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 (PVC) and other polymers, has been orally administered to female Wistar rats with four doses (150, 475, 780 and 1500 mg/kg body weight/day) for 3 consecutive days. Metabolites recovered in urines were analysed by gas chromatography-mass spectrometry (GC-MS) after 24, 48 and 72 hours. Six metabolites were identified. Mono-n-butyl phthalate (MBuP) and mono-n-benzyl phthalate (MBeP) represented respectively 29-34% and 7-12% of the total recovered metabolites. Hippuric acid, the main metabolite of benzoic acid, represented the second major metabolite (51-56%). Phthalic acid, benzoic acid and an omega-oxidized metabolite of MBuP were also recovered in urine but in small quantities. BBP was never identified in urines. Total urinary metabolites recovery represented 56% of the dose administered in the first 24 hours. However, 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 proportions for the two lowest doses. Discrepancy in metabolites quantities expressed 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 recovery has significantly increased at day 3. Metabolic profile of BBP in female rats has been established. The aim of the present study is to identify further the active(s) agent(s) involved in the BBP malformations and teratogenic effects.
Nativelle
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Laboratoire de Toxicologie, ENSBANA, Dijon, France.
Picard
K
K
Valentin
I
I
Lhuguenot
J C
JC
Chagnon
M C
MC
D000818:Animals; D003978:Diazomethane; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006626:Hippurates / Q000652:urine; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010795:Phthalic Acids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D010968:Plasticizers / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000493:pharmacokinetics*
D006626:Hippurates; D010795:Phthalic Acids; D010968:Plasticizers; D013723:Teratogens; C103325:mono-benzyl phthalate; D003978:Diazomethane; C030514:hippuric acid; C027561:butylbenzyl phthalate; C028577:monobutyl phthalate