Fate of water-insoluble and water-soluble dichlorobenzidine-based pigments in Fisher 344 rats

The fate of two water-insoluble (WI) dichlorobenzidine-based pigments, chlorodiane blue (CDB) and pigment yellow 12 (PY12), and of their sulfonated water-soluble (WS) analogs was studied in male Fischer 344 rats. Water-soluble analogs of chlorodiane blue and pigment yellow 12 were synthesized in order to study the effect of water solubility on the absorption and metabolism of dichlorobenzidine-based pigments. [14C]WI-CBD, [14C]WI-PY12, and the water-soluble analogs [14C]WS-CDB and [14C]WS-PY12 were administered by gastric intubation or dermal application at doses of 1.24-2.65 mumol/kg. Neither [14C]WI-CDB nor [14C]WI-[Y12 could be detected in any tissue at time points up to 1 d. The entire dose was accounted for in the feces after oral administration, and at the application site after dermal administration. Water-insoluble CDB is a component of a photoconductor (Weaver, 1981). Approximately 4.1% of [14C]CDB was observed and located primarily in the urine and liver after oral administration, but no detectable amount was absorbed after dermal application. Metabolites of [14C]WS-CDB identified in the urine were 3,3'-dichlorobenzidine diacetate, 3.3'-dichlorobenzidine and its glucuronide conjugate, and 3,3'-dichlorobenzidine monacetate and its glucuronide conjugate. Only 0.02% of [14C]WS-PY12 was absorbed after oral administration. Thus, some degree of water solubility was prerequisite for even a small amount of absorption or metabolism in vivo.