Inhalation toxicology and carcinogenesis studies of propylene glycol mono- t-butyl ether in rats and mice

• Published in: Toxicology (Amsterdam) 2004-06, Vol.199 (1), p.1-22
• Main Authors: Doi, Adriana M, Roycroft, Joseph H, Herbert, Ronald A, Haseman, Joseph K, Hailey, James R, Chou, Billy J, Dill, Jeffrey A, Grumbein, Sondra L, Miller, Rodney A, Renne, Roger A, Bucher, John R
• Format: Article
• Language: English
• Subjects: Adenoma, Liver Cell - chemically induced; Adenoma, Liver Cell - pathology; Administration, Inhalation; Alpha-Globulins - metabolism; Animals; Biological and medical sciences; Carcinogenicity Tests; Carcinogens - administration & dosage; Carcinogens - toxicity; Carcinoma, Hepatocellular - chemically induced; Carcinoma, Hepatocellular - pathology; Chemical and industrial products toxicology. Toxic occupational diseases; Dose-Response Relationship, Drug; Female; Hepatoblastoma; Hepatoblastoma - chemically induced; Hepatoblastoma - pathology; Hepatocellular adenoma; Hepatocellular carcinoma; Kidney Neoplasms - chemically induced; Kidney Neoplasms - pathology; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Kidney Tubules - pathology; Liver Neoplasms - chemically induced; Liver Neoplasms - pathology; Male; Medical sciences; Mice; Mice, Inbred Strains; Mutagens - toxicity; Propylene Glycols - administration & dosage; Propylene Glycols - toxicity; Rats; Rats, Inbred F344; Renal tubular neoplasm; Salmonella typhimurium - drug effects; Salmonella typhimurium - genetics; Solvent; Solvents; Solvents - administration & dosage; Solvents - toxicity; Toxicology; α 2u-Globulin
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2003.12.020

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 α 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 α 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.