There are concerns about human health effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in drinking water. A provisional target value has been notified for each or combined PFOS and PFOA as 50 ng/L in drinking water in Japan. We previously reported the results of our derived target values for PFOA, and we here report the results for PFOS. We selected a 2-generation study as a key study (same study for the current provisional target value), in which PFOS was orally administered to male and female rats at 0.1, 0.4, 1.6 and 3.2 mg/kg/day, and reductions in parental weight gain and feed consumption were observed at 0.4 mg/kg/day. The no observed adverse effect level of 0.1 mg/kg/day was used as the point of departure (POD). Species differences were reported for pharmacokinetics property of PFOS, and the average serum level for the POD was assessed using a rat PBPK model concerning renal reabsorption as 7.3 mg/L. The human equivalent doses (HEDs) were calculated with publicly available human half-life data of PFOS (1.7-5.4 years), and reference doses were derived with the HEDs and an uncertainty factor of 30 (intraspecies:10, interspecies:3) as 2.0 × 10-5 to 6.3 × 10-5 mg/kg/day. The target value was calculated from 50 to 158 ng/L in drinking water. Our results support the current provisional target value for PFOS, 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 (22LA1007).
