Derivation of Provisional Chronic Oral Toxicity Values (PCOTV) for Novel Short-Chain PFAS Congeners

Short-chain PFAS congeners containing five carbons or less were introduced as replacements for longer chain (more than six carbons) legacy congeners, such as PFOA and PFOS, due to their lower bioaccumulation potential and reduced toxicity. However, toxicological data are limited for the newer short-chain congeners. Although some experts have suggested that PFAS can be treated as a single class with similar toxicity characteristics, it has been demonstrated that congener potency varies by orders of magnitude, even within groups of similar congeners. Using the available toxicological data, we derived provisional chronic oral toxicity values (PCOTVs) for short-chain congeners that can be used in future risk assessment evaluations. A literature review of in vivo animal toxicity studies identified two mouse studies of short-chain congeners; when necessary, benchmark dose (BMD) modeling was used to determine the point of departure. PCOTVs and drinking water equivalent levels (DWELs) were derived for perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-4-methoxybutanioc acid (PFMOBA), 2,2,3,3-(trifluoromethoxy) propionic acid (PFMOPrA), perfluoro-(3,5-dioxahexanoic) acid (PFO2HxA), and perfluoro-(3,5,7-trioxaoctanoic) acid (PFO3OA). The PCOTVs ranged from 0.00011 mg/kg/day for PFMOAA to 0.00072 mg/kg/day for PFMOPrA. The DWELs were calculated using the default 20% relative source contribution (RSC) and the United States Environmental Protection Agency (USEPA) recommended ceiling of 80% RSC. The lower-bound (20% RSC) and upper-bound (80% RSC) DWELs for PFMOAA, PFMOBA, PFMOPrA, PFO2HxA, and PFO3OA were 1444-5778 ppt, 8349-33,396 ppt, 9609-38,436, 5867-23,467, and 5867-23,467, respectively. Given the lack of formal environmental standards, the PCOTVs and DWELs derived in this analysis may be helpful for future investigations involving short-chain PFAS congeners.