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4,4'-Methylene-bis(2-chloroaniline) (MOCA): comparison of macromolecular adduct formation after oral or dermal administration in the rat.
Cheever-KL; Richards-DE; Weigel-WW; Begley-KB; Debord-DG; Swearengin-TF; Savage-RE Jr.
Fundam Appl Toxicol 1990 Feb; 14(2):273-283
A comparison of the effects of oral and dermal administration of 4,4'-methylene-bis(2-chloroaniline) (101144) (MOCA) upon DNA and hemoglobin (Hb) adduct formation in rats was performed. Male Sprague-Dawley-rats were given either oral or dermal doses of MOCA at concentrations of 281 micromoles per kilogram body weight. Rats were sacrificed 1, 3, 7, 10, 14 or 29 days after the administration of radiolabeled MOCA and blood and tissue samples were obtained. The radioactivity levels in the blood 24 hours following the injection or dermal exposure were 7.45 and 0.07 picomoles per milligram (pm/mg) blood, respectively. DNA adduct formation in the liver after 24 hours was 49.11pm/mg of DNA for the oral exposure. Covalent DNA binding was greatest in the liver and lowest in the lymphocytes with bladder levels falling between these two. Dermal exposures resulted in decreased DNA adduct formation by a factor of 100 compared to the oral dosage. Radiolabeled binding was also assessed in globin with the biological half lives of DNA adducts being similar for globin, liver and bladder DNA. The subcellular distribution of radiolabeled MOCA was evaluated for the oral dosage after 24 hours and determined to be 169.24, 89.49, 244.45, and 282.64pmol/mg for nuclear, mitochondrial, microsomal and supernatant protein fractions, respectively. The authors conclude that adduct formation in different tissues occurs at significant levels following either oral or dermal exposure.
NIOSH-Author; Cell-biology; Exposure-methods; Exposure-levels; DNA-adducts; Blood-analysis; Laboratory-animals; Radioassays; Protein-biochemistry
Issue of Publication
Fundamental and Applied Toxicology
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