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
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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.