4,4'-Methylenebis(2-chloroaniline) (MOCA): the effect of multiple oral administration, route, and phenobarbital induction on macromolecular adduct formation in the rat
| Autor: | Kenneth L. Cheever, D. Gayle DeBord, Terri F. Swearengin |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
Risk medicine.medical_specialty Serum albumin Administration Oral Toxicology Adduct chemistry.chemical_compound 4 4'-Methylenebis(2-chloroaniline) Cytochrome P-450 Enzyme System Oral administration Internal medicine medicine Animals Tissue Distribution Globin Chromatography High Pressure Liquid Serum Albumin biology Chemistry Albumin Rats Inbred Strains Globins Rats Endocrinology Biochemistry Enzyme Induction Methylenebis(chloroaniline) Phenobarbital Toxicity biology.protein Chromatography Thin Layer medicine.drug Half-Life |
| Zdroj: | Fundamental and applied toxicology : official journal of the Society of Toxicology. 16(1) |
| ISSN: | 0272-0590 |
| Popis: | 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 mumol/kg body wt (5 microCi/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 (t1/2 = 4.6 days) in relation to globin adduct levels (t1/2 = 16.1 days). The MOCA-globin adduct t1/2 is consistent with that determined after a single 281 mumol/kg oral dose of MOCA. Significant differences related to route of administration were detected for 24-hr globin covalent binding with ip greater than po greater than dermal. Distribution of undifferentiated [14C]MOCA was highest in the liver at 24 hr with tissue levels for liver greater than kidney greater than lung greater than spleen greater than testes greater than urinary bladder. Induction of cytochrome P450 enzymes by administration of phenobarbital (100 mg/kg/day/3 days) resulted in a significant (p less than 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|