Summary

Reproductive toxicity in humans can show up in the form of increased tendency towards miscarriage, infertility, stillbirth, and birth defects. Studies, including some by industry, show that glyphosate and Roundup cause malformations in laboratory animals. The malformations are similar to those seen in people exposed to spraying of Roundup on genetically modified (GM) soy in Argentina. Human epidemiological studies have found a modest association between Roundup exposure and one type of birth defect, as well as with late miscarriage and premature birth. Further long-term studies in animals dosed over the long term with low, realistic doses of Roundup, are needed to confirm these findings. However, there is enough evidence of harm to justify a ban.

The pesticide industry website “Glyphosate Facts” claims, “Comprehensive toxicological studies in animals have demonstrated that glyphosate does not cause … birth defects… or reproductive problems.”¹ But what the website does not tell us is that all the references it gives to back up this claim are to government assessments of unpublished and commercially confidential tests done by the pesticide companies themselves in order to gain regulatory authorization for their products. Government agencies that carry out these assessments generally do no independent testing. They rely on what industry tells them.

In addition, the industry studies are on glyphosate alone – whereas people are actually exposed to Roundup or other complete formulations. The formulations are much more toxic than glyphosate alone (see “Roundup is more toxic than glyphosate”).

Independent studies show that glyphosate and Roundup cause birth defects and developmental and reproductive problems.

Malformations (birth defects)

• Studies on glyphosate alone commissioned by industry in support of regulatory authorization showed that it caused malformations in rabbits and rats. These effects were not only found at high maternally toxic doses but also at lower doses. Statistical significance was not always achieved at lower doses, perhaps because too few animals were used. Germany, the “rapporteur” member state for glyphosate, responsible for liaising between industry and the EU authorities during the approval process, dismissed the findings, using unscientific reasoning and practices.²
• Roundup and glyphosate caused malformations in chicken and frog embryos at doses far below those used in agricultural spraying. Malformations were of a similar type as those reported in human populations exposed to Roundup in Argentina where genetically modified (GM) Roundup-tolerant soy is grown [Birth defects and cancer in Argentina]. Glyphosate itself was responsible for the malformations in the chicken and frog embryos, rather than the adjuvants in the commercial formulation.3 The study identified the mechanism of toxicity as interference with the retinoic acid signalling pathway. This pathway is present in higher animals and affects gene expression. When disrupted, it can result in the development of malformations.³ This finding counters claims or implications by industry authors that glyphosate is non-toxic to animals on the supposed grounds that its sole mechanism of toxicity is the shikimate biochemical pathway, which plants have but animals lack.⁴
• Roundup was found to cause skeletal malformations in rat foetuses after the mothers were dosed during pregnancy. The authors observed that the findings were not due to poisoning of the mother (maternal toxicity) and concluded that Roundup had a direct toxic effect on the foetuses. They also noted that the Roundup formulation was more toxic than glyphosate alone.⁵
• Glyphosate herbicide caused malformations in tadpoles, even at concentrations that caused low mortality.⁶
• An epidemiological study carried out in California showed a modest association between Roundup exposure and anencephaly, a type of birth defect in which part of the skull and brain are missing.^{7 8} The authors found that the association was present using one type of analytical model (a multiple pesticide model), but not with another (a single pesticide model). The authors did not show the data in which they applied either model. But Table 2 of their publication reveals modest associations between glyphosate and neural tube defects for both the single pesticide and multiple pesticide models – with an odds ratio (OR, a statistical measure of a possible link) of 1.5 for both. For the hierarchical model they found an OR of 1.4. Their criteria for significant effects were that the OR should be greater than or equal to 1.4 and the lower limit of the confidence interval (CI) should be greater than or equal to 0.9.⁸ The OR requirement is met for glyphosate and neural tube defects using both models, but both models deliver CIs that are just below the cut-off: 0.8. These results could reasonably be interpreted as indicating a modest association between glyphosate herbicide exposure, neural tube defects, and anencephaly. This finding is consistent with findings in frog and chicken embryos³ and rats,⁵ which also linked glyphosate/Roundup exposure to impaired development of the structures of the central nervous system. It is also consistent with findings of industry studies on the effects of glyphosate alone in rats, in which the observed malformations included “reduced ossification of one or more cranial centres”.⁹ These malformations involving the structures of the central nervous system are consistent with descriptions of retinoic acid-induced malformations in the literature.^{2 10}

Adverse effects on sperm

• A study on the reproductive effects of Roundup on male and female offspring of rats exposed during pregnancy and lactation found significant adverse effects at non-maternally toxic doses. Findings in male offspring included a decrease in sperm number and daily sperm production during adulthood, an increase in the percentage of abnormal sperms, a dose-related decrease in serum testosterone level at puberty, and sperm cell degeneration. The authors noted that Roundup had been found in other experiments to inhibit steroidogenesis (formation of steroid hormones) in vitro by disrupting the expression of a regulatory protein, but glyphosate did not, indicating that at least one other component of the formulation is required to disrupt steroidogenesis.¹¹

Miscarriage and premature births

• A study of farming families in Ontario, Canada found a higher than normal rate of late miscarriages and premature births associated with male glyphosate herbicide exposure.¹² Monsanto claimed in non-peer-reviewed articles that the association for glyphosate was weak and not statistically significant.^{13 14} But in the study, the odds ratios (a statistical measure of a possible link) were 1.5 for an association between glyphosate herbicide exposure and miscarriage and 2.4 between glyphosate herbicide exposure and premature birth. 1.5 is near the lower limit but 2.4 is fairly strong. Both indicate an association.

Further studies are needed in animals dosed over the long term with realistic levels of Roundup that humans could be exposed to, in order to conclusively confirm the above findings. However, there is enough evidence of harm from animal studies to justify a ban on glyphosate herbicides on the grounds of risk to human health.

References:

1. Glyphosate Task Force. What do toxicology studies tell us about glyphosate? Glyphosate Facts. 2013. Available at: http://www.glyphosate.eu/what-do-toxicology-studies-tell-us-about-glyphosate.
2. Antoniou M, Habib MEM, Howard CV, et al. Teratogenic effects of glyphosate-based herbicides: Divergence of regulatory decisions from scientific evidence. J Env Anal Toxicol. 2012;S4:006. doi:10.4172/2161-0525.S4-006.
3. Paganelli A, Gnazzo V, Acosta H, López SL, Carrasco AE. Glyphosate-based herbicides produce teratogenic effects on vertebrates by impairing retinoic acid signaling. Chem Res Toxicol. 2010;23:1586–1595. doi:10.1021/tx1001749.
4. Williams GM, Kroes R, Munro IC. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol. 2000;31:117-65. doi:10.1006/rtph.1999.1371.
5. Dallegrave E, Mantese FD, Coelho RS, Pereira JD, Dalsenter PR, Langeloh A. The teratogenic potential of the herbicide glyphosate-Roundup in Wistar rats. Toxicol Lett. 2003;142:45-52.
6. Lajmanovich RC, Sandoval MT, Peltzer PM. Induction of mortality and malformation in Scinax nasicus tadpoles exposed to glyphosate formulations. Bull Env Contam Toxicol. 2003;70:612–618. doi:10.1007/s00128-003-0029-x.
7. Rull RP, Ritz B, Shaw GM. Neural tube defects and maternal residential proximity to agricultural pesticide applications. Epidemiology. 2004;15:S188.
8. Rull RP, Ritz B, Shaw GM. Neural tube defects and maternal residential proximity to agricultural pesticide applications. Am J Epidemiol. 2006;163:743-53. doi:10.1093/aje/kwj101.
9. Rapporteur member state Germany. Monograph on Glyphosate: Glyphosate: Annex B-5: Toxicology and Metabolism: Vol 3-1 Glyphosat 04. German Federal Agency for Consumer Protection and Food Safety (BVL); 1998. Available at: http://bit.ly/QwOnPA.
10. Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med. 1985;313:837–41. doi:10.1056/NEJM198510033131401.
11. Dallegrave E, Mantese FD, Oliveira RT, Andrade AJ, Dalsenter PR, Langeloh A. Pre- and postnatal toxicity of the commercial glyphosate formulation in Wistar rats. Arch Toxicol. 2007;81:665–73. doi:10.1007/s00204-006-0170-5.
12. Savitz DA, Arbuckle T, Kaczor D, Curtis KM. Male pesticide exposure and pregnancy outcome. Am J Epidemiol. 1997;146:1025-36.
13. Monsanto. Backgrounder: Glyphosate and reproductive outcomes. 2004. Available at: http://www.monsanto.com/products/documents/glyphosate-background-materials/gly_reprooutcomes_bkg.pdf.
14. Monsanto. Backgrounder: Response to “Glyphosate toxic and Roundup worse.” 2006. Available at: http://www.monsanto.com/products/documents/glyphosate-background-materials/response_isis_apr_06.pdf.

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