US EPA

2215381 

Journal Article 

Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters 

Isling, LK; Boberg, J; Jacobsen, PR; Mandrup, KR; Axelstad, M; Christiansen, S; Vinggaard, AM; Taxvig, C; Kortenkamp, A; Hass, U 

2014 

1 

Reproduction
ISSN: 1470-1626
EISSN: 1741-7899 

147 

4 

465-476 

English 

24287426 

10.1530/REP-13-0448 

WOS:000334287700015 

This study examined late life effects of perinatal exposure of rats to a mixture of endocrine disrupting contaminants. Four groups of 14 time-mated Wistar rats were exposed by gavage from gestation day 7 to pup day 22 to a mixture of 13 anti-androgenic and estrogenic chemicals including phthalates, pesticides, UV-filters, bisphenol A, parabens and the drug paracetamol. The groups received vehicle (control), a mixture of all 13 chemicals at 150-times (TotalMix150) or 450-times (TotalMix450) high end human exposure, or a 450-times mixture of 9 predominantly anti-androgenic chemicals (AAMix450). Onset of puberty and estrous cyclicity at 9 and 12 months of age was assessed. Significantly fewer females showed regular estrus cyclicity at 12 months of age in the TotalMix450 and AAMix450 groups compared to controls. In 19 months old male offspring, epididymal sperm counts were lower than controls and in ventral prostate, an over-representation of findings related to hyperplasia was observed in exposed groups compared to controls particularly in the group dosed with anti-androgens. A higher incidence of pituitary adenoma at 19 months of age was found in males and females in the AAMix450 group. Developmental exposure of rats to the highest dose of a human relevant mixture of endocrine disrupters induced adverse effects late in life manifested as earlier female reproductive senescence, reduced sperm counts, higher score for prostate atypical hyperplasia and higher incidence of pituitary tumors. These delayed effects highlight the need for further studies on the role of endocrine disrupters in hormone-related disorders in aging humans.