Effects on metabolic parameters in young rats born with low birth weight after exposure to a mixture of pesticides

Abstract Pesticide exposure during fetal life can lead to low birth weight and is commonly observed in reproductive toxicology studies. Associations have also been found in low birth weight babies born from pesticide-exposed gardeners. Since low birth weight is also linked to metabolic disorders, it can be speculated that early life exposure to pesticides could increase the risk of becoming obese or developing diabetes later in life. We have analyzed potential long-term effects of gestational and lactational exposure to a low dose mixture of six pesticides that individually can cause low birth weight: Cyromazine, MCPB, Pirimicarb, Quinoclamine, Thiram, and Ziram. Exposed male offspring, who were smaller than controls, displayed some degree of catch-up growth. Insulin and glucagon regulation was not significantly affected, and analyses of liver and pancreas did not reveal obvious histopathological effects. Efforts towards identifying potential biomarkers of metabolic disease-risk did not result in any strong candidates, albeit leptin levels were altered in exposed animals. In fat tissues, the key genes Lep, Nmb and Nmbr were altered in high dosed offspring, and were differentially expressed between sexes. Our results suggest that early-life exposure to pesticides may contribute to the development of metabolic disorders later in life

Synergistic disruption of external male sex organ development by a mixture of four antiandrogens

Reproduced with permission from Environmental Health Perspectives.Background: By disrupting the action of androgens during gestation, certain chemicals present in food, consumer products, and the environment can induce irreversible demasculinization and malformations of sex organs among male offspring. However, the consequences of simultaneous exposure to such chemicals are not well described, especially when they exert their actions by differing molecular mechanisms. Objectives: To fill this gap, we investigated the effects of mixtures of a widely used plasticizer, di(2-ethylhexyl) phthalate (DEHP); two fungicides present in food, vinclozolin and prochloraz; and a pharmaceutical, finasteride, on landmarks of male sexual development in the rat, including changes in anogenital distance (AGD), retained nipples, sex organ weights, and malformations of genitalia. These chemicals were chosen because they disrupt androgen action with differing mechanisms of action. Results: Strikingly, the effect of combined exposure to the selected chemicals on malformations of external sex organs was synergistic, and the observed responses were greater than would be predicted from the toxicities of the individual chemicals. In relation to other hallmarks of disrupted male sexual development, including changes in AGD, retained nipples, and sex organ weights, the combined effects were dose additive. When the four chemicals were combined at doses equal to no observed adverse effect levels estimated for nipple retention, significant reductions in AGD were observed in male offspring. Conclusions: Because unhindered androgen action is essential for human male development in fetal life, these findings are highly relevant to human risk assessment. Evaluations that ignore the possibility of combination effects may lead to considerable underestimations of risks associated with exposures to chemicals that disrupt male sexual differentiation.European Union and the Danish Environmental Protection Agency