In utero exposure to a mixture of the perfluoroalkyl pesticide pyrifluquinazon and dibutyl phthalate disrupt male rat reproductive development in a dose additive manner.

Exposure to chemicals, either individually or in mixtures, during sexual differentiation commonly induce reproductive abnormalities in male rats.  In the current study, pregnant rats were exposed by oral gavage to doses of a mixture of the pesticide pyrifluquinazon (PFQ), which contains a perfluroalkyl-isopropyl side chain, and dibutyl phthalate (DBP) from gestational days 14 to 18.  Both chemicals have been shown individually to disrupt male reproductive tract differentiation in a dose-dependent manner, including reduction of anogenital distance (AGD), androgen-dependent tissue weights and sperm counts, and inducing reproductive malformations via mechanistically diverse pathways. However, the potential joint toxicity associated with co-exposure has not been examined previously.    The study entailed a fixed-ratio dilution design; rats were dosed with 0, 12.5, 25, 50, 75 or 100% of the top dose (100 mg/kg for PFQ and 750 mg/kg for DBP) such that each chemical would contribute equipotently to effects on AGD and other reproductive effects. Further, the dose range was designed so that mixtures interactions, such as synergism, antagonism, or additivity could be interrogated against dose-response associated with the individual chemicals.  Based on the results of the study, the binary mixture reduced AGD, reproductive organ weights and sperm counts and induced reproductive malformations in male rat offspring in an additive manner.  For example, the ED50 for AGD and multiple reproductive tract organ weights in male rats exposed in utero to the mixture were shifted downward by approximately 50% compared to PFQ alone.  These results confirmed our hypothesis that chemicals that disrupt  androgen signaling induce dose-additive male reproductive abnormalities regardless of the mechanistic pathway of toxicity. This is an abstract of a proposed presentation and does not necessarily reflect Agency opinion.  

Impact/Purpose

Abstract for a Oct FLUOROS Global 2021 Meeting on PFAS to be held at the University of Rhode Island.  I presented a poster virtually.  We have in vivo/in utero dose effect  data on the in utero effects of mixing perfluoro isopropyl pesticide with a phthalate on male reproductive development. 

Citation

Gray, E. In utero exposure to a mixture of the perfluoroalkyl pesticide pyrifluquinazon and dibutyl phthalate disrupt male rat reproductive development in a dose additive manner. FLUROS Global 2021-Virtual, Providence, Rhode Island, October 03 - 08, 2021.