Hprt mutant frequencies in splenic T-cells of male F344 rats exposed by inhalation to propylene.
Propylene is a major industrial intermediate and atmospheric pollutant to which humans are exposed by inhalation. In this study, 6-week-old male F344 rates were exposed to 0, 200, 2000, or 10,000 ppm propylene by inhalation for 4 weeks (6 h/day, 5 days/week), and mutant frequencies were determined in the Hprt gene of splenic T-lymphocytes. Twenty milligrams of cyclophosphamide monohydrate (CPP)/kg bw, given on the penultimate day of propylene exposure, was used as a positive control mutagen. Rats (n = 8/group) were necropsied for isolation of T-cells 8 weeks after the last dose, a sampling time that produced peak spleen Hprt mutant frequencies (Mfs) in a preliminary mutant manifestation study using CCP treatment. Hprt Mfs were measured via the T-cell cloning assay, which was performed without knowledge of the animal treatment groups. Mean Hprt Mfs were significantly increased over control values (mean Mf = 5.24 +/- 1.55 (SD) x 10(-6)) in CPP-treated rats (10.37 +/- 4.30 x 10(-6), P = 0.007). However, Hprt Mfs in propylene-exposed rats were not significantly increased over background, with mean Mfs of 4.90 +/- 1.84 x 10(-6) (P = 0.152), 5.05 +/- 3.70 x 10(-6) (P = 0.895), and 5.95 +/- 2.49 x10(-6) (P = 0.500) for animals exposed to 200, 2000, or 10,000 ppm propylene, respectively. No significant increase in F344 rat or B6C3F1 mouse cancer incidence was reported in the National Toxicology Program carcinogenicity studies of propylene across this same exposure range. Taken together, these findings support the conclusion that inhalation exposure of rats to propylene does not cause mutations or cancer.
Walker
Dale M
DM
Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
Seilkop
Steven K
SK
Scott
Bobby R
BR
Walker
Vernon E
VE
D000280:Administration, Inhalation; D000475:Alkenes / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors
D000475:Alkenes; C013658:propylene; D007041:Hypoxanthine Phosphoribosyltransferase