Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

•Emix increased mammary outgrowth in prepubertal female mammary glands.•Mmp3 may be a potential marker for increased mammary outgrowth.•Duct hyperplasia in male mammary glands was seen in Amix, Emix and TotalMix groups.•Hypertrophy was seen in mammary glands of males exposed perinatally to paracetamol.

Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action.Pregnant rat dams were exposed during gestation and lactation to mixtures of environmentally relevant EDCs with estrogenic, anti-androgenic or dissimilar modes of action (TotalMix) of 100-, 200- or 450-fold high end human intake estimates. Mammary glands of prepubertal and adult female and male offspring were examined.Oestrogens increased mammary outgrowth in prepubertal females and the mRNA level of matrix metalloproteinase-3, which may be a potential biomarker for increased outgrowth. Mixtures of EDCs gave rise to ductal hyperplasia in adult males. Adult female mammary glands of the TotalMix group showed morphological changes possibly reflecting increased prolactin levels. In conclusion both estrogenic and anti-androgenic chemicals given during foetal life and lactation affected mammary glands in the offspring.