4,4'-Methylene-bis(2-chloroaniline) (MOCA): Comparison of macromolecular adduct formation after oral or dermal administration in the rat

Journal Article · Wed Jan 31 23:00:00 EST 1990 · Fundamental and Applied Toxicology; (USA)

DOI:https://doi.org/10.1016/0272-0590(90)90207-Z· OSTI ID:7004457

Cheever, K L; Richards, D E; Weigel, W W; Begley, K B; DeBord, D G; Swearengin, T F; Savage, Jr, R E ^[1]

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1. National Institute for Occupational Safety and Health, Cincinnati, OH (USA)

The macromolecular binding of 4,4'-methylenebis(2-chloroaniline) (MOCA), a suspect human carcinogen, was studied in the adult male Sprague-Dawley rat after both oral and dermal administration. Rats were euthanized 1, 3, 7, 10, 14, and 29 days after a single 281 mumol/kg body wt dose of (14C)MOCA (oral, 213 muCi/kg; dermal, 904 muCi/kg). DNA from various tissues and hemoglobin were isolated for determination of the time course of MOCA macromolecular binding. After oral administration adduct formation was rapid with maximum levels appearing at 24 hr. The 24-hr covalent binding associated with the globin was 7.84 pmol/mg globin (t1/2 = 14.3 days). More extensive 24-hr covalent binding was detected for liver DNA with 49.11 pmol/mg DNA (t1/2 = 11.1 days). After dermal administration of MOCA the major portion of the dose, 86.2%, remained at the application site throughout the study. For these rats the 24-hr covalent binding determined for liver DNA was 0.38 pmol/mg DNA (t1/2 = 15.6 days). Although lower levels were detected after dermal application, similar stability of MOCA-DNA adducts indicates that quantification of such MOCA adducts may be useful for the long-term industrial biomonitoring of MOCA exposure and for the evaluation of human DNA-MOCA adduct formation, a lesion thought to be associated with the production of cancer.

• OSTI ID: 7004457
• Journal Information: Fundamental and Applied Toxicology; (USA), Journal Name: Fundamental and Applied Toxicology; (USA) Vol. 14:2; ISSN FAATD; ISSN 0272-0590
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ABSORPTION
ADDUCTS
AMINES
ANILINE
ANIMALS
AROMATICS
BIOLOGICAL HALF-LIFE
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARCINOGENESIS
COMPARATIVE EVALUATIONS
COUNTING TECHNIQUES
DNA
DNA ADDUCTS
GLOBIN
GLOBINS
HEMOGLOBIN
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
NUCLEIC ACIDS
ORAL ADMINISTRATION
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PIGMENTS
PORPHYRINS
PROTEINS
RATS
RODENTS
SCINTILLATION COUNTING
SKIN ABSORPTION
SYNTHESIS
TRACER TECHNIQUES
UPTAKE
VERTEBRATES