The Weed Killer Atrazine is the most commonly used Herbicide in the U.S. and probably in the World. Atrazine induces complete Feminization of Frogs and all other Animal Species, including Mammals (Humans)

by
Robert W.D. Gorter, MD, PhD.

August 20^th, 2024

Bill Gates’ Rainforest Alliance uses the above logo with the frog to identify all products from (sub-) tropical countries like coffee and chocolate, nuts, avocados, etc. that have been laced with Atrazine.

The herbicide Atrazine is currently one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is already active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of Atrazine exposure in adult amphibians. Atrazine-exposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazine-exposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized /feminized laryngeal development, and suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of Atrazine observed in other vertebrate classes and in humans. The present findings exemplify the role that Atrazine and other endocrine-disrupting herbicides and pesticides certainly play in global amphibian declines (1).

Demasculinization and feminization of male gonads by atrazine: consistent effects across all studied vertebrate classes

Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called “Hill criteria” (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause-effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects. Atrazine demasculinizes male gonads producing testicular lesions associated with significantly reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals (including humans), and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis – demonstrated in fish, amphibians, reptiles, and mammals – represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus the case for Atrazine as an endocrine disruptor that demasculinizes and feminizes male vertebrates meets all nine of the “Hill criteria”. (2).

Demasculinization and feminization of male gonads by Atrazine: Consistent effects across all vertebrate classes

Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, reptiles. And vertebrae, including humans.

Atrazine is the most commonly detected pesticide contaminant of ground water, surface water, and precipitation. Atrazine is also an endocrine disruptor that, among other effects, alters male reproductive tissues when animals are exposed during development. Here, we apply the nine so-called “Hill criteria” (Strength, Consistency, Specificity, Temporality, Biological Gradient, Plausibility, Coherence, Experiment, and Analogy) for establishing cause–effect relationships to examine the evidence for atrazine as an endocrine disruptor that demasculinizes and feminizes the gonads of male vertebrates. We present experimental evidence that the effects of Atrazine on male development are consistent across all vertebrate classes examined and we present a state of the art summary of the mechanisms by which atrazine acts as an endocrine disruptor to produce these effects.

Atrazine demasculinizes male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. These effects are strong (statistically significant), consistent across vertebrate classes, and specific. Reductions in androgen levels and the induction of estrogen synthesis – demonstrated in fish, amphibians, reptiles, and mammals – represent plausible and coherent mechanisms that explain these effects. Biological gradients are observed in several of the cited studies, although threshold doses and patterns vary among species. Given that the effects on the male gonads described in all of these experimental studies occurred only after atrazine exposure, temporality is also met here. Thus, the case for Atrazine as an endocrine disruptor that demasculinizes and feminizes all male vertebrates and meets all nine of the “Hill criteria” (3).

An additional way to depopulate the world is to cause infertility in human males and thus, using Atrazine to sterilizing males this way without their consent or noticing.

References:

(1) Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis). Proc Natl Acad Sci U S A. 2010 Mar 9; 107(10): 4612–4617. Published online 2010 Mar 1. doi: 10.1073/pnas.0909519107
(2) Demasculinization and feminization of male gonads by atrazine: consistent effects across all studied vertebrate classes. PMID: 21419222 PMCID: PMC4303243 DOI: 10.1016/j.jsbmb.2011.03.015

(3) Atrazine demasculinizes all male gonads producing testicular lesions associated with reduced germ cell numbers in teleost fish, amphibians, reptiles, and mammals, and induces partial and/or complete feminization in fish, amphibians, and reptiles. https://doi.org/10.1016/j.jsbmb.2011.03.015

(4) U.S. Environmental Protection Agency (.gov) https://archive.epa.gov › pdf › atrazine_summary

(5) U.S. Environmental Protection Agency (.gov) https://archive.epa.gov › meetings › web › pdf

(6) The herbicide atrazine is one of the most commonly used, well studied, and controversial pesticides on the planet:

https://www.farmlandbirds.net › files › ETC_2007

Further references to scientific studies in regards to Atrazine.

Solomon K, et al. Ecological risk assessment of atrazine in North American surface waters. Environ. Toxicol. Chem. 1996;15:31–76. – PubMed

Boyd R. Herbicides and herbicide degradates in shallow groundwater and the Cedar River near a municipal well field, Cedar Rapids, Iowa, Sci. Total Environ. 2000;248:241–253. – PubMed

Capel P, Larson S. Effect of scale on the behavior of atrazine in surface waters. Environ. Sci. Technol. 2001;35(4):648–657. – PubMed

Du Preez LH, et al. Seasonal exposures to triazine and other pesticides in surface waters in the western Highveld corn-production region in South Africa. Environ. Pollut. 2005;135(1):131–141. – PubMed

Fenelon J, Moore R. Transport of agrichemicals to ground and surface waters in a small central Indiana watershed. J. Environ. Qual. 1998;27:884–894.

Fischer J, Apedaile B, Vanclief L. Seasonal loadings of atrazine and metolachlor to a southeastern Ontario river from surface runoff and groundwater discharge, Water Qual. Res. J. Canada. 1995;30(3):533–553.

Frank R, Logan L. Pesticide and industrial chemical residues at the mouth of the Grand, Saugeen and Thames rivers, Ontario, Canada, 1981-85. Arch. Environ. Contam. Toxicol. 1988;17:741–754. – PubMed

Frank R, Logan L, Clegg B. Pesticide and polychlorinated biphenyl residues in waters at the mouth of the Grand, Saugeen and Thames rivers, Ontario, Canada, 1986-1990. Arch. Environ. Contam. Toxicol. 1991;21:585–595. – PubMed

Frank R, et al. Survey of farm wells for pesticides, Ontario, Canada. Arch. Environ. Contam. Toxicol. 1987;16:1–8. – PubMed

Frank R, Sirons G. Atrazine: its use in corn production and its loss to stream waters in southern Ontario. Sci. Total Environ. 1979;12:223–239.

Graymore M, Stagnitti F, Allinson G. Impacts of atrazine in aquatic ecosystems. Environ. Int. 2001;26(7-8):483–495. – PubMed

Rudolph D, Goss M. Ontario farm groundwater quality survey—summer 1992, A report prepared for Agriculture Canada, Agri-Food Development Branch, Guelph, Ontario, Agriculture Canada. 1993

Hatfield JL, et al. Herbicide and nitrate distribution in central Iowa rainfall. J. Environ. Qual. 1996;25(2):259–264.

Lode O, et al. Pesticides in precipitation in Norway. Sci. Total Environ. 1995;160-161:421–431.

Mast MA, Foreman WT, Skaates SV. Current-use pesticides and organochlorine compounds in precipitation and lake sediment from two high-elevation national parks in the Western United States. Arch. Environ. Contam. Toxicol. 2007;52(3):294–305. – PubMed

Miller S, et al. Atrazine and nutrients in precipitation: results from the Lake Michigan mass balance study. Environ. Sci. Technol. 2000;34(1):55–61.

Vogel JR, Majewski MS, Capel PD. Pesticides in rain in four agricultural watersheds in the United States. J. Environ. Qual. 2008;37(3):1101–1115. – PubMed

Thurman E, Cromwell A. Atmospheric transport, deposition, and fate of triazine herbicides and their metabolites in pristine areas at Isle Royale National Park. Environ. Sci. Technol. 2000;34:3079–3085.

Crain D, et al. Alterations in steroidogenesis in alligators (Alligator mississippiensis) exposed naturally and experimentally to environmental contaminants. Environ. Health Perspect. 1997;105:528–533. – PMC – PubMed

Reeder A, et al. Forms and prevalence of intersexuality and effects of environmental contaminants on sexuality in cricket frogs (Acris crepitans) Environ. Health Perspect. 1998;106:261–266. – PMC – PubMed

Sanderson J, et al. Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol. Appl. Pharmacol. 2002;182:44–54. – PubMed

Sanderson JT, et al. Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. Environ. Health Perspect. 2001;109:1027–1031. – PMC – PubMed

Sanderson JT, et al. 2-Chloro-triazine herbicides induce aromatase (CYP19) activity in H295R human adrenocortical carcinoma cells: a novel mechanism for estrogenicity? Toxicol Sci. 2000;54:121–127. – PubMed

Stoker T, et al. The effect of atrazine on puberty in male Wistar rats: an evaluation in the protocol for the assessment of pubertal development and thyroid function. Toxicol. Sci. 2000;58(1):50–59. – PubMed

Hayes TB, et al. Feminization of male frogs in the wild. Nature. 2002;419:895–896. – PubMed

Hayes TB, et al. Atrazine-induced hermaphroditism at 0.1 ppb in American leopard frogs (Rana pipiens): laboratory and field evidence. Environ. Health Perspect. 2002;111:568–575. – PMC – PubMed

Murphy MB, et al. Atrazine concentrations, gonadal gross morphology and histology in ranid frogs collected in Michigan agricultural areas. Aquat. Toxicol. 2006;76(3-4):230–245. – PubMed

McCoy KA, et al. Agriculture alters gonadal form and function in the toad Bufo marinus. Environ. Health Perspect. 2008;116(11):1526–1532. – PMC – PubMed

Hill A. The environment and disease: association or causation. Proc. R. Soc. Med. 1965;58:295–300. – PMC – PubMed

International Program of Chemical Safety. World Health Organization; Geneva: 2002. IPCS global assessment of the state-of-the-science of endocrine disruptors.

Daxenberger A. Pollutants with androgen-disrupting potency. Eur. J. Lipid Sci. Technol. 2002;104(2):124–130.

Markey CM, et al. Endocrine disruptors: from Wingspread to environmental developmental biology. J. Steroid Biochem. Mol. Biol. 2002;83(1-5):235–244. – PubMed

Reeder AL, et al. Intersexuality and the cricket frog decline: historic and geographic trends. Environ. Health Perspect. 2005;113(3):261–265. – PMC – PubMed

Sowers AD, Mills MA, Klaine SJ. The developmental effects of a municipal wastewater effluent on the northern leopard frog, Rana pipiens. Aquatic Toxicology. 2009;94(2):145–152. – PubMed

Howe C, et al. Toxicity of glyphosate-based pesticides to four North American frog species. Environ. Toxicol. Chem. 2004;23(8):1928–1938. – PubMed

Hogan NS, et al. Estrogenic exposure affects metamorphosis and alters sex ratios in the northern leopard frog (Rana pipiens): Identifying critically vulnerable periods of development. General and Comparative Endocrinology. 2008;156(3):515–523. – PubMed

Jofre MB, Karasov WH. Effect of mono-ortho and di-ortho substituted polychlorinated biphenyl (PCB) congeners on leopard frog survival and sexual development. Chemosphere. 2008;70(9):1609–1619. – PubMed

Spano L, et al. Effects of atrazine on sex steroid dynamics, plasma vitellogenin concentration and gonad development in adult goldfish (Carassius auratus) Aquat. Toxicol. (Amsterdam) 2004;66(4):369–379. – PubMed

Hayes TB, et al. Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis) Proc. Natl. Acad. Sci. U.S.A. 2010;107(10):4612–4617. – PMC – PubMed

Rey F, et al. Prenatal exposure to pesticides disrupts testicular histoarchitecture and alters testosterone levels in male Caiman latirostris. Gen. Comp. Endocrinol. 2009;162(3):286–292. – PubMed

Victor-Costa AB, et al. Changes in testicular morphology and steroidogenesis in adult rats exposed to Atrazine. Reprod. Toxicol. 2010;29(3):323–331. – PubMed

Kniewald J, et al. Disorders of male rat reproductive tract under the influence of atrazine. J. Appl. Toxicol. 2000;20:61–68. – PubMed

Tillitt DE, et al. Atrazine reduces reproduction in fathead minnow. Marine Environ. Res. 2008;66(1):51–151.

Hayes TB, et al. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses, Proc. Natl. Acad. Sci. U.S.A. 2002;99:5476–5480. – PMC – PubMed

Hayes TB, et al. Characterization of atrazine-induced gonadal malformations and effects of an androgen antagonist (cyproterone acetate) and exogenous estrogen (estradiol 17β): support for the demasculinization/feminization hypothesis. Environ. Health Perspect. 2006;114(Suppl. 1):134–141. – PMC – PubMed

Orton F, Carr J, Handy R. Effects of nitrate and atrazine on larval development and sexual differentiation in the northern leopard frog Rana pipiens. Environ. Toxicol. Chem. 2006;25(1):65–71. – PubMed

De Solla SR, et al. Effects of environmentally relevant concentrations of atrazine on gonadal development of snapping turtles (Chelydra serpentina) Environ. Toxicol. Chem. 2006;25(2):520–526. – PubMed

Suzawa M, Ingraham H. The herbicide atrazine activates endocrine gene networks via non-steroidal NR5A nuclear receptors in fish and mammalian cells. PLoS One. 2008;3:2117. – PMC – PubMed

Oka T, et al. Effect of atrazine on metamorphosis and sexual differentiation in Xenopus laevis. Aquat. Toxicol. 2008;87(4):215–226. – PubMed

Langlois V, et al. Low levels of the herbicide atrazine alters sex ratios and reduces metamorphic success in Rana pipiens tadpoles raised in outdoor mesocosms. Environ. Health Perspect. 2009 – PMC – PubMed

Willingham EJ. The effects of atrazine and temperature on turtle hatchling size and sex ratios. Front. Ecol. Environ. 2005;3(6):309–313.

Fox G. Practical causal inference for epidemiologists. J. Toxicol. Environ. Health. 1991;33:359–373. – PubMed

Tavera-Mendoza L, et al. Response of the amphibian tadpole (Xenopus laevis) to atrazine during sexual differentiation of the testis. Environ. Toxicol. Chem. 2002;21:527–531. – PubMed

Tavera-Mendoza L, et al. Response of the amphibian tadpole Xenopus laevis to atrazine during sexual differentiation of the ovary. Environ. Toxicol. Chem. 2002;21(6):1264–1267. – PubMed

Hayes TB. There is no denying this: defusing the confusion about atrazine. Bioscience. 2004;54(12):1138–1149.

Carr J, et al. Response of larval Xenopus laevis to atrazine: assessment of growth, metamorphosis, and gonadal and laryngeal morphology. Environ. Toxicol. Chem. 2003;22:396–405. – PubMed

Hecker M, et al. Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine. Aquat. Toxicol. (Amsterdam) 2005;72(4):383–396. – PubMed

Gojmerac T, Kniewald J. Atrazine biodegradation in rats—a model for mammalian metabolism. Bull. Environ. Contam. Toxicol. 1989;43(2):199–206. – PubMed

Moore A, Waring C. Mechanistic effects of a triazine pesticide on reproductive endocrine function in mature male Atlantic salmon (Salmo salar L.) parr. Pesticide Biochem. Physiol. 1998;62:41–50.

Friedmann A. Atrazine inhibition of testosterone production in rat males following peripubertal exposure. Reprod. Toxicol. 2002;16(3):275–279. – PubMed

Wilhelms KW, et al. Effects of atrazine on sexual maturation in female Japanese quail induced by photostimulation or exogenous gonadotropin. Environ. Toxicol. Chem. 2006;25(1):233–240. – PubMed

Cummings A, Rhodes B, Cooper R. Effect of atrazine on implantation and early pregnancy in 4 strains of rats. Toxicol. Sci. 2000;58(1):135–143. – PubMed

Cooper RL, et al. Atrazine disrupts the hypothalamic control of pituitary-ovarian function. Toxicol. Sci. 2000;53:297–307. – PubMed

Narotsky M, et al. Strain comparisons of atrazine-induced pregnancy loss in the rat. Reprod. Toxicol. 2001;15(1):61–69. – PubMed

Foradori CD, et al. Effects of atrazine and its withdrawal on gonadotropin-releasing hormone neuroendocrine function in the adult female Wistar rat. Biol. Reprod. 2009;81(6):1099–1105. – PubMed

Babic-Gojmerac T, Kniewald Z, Kniewald J. Testosterone metabolism in neuroendocrine organs in male rats under atrazine and deethylatrazine influence. J. steroid. Biochem. 1989;33(1):141–146. – PubMed

Foradori CD, et al. Atrazine inhibits pulsatile luteinizing hormone release without altering pituitary sensitivity to a gonadotropin-releasing hormone receptor agonist in female Wistar rats. Biol. Reprod. 2009;81(1):40–45. – PubMed

McMullin T, et al. Evidence that atrazine and diaminochlorotriazine inhibit the estrogen/progesterone induced surge of luteinizing hormone in female Sprague-Dawley rats without changing estrogen receptor action. Toxicol. Sci. 2004;79:278–286. – PubMed

Kniewald J, et al. Effect of s-triazine compounds on testosterone metabolism in the rat prostate. J. Appl. Toxicol. 1995;15(3):215–218. – PubMed

Kniewald J, Mildner P, Kniewald Z. Effects of s-triazine herbicides on hormone-receptor complex formation, 5α reductase and 3α hydroxysteroid dehydrogenase activity at the anterior pitiuitary level. J. Steroid Biochem. 1979;11(1):833–838. – PubMed

Danzo BJ. Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. Environ. Health Perspect. 1997;105(3):294–301. – PMC – PubMed

Kniewald J, Mildner P, Kniewald Z. Effects of s-triazine herbicides on 5-alpha dihydrotestosterone receptor complex formation in hypothalamus and ventral prostate. In: Action E, Genazzani F, DiCarlo, Mainwaring WIP, editors. Pharmacological Modulation of Steroid Action. Raven Press; New York: 1980. pp. 159–169.

Orton F, et al. Endocrine disrupting effects of herbicides and pentachlorophenol: In vitro and in vivo evidence. Environmental Science & Technology. 2009;43(6):2144–2150. – PubMed

Pogrmic K, et al. Atrazine oral exposure of peripubertal male rats downregulates steroidogenesis gene expression in Leydig cells. Toxicol. Sci. 2009;111(1):189–197. – PubMed

Pogrmic K, et al. Assesment of in vitro effects of atrazine on peripubertal rat Leydig cell steroidogenesis. FEBS J. 2008;275:462–1462.

Fraites MJP, et al. Characterization of the hypothalamic-pituitary-adrenal axis response to atrazine and metabolites in the female rat. Toxicol. Sci. 2009;112(1):88–99. – PubMed

Laws SC, et al. Chlorotriazine herbicides and metabolites activate an ACTHdependent release of corticosterone in male Wistar rats. Toxicol. Sci. 2009;112(1):78–87. – PubMed

Zorrilla LM, Gibson EK, Stoker TE. The effects of simazine, a chlorotriazine herbicide, on pubertal development in the female Wistar rat. Reproductive Toxicology. 2010;29(4):393–400. – PubMed

Stoker TE, Robinette CL, Cooper RL. Maternal exposure to atrazine during lactation suppresses suckling-induced prolactin release and results in prostatitis in the adult offspring. Toxicol. Sci. 1999;52:68–79. – PubMed

Roberge M, Hakk H, Larsen G. Atrazine is a competitive inhibitor of phosphodiesterase but does not affect the estrogen receptor. Toxicol. Letters. 2004;154:61–68. – PubMed

Fan W, et al. Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II. Biochem. Biophys. Res. Commun. 2007;355(4):1012–1018. – PubMed

Fan W, et al. Atrazine-induced aromatase expression is SF-1-dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans. Environ. Health Perspect. 2007;115(5):720–727. – PMC – PubMed

Holloway AC, et al. Atrazine-induced changes in aromatase activity in estrogen sensitive target tissues. J. Appl. Toxicol. 2008;28(3):260–270. – PubMed

Piferrer F. Endocrine sex control strategies for the feminization of teleost fish. Aquaculture. 2001;197(1-4):229–281.

Guiguen Y, et al. Ovarian aromatase and estrogens: a pivotal role for gonadal sex differentiation and sex change in fish. Gen. Comp. Endocrinol. 2010;165(3 (Sp. Iss. SI):352–366. – PubMed

Hayes TB. Hormonal regulation of sex differentiation in amphibians, reptiles, and birds. In: Knobil E, Neill J, editors. Encyclopedia of Reproduction. Academic Press; San Diego: 1998. pp. 102–109.

Hayes TB. Sex determination and primary sex differentiation in amphibians. J. Exp. Zool. 1998;281:373–399. – PubMed

Crews D. Temperature-dependent sex determination: the interplay of steroid hormones and temperature. Zool. Sci. 1996;13(1):1–13. – PubMed

Gutzke WHN, Bull JJ. Steroid hormones reverse sex in turtles. Gen. Comp. Endocrinol. 1986;64(3):368–372. – PubMed

Hayes TB. Comparative endocrinology: a tool for understanding mechanisms and predicting effects of endocrine mimicking xenobiotics. In: Guillette LJ, editor. Environmental Endocrine Disruptors: An Evolutionary Perspective. Taylor and Francis; NY: 1999.

Wilhelms KW, et al. In ovo exposure to a triazine herbicide: Effects of atrazine on circulating reproductive hormones and gonadal histology in young Japanese quail. Archives of Environmental Contamination and Toxicology. 2006;51(1):117–122. – PubMed

Matsushita S, et al. Effects of in ovo exposure to imazalil and atrazine on sexual differentiation in chick gonads. Poultry Science. 2006;85(9):1641–1647. – PubMed

Swan S, et al. Semen quality in relation to biomarkers of pesticide exposure. Environ. Health Perspect. 2003;111(12):1478–1484. – PMC – PubMed

Rayner J, Enoch R, Fenton S. Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth. Toxicol. Sci. 2005;87(1):255–266. – PubMed

Rayner J, Wood C, Fenton S. Exposure parameters necessary for delayed puberty and mammary gland development in Long-Evans rats exposed in utero to atrazine. Toxicol. Appl. Pharmacol. 2004;195(23-34) – PubMed

Rayner JL, et al. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats. Toxicol. Appl. Pharmacol. 2007;218(3):238–248. – PubMed

Pintér A, et al. Long-term carcinogenecity bioassay of the herbicide atrazine in F344 rats. Neoplasma. 1980;37:533–544. – PubMed

Ueda M, et al. Possible enhancing effects of atrazine on growth of 7,12-dimethylbenz(a) anthracene induced mammary tumors in ovariectomized Sprague-Dawley rats. Cancer Sci. 2005;96(1):19–25. – PMC – PubMed

Eldridge J, et al. Factors affecting mammary tumor incidence in chlorotriazine-treated female rats: hormonal properties, dosage, and animal strain. Environ. Health Perspect. 1994;102(11):29–36. – PMC – PubMed

Stevens J, et al. Hypothesis for mammary tumorigenesis in Sprague-Dawley rats exposed to certain triazine herbicides. J. Toxicol. Environ. Health. 1994;43:139–154. – PubMed

Wetzel LT, et al. Chronic effects of atrazine on estrus and mammary gland formation in female Sprague-Dawley and Fischer-344 rats. J. Toxicol. Environ. Health. 1994;43:169–182. – PubMed

Kettles MA, et al. Triazine exposure and breast cancer incidence: an ecologic study of Kentucky counties. Environ. Health Perspect. 1997;105(11):1222–1227. – PMC – PubMed

Brodkin M, et al. Atrazine is an immune disruptor in adult northern leopard frogs (Rana pipiens) Environ. Toxicol. Chem. 2007;26(1):80–84. – PubMed

Cantemir C, et al. p53 protein expression in peripheral lymphocytes from atrazine chronically intoxicated rats. Toxicol. Lett. 1987;93(2-3):87–94. – PubMed

Christin MS, et al. Effects of agricultural pesticides on the immune system of Rana pipiens and on its resistance to parasitic infection. Environ. Toxicol. Chem. 2003;22(5):1127–1133. – PubMed

Christin MS, et al. Effects of agricultural pesticides on the immune system of Xenopus laevis and Rana pipiens. Aquat. Toxicol. 2004;67(1):33–43. – PubMed

Filipov N, et al. Immunotoxic effects of short-term atrazine exposure in young male C57BL/6 mice. Toxicol. Sci. 2005;86(2) – PubMed

Forson D, Storfer A. Atrazine increases Ranavirus susceptibility in the tiger salamander Ambystoma tigrinum. Ecol. Appl. 2006;16(6):2325–2332. – PubMed

Forson D, Storfer A. Effects of atrazine and iridovirus infection on survival and life history traits of the long-toed salamander (Ambystoma macrodatylum) Environ. Toxicol. Chem. 2006;25(1):168–173. – PubMed

Gendron AD, et al. Exposure of leopard frogs to a pesticide mixture affects life history characteristics of the lungworm Rhabdias ranae. Oecologia. 2003;135(3):469–476. – PubMed

Hooghe R, Devos S, Hooghe-Peters E. Effects of selected herbicides on cytokine production in vitro. Life Sci. 2000;66(26):2519–2525. – PubMed

Houck A, Sessions S. Could atrazine affect the immune system of the frog Rana pipiens? Bios. 2006;77(4):107–112.

Karrow NA, et al. Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice. Toxicology. 2005;209(1):15–28. – PubMed

Kim KR, et al. Immune alterations in mice exposed to the herbicide simazine. J. Toxicol. Environ. Health A: Curr. Issues. 2003;66(12):1159–1173. – PubMed

Langerveld AJ, et al. Chronic exposure to high levels of atrazine alters expression of genes that regulate immune and growth-related functions in developing Xenopus laevis tadpoles. Environ. Res. 2009;109(4):379–389. – PubMed

Liskova A, et al. Effect of the herbicide atrazine on some immune parameters in mice. J. Trace Micropr. Tech. 2000;18(2):235–240.

Mizota K, Ueda H. Endocrine disrupting chemical atrazine causes degranulation through G(q/11) protein-coupled neurosteroid receptor in mast cells. Toxicol. Sci. 2006;90(2):362–368. – PubMed

Pistl J, et al. Determination of the immunotoxic potential of pesticides on functional activity of sheep leukocytes in vitro. Toxicology. 2003;188(1):73–81. – PubMed

Porter W, Jaeger J, Carlson I. Endocrine, immune, and behavioral effects of aldicarb (carbamate), atrazine (triazine) and nitrate fertilizer mixtures at groundwater concentrations. Toxicol. Ind. Health. 1999;15:133–150. – PubMed

Pruett S, et al. Modeling and predicting immunological effects of chemical stressors: characterization of a quantitative biomarker for immunological changes caused by atrazine and ethanol. Toxicol. Sci. 2003;75(2):343–354. – PubMed

Rooney A, Matulka R, Luebke R. Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats. Toxicol. Sci. 2003;76:366–375. – PubMed

Rowe A, et al. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice. Toxicol. Appl. Pharmacol. 2006;214(1):69–77. – PMC – PubMed

Rowe AM, Brundage KM, Barnett JB. Developmental immunotoxicity of atrazine in rodents. Basic Clin. Pharmacol. Toxicol. 2008;102(2):139–145. – PubMed

Rymuszka A, et al. Application of immunostimulants after suppression induced byxenobiotics: effect of lysozyme dimer (KLP-602) after immunosuppression induced by atrazine in rabbits. Pol. J. Food Nutr. Sci. 2004;13(2):51–54.

Whalen M, et al. Immunomodulation of human natural killer cell cytotoxic function by triazine and carbamate pesticides. Chem.-Biol. Interact. 2003;145(3):311–319. – PubMed

Zeljezic D, et al. Evaluation of DNA damage induced by atrazine and atrazinebased herbicide in human lymphocytes in vitro using a comet and DNA diffusion assay. Toxicol. In Vitro. 2006;20(6):923–935. – PubMed

Rohr JR, et al. Agrochemicals increase trematode infections in a declining amphibian species. Nature. 2008;455(7217):1235–1239. – PubMed

Giusi G, et al. The endocrine disruptor atrazine accounts for a dimorphic somatostatinergic neuronal expression pattern in mice. Toxicol. Sci. 2006;89(1):257–264. – PubMed

Hossain MM, Filipov NM. Alteration of dopamine uptake into rat striatal vesicles and synaptosomes caused by an in vitro exposure to atrazine and some of its metabolites. Toxicology. 2008;248(1):52–58. – PMC – PubMed

Martyniuk CJ, et al. Aquatic contaminants alter genes involved in neurotransmitter synthesis and gonadotropin release in largemouth bass. Aquat. Toxicol. 2009;95(1):1–9. – PubMed

Rodriguez V, Thiruchelvam M, Cory-Slechta D. Sustained exposure to the widely used herbicide atrazine: altered function and loss of neurons in brain monoamine systems. Environ. Health Perspect. 2005;113(6):708–715. – PMC – PubMed

Tierney KB, et al. Relating olfactory neurotoxicity to altered olfactory-mediated behaviors in rainbow trout exposed to three currently-used pesticides. Aquat. Toxicol. 2007;81(1):55–64. – PubMed

Alvarez MD, Fuiman LA. Environmental levels of atrazine and its degradation products impair survival skills and growth of red drum larvae. Aquat. Toxicol. 2005;74(3):229–241. – PubMed

de Noyelles F, Kettle W, Sinn D. The response of plankton communities in experimental ponds to atrazine, the most heavily used pesticide in the United States. Ecology. 1285;63(1982):1293.

Dewey SL. Effects of the herbicide atrazine on aquatic insect community structure and emergence. Ecology. 1986;67(1):148–162.

Griggs JL, Belden LK. Effects of atrazine and metolachlor on the survivorship and infectivity of Echinostoma trivolvis trematode cercariae. Arch. Environ. Contam. Toxicol. 2008;54(2):195–202. – PubMed

Koprivnikar J, Baker RL, Forbes MR. Environmental factors influencing community composition of gastropods and their trematode parasites in southern Ontario. J. Parasitol. 2007;93:992–998. – PubMed

Koprivnikar J, Forbes MR, Baker RL. Contaminant effects on host-parasite interactions: atrazine, frogs, and trematodes. Environ. Toxicol. Chem. 2007;26:2166–2170. – PubMed

Rohr J, Crumrine P. Effects of an herbicide and an insecticide on pond community structure and processes. Ecol. Appl. 2005;15:1135–1147.

Rohr JR, et al. Understanding the net effects of pesticides on amphibian trematode infections. Ecol. Appl. 2008;18(7):1743–1753. – PubMed

Russo J, Lagadic L. Effects of parasitism and pesticide exposure on characteristics and functions of hemocyte populations in the freshwater snail Lymnaea palustris (Gastropoda Pulmonata) Cell Biol. Toxicol. 2000;16(1):15–30. – PubMed