Citation:

Conley, J., C. Lambright, N. Evans, J. Bangma, J. Ford, D. Jenkins-Hill, E. Medlock Kakaley, AND L. Gray. Maternal and neonatal effects of maternal oral exposure to perfluoro-2-methoxyacetic acid (PFMOAA) during pregnancy and early lactation in the Sprague-Dawley rat. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 58(2):1064-1075, (2024). https://doi.org/10.1021/acs.est.3c08559

Impact/Purpose:

Perfluoromethoxyacetic acid (PFMOAA) was reported by EPA chemists Mark Strynar and James McCord to be the PFAS in the highest detected drinking water concentrations in the Cape Fear River region of NC.  Since then studies in China have reported high concentrations in seafood, drinking water, and human breast milk.  As such, evaluation and risk assessment of PFMOAA is one of the highest priorities for NC DEQ and other health based agencies.  However, there is currently only a single mammalian toxicity study published in the literature and no developmental toxicity data.  Here, we exposed pregnant rats during pregnancy and early lactation, similar to our prior PFAS developmental toxicity studies, and report numerous dose responsive adverse effects in maternal animals and pups at all doses tested (10-450 mg/kg/d).  PFMOAA is a very short chain PFAS with a very low molecular weight.  It is generally thought that the smaller PFAS are less toxic than the “long chain” PFAS; however here we observed essentially identical results to those we reported for PFOA and the potency for PFMOAA was about 2-4-fold weaker than PFOA for most endpoints but PFMOAA was more potent that PFOA for effects on liver weight.  These data indicate the need to evaluate risk to human health from documented exposures via drinking water and other matrices. 

Description:

PFMOAA was identified by EPA chemists to be the highest concentration PFAS in eastern NC drinking water samples, however only a single published study exists for this compound.  Further, it is a very short chain PFAS and toxicological questions exist as to the ability for short chain compounds to elicit effects. Perfluoro-2-methoxyacetic acid (PFMOAA) is a short-chain perfluoroalkyl ether carboxylic acid that has been detected at high concentrations (∼10 μg/L) in drinking water in eastern North Carolina, USA, and in human serum and breastmilk in China. Despite documented human exposure there are almost no toxicity data available to inform risk assessment of PFMOAA. Here we exposed pregnant Sprague–Dawley rats to a range of PFMOAA doses (10–450 mg/kg/d) via oral gavage from gestation day (GD) 8 to postnatal day (PND) 2 and compared results to those we previously reported for perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide–dimer acid (HFPO–DA or GenX). Newborn pups displayed reduced birthweight (≥30 mg/kg), depleted liver glycogen concentrations (all doses), hypoglycemia (≥125 mg/kg), and numerous significantly altered genes in the liver associated with fatty acid and glucose metabolism similar to gene changes produced by HFPO–DA. Pup survival was significantly reduced at ≥125 mg/kg, and at necropsy on PND2 both maternal and neonatal animals displayed increased liver weights, increased serum aspartate aminotransferase (AST), and reduced serum thyroid hormones at all doses (≥10 mg/kg). Pups also displayed highly elevated serum cholesterol at all doses. PFMOAA concentrations in serum and liver increased with maternal oral dose in both maternal and F1 animals and were similar to those we reported for PFOA but considerably higher than HFPO–DA. We calculated 10% effect levels (ED10 or EC10) and relative potency factors (RPF; PFOA = index chemical) among the three compounds based on maternal oral dose and maternal serum concentration (μM). Reduced pup liver glycogen, increased liver weights and reduced thyroid hormone levels (maternal and pup) were the most sensitive end points modeled. PFMOAA was ∼3–7-fold less potent than PFOA for most end points based on maternal serum RPFs, but slightly more potent for increased maternal and pup liver weights. PFMOAA is a maternal and developmental toxicant in the rat producing a constellation of adverse effects similar to PFOA and HFPO–DA.

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