Two generation reproductive and developmental toxicity following subchronic exposure of pubescent male mice to di(2-ethylhexyl)phthalate

Abstract

Di-(2-ethylhexyl)phthalate (DEHP) is widely present in the human environment. The study aimed at the investigation of potential genotoxic effects induced by subchronic exposure to DEHP in germ cells of male mice in the first period of puberty, and to check if the transmission of mutation to the next generation via the sperm is possible. 8-weeks exposure to 2,000 mg/kg and 8,000 mg/kg of DEHP diminished sperm count and quality, leading to a reduced percentage of pregnant females mated to exposed males. A slight increase in the frequency of prenatal deaths and dominant lethal mutations, as well as a significantly increased percentage of abnormal skeletons among the F1 offspring of males exposed to 8,000 mg/kg of DEHP, were observed. Exposure of the fathers did not cause a delay in the postnatal development of the offspring, except for fur development in the group of 8,000 mg/kg of DEHP. Gametes of male offspring of exposed fathers showed reduced motility. The results may suggest that diminished spermaozoa quality induced by DEHP may be coincidental with mutations leading to intrauterine deaths and skeletal abnormalities in the offspring