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

Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

<div><p>Humans are exposed to a large number of environmental chemicals in their daily life, many of which are readily detectable in blood or urine. It remains uncertain if these chemicals can cause adverse health effects when present together at low doses. In this study we have tested whether a mixture of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid dose) or 1.6 (High dose) mg/kg bw/day. The lowest dose was designed with the aim of obtaining plasma or urine concentrations in rats at levels approaching those observed in humans. Some single congeners were administered at doses representative of combined doses for chemical groups. With this baseline, we found effects on weight, histology and gene expression in the liver, as well as changes to the blood plasma metabolome in all exposure groups, including low-dose. Additional adverse effects were observed in the higher dosed groups, including enlarged kidneys and alterations to the metabolome. No significant effects on reproductive parameters were observed.</p></div