A mixture of seven antiandrogens induces reproductive malformations in rats.

摘要: To date, regulatory agencies have not considered conducting cumulative risk assessments for mixtures of chemicals with diverse mechanisms toxicity because it is assumed that the will act independently and individual chemical doses are additive. However, this assumption supported by new research addressing joint effects disrupt reproductive tract development in male rat disrupting androgen signalling pathway via [i.e. receptor (AR) antagonism vs. inhibition synthesis foetal testis]. In study, pregnant rats were exposed to four dilutions a mixture containing vinclozolin, procymidone, linuron, prochloraz, benzyl butyl phthalate, dibutyl phthalate diethylhexyl during period sexual differentiation offspring assessed on hormone sensitive endpoints including: anogenital distance, infant areolae retention tissue weights malformations. The ratio was based upon each chemical's ED(50) inducing malformations (hypospadias or epididymal agenesis). observed responses from compared predicted generated toxic equivalency approach models dose addition, response addition integrated addition. As hypothesized, we found alter disrupted induced cumulative, dose-additive manner. provided best fit even though do common cellular mechanism action. current framework needs consider results, including those presented herein, which indicate tissues manner irrespective specific toxicity.