The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 18 , Issue SupplementII
Showing 1-6 articles out of 6 articles from the selected issue
  • Sung-Hoon KIM, Moon-Koo CHUNG, Sang-Seop HAN, Jung-Koo ROH
    1993 Volume 18 Issue SupplementII Pages 1-17
    Published: 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A teratogenicity study was carried out in Sprague-Dawley rats subcutaneously injected recombinant Granulocyte-Macrophage Colony Stimulating Factors (LBD-005), the growth of stem cell and the development of the hematopoietic cell, at dose levels of 250, 500 and 1000 μg/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on day 20 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offspring was observed. The incidences of external, internal and skeletal anomalies were not significantly increased in the fetuses of any treated groups. Recombinant GM-CSF caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offsprings.
    Download PDF (1030K)
  • Sung-Hoon KIM, Moon-Koo CHUNG, Sang-Seop HAN, Jung-Koo ROH
    1993 Volume 18 Issue SupplementII Pages 19-35
    Published: 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A perinatal and postnatal study was carried out in Sprague-Dawley rats subcutaneously injected recombinant Granulocyte-Macrophage Colony Stimulating Factors (LBD-005), the growth of stem cell and the development of the hematopoietic cell, at dose levels of 250, 500 and 1000 μg/kg/day for a period from day 17 of gestation to day 21 after delivery. All pregnant dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal and skeletal anomalies were not significantly increased in the F1 and F2 fetuses of any treated groups. Recombinant GM-CSF caused no effects on parturition, lactation, postnatal growth and differentiation, behaviour and reproductive ability of the male and female offsprings.
    Download PDF (968K)
  • Hyoung-Chin KIM, Boo-Hyon KANG, Chang-Su HA, Sang-Seop HAN, Jung-Koo R ...
    1993 Volume 18 Issue SupplementII Pages 37-42
    Published: 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The acute toxicity of a recombinant human interferon αA (code name: LBD-007) was evaluated in both sexes of Sprague-Dawley rats, 5 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results, LBD-007was not considered to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD&lt50&gt values in rats would be &gt48×108 IU/kg in the study of oral administration and &gt24×108 IU/kg in the study of subcutaneous or intravenous administration.
    Download PDF (604K)
  • Hyoung-Chin KIM, Boo-Hyon KANG, Chang-Su HA, Sang-Seop HAN, Jung-Koo R ...
    1993 Volume 18 Issue SupplementII Pages 43-56
    Published: 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Recombinant human interferon αA (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 6, 12 and 24×106 IU/kg of body weight five days per week for 4 weeks to evaluate the subchronic toxicity. 20 to 50% of rats except the male control group showed minimal to mild, focal to multifocal renal mineralization. Whether renal mineralization is related to the test substance is not elucidated. Male rats dosed at 24×106 IU/kg showed the decrease of the absolute kidney weights and the increase of the brain relative weights. Female rats dosed at 24×106 IU/kg showed the increase of the absolute and relative ovary weights, and the decreases of specific gravity, bilirubin and urobilinogen in urine. However, no drug-related changes were noted in clinical findings, body weights, food consumption, water consumption, hematology, blood clinical chemistry and necropsy findings. Based on the results it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon αA (LBD-007) in rats is (6∼12)×106 IU/kg.
    Download PDF (996K)
  • Hyoung-Chin Kim, Boo-Hyon Kang, Chang-Su Ha, Sang-Seop Han, Jung-Koo R ...
    1993 Volume 18 Issue SupplementII Pages 57-76
    Published: 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Recombinant human interferon αA (code name: LBD-007) was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 3, 6 and 12×106 IU/kg of body weight six days per week for 6 months to evaluate the chronic toxicity. Male rats dosed at 12×106 IU/kg for 26 weeks showed a decrease of ketone body in the urine, and female rats dosed at 12×106 IU/kg for 26 weeks showed a decrease of serum alkaline phosphatase. Microscopic changes with remarkable incidence were nephropathy, renal mineralization and ultimobranchial cysts of the thyroid gland in all groups of both sexes of rats. These changes were not considered to be drug-related toxicity because they appeared to be minimal, occasionally mild in severity and did not have dose-dependency as well as chinical significance. In general, no drug-related change was noted in clinical findings, body weights, food consumption, water consumption, hematology, organ weights and necropsy findings. Based on the results, it is concluded that the estimated subcutaneous non-toxic dose of the recombinant human interferon αA (LBD-007) in rats would be 6×106 IU/kg.
    Download PDF (1292K)
  • Jong-Il Park, Sang-Seop Han, Jung-Koo Roh, Sang-Gi Paik
    1993 Volume 18 Issue SupplementII Pages 77-82
    Published: 1993
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Antigenicity of recombinant human interferon αA (LBD-007), a newly developed drug for myeloid leukemia and hepatitis, was investigated in mice and guinea pigs. The following results were obtained: 1. Mice showed no production of antibodies against LBD-007 inoculated with aluminum hydroxide gel (alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-007 only and of LBD-007 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-007 has no antigenic potential in mice or guinea Pigs.
    Download PDF (651K)
feedback
Top