title: Effect of sorbic acid administration on urinary trans,trans-muconic acid excretion in rats exposed to low levels of benzene.
abstract: Trans,trans-muconic acid (t,t-MA) is a biomarker of benzene exposure reflecting metabolic activation to trans,trans-muconaldehyde. t,t-MA background urinary levels are highly variable, thus limiting its use to exposure monitoring of levels over 1 ppm of benzene. Actually, sorbic acid (SA) is known to influence background excretion of t,t-MA in man, but only a few examples suggest that SA ingestion can enhance t,t-MA levels occurring together with benzene exposure. In this study, the effect of SA was investigated in benzene-exposed male Sprague-Dawley rats exposed to 1 ppm benzene for 6 h. Exposed animals had a 24-h urinary t,t-MA excretion higher than that observed in non-exposed animals (87+/-13 microg/kg vs 19+/-3 microg/kg body weight). The oral dose of 8 mg/kg body weight SA had no effect on urinary t,t-MA both in control and in benzene-exposed rats. Increases of t,t-MA levels in urine occurred at SA doses of 50-200 mg/kg body weight, and co-exposure to benzene and SA (50 and 100 mg/kg body weight) produced additive enhancement of t,t-MA excretion. These data demonstrate the dose-response relationship between SA administration and t,t-MA excretion. Our study showed that SA ingestion at doses equal to or greater than 50 mg/kg body weight significantly affects the t,t-MA urinary levels in rats exposed to 1 ppm of benzene for 6 h. These data support the conclusion that in man t,t-MA is not suitable for biomonitoring of low levels of benzene exposure.
authors.affiliation: Laboratory for Pharmacokinetics and Analytical Toxicology, Clinical Toxicology Division, Department of Internal Medicine, University of Pavia, Via Brodolini 7, 27028 San Martino Siccomario, Italy. gmarrubini@fsm.it
authors.forename: G
authors.initials: G
authors.lastname: Marrubini
authors.forename: T
authors.initials: T
authors.lastname: Coccini
authors.forename: L
authors.initials: L
authors.lastname: Maestri
authors.forename: L
authors.initials: L
authors.lastname: Manzo
mesh_terms: D000818:Animals; D001554:Benzene / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods; D005520:Food Preservatives / Q000008:administration & dosage*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013011:Sorbic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics*
chemical_list: D015415:Biomarkers; D005520:Food Preservatives; C005939:muconic acid; D001554:Benzene; D013011:Sorbic Acid