Toxicokinetics of propylene glycol mono-t-butyl ether following intravenous or inhalation exposure in rats and mice.
Propylene glycol mono-t-butyl ether (PGMBE) is a widely used solvent in industry and in consumer products, posing a potential for human exposure via inhalation or dermal routes. Toxicokinetic studies were conducted on F344/N rats and B6C3F1 mice of both sexes to evaluate single or repeated dose, species, and/or sex differences in PGMBE elimination kinetics following intravenous or inhalation exposure. In the first study, rats and mice received a single intravenous dose of 15 or 200 mg PGMBE/kg and serial blood samples were collected and analyzed for PGMBE. In the second study, rats and mice received a single 6-h whole-body inhalation exposure to 75, 300, or 1200 ppm PGMBE and serial blood samples were collected and analyzed for PGMBE. In the third study, rats and mice received whole-body inhalation exposures to 75, 300, or 1200 ppm PGMBE for 6 h/day, 5 days/wk for 14 (rats) or 16 (mice) wk. Serial blood samples were analyzed for PGMBE after 2, 6, 14 (rats), and 16 (mice) wk on study. Urine samples were also collected for 16 h postexposure and analyzed for creatinine and PGMBE sulfate and PGMBE glucuronide conjugates. These studies revealed that: (1) PGMBE was eliminated from blood following concentration-dependent nonlinear kinetics in both species; (2) saturable Michaelis-Menten kinetics were clearly exhibited following a single inhalation exposure at 1200 ppm, but were less obvious following repeated exposures; (3) mice were more efficient in eliminating PGMBE from blood at lower exposure concentrations (i.e., < or = 300 ppm), but at exposure concentrations potentially exceeding their elimination capacity, mice had a greater concentration-dependent decrease in PGMBE elimination than rats; (4) there were minimal but consistent sex differences in PGMBE elimination profiles for rats, with females having higher blood concentrations at all exposure concentrations and sampling times; and (5) sex differences in PGMBE elimination were in part associated with differences in urinary excretion of PGMBE metabolites.
Dill
Jeffrey
J
Battelle, Toxicology Northwest, Richland, Washington 99352, USA. dillj@battelle.org
Fuciarelli
Alfred
A
Lee
Kyeonghee
K
Mellinger
Kathleen
K
Burka
Leo
L
Roycroft
Joseph
J
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008658:Inactivation, Metabolic; D019570:Inhalation Exposure; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011409:Propylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013045:Species Specificity
D000393:Air Pollutants; D011409:Propylene Glycols; C005216:propylene glycol methyl ether