Risk assessment on butylphenol, octylphenol and nonylphenol, and estimated human exposure of alkylphenols from Swedish fish

Present report is a review of the knowledge about the alkylphenols butylphenol (BP), octylphenol (OP) and nonylphenol (NP) with focus on mammalian toxicology and human exposure. The report includes an estimation of human OP and NP intake from Swedish fish. Because of few available data on BP, no conclusion could be drawn about human health risks due to BP-exposure. Alkylphenols have low acute toxicity, OP and NP are not genotoxic and have low carcinogenic potential. OP and NP have been found to be estrogenic in several in vitro and in vivo systems, where OP is most potent of the alkylphenols. The critical effects due to OP exposure are changes in sperm morphology in rats (LOAEL 20 ng/kg bw/day) and increased length of gestation in pigs (LOAEL 0.01 mg/kg bw/day). The critical effect of NP exposure is increased kidney weight (LOAEL 15 mg/kg bw/day). In present study, tolerable daily intake (TDI) of OP is suggested to 0.067 ng/kg bw/day and 33.3 ng/kg bw/day for men and women, respectively. A TDI for NP is suggested to 50 000 ng/kg bw/day. The general population is mainly exposed to OP and NP from food, especially fish, and to some degree drinking water. For NP, migration from food wrapping plastics may also be an important exposure source. In Swedish freshwater fish, median concentration of OP was 0.15 ng/g f.wt in perch, 1.2 ng/g f.wt in artic char and 11 ng/g f.wt in bream from a polluted area. For NP, the median concentration was 0.99 ng/g f.wt in perch and 15 ng/g f.wt in perch from a polluted area. A realistic estimation of average OP intake from fish for the Swedish population is within the range 0.011-0.1 ng/kg bw/day. A mean worst-case intake of OP and NP from Swedish fish is 3.66 and 5.23 ng/kg bw/day, respectively. Based on animal data, the safety margin between intake of OP from fish among Swedish men and exposure levels causing effects on sperm quality in rats is low. However, the data on OP effects on sperm quality in rats are uncertain and the single study on rats needs to be replicated before firm conclusions can be drawn about sperm effects. In rat studies, no adverse effect on reproduction ability has been reported. The risk for negative effects on sperm quality in men due to OP exposure is unknown. Women have higher average OP exposure from fish than men, but are not at risk of exceeding TDI suggested in present study. A MOS (margin of safety) between case intake of OP from fish (45.4 ng/kg bw/day) and LOAEL for increased length of gestation in pigs is about 200. The risk for human effects due to exposure to NP is low, where a MOS between worst-case intake of NP from fish and LOAEL for kidney weight in rats of 15 mg/kg bw /day is about 230 000-fold.