title: Propylene glycol monomethyl ether (PGME): inhalation toxicity and carcinogenicity in Fischer 344 rats and B6C3F1 mice.
abstract: A series of inhalation studies with propylene glycol monomethyl ether (PGME) vapor were undertaken to characterize its subchronic toxicity in mice and chronic toxicity/oncogenicity in rats and mice. Groups of male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 300, 1,000, or 3,000 ppm vapor from 1 week to 2 years. Primary treatment-related effects included: initial sedation of animals exposed to 3,000 ppm and its subsequent resolution correlating with induction of hepatic mixed function oxidase activity and S-phase DNA synthesis; elevated mortality in high-exposure male rats and mice (chronic study); elevated deposition of alpha2u-globulin (alpha2U-G) and associated nephropathy and S-phase DNA synthesis in male rat kidneys; accelerated atrophy of the adrenal gland X-zone in female mice (subchronic study only); and increased occurrence and/or severity of eosinophilic foci of altered hepatocytes in male rats. No toxicologically relevant statistically significant increases in neoplasia occurred in either species. A numerical increase in the incidence of kidney adenomas occurred in intermediate-exposure male rats; however, the association with alpha2U-G nephropathy, a male rat specific effect, indicated a lack of relevance for human risk assessment.
authors.affiliation: Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674, USA. pjspencer@dow.com
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Spencer
authors.forename: James W
authors.initials: JW
authors.lastname: Crissman
authors.forename: William T
authors.initials: WT
authors.lastname: Stott
authors.forename: Richard A
authors.initials: RA
authors.lastname: Corley
authors.forename: Frank S
authors.initials: FS
authors.lastname: Cieszlak
authors.forename: Alan M
authors.initials: AM
authors.lastname: Schumann
authors.forename: Jerry F
authors.initials: JF
authors.lastname: Hardisty
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000280:Administration, Inhalation; D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology; D011409:Propylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D016196:S Phase / Q000187:drug effects / Q000502:physiology
chemical_list: D000510:Alpha-Globulins; D002273:Carcinogens; D011409:Propylene Glycols; C013803:alpha 2u globulin; C005216:propylene glycol methyl ether; D004247:DNA; D006899:Mixed Function Oxygenases