Inhalation toxicology and carcinogenesis studies of propylene glycol mono-t-butyl ether in rats and mice.
Propylene glycol mono-t-butyl ether (PGMBE) is used as a solvent in a variety of commercial applications. Male and female F344/N rats and B6C3F(1) mice were exposed to PGMBE by whole-body inhalation for 2 or 14 weeks (0, 75, 150, 300, 600, or 1200 ppm) or 2 years (0, 75, 300, or 1200 ppm); male NBR rats were exposed for 2 weeks. The kidney and the liver were targets of PGMBE toxicity in rats. Renal lesions suggestive of alpha(2u)-globulin nephropathy were observed in male F344/N, in the 2 and 14-week studies, no kidney lesions were seen in NBR rats. In the 2-year study, male rats displayed exposure-related nonneoplastic lesions in the kidney, and may have shown marginal increases in tubular neoplasms. In the liver, the incidences of hepatocellular adenomas occurred with a positive trend in male rats, and may have been related to PGMBE exposure. In mice of both sexes, the major target of PGMBE toxicity was the liver. In the 2-week study, liver weights and in the 14-week study, liver weights and the incidences of centrilobular hypertrophy were increased. In the 2-year study, the incidences of exposure-related hepatocellular adenoma, adenoma or carcinoma combined, and hepatoblastoma occurred with a positive trend, and were significantly increased in 1200 ppm groups. In summary, exposure to PGMBE resulted in nonneoplastic lesions of the kidney characteristic of alpha(2u)-globulin nephropathy, and may have increased renal tubular neoplasms in male rats. Exposure to PGMBE also produced increases in hepatic tumors in male and female mice.
Doi
Adriana M
AM
National Institute of Environmental Health Sciences, 79 Alexander Dr., Mail Drop EC-34, Research Triangle Park, NC 27709, USA. doi@niehs.nih.gov
Roycroft
Joseph H
JH
Herbert
Ronald A
RA
Haseman
Joseph K
JK
Hailey
James R
JR
Chou
Billy J
BJ
Dill
Jeffrey A
JA
Grumbein
Sondra L
SL
Miller
Rodney A
RA
Renne
Roger A
RA
Bucher
John R
JR
D018248:Adenoma, Liver Cell / Q000139:chemically induced / Q000473:pathology; D000280:Administration, Inhalation; D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D018197:Hepatoblastoma / Q000139:chemically induced / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000633:toxicity; D011409:Propylene Glycols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D000510:Alpha-Globulins; D002273:Carcinogens; D009153:Mutagens; D011409:Propylene Glycols; D012997:Solvents; C013803:alpha 2u globulin; C487282:propylene glycol mono-t-butyl ether