Add time:09/05/2019         Source:sciencedirect.com

The effect of multiple oral administration of MOCA, a suspect human carcinogen, was studied in the adult male rat. As many as 28 consecutive daily doses of [14C]MOCA at 28.1 μmol/kg body wt (5 μCi/day) were administered and rats were euthanized at weekly intervals for 7 weeks. MOCA adduct formation for globin and serum albumin was evaluated by determination of [14C]MOCA covalent binding. The covalent binding associated with globin showed a linear increase over the 28-day exposure period with 342 fmol/mg globin 24 hr after the final dose. More extensive covalent binding was detected for albumin with 443 fmol/mg albumin after the final dose, but increases were not linear. After cessation of dosing, the albumin adduct levels decreased rapidly (t12 = 4.6 days) in relation to globin adduct levels (t12 = 16.1 days). The MOCA-globin adduct t12 is consistent with that determined after a single 281 μmol/kg oral dose of MOCA. Significant differences related to route of administration were detected for 24-hr globin covalent binding with ip > po > dermal. Distribution of undifferentiated [14C]MOCA was highest in the liver at 24 hr with tissue levels for liver > kidney > lung > spleen > testes > urinary bladder. Induction of cytochrome P450 enzymes by administration of phenobarbital (100 mg/kg/day/3 days) resulted in a significant (p < 0.05) increase in MOCA-globin adduct formation detected with 33.5 pmol/mg globin for induced rats versus 13.6 pmol/mg globin for control rats. Although MOCA-globin and albumin adducts show differing stability, quantification of such MOCA adducts may be useful for long-term industrial biomonitoring of MOCA.

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