title: Tissue distribution and binding of radioactivity in mouse after intravenous administration of [14C]3-chloro-p-toluidine.
abstract: The avicide [14C]3-chloro-p-toluidine (CPT) HCL, ring labeled, was injected intravenously to mice. The radioactivity associated with this compound was found to be unevenly distributed in different parts of the body. It leaves the plasma, as well as many tissues, with 2 elimination rate constants, the fast and the slow. The faster component of the [14C]CPT decay curve of the plasma was similar to the faster components of the decay curves of brain, lung, heart, intestine, testicle and kidney. The retention half-life of the radioactivity for the slower component of the decay curve varied a great deal from tissue to tissue, being shortest (14.55 h) in the intestine and longest (326 h) in the adipose tissue. Of the 10 tissues examined, a substantial amount of [14C]CPT radioactivity was found to be covalently bound only to liver, kidney, lung and RBC protein. There was no cause and effect relationship between the covalent binding of radioactivity and the tissue pathology, since no remarkable histopathological lesions were found in the liver and kidney of treated mice. The tissue retention of [14C]CPT radioactivity did not parrallel the covalent binding of the compound to tissue protein. The covalent binding of [14C]CPT radioactivity to RBC was suggestive of the conversion of the parent compound into a reactive metabolite responsible for the generation of methemoglobin in mice. The percent distribution of radioactivity in subcellular fractions of liver and kidney correlated with the amount of protein associated with subcellular fractions. The 102 000 g supernatant fraction of the liver contained the highest proportion of radioactivity, both in terms of absolute percent radioactivity as well as specific activity (dpm/mg of protein). This was also true for the 102 000 g supernatant fraction of the kidney. The majority of radioactivity in the 102 000 g supernatant fraction of liver appears to be bound to one or more polypeptide sized proteins with a mol. wt. of approx. 1000--2000.
mesh_terms: D000818:Animals; D006207:Half-Life; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D008168:Lung / Q000032:analysis; D008297:Male; D051379:Mice; D010575:Pesticides / Q000032:analysis / Q000378:metabolism*; D011485:Protein Binding; D014018:Tissue Distribution; D014052:Toluidines / Q000378:metabolism*
chemical_list: D010575:Pesticides; D014052:Toluidines