ORAL CHRONIC TOXICITY AND CARCINOGENICITY TEST OF POLYOXYETHYLENE(10)NONYLPHENYL ETHER (NP-10) IN FEMALE F344 RATS

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Chronic toxicity and carcinogenicity of polyoxyethylene(10)nonylphenyl ether (NP-10) to Fischer 344 rats were investigated using 70 females per group in 4 study groups, or 280 rats in total. Diets containing NP-10 at 0, 1000, 3000 and 9000 ppm were prepared and orally administered to the animals repeatedly for 52 weeks for a chronic toxicity study and for 104 weeks for a carcinogenicity study. Observations of general condition, body weight analysis, food consumption analysis, hematologic examination, blood chemistry examination (only at Week 52 of administration), urinalysis (only at Week 52), ophthalmologic examination (immediately prior to administration and at Week 52), organ weight analysis and pathological examination were performed. The results are summarized as follows. The mean intake of the test substance was 60.5, 182 and 559 mg/kg/day in the chronic toxicity study for 52 weeks and 55.2, 166 and 520 mg/kg/day in the carcinogenicity study for 104 weeks in the 1000, 3000 and 9000 ppm groups, respectively. Mortality decreased approximately in a dose-related manner, with 28% in the control group, 26% in the 1000 ppm group, and 14% each in the 3000 and 9000 ppm groups. In general condition, there were no signs attributed to the treatment with NP-10. Body weight gain was suppressed in the 9000 ppm group throughout the administration period and in the 3000 ppm group during Weeks 21-88. Food consumption decreased in the 9000 and 3000 ppm groups. Food efficiency was lower in the 9000 and 3000 ppm groups. As a result of the hematologic examination, hematocrit value, hemoglobin value, red blood cell count, platelet count and MCV were lower and MCH and MCHC higher in the 9000 ppm group at Week 52 of administration. At Week 104, the neutrophil ratio was higher and lymphocyte ratio lower in the 3000 and 9000 ppm groups, and furthermore, hematocrit value, hemoglobin value, MCV and MCH were slightly lower in the 9000 ppm group. In the blood coagulability tests, prothrombin time was slightly shortened in the 9000 ppm group at Week 52. As a result of the blood chemistry examination, total protein and albumin values were higher and total bilirubin, uric acid and trygliceride value lower in the 3000 ppm and higher dose groups. Furthermore, the free cholesterol value was higher and the values of potassium, cholesterol ester ratio, GOT, GPT, ALP and cholinesterase were lower in the 9000 ppm group. As a result of the urinalysis, the specific gravity of urine was higher and urine pH acidic in some animals. As a result of the ophthalmologic examination, no abnormal animals were found in the 9000 ppm group. As a result of the organ weight analysis, absolute and relative weights of the liver and adrenals were higher in the 3000 and/or 9000 ppm groups as changes which were considered attributable to the test substance and, in addition, organs with a lower absolute weight and higher relative weight with the suppressed body weight gain were observed in the 9000 ppm group. The histopathological examination revealed no marked findings in necropsy observation or histology in the treated groups in the animals killed at Weeks 52, 104 as well as those killed moribund and dead animals. In the histological findings, bile duct hyperplasia of liver in the animals killed at Week 52, proliferative duct of pancreas in the animals killed at Week 104, pigment of deposit in pituitary and angiectasis of adrenals in the animals killed at moribund and dead animals were observed in a slightly larger number in the treated groups, but none of these changes were different in degree from the control and were not considered to be specific lesions. As a result of the overall study of the neoplastic lesions of all animals killed on schedule and of moribund and dead animals, no tumors were found in the treated groups which had increased in occurrence. Based on the above findings, it was determined that the no-adverse-effect level in the chronic toxicity study was 1000 ppm (
日本トキシコロジー学会の論文
1999-12-20

ORAL CHRONIC TOXICITY AND CARCINOGENICITY TEST OF POLYOXYETHYLENE(10)NONYLPHENYL ETHER (NP-10) IN FEMALE F344 RATS

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