Comparative metabolism of methyl isobutyl carbinol and methyl isobutyl ketone in male rats.
Methyl isobutyl carbinol (MIBC) is an oxygenated solvent that is metabolized to methylisobutyl ketone (MIBK) and then to 4-hydroxymethyl-4-methyl-2-pentanone (HMP). Plasma levels of MIBC, MIBK and HMP were determined up to 12 h after a single oral 5 mmol/kg dose of MIBC or MIBK to male rats. The major material in the plasma in both cases was HMP, with similar areas-under-the-curve (AUC) and C(max) at 9 h after dosing. MIBK plasma levels and AUC were also comparable after MIBK or MIBC administration. MIBC AUC was only about 6% of the total material in the blood after MIBC, and insignificant after MIBK administration. No other metabolites were detected in the plasma under the analytical conditions used. The extent of metabolism of MIBC to MIBK, by comparing combined AUCs for MIBK and HMP, was at least 73%. The limited systemic toxicity data for MIBC are consistent with those for MIBK, which has been well studied. The metabolic equivalency of MIBC with MIBK indicates that MIBC will have a low potential for toxicity similar to that of MIBK, and reduces the need for additional animal studies.
Gingell
Ralph
R
Shell Chemicals, PO Box 4320, Houston, TX 77210, USA. rgingell@shellus.com
Régnier
Jean-François
JF
Wilson
Daniel M
DM
Guillaumat
Pierre-Olivier
PO
Appelqvist
Terence
T
D000280:Administration, Inhalation; D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D002138:Calibration; D008297:Male; D008742:Methyl n-Butyl Ketone / Q000493:pharmacokinetics* / Q000633:toxicity; D000439:Pentanols / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents
D000439:Pentanols; D012997:Solvents; D008742:Methyl n-Butyl Ketone; C024821:isobutylmethylcarbinol; C005458:methyl isobutyl ketone