The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 24 , Issue SupplementII
Showing 1-5 articles out of 5 articles from the selected issue
  • Sunao ASO, Shojiro SUETA, Yasuhiro KAJIWARA, Satoshi MORITA, Shin-ichi ...
    1999 Volume 24 Issue SupplementII Pages 115-128
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A surfactant NP-10 was administered subcutaneously to 7-week-old Jcl:Wistar female rats at dose levels of 2 and 20 mg/kg/day for 15 weeks to assess its effects on their reproductive ability and fetal development, and on the growth, behavior and functions of the offspring they delivered. In the general condition of the F0 dams, changes that were considered to be the local irritation effect of the test substance, such as scab formation and loss of hair at the test substance administration site in the 2 and 20 mg/kg groups and induration of the skin at the test substance administration site in the 20 mg/kg group were observed. Whitish changes of the subcutis were detected at the test substance administration site in the 2 and 20 mg/kg groups and adhesion of abdominal organs in the 20 mg/kg group in the necropsy findings. In addition, an increase was observed in body weight and in food consumption in the 20 mg/kg group. The reproductive ability test failed to reveal any evidence of an effect that could be ascribed to the test substance. The observations at cesarean section or external, visceral and skeletal examinations revealed no effects attributable to the test substance in the F1 fetuses. The observations on the day of birth and during the period of lactation, external examination, physical development test, general condition, body weight and necropsy findings for F1 and F2 offspring and reflex test, open-field test, water-maze test, organ weight and reproductive ability test performed on the F1 offspring failed to reveal any evidence that could be ascribed to the test substance. These results indicate that under the conditions of this study, NP-10 had no effect on the reproductive ability of females or the fetal development or growth, behavior and functions of their offspring.
    Download PDF (1436K)
  • Sunao ASO, Hatsune EHARA, Makiko ANAI, Koji KAWAZU, Shuji NODA, Toshik ...
    1999 Volume 24 Issue SupplementII Pages 129-140
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A surfactant NP-10 was administered subcutaneously to Jcl:Wistar female rats at dose levels of 5, 20 and 80 mg/kg/day from date of birth to day 21 after birth of F1 offspring to assess its effects on the growth, behavior and functions of the offspring. For F0 dams, scab formation and loss of hair at the test substance administration site were observed in all treatment groups and induration of the skin at the test substance administration site in the 20 and 80 mg/kg groups in general condition and necropsy findings at the end of the dosing period. In necropsy findings, in addition to these changes, hemorrhage and whitish change of the subcutis at the test substance administration site were seen in all treatment groups, adhesion to the somatic muscles and granulation of the subcutis at the test substance administration site in the 20 and 80 mg/kg groups, and swelling of the spleen and adrenals in the 80 mg/kg group. Reduction or a tendency for reduction in food consumption was also detected from the initial day of dosing (day 0) to day 17 after birth F1 offspring in the 80 mg/kg group. Body weight or the findings on the day after birth and day of weaning failed to reveal any evidence of an effect that could be ascribed to the test substance. In F1 born offspring, a decrease or tendency for decrease in body weight was observed from day 7 after birth in both sexes and for females during the gestation period in the 80 mg/kg group. However, body weight gains based on the weights at 4 weeks after birth or on day 0 of gestation in the 80 mg/kg group failed to reveal any difference from that in the control group. The observation on the day of birth and during the period of lactation, physical development test, reflex test, general condition, open-field test, water-maze test, reproductive ability test, observations at cesarean section, necropsy findings, organ weights, histopathological findings of females or males that did not achieve successful gestation, skeletal examination, and the observations at cesarean section and external examination of F2 fetuses failed to reveal any evidence that could be ascribed to the test substance. These results indicate that NP-10 had no effect on the behavior or functions of the offspring, although it affected the growth of the offspring born, under the conditions of this study. The non-effective dose level is considered to be 20 mg/kg for general toxicity of the dams and for their offspring.
    Download PDF (1315K)
  • Kazuhiro SHIMOMURA, Toshikazu SATO
    1999 Volume 24 Issue SupplementII Pages 141-148
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The effects of exposure of a surfactant, nonoxynol(NP-10), to sperm on embryonic and fetal development were studied using rabbits. In the preliminary test, the concentration of NP-10 at which total sperm immobility was 0.01% and nonfertilizing was 0.008% in vitro. No implantation was observed at the concentration of 0.032% NP-10 in vivo. Based on these results, the rabbit semen was treated either with 0.04, 0.01 or 0.0025% NP-10 solution, and used for artificial insemination to examine if the sperm was fertile as well as to determine the effect of NP-10-terated sperm on embryonic and fetal development. Gestation was not observed after insemination with semen treated with 0.04% NP-10; after insemination with semen treated with 0.01 and 0.0025% NP-10, it occurred without impairing the viability, organogenesis or growth of embryos or fetuses. These results may indicate that gestation may not be possible with sperm severely impaired by exposure to NP-10, but no untoward effect on embryonic or fetal development may be observed when gestation is initiated with exposed semen.
    Download PDF (864K)
  • Hiroyuki INOUE, Toshio YAMAMOTO, Akinori SHOJI, Nobuaki WATARI, Yasuhi ...
    1999 Volume 24 Issue SupplementII Pages 149-166
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A carcinogenicity study of polyoxyethylene(10)nonylphenyl ether (NP-10) to B6C3F1 mouse was performed using 50 females per group of 4 study groups, or 200 mice in total. Diets containing NP-10 at 0, 500, 1500 and 4500 ppm were prepared and orally administered to the animals repeatedly for 104 weeks, and observation of general conditions, body weight analysis, food consumption analysis, hematologic examination, organ weight analysis and pathological examination were performed. The results are summarized as follows. The mean intake of the test substance in the 500, 1500 and 4500 ppm groups for 104 weeks was 81.5, 254 and 873 mg/kg/day, respectively. There were no differences observed in mortality among the groups and the mortality did not exceed the background data in any groups. There were no signs attributable to the administration of the test substance, and various signs which increased in occurrence with aging were observed in all groups at a similar frequency. Body weight gain was suppressed only in the 4500 ppm group throughout the entire administration period. Food consumption was increased in all treated groups around the early stage of administration and, thereafter, in the 1500 and 4500 ppm groups until the mid-stage of administration. Decreased food efficiency was observed in the 4500 ppm group alone. As a result of the hematologic examination, no changes attributable to the administration of the test substance were observed in any groups. As a result of the organ weight analysis, lower absolute weights of the liver and kidney and higher relative weights of the brain, liver and kidney, which were considered to be changes accompanying the suppressed body weight gain, were observed in the 4500 ppm group. The pathological examination revealed no marked changes in the gross findings in the treated groups. As a result of the histological examination, there were no neoplastic or non-neoplastic lesions in the treated groups which were unequivocally observed to have increased in occurrence. As the above findings show, NP-10 did not cause any increase in the incidence of neoplastic lesions in the mouse by oral administration for 2 years at 873 mg/kg/day (4500 ppm) and was determined to have no carcinogenicity..
    Download PDF (1404K)
  • Hiroyuki INOUE, Toshio YAMAMOTO, Akinori SHOJI, Nobuaki WATARI, Yasuhi ...
    1999 Volume 24 Issue SupplementII Pages 167-193
    Published: December 20, 1999
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    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 (
    Download PDF (2072K)
feedback
Top