A comparison of the pharmacokinetics of perfluorobutanesulfonate (PFBS) in rats, monkeys, and humans

Abstract

Materials derived from perfluorobutanesulfonyl fluoride (PBSF, C 4F 9SO 2F) have been introduced as replacements for eight-carbon homolog products that were manufactured from perfluorooctanesulfonyl fluoride (POSF, C 8F 17SO 2F). Perfluorobutanesulfonate (PFBS, C 4F 9SO 3 −) is a surfactant and potential degradation product of PBSF-derived materials. The purpose of this series of studies was to evaluate the pharmacokinetics of PFBS in rats, monkeys, and humans, thereby providing critical information for human health risk assessment. Studies included: (1) intravenous (i.v.) elimination studies in rats and monkeys; (2) oral uptake and elimination studies in rats; and (3) human serum PFBS elimination in a group of workers with occupational exposure to potassium PFBS (K +PFBS). PFBS concentrations were determined in serum (all species), liver (rats), urine (all species), and feces (rats). In rats, the mean terminal serum PFBS elimination half-lives, after i.v. administration of 30 mg/kg PFBS, were: males 4.51 ± 2.22 h (standard error) and females 3.96 ± 0.21 h. In monkeys, the mean terminal serum PFBS elimination half-lives, after i.v. administration of 10 mg/kg PFBS, were: males 95.2 ± 27.1 h and females 83.2 ± 41.9 h. Although terminal serum half-lives in male and female rats were similar, without statistical significance, clearance (CL) was significantly greater in female rats (469 ± 40 mL/h) than male rats (119 ± 34 mL/h) with the area under the curve (AUC) significantly larger in male rats (294 ± 77 μg·h/mL) than female rats (65 ± 5 μg·h/mL). These differences were not observed in male and female monkeys. Volume of distribution estimates suggested distribution was primarily extracellular in both rats and monkeys, regardless of sex, and urine appeared to be a major route of elimination. Among 6 human subjects (5 male, 1 female) followed up to 180 days, the geometric mean serum elimination half-life for PFBS was 25.8 days (95% confidence interval 16.6–40.2). Urine was observed to be a pathway of elimination in the human. Although species-specific differences exist, these findings demonstrate that PFBS is eliminated at a greater rate from human serum than the higher chain homologs of perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonate (PFHxS). Thus, compared to PFOS and PFHxS, PFBS has a much lower potential for accumulation in human serum after repeated occupational, non-occupational (e.g., consumer), or environmental exposures.