Reproductive toxicity of endocrine-disrupting chemicals and the mechanism via peroxisome proliferators-activated receptor in relation to the risk assessment

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Phthalic acid esters are typical plasticizer, which is recently noted as an endocrine-disrupting chemical. These chemicals are known as a ligand to peroxisome proliferators-activated receptor a (PPARα). Reproductive toxicity of di(2-ethylhexyl) phthalate (DEHP) and the mechanism were investigated using wild-type Sv/129 mice and PPARα-null mice on the same genetic background. A 0.05% DEHP diet was prepared with commercial rodent chow. DEHP treatment increased the resolution of fetus and mortality of new born pups per pair in wild-type mice, but not in the PPARα-null mice. Although PPARα was related to testosterone level in serum of male mice, DEHP also decreased the level in wild-type mice, not in the PPARα-null mice. These results suggest that the reproductive effect of DEHP and effect on testosterone level in serum are closely related to the expression of PPARα. Phthalic acid esters other than DEHP induced PPARα dependently on the lipid solubility. 2,4-Dichlorophenoxyacetic acid, one of herbicides, induced PPARα and decreased testosterone level in male mice, which is due, in part, to downregulate cholesterol-synthetic enzymes.We also measured DEHP concentration in meals including coffee or tea of 16 persons, and then calculated the total intake per day. DEHP was found in all samples, and the concentration levels were 30〜370ug/kg, and the average was 124ug/kg, which was estimated at 70〜1200ug/day (average 320ug/day).