The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 7 , Issue SupplementII
Showing 1-6 articles out of 6 articles from the selected issue
  • Ueto TAKADA, Masahide MORIGUCHI, Toshiaki HATA, Atsuko YAMAMOTO
    1982 Volume 7 Issue SupplementII Pages 57-61
    Published: December 25, 1982
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    We subcutaneously injected collagen wound dressing (CAS) extracts equivalent to the area covering human body surface by 35 and 70%, respectively, into mouse dams from days 6 to 15 of pregnancy. No toxicity was observed in dams and no external, skeletal and visceral anomalies related to CAS treatment were observed in fetuses. It is, therefore, concluded that CAS extracts produces no teratogenesis after subcutaneous injection during organogenesis in mice.
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  • Ueto TAKEDA, Masuzo ODAKI, Masayuki YOKOTA, Hitoshi SASAKI, Tetsutaro ...
    1982 Volume 7 Issue SupplementII Pages 63-91
    Published: December 25, 1982
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Single administration of collagen wound dressing (CAS) made from bovine derm in the form of finely ground powders was given to mice and rats via i.p., s.c. and p.o. routes and via i.v. route in the form of physiological Saline extracts and it was continuously injected into mice for 28 days via s.c. route to study its acute and subacute toxicity. Examinations were made of on general conditions, body weight, food and water consumption; hematology, serum biohcemistry, organ weight, and gross and microscopic findings. Results showed no marked toxicity except for local irritation which was seen only after parenteral administration. We concluded on the basis of these animal experiments that there should be no problem in regard to safety after somewhat more extensive therapuetic application of CAS as a wound dressing in clinical practice.
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  • Kenichi AKATSUKA, Takao HASHIMOTO, Kouichi TAKEUCHI
    1982 Volume 7 Issue SupplementII Pages 93-105
    Published: December 25, 1982
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Guanabenz (WY-8678) was given to rats to examine its effects on their reproductive ability, dams and their fetuses. The drug was adininistered orally to rats at 30, 15, and 1 mg/kg/day. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg, and a control experiment where only vehicle was administered was also conducted. Male rats were treated for 60 days before mating and the treatment continued through mating. Female rats were treated 14 days before mating and the treatment continued from mating to the 7th day of gestation. The results obtained were as follows. 1. In male rats before mating in the 30, 15, and 5mg/kg groups, the increase of body weight tended to be suppressed, and decrease of food consumption and increase of water intake were found. In female rats before mating in the 30 and 15 mg/kg groups, increase of body weight tended to be repressed, and decrease of food consumption and increase of water intake were found in each group. 2. In the observation of males and females, the drug induced decrease in spontaneous movement, sedation, lacrimation of red exsudate and nebula of the eyeball. 3. In the reproduction test, copulations were confirmed in almost all rats by the second cycle of matings. However, the pregnancy rate tended to decrease a little in the 30 and 15 mg/kg groups. 4. Body weight increase during gestation was not affected by oral administration of 1 mg/kg, but was inhibited dose-dependently by administration of more than 5 mg/kg/day of Guanabenz. Food consumption and water intake tended to increase in drug-treated groups. 5. In the observation of the fetuses, the average number of corpora lutea were decreased in the 15 mg/kg group. The average number of implantations decreased in the 30 and 15 mg/kg groups. The implantation rate decreased in the 30 mg/kg group. No difference was observed in each group on the number of resorptions, the number of live fetuses, and the sex ratio. 6. No difference was observed in each group as to external and visceral malformations. In the skeletal observation, retardation of ossification was observed in the 30 mg/kg group. From these results, it is concluded that Guanabenz shows neither fatal effect nor teratogenic potential on fetuses in rats and the safe dosage level seems to be below 5 mg/kg/day.
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  • Kenichi AKATSUKA, Takao HASHIMOTO, Kouichi TAKEUCHI, Yoshiko YANAGISAW ...
    1982 Volume 7 Issue SupplementII Pages 107-121
    Published: December 25, 1982
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Guanabenz (WY-8678) was given to pregnant rats to examine its effects on dams, their fetuses, and offspring. The drug was administered orally to rats at 15, 5 and 1 mg/kg/day from the 7th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. In the observation of the dams, the increase of body weight tended to be repressed in the 15 mg/kg group, and body weight decreased in the 30 mg/kg group. 2. The drug produced decreased spontaneous movement, sedation, and lacrimation of red exsudate in dams. 3. Half of the 30 mg/kg group had a resorption, but there were no remarkable effects on length of gestation and nursing in the nursing group. 4. The weight of the thymus decreased dose-dependenly. 5. No difference was observed in each group in the number of corpora lutea, the number of resorptions, the number of live fetuses, sex ratio, and mean placental weight of the fetuses. The mean body weight of the fetuses decreased in the 30 and among 15 mg/kg groups. 6. In observation of the fetuses, no difference was observed among groups regarding external and visceral malformations. In the skeletal observation, retardation of ossification of the forelimb and hind limb was observed in the 30 and 15 mg/kg groups, and retardation of ossification of the sternebra was observed in the 30 mg/kg group. 7. In obervation of the offspring, the number of implantations, the number of live fetuses, delivery rate, and viability rate decrease in the 30 mg/kg group. No differense was observed among groups as to postnatal development symptoms, the faculties of sensation, and emotion. From these results, it is conducted that Guanabenz has no teratogenic potential in rats and the safe dosage level seems to be below 5 mg/kg/day.
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  • Kenichi AKATSUKA, Takao HASHIMOTO, Kouichi TAKEUCHI, Yoshiko YANAGISAW ...
    1982 Volume 7 Issue SupplementII Pages 123-139
    Published: December 25, 1982
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Guanabenz (WY-8678) was given to rats to examine its effects on dams and offspring in terms of influence on postnatal development emotion, learning and reproductive ability. The drug was administered orally to rats at 15, 8, 5, 2 and 1 mg/kg/day from the 17th day of gestation to the 21th post-partum day. The vehicle used was 5%-Arabic Gum at dose level of 5ml/kg and a tontrol experiment where only vehicle was administered was also conducted. The results obtained were as follows. 1. In observation of the dams, increase in body weight tended to be repressed after administration in the 8 mg/kg group, and in the 15 mg/kg group body weight decreased. Food consumption and water intake tended to be suppressed in the 15 mg/kg group. During nursing, changes of body weight, food consumption and water intake were not influenced by Guanabenz in each group. 2. The drug produced sedation, abnormal walking, decrease in a reflex test and lacrimation of red exsudate in dams. 3. In the 15 mg/kg group, the length of gestation was prolonged. Furthermore, abnormal delivery and nursing were observed, and in one-third of dams in the 8 mg/kg group and in all dams of 15 mg/kg group, the still-birth of all offspring was observed. No difference was observed among groups as to the organ weights at weaning. 4. In observation of the offspring, differences were observed in the viability rate and the weaning rate. No difference was observed among groups as to the viability rate, changes of body weight, postnatal development, and behavioral development on the 7th day. No differences were observed in each group regarding emotion, motion, perception and learning. 5. No difference was observed among groups in the reproduction test. As to symptoms seen in gestation, the dams and fetuses were not influenced by dosage of Guanabenz. From these results, the safe dose level seems to be below 5 mg/kg/day.
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  • Kenichi AKATSUKA, Takao HASHIMOTO, Kouichi TAKEUCHI, Yoshiko YANAGISAW ...
    1982 Volume 7 Issue SupplementII Pages 141-150
    Published: December 25, 1982
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Guanabenz (WY-8678) was given to pregnant rabbits to examine its effects on the dams and their fetuses. The drug was adimistered orally to rabbits at does of 10; 8, 5 and 1mg/kg/day from the 6th to 18th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 10 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. Concerning the effects on the dams, the symptoms of decrease in spontaneous movement and sedation were observed at 10mg/kg. However, mean body weight, food consumption, and organ weight were not influenced by Guanabenz. 2. In the observation of the fetuses, no difference was observed among groups in the number of corpora lutea, the number of implantations, implantation rate, the number of resorption, the number of dead fetuses, the number of live fetuses, sex ratio, mean body weight of the fetuses, mean body length of the fetuses, and mean placenta weight of the fetuses. 3. No difference was observed among groups regarding external malformations, visceral malformations, visceral malformations, skeletal variations and degree of ossification in the fetuses. From these results, it is concluded that Guanabenz has no teratogenic potential in pregnant rabbits and on effect no fetuses at doses of 8 mg/kg or lower.
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