Metabolism of n-butyl benzyl phthalate in the female Wistar rat. Identification of new metabolites

n-Butyl benzyl phthalate (BBP), a plasticizer used in polyvinylchloride (PV C) and other polymers, has been orally administered to female Wistar rats w ith four doses (150, 475, 780 and 1500 mg/kg body weight/day) for 3 consecu tive days. Metabolites recovered in urines were analysed by gas chromatogra phy-mass spectrometry (GC-MS) after 24, 48 and 72 hours. Six metabolites we re identified. Mono-n-butyl phthalate (MBuP) and mono-n-benzyl phthalate (M BeP) represented respectively 29-34% and 7-12 % of the total recovered meta bolites. Hippuric acid, the main metabolite of benzoic acid, represented th e second major metabolite (51-56%). Phthalic acid, benzoic acid and an omeg a-oxidized metabolite of MBuP were also recovered in urine but in small qua ntities. BBP was never identified in urines. Total urinary metabolites reco very represented 56% of the dose administered in the first 24 hours. Howeve r, total recovery decreased when the dose increases (43% at 780 mg/kg body weight/day, only 30% at 1500 mg/kg body weight/day). Whatever the time was, BBP metabolites recovered in urines were all present and in the same propo rtions for the two lowest doses. Discrepancy in metabolites quantities expr essed as percentages of the dose observed in urine of rat treated with the highest BBP dose disappeared with time as MBuP, MBeP and hippuric acid reco very has significantly increased at day 3. Metabolic profile of BBP in fema le rats has been established. The aim of the present study is to identify f urther the active(s) agent(s) involved in the BBP malformations and teratog enic effects. (C) 1999 Elsevier Science Ltd. All rights reserved.