Hematological toxicity following percutaneous exposure of 3,3'-dichloro-4,4'-diaminodiphenylmethane in rats

抄録

A relationship has been previously reported between exposure to aromatic amines, including 3,3'-dichloro-4,4'-diaminodiphenylmethane (MOCA), and the development of diseases such as bladder cancer. Skin absorption is believed to be one of the primary routes of exposure. Although hematological toxicity of MOCA through oral exposure has been reported in animals, detailed information on its toxicity (e.g., the origin of toxicity and possible biomarkers), particularly via percutaneous exposure, has not been fully elucidated. Therefore, we investigated whether MOCA has hematological toxicity following percutaneous administration in rats. To this end, young adult male rats were administered MOCA (0, 60, or 120 mg/kg/day) three times per week for four weeks (12 administrations in total). At the end of the treatment period, hematological indices of whole blood samples were measured using a multiparameter automated analyzer, and the major organs, including the target ones, were weighed. The 120 mg/kg/day group showed a significant increase in spleen and liver weights compared to the control group. Although kidney weights showed a slight increasing trend, it was not statistically significant. Hematological examination results showed elevated erythrocyte counts and hematocrit levels. Together with the increased spleen weight, these results suggest that MOCA is hematotoxic when administered percutaneously. As these hematological changes were already relatively prominent during the early stages of exposure, they may be a novel and valid indicator of MOCA exposure through the skin. Currently, we are analyzing RNA sequencing and the effects on hematopoietic cells derived from the femur to further investigate the underlying mechanism(s) of these hematological changes.