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Macromolecular adduct formation by 4,4'-methylene-bis(2- chloroanaline) in adult male rat.
Cheever KL; Richards DE; Weigel WW; Begley KB; Savage RE Jr.; Daniel FB
Scand J Work Environ Health 1988 May/Jun; 14(Suppl 1):57-59
Formation of macromolecular 4,4'-methylene-bis(2-chloroaniline) (101144) (MOCA) adducts was studied in rats. Male Sprague-Dawley- rats were given a single oral dose of 0 or 281 micromoles per kilogram carbon-14 (C-14) labeled MOCA, and killed 1, 3, 7, 10, 14, or 29 days after dosing. The livers were taken and the blood collected. C-14 activity in the blood and liver was measured. C-14 binding to globin, hemin, and erythrocyte cell debris in the blood and hepatic DNA was determined. The amounts of radiolabel found in the whole blood, liver, hemin, erythrocyte cell debris, and globin after 24 hours were 3417, 5181, 646, 2912, and 3595 femtomoles per milligram, respectively. The ratio of C-14 in liver DNA to whole liver C-14 activity increased from 4.3 after 1 day to 70.8 after 29 days. The ratio of liver DNA/globin C-14 activity, 5.4, did not change significantly over the 29 day period. The biological halflives for MOCA derived C-14 activity in the globin, hepatic DNA, hemin, liver, whole blood, and erythrocyte cell debris were 14.3, 11.1, 8.6, 4.4, 16.7, and 27.4 days, respectively. The authors conclude that since the biological halflives for rat globin and liver DNA/MOCA adducts are similar and the DNA/globin C-14 activity ratio does not change very much over time, quantitating globin/MOCA adducts may be a useful technique for monitoring exposure to MOCA.
NIOSH-Author; In-vivo-studies; Laboratory-animals; Anilines; Organo-chlorine-compounds; Chemical-binding; Nucleic-acids; Physiological-chemistry; Pharmacodynamics
National Institute for Occupational Safety and Health, Cincinnati. Ohio, USA
Scandinavian Journal of Work, Environment & Health
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division