title: Effect of exposure concentration on the disposition of inhaled butoxyethanol by F344 rats.
abstract: The glycol ethers are a class of solvents widely used due to their range of vapor pressures and miscibility in aqueous and organic media. Butoxyethanol (BE) causes anemia and lowered hematocrits in rats due to direct hemolysis of red blood cells. Exposure to BE is most likely to occur by dermal contact or by inhalation. In this paper, we report the uptake, metabolism, and excretion of BE following 6-hr exposure at different inhaled concentrations. The uptake and metabolism of BE were essentially linear up to 438 ppm. The majority of the inhaled butoxy-[14C]ethanol was eliminated in the urine with butoxyacetic acid (BAA) being the major urinary metabolite, accompanied by lesser amounts of ethylene glycol and BE glucuronide. A small proportion (5-8%) of the retained BE was exhaled as 14CO2. Most (greater than 80%) of the [14C]BE-derived material in blood was in the plasma. BAA was the major metabolite of BE in plasma. Ratios of ethylene glycol to BAA in plasma were higher than those in urine. The BE-derived 14C in plasma rapidly became associated with the acid-precipitable (protein) fraction, probably due to binding of metabolites to proteins or incorporation of the BE metabolites into the carbon pool. These results indicate that, in rats, overall metabolism of BE to BAA, the hemolytic metabolite, was linearly related to the exposure concentration up to a concentration that caused severe toxicity (438 ppm). Assuming that the toxicity of inhaled BE is directly proportional to the formation of BAA, the toxicity of inhaled BE can be expected to be linearly related to the exposure concentration up to exposure concentrations that cause mortality.
authors.affiliation: Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
authors.forename: P J
authors.initials: PJ
authors.lastname: Sabourin
authors.forename: M A
authors.initials: MA
authors.lastname: Medinsky
authors.forename: L S
authors.initials: LS
authors.lastname: Birnbaum
authors.forename: W C
authors.initials: WC
authors.lastname: Griffith
authors.forename: R F
authors.initials: RF
authors.lastname: Henderson
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005026:Ethylene Glycols / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000187:drug effects; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D005026:Ethylene Glycols; C017096:n-butoxyethanol