect. This is because EDCs do not function like normal poisons, where a higher dose gives greater toxicity. Often, endocrine disruptive effects are seen at lower doses but not at higher doses.^3,4 The studies conducted by industry for regulatory purposes use relatively high doses and are not able to detect these effects.

Peer-reviewed study findings include the following:

• Glyphosate herbicide altered hormone levels in female catfish and decreased egg viability. The study concluded that the herbicide is harmful to catfish reproduction.⁵
• Roundup disrupted production of the steroid hormone progesterone in mouse cells.⁶
• Glyphosate herbicide was a potent EDC in rats, causing disturbances in reproductive development after exposure during puberty.⁷
• In an in vitro experiment in human cells, glyphosate herbicides prevented the action of androgens, the masculinizing hormones, at levels up to 800 times lower than glyphosate residue levels allowed in some GM crops used for animal feed in the USA. DNA damage was found in human cells treated with glyphosate herbicides at these levels. Glyphosate herbicides disrupted the action and formation of estrogens, the feminizing hormones. The first toxic effects were found at the low dose of 5 ppm and the first endocrine disruption at 0.5 ppm – 800 times less than the 400 ppm level authorized for some animal feeds.⁸
• Roundup herbicide at environmentally relevant exposure levels (down to 0.00023% glyphosate dilution of the commercial formulation) caused the dysregulation of genes in human breast cancer cells grown in the laboratory in vitro. Of the 1,550 genes analyzed, expression of 680 was either increased or decreased. Roundup was able to replace and work synergistically with estrogen, which is required for growth of the breast cancer cells. This demonstrates the strong potential endocrine disruptive potential of glyphosate in this hormonal system. The authors commented, “There remains an unclear pattern of very complex events following exposure of human cells to low levels of glyphosate, but events surrounding the altered levels of expression of only three genes… out of the entire battery tested, are both complicated and potentially damaging to adult and fetal cells.”⁹
• Glyphosate alone increased the proliferation of estrogen-dependent breast cancer cells by estrogenic mechanisms in vitro¹⁰ at a level permitted in drinking water in the EU (see “Potentially dangerous levels of glyphosate found in GM soy” for more on this study).
• An in vivo study of Roundup administered to rats in drinking water diluted to 50ng/L glyphosate equivalence – half of the level permitted in drinking water in the EU¹¹ and 14,000 times lower than that permitted in drinking water in the USA¹² – resulted in severe organ damage and a trend of increased incidence of mammary tumours in female animals over a 2-year period of exposure. The latter observation of tumours needs to be confirmed in an experiment with larger numbers of rats.¹³
• Roundup was an endocrine disruptor through its toxicity to human cells in vitro at levels permitted in drinking water in Australia. The endocrine disruption occurred through a mechanism of toxicity to the cells, making them unable to produce the hormone progesterone. The lowest level consistently found to be toxic was 720ug/L. As the Australian Drinking Water Guideline is set at the relatively high level of 1mg/L (higher than the permitted US levels of 700ug/L or 0.7mg/L), the levels found toxic in the experiment are within the range permitted in Australia.¹⁴

Due to the activities of the powerful agrochemical lobby and its allies in government, dispute will continue about how relevant these findings are to humans until more experiments are done in animals using low, presumed safe doses, over a long period of time.

References:

1. European Parliament and Council. Regulation (EC) No 1107/2009 of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. Off J Eur Union. 2009:1-50.
2. Glyphosate Task Force. Industry Task Force welcomes important step in the EU review of glyphosate. Glyphosate Facts. 2014. http://www.glyphosate.eu/news/industry-task-force-welcomes-important-step-eu-review-glyphosate.
3. Vandenberg LN, Colborn T, Hayes TB, et al. Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012;33(3):378-455. doi:10.1210/er.2011-1050.
4. Vom Saal FS, Akingbemi BT, Belcher SM, et al. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol. 2007;24:131-138. doi:10.1016/j.reprotox.2007.07.005.
5. Soso AB, Barcellos LJG, Ranzani-Paiva MJ, et al. Chronic exposure to sub-lethal concentration of a glyphosate-based herbicide alters hormone profiles and affects reproduction of female Jundiá (Rhamdia quelen). Environ Toxicol Pharmacol. 2007;23:308-313.
6. Walsh LP, McCormick C, Martin C, Stocco DM. Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Env Health Perspect. 2000;108:769-776.
7. Romano RM, Romano MA, Bernardi MM, Furtado PV, Oliveira CA. Prepubertal exposure to commercial formulation of the herbicide Glyphosate alters testosterone levels and testicular morphology. Arch Toxicol. 2010;84:309-317.
8. Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Séralini GE. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology. 2009;262:184-191. doi:10.1016/j.tox.2009.06.006.
9. Hokanson R, Fudge R, Chowdhary R, Busbee D. Alteration of estrogen-regulated gene expression in human cells induced by the agricultural and horticultural herbicide glyphosate. Hum Exp Toxicol. 2007;26:747-752. doi:10.1177/0960327107083453.
10. Thongprakaisang S, Thiantanawat A, Rangkadilok N, Suriyo T, Satayavivad J. Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol. 2013;59:129-136. doi:10.1016/j.fct.2013.05.057.
11. Council of the European Union. Council directive 98/83/EC of 3 November 1998 on the quality of water intended for human consumption. Off J Eur Communities. 1998. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1998:330:0032:0054:EN:PDF.
12. US Environmental Protection Agency (EPA). Basic information about glyphosate in drinking water. 2014. http://water.epa.gov/drink/contaminants/basicinformation/glyphosate.cfm#four.
13. Séralini G-E, Clair E, Mesnage R, et al. Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Environ Sci Eur. 2014;26(14). doi:10.1186/s12302-014-0014-5.
14. Young F, Ho D, Glynn D, Edwards V. Endocrine disruption and cytotoxicity of glyphosate and roundup in human JAr cells in vitro. Integr Pharmacol Toxicol Genotoxicol. 2015;1(1):12-19.