title: Concentrations of the propylene metabolite propylene oxide in blood of propylene-exposed rats and humans--a basis for risk assessment.
abstract: Propylene (PE) was not carcinogenic in long-term studies in rodents. However, its biotransformation to propylene oxide (PO) raises questions about a carcinogenic risk. PO alkylates macromolecules, is a direct mutagen, and caused tumors in rodents at high concentrations. In order to acquire knowledge on the species-specific PO concentrations in blood resulting from PE exposure, we exposed male Fischer 344/N rats in closed exposure chambers to constant PE concentrations, between 20.1 and 3000 ppm (7 h at least), and four male volunteers to mean constant PE concentrations of 9.82 and 23.4 ppm (180 min) in inhaled air. In the animal experiments, PE and PO were measured in the chamber atmosphere, PE by gas chromatography with flame ionization detection (GC/FID), PO by GC/FID or GC with mass-selective detection (GC/MSD). In the human studies, PE was measured in inhaled and exhaled air by GC/FID. PO was quantified by GC/MSD from exhaled breath collected in gasbags. Blood concentrations of PO were calculated based on the measured PO concentrations in air using the blood-to-air partition coefficients of 60 (rat) and 66 (human). In rats, PO blood concentrations ranged from 53 nmol/l at 20.1 ppm PE to 1750 nmol/l at 3000 ppm PE. In humans, mean blood concentrations of PO were 0.44 and 0.92 nmol/l at mean PE concentrations of 9.82 and 23.4 ppm, respectively. These findings should be taken into consideration when estimating the carcinogenic risk of PE to humans based on carcinogenicity studies in PE- or PO-exposed rats.
authors.affiliation: Institute of Toxicology, Helmholtz Zentrum München, D-85764 Neuherberg, Germany. johannes.filser@helmholtz-munchen.de
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Filser
authors.forename: Christoph
authors.initials: C
authors.lastname: Hutzler
authors.forename: Florian
authors.initials: F
authors.lastname: Rampf
authors.forename: Winfried
authors.initials: W
authors.lastname: Kessler
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Faller
authors.forename: Edgar
authors.initials: E
authors.lastname: Leibold
authors.forename: Christian
authors.initials: C
authors.lastname: Pütz
authors.forename: Stefan
authors.initials: S
authors.lastname: Halbach
authors.forename: György A
authors.initials: GA
authors.lastname: Csanády
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000475:Alkenes / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D001944:Breath Tests; D002273:Carcinogens / Q000378:metabolism*; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000097:blood*; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008875:Middle Aged; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D013045:Species Specificity
chemical_list: D000475:Alkenes; D002273:Carcinogens; D004852:Epoxy Compounds; C013658:propylene; C009068:propylene oxide