Propylene glycol monomethyl ether acetate (PGMEA) metabolism, disposition, and short-term vapor inhalation toxicity studies.
Male Fischer 344 rats were given a single po dose of approximately 8.7 mmol/kg of [1-14C]propylene glycol monomethyl ether acetate (PGMEA) or exposed to 3000 ppm [1-14C]PGMEA for 6 hr. After dosing, expired air, excreta, and tissues were analyzed for 14C activity, and metabolites in urine were isolated and identified. Approximately 64% of the administered 14C activity was eliminated as 14CO2 and about 24% was excreted in urine within 48 hr after a single po dose of radiolabeled PGMEA. Similarly, 53% was eliminated as 14CO2 and 26% was excreted in urine within 48 hr after the inhalation exposure. Propylene glycol, propylene glycol monomethyl ether (PGME), and the sulfate and glucuronide conjugates of PGME were identified as urinary metabolites after po dosing, as well as after inhalation exposure to PGMEA. The urinary metabolite profile and disposition of [14C]PGMEA were nearly identical to results previously obtained with propylene glycol monomethyl ether (PGME), indicating that PGMEA is rapidly and extensively hydrolyzed to PGME in vivo. A short-term vapor inhalation toxicity study in which male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 300, 1000, or 3000 ppm PGMEA confirmed that there were no substantial differences in the systemic effects of PGMEA as compared to PGME. However, histopathologic examination did reveal changes in the olfactory portions of the nasal mucosa of rats and mice exposed to PGMEA, which may be related to acetic acid resulting from hydrolysis of PGMEA in the nasal epithelium.
D000818:Animals; D001769:Blood / Q000187:drug effects; D002250:Carbon Radioisotopes; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009297:Nasal Mucosa / Q000187:drug effects; D011409:Propylene Glycols / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012220:Rhinitis / Q000139:chemically induced; D014018:Tissue Distribution; D014835:Volatilization
D002250:Carbon Radioisotopes; D011409:Propylene Glycols; C005216:propylene glycol methyl ether