Oral Carcinogenicity and Toxicity of 2‐Amino‐4‐chlorophenol in Rats

Abstract

Oral Carcinogenicity and Toxicity of 2-Amino-4-chlorophenol in Rats: Kazunori YAMAZAKI, et al. Japan Bioassay Research Center, Japan Industrial Safety and Health AssociationObjectives: This study was carried out to clarify the subchronic and chronic toxicity, and carcinogenicity of 2 -a m i n o -4 -c h l o r o p h e n o l ( A C P ) . M e t h o d s : Carcinogenicity, and chronic and subchronic toxicity of ACP were examined by feeding 10 rats of both sexes ACP-containing diet at a dose level of 0 (control), 512, 1,280, 3,200, 8,000 or 20,000 ppm (w/w) for 13 wk and 50 rats of both sexes at a dose level of 0, 1,280, 3,200 or 8,000 ppm for 2 yr. Results: The 13-wk oral subchronic toxicity of ACP was characterized by proliferative lesions leading to development of tumors in the forestomach and urinary bladder and by erythrocyte toxicity as evidenced by decreases in red blood cell counts, hemoglobin and hematocrit and concurrent increases in methemoglobin levels and reticulocyte counts. Both simple and papillary and/or nodular types of transitional cell hyperplasias were observed in the urinary bladder of ACP-fed male rats. The proliferative lesions appeared at higher doses of ACP after the 13-wk administration than clear erythrocyte toxicity did. The 2-yr oral administration of ACP significantly increased incidences of squamous cell papillomas and carcinomas in the forestomach of male and female rats and transitional cell carcinomas in the urinary bladder of male rats. These tumor incidences increased dose-dependently. Notably, clear signs of erythrocyte toxicity were not evident after the 2-yr administration of ACP. Conclusion: Clear evidence of carcinogenic activity of ACP was shown in male and female rats. These data might be useful for the health risk assessment of workers exposed to ACP. (J Occup Health 2009; 51: 249-260)

Stability‐indicating method for quantification of potential genotoxic impurity and other organic impurities of chlorzoxazone using hyphenated techniques

“…Also as the product contains genotoxic impurity (2-amino-4-chlorophenol), it is essential to have a more sophisticated method/technique for the quantification of the same. Considering the sensitivity and toxicity of this impurity (its consumption of high levels will cause cancer), we have selected the RP-HPLC-MS/MS technique for the estimation of 2-amino-4-chlorophenol in ppm level (Figure 1) [19][20][21][22][23]. Both methods were developed and validated considering the International Council for Harmonization (ICH) requirements, which met its acceptance criteria and were found to be specific, linear, accurate, precise, and robust [24][25][26][27][28].…”