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Hprt mutant frequencies in splenic T‐cells of male F344 rats exposed by inhalation to propylene
Author(s) -
Walker Dale M.,
Seilkop Steven K.,
Scott Bobby R.,
Walker Ver E.
Publication year - 2004
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20020
Subject(s) - mutagen , inhalation , hypoxanthine guanine phosphoribosyltransferase , inhalation exposure , carcinogen , mutant , spleen , chemistry , toxicology , medicine , microbiology and biotechnology , zoology , immunology , biology , biochemistry , anesthesia , gene
Abstract 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 (M f s) in a preliminary mutant manifestation study using CCP treatment. Hprt M f s were measured via the T‐cell cloning assay, which was performed without knowledge of the animal treatment groups. Mean Hprt M f s were significantly increased over control values (mean M f = 5.24 ± 1.55 (SD) × 10 −6 ) in CPP‐treated rats (10.37 ± 4.30 × 10 −6 , P = 0.007). However, Hprt M f s in propylene‐exposed rats were not significantly increased over background, with mean M f s of 4.90 ± 1.84 × 10 −6 ( P = 0.152), 5.05 ± 3.70 × 10 −6 ( P = 0.895), and 5.95 ± 2.49 ×10 −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. Environ. Mol. Mutagen. 43:265–272, 2004. © 2004 Wiley‐Liss, Inc.