4,4'-Methylene-bis(2-chloroaniline) (MOCA): comparison of macromolecular adduct formation after oral or dermal administration in the rat.
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.
Cheever
K L
KL
Centers for Disease Control, National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226.
Richards
D E
DE
Weigel
W W
WW
Begley
K B
KB
DeBord
D G
DG
Swearengin
T F
TF
Savage
R E
RE
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D005914:Globins / Q000302:isolation & purification; D006207:Half-Life; D006427:Hemin / Q000302:isolation & purification; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D008753:Methylenebis(chloroaniline) / Q000008:administration & dosage / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D013347:Subcellular Fractions / Q000032:analysis
D001559:Benzhydryl Compounds; D006454:Hemoglobins; D008753:Methylenebis(chloroaniline); D006427:Hemin; D005914:Globins; D004247:DNA