There are concerns about human health effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in drinking water. In April 2020, a provisional target value was notified for combined PFOS and PFOA as 50 ng/L in drinking water in Japan. We assessed both substances and here report the results for PFOA. After reviewing toxicological data of PFOA, we selected a prenatal toxicity study as a key study, in which PFOA was orally administered to pregnant mice for 17 days, and developmental toxicity effects were observed at 1 mg/kg/day. The lowest observed adverse effect level (LOAEL) of 1 mg/kg/day was used as the point of departure (POD). Species differences were reported for pharmacokinetics property of PFOA, and the average serum level for POD was assessed using a PBPK model concerning renal reabsorption as 38.9 mg/L. The human equivalent values (HEDs) were calculated with publicly available human half-life data (0.5-14.9 years), and reference doses were derived with the HEDs and an uncertainty factor of 300 (intraspecies:10, interspecies:3, LOAEL:10) as 2.8× 10-6 to 8.4× 10-5 mg/kg/day (30-fold difference). By using more appropriate human half-lives for evaluation, the target value was calculated from 45 to 70 ng/L in drinking water. Our results support the current provisional target value for PFOA, but by accumulating knowledge such as human half-life and epidemiological information in the future, more appropriate target values can be obtained. This study was supported by a Health and Labour Sciences Research Grant (19LA1005) from the MHLW, Japan.
