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.
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.
Sumner
Susan C J
SC
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2194, USA.
Janszen
Derek B
DB
Asgharian
Bahman
B
Moore
Timothy A
TA
Parkinson
Horace D
HD
Fennell
Timothy R
TR
D000284:Administration, Oral; D000393:Air Pollutants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D005260:Female; D019570:Inhalation Exposure; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051379:Mice; D000439:Pentanols / Q000652:urine; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D014018:Tissue Distribution
D000393:Air Pollutants; D002250:Carbon Radioisotopes; D008738:Methyl Ethers; D000439:Pentanols; D002245:Carbon Dioxide; C032765:tert-amyl alcohol; C096680:tertiary-amyl methyl ether