Citation:

Conley, J. Adverse effects of a mixture of 15 pesticides and phthalates on reproductive tract development in the male rat. Endocrine Disrupting Chemicals - North Carolina, Research Triangle Park, NC, February 23, 2018.

Impact/Purpose:

This presentation is an invited talk at the first annual meeting of the Endocrine Disrupting Chemicals - North Carolina (EDC-NC) group being held at the NIEHS. This talk covers our group's most recent experiments involving complex mixtures of anti-androgenic chemicals which target multiple molecular initiating events in the anti-androgen AOP network. Despite multiple mechanisms, our work provides evidence that these chemicals act cumulatively to disrupt male reproductive tract develop even when each chemical is at a dose that would not be expected to produce an effect alone and these effects can be relatively well predicted using dose addition modeling.

Description:

This presentation highlights our "supermix" study which included 15 different environmental anti-androgens (6 pesticides and 9 phthalates) with a dosing structure based on the individual chemical NOAELs. Exposures were conducted in utero (dam oral gavage) during the masculinizing window of gestation with fetal, perinatal, and adult effects evaluated on male and female offspring. Male offspring displayed a reductions in testis gene expression, testis testosterone production, ano-genital distance, and multiple sex accessory tissues. Importantly these effects occurred when the individual chemicals were present at 2-8-fold below their NOAEL values, however dose addition modeling was able to produce accurate estimates of mixture dose response for ano-genital distance reduction and incidence of hypospadias.

Record Details: