Oral carcinogenicity and toxicity of 2-amino-4-chlorophenol in rats.
OBJECTIVE
This study was carried out to clarify the subchronic and chronic toxicity, and carcinogenicity of 2-amino-4-chlorophenol(ACP).


METHODS
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.


CONCLUSIONS
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.
Yamazaki
Kazunori
K
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Hirasawa, Hadano, Kanagawa, Japan. k-yamazaki@jisha.or.jp
Suzuki
Masaaki
M
Kano
Hirokazu
H
Umeda
Yumi
Y
Matsumoto
Michiharu
M
Asakura
Masumi
M
Nagano
Kasuke
K
Arito
Heihachiro
H
Fukushima
Shoji
S
D000818:Animals; D002733:Chlorophenols / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006965:Hyperplasia; D008297:Male; D009062:Mouth Neoplasms / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D002733:Chlorophenols; C027296:2-amino-4-chlorophenol