The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 13, Issue SupplementII
Displaying 1-4 of 4 articles from this issue
  • Shigeo KAWANO, Hisashi KOHMURA, Satoshi OHTA, Norimitsu TAKAHASHI
    1988 Volume 13 Issue SupplementII Pages 1-21
    Published: July 20, 1988
    Released on J-STAGE: February 21, 2008
    JOURNAL FREE ACCESS
    Carboplatin and carboplatin-ovalbumin mixture were examined for their antigenicity in Hartley guinea pigs as well as BALB/c and C3H/He mice in comparison with ovalbumin (OVA) and 2, 4-dinitrochlorobenzene (DNCB)-OVA conjugate. The results obtained were as follows : 1. When guinea pigs were sensitized with carboplatin or carboplatin-OVA emulsified with Freund's complete adjuvant (FCA), these animals showed negative reactions in active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA), passive cutaneous anaphylaxis (PCA), passive hemagglutination (PHA) and Schultz-Dale test. 2. When mice were sensitized with carboplatin or carboplatin-OVA adsorbed to alum, these animals revealed a negative reaction in PCA using rats. 3. As positive controls, guinea pigs were sensitized with OVA or DNCB-OVA emulsified with FCA, and mice with OVA or DNCB-OVA adsorbed to alum. As a result, these animals disclosed positive reactions in ASA, ACA, PCA, PHA and Schultz-Dale test. As shown above, carboplatin was considered to possess neither antigenic nor haptenic properties. In addition, the dose levels of carboplatin employed in the present experiment were confirmed not to suppress immune reactions.
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  • Shuichi KAI, Hisashi KOHMURA, Katsumi ISHIKAWA, Yukako TAKEUCHI, Satos ...
    1988 Volume 13 Issue SupplementII Pages 23-34
    Published: July 20, 1988
    Released on J-STAGE: February 21, 2008
    JOURNAL FREE ACCESS
    Carboplatin, an oncostatic drug, was administered intravenously to male Crj : CD (Sprague-Dawley) rats for 63 days and to female rats of the same strain for 14 days prior to mating at dose levels of 1, 2 and 4 mg/kg/day. These animals were than mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation. The summerized results obtained are as follows : 1. Carboplatin 2 mg/kg and higher suppressed body weight gains accompanied by the decreases in food and water consumption in male rats. Further, body weight gains were suppressed in female rats followed by the decreases in food consumption at the same dose levels. 2. Though there were no differences between dosed animals and controls regarding the organ weights, the incidence of necrosis of the tails around the injection site was increased in male rats at 4 mg/kg. 3. Carboplatin failed to affect the reproductive ability of both sexes. 4. As for fetuses, the mortality was elevated at 2 mg/kg and higher and the number of live fetuses reduced at 4 mg/kg, but the influences on prenatal development were not apparently observed for live fetuses even at the highest dose level. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against parent rats of both sexes and their offspring.
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  • Shuichi KAI, Hisashi KOHMURA, Katsumi ISHIKAWA, Yukako TAKEUCHI, Satos ...
    1988 Volume 13 Issue SupplementII Pages 35-61
    Published: July 20, 1988
    Released on J-STAGE: February 21, 2008
    JOURNAL FREE ACCESS
    Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj : CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows : 1. Carboplatin 4 mg/kg supperssed the maternal body weight gains from day 13 through 20 of gestation. 2. Uterine weights were reduced in F0 dams at term at carboplatin 4 mg/kg. 3. Carboplatin 4 mg/kg brought the inhibition of fetal growth accompanied by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidences of unossified 5th and 6th sternums, as well as retarded ossification of sacrococcygeal vertebtae were also noted in this dose level. 4. The birth rate was reduced in neonates (F1) at carboplatin 4 mg/kg. 5. Body weight gains in male F1 rats were suppressed at carboplatin 4 mg/kg from 4 to 8 weeks of age. 6. Carboplatin 4 mg/kg decreased the brain weights on an absolute basis in female F1 rats, but failed to affect their postnatal differentiations, early behavioral developments, learning ability, mortor activity or emotional development. 7. Reproductive ability in F1 rats of both sexes were not affected by carboplatin. 8. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the organogenetic period. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.
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  • Shuichi KAI, Hisashi KOHMURA, Katsumi ISHIKAWA, Yukako TAKEUCHI, Satos ...
    1988 Volume 13 Issue SupplementII Pages 63-81
    Published: July 20, 1988
    Released on J-STAGE: February 21, 2008
    JOURNAL FREE ACCESS
    Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj : CD (Sprague-Dawley) rats from day 17 of gestation through day 21 of pospartum at dose levels of 1, 2 and 4 mg/kg/day. The summerized results obtained are as follows : 1. Maternal body weight gains were suppressed during the former part of the lactation period at carboplatin 2 mg/kg and higher. 2. Thymic weights were decreased and lung weights were increased in dams (F0) at carboplatin 2 mg/kg and higher. Further, ovarian weights were reduced in dams (F0) at carboplatin 4 mg/kg. 3. Carboplatin failed to affect the parturition of F0 dams. 4. Carboplatin did not affect the viability of newborns (F1), and postnatal differentiations, early behavioral developments, learning ability, mortor activity or emotional development in F1 animals. 5. Carboplatin 4 mg/kg brought a suppression of pituitary weights after mating in F1 male rats and decreases of adrenal and genital organ weights at weaning in F1 female rats, but failed to affect their reproductive ability. 6. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever recieved carboplatin during the perinatal and lactation periods. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 1 mg/kg/day against dams and 2mg/kg/day against their offspring.
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