Citation:

Conley, J., C. Lambright, N. Evans, E. MedlockKakaley, AND E. Gray. Exposure to a mixture of PFOA and PFOS during pregnancy produces cumulative effects on F1 bodyweight, liver weight, and survival in the Sprague-Dawley rat. FLUOROS Global 2021, Providence, RI, October 03 - 07, 2021.

Impact/Purpose:

Per- and poly-fluoroalkyl substance (PFAS) health effects is a critical research area due to issues associated with environmental persistence, widespread occurrence, biological half-life, toxicity, and nearly ubiquitous human and environmental exposure.  Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two of the most widely detected and extensively studied PFAS; however the literature does not contain a single published study addressing a hypothesis of additivity for these two compounds in laboratory animals.  OW requested and partially funded the series of experiments described in the present abstract, which address the combined developmental toxicity of PFOA and PFOS in the Sprague-Dawley rat. The combination of PFOA and PFOS clearly produced cumulative adverse effects from combined exposure. This is the first data generated from a rigorous experimental examination of the combined effects of PFOA and PFOS in a laboratory animal model. The data from this project will be highly useful to the USEPA Office of Water, who formally requested this study, in their effort to update the PFOA and PFOS Health Effect Support Documents, determine MCLGs, and formalize NPDWRs.  Further, other state and international health-based regulatory agencies will benefit from clear evidence of combined toxicity of PFOA and PFOS. The apical effect data along with the additional data streams that will be investigated as part of these experiments will be highly instructive in furthering the characterization of adverse outcome pathways relevant to the developmental toxicity of PFAS.  The in-life phase of the experiments is completed, however multiple analyses will take place on collected samples in the coming months, including histopathology of liver and kidney, liver gene expression, analytical chemistry of test chemicals, and maternal metabolomics.  These key events will further the scientific knowledge of how PFOA and PFOS (among other PFAS) perturb maternal and feta/neonatal physiology during pregnancy.

Description:

Human and environmental monitoring studies have demonstrated that exposure to more than a single per- and polyfluoroalkyl substance (PFAS) frequently occurs and numerous adverse effects from individual exposure studies have been described in laboratory animals.  Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are the two most commonly detected and studied PFAS, however a study of their cumulative in vivo effects has not been conducted.  Here we performed a series of oral exposure experiments in pregnant Sprague-Dawley rats (dosed GD8 – PND2) beginning with single chemical dose response evaluations of PFOA (10-250 mg/kg/d) and PFOS (0.1-5 mg/kg/d), followed by a binary mixture study in which we repeated a dose response of PFOA (3-80 mg/kg/d) but with a fixed dose of PFOS (2 mg/kg/d) added to each PFOA dose.  Numerous significant apical effects from each chemical and the mixture were identified including reduced maternal gestational weight gain, reduced pup body weight, reduced pup viability, and increased maternal and pup liver weight.  As a clear demonstration of cumulative effects, isolated exposure to 62.5 mg/kg PFOA and 2 mg/kg PFOS produced 12.2±7.2% and 8.2±5.9% post-implantation loss (PIL) by PND2, respectively; while a mixture of the two (62.5 mg/kg PFOA+2 mg/kg PFOS) produced 65.5±15% PIL.  Further, the addition of PFOS significantly (p<0.0001) shifted the PFOA dose response curve towards effects at lower doses for pup bodyweight and maternal and pup liver weights.  Study is on-going but preliminary data indicate additive effects of combined exposure to PFOA and PFOS.  Abstract does not necessarily reflect USEPA views or policy.  

Record Details: