Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration

• Published in: Journal of applied toxicology Vol. 23; no. 6; pp. 427 - 436
• Main Authors: Sumner, Susan C. J., Janszen, Derek B., Asgharian, Bahman, Moore, Timothy A., Parkinson, Horace D., Fennell, Timothy R.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-11-2003; Wiley
• Subjects: Administration, Oral; Air Pollutants - blood; Air Pollutants - pharmacokinetics; Air Pollutants - urine; Animals; Biological and medical sciences; Carbon Dioxide - metabolism; Carbon Radioisotopes; Chemical and industrial products toxicology. Toxic occupational diseases; distribution; Feces - chemistry; Female; gavage; inhalation; Inhalation Exposure; Male; Medical sciences; metabolism; metabolism, distribution; Methyl Ethers - administration & dosage; Methyl Ethers - blood; Methyl Ethers - pharmacokinetics; Methyl Ethers - urine; Mice; Pentanols - urine; Rats; Sex Factors; Species Specificity; tertiary amyl methyl ether; Tissue Distribution; Toxicology; Various organic compounds; Rat; Interspecific comparison; Rodentia; Sex; Oral administration; Metabolism; Inhalation; Toxicokinetics; Vertebrata; Additive; Mammalia; Mouse; Animal; Gasoline; Distribution; Pharmacokinetics; distribution; inhalation; gavage; tertiary amyl methyl ether; metabolism
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.931

Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce emissions. Understanding the metabolism and distribution of TAME is needed to assess potential human health issues. The effect of dose level, duration of exposure and route of administration on the metabolism and distribution of TAME were investigated in male and female F344 rats and CD‐1 mice following inhalation or gavage administration. By 48 h after exposure, >96% of the administered radioactivity was expired in air (16–71%) or eliminated in urine and feces (28–72%). Following inhalation exposure, mice had a two‐ to threefold greater relative uptake of [14C]TAME compared with rats. Metabolites were excreted in urine of rats and mice that are formed by glucuronide conjugation of tertiary amyl alcohol (TAA), oxidation of TAA to 2,3‐dihydroxy‐2‐methylbutane and glucuronide conjugation of 2,3‐dihydroxy‐2‐methylbutane. A saturation in the uptake and metabolism of TAME with increased exposure concentration was indicated by a decreased relative uptake of total [14C]TAME equivalents and an increase in the percentage expired as volatiles. A saturation of P‐450 oxidation of TAA was indicated by a disproportional decrease of 2,3‐dihydroxy‐2‐methylbutane and its glucuronide conjugate with increased exposure concentration. Copyright © 2003 John Wiley & Sons, Ltd.