The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 2 , Issue 2
Showing 1-8 articles out of 8 articles from the selected issue
  • Masayoshi TSUJI, Masaru SAITA, Tetsuo AOKI, Keiko YAMACHIKA, Hidetoshi ...
    1977 Volume 2 Issue 2 Pages 115-127
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Tolerance was provoked to all the pharmacological activities of H-88 examined, such as anti-inflammatory (Carrageenin-induced rat paw edema), analgetic (Tail pressure method in mice), hypothermic (Rectal temperature in mice), hypomotor activity (Wheal cage method in mice), prolongation of the sleeping time induced by pentobarbital Na (rats and mice), depression of gastric emptying and intestinal transport (rats) and stimulation to hypothalmo-hypophyse-adrenal axis (rats). The effect of H-88 on the pentobarbital Na-induced sleeping time in rats was not dissipated by adrenalectomy, and did not depend on the depression of intestinal absorption. The development of tolerance to H-88 was antagonized by ethionine pretreatment. It is suggested that tolerance to H-88 is mainly due to the hepatic enzyme induction.
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  • Yoshio OHMIYA
    1977 Volume 2 Issue 2 Pages 129-139
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Binding of methylmercury by human erythrocyte membranes was examined in association with the mercury-induced hemolysis. Organic mercurials such as p-chloromercuribenzoate and methylmercury showed less potent hemolytic activity than HgCl2. Entry of methylmercury into the erythrocytes was very rapid. Over 95 % of methylmercury was taken up by the cells within 5 min over the concentration range studied. Percent binding by the membrane of methylmercury was lower than HgCl2. Affinity of the intact membranes as well as of the isolated membranes was found to be lower for methylmercury than for HgCl2. Analysis by means of the Scatchard plot indicated a variety of binding sites of the erythrocyte membranes for the mercurials. The critical level of methylmercury required for hemolysis was about 200 nmole/mg membrane protein. No close correlation was observed between membrane sulfhydryl inhibition and hemolysis. The results presented here suggested that affinity of the erythrocyte membranes for the mercuials is one of the determining factors in hemolysis.
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  • Toshi HORIUCHI, Masao MAKINO, Takaharu NAKAYAMA, Shuji MASUDA, Kiyoko ...
    1977 Volume 2 Issue 2 Pages 141-147
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Treatment with 0.01, 0.1 and 1.0% chlormadinone acetate (CMA) contained diets for 33 days to guinea pigs showed no signs of the depression in adrenal, thymus and leucocyte count and no elevation of serum cholesterol. By the treatment with 0.01 and 0.1% cortisol contained diets, however, the atrophy of adrenal and thymic cortex, hypercholesterolemia and the enlargement of liver were noted in this species. It was therefore concluded that CMA had no cortisone-like properties in guinea pigs even at the excessive doses.
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  • Satoru TANAKA, Kin-ichi ONODA, Kunio KAWASHIMA, Shinsuke NAKAURA, Shig ...
    1977 Volume 2 Issue 2 Pages 149-159
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Pregnant Wistar rats received a single oral dose of 70 μCi/20mg/3ml/kg of 14C-labelled furylfuramide on the 20th day of gestation, and the radioactivity in maternal and fetal tissues was measured. High radioactivity was observed in the maternal liver and kidney at 3 hours after the administration, and the radioactivity of the maternal serum was lower than that of these two organs, but higher than that in other organs including placenta. The fetal body level of the radioactivity was about one-seventh of the maternal serum and about 0.4% of the dosed radioactivity was distributed in the fetuses. Dietary furylfuramide at the levels of 0.02, 0.06, 0.2 and 0.6% was given to pregnant Wistar rats ad libitum during pregnancy, and its teratogenic effects were examined in the fetuses and offspring. With the highest dose level a marked suppression in the maternal weight gain and food and water consumptions, and a considerable retardation in the embryonic developments were observed. A dose-dependent increase in the maternal liver weights was also noticed in the furylfuramide treated groups compared with the control. However, no evidences of increase in fetal death as well as malformation to be attributable to the treatment of furylfuramide were obtained, and the postnatal developments of the newborns were well maintained without any disorders in morphological and functional examinations.
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  • Miyakichi YAHARA, Toshio INOUYE, Fumio OGINO, Takashi UNNO, Mariko TER ...
    1977 Volume 2 Issue 2 Pages 161-198
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    At dose levels of 5, 20 and 60 mg/kg, dehydroepiandrosterone sulfate (DHA-S) was given intravenously for 30 successive days to female beagle dogs with the following results. 1) The chief general symptoms were vomiting, salivation and discharge of milk. Vomiting and salivation developed after the drug in doses of more than 20 mg/kg and in the dose of 60 mg/kg respectively, while discharge of milk was seen in dogs treated with the drug of more than 20mg/kg. 2) Hematological, serum biochemical and urinary examinations revealed no abnormalities. 3) Examination of organ weights disclosed only an increasing tendency of the liver weight in 60mg/kg group. 4) Histological findings were slight degranulation of the pituitary basophil in 60mg/kg group and atrophic tendency of the thymus in 1 out of the 3 dogs of the same group. Narrowing of the adrenal zona fasciculata occurred in 1 out of the 3 dogs of 60mg/kg group. Luteinization in the ovary was especially remarkable in 60mg/kg group. Secretion from the uterine glandular cell and edematous tendency of the endometrium were detected mostly in 60mg/kg group. Dogs of 20 and 60mg/kg groups showed proliferation of mammary gland cells with discharge of milk. 5) There were no abnormalities on electron micrography of the liver. 6) All changes mentioned above essentially disappeared during the recovery test of 1 month's duration. Therefore, a possible maximum dose of DHA-S which does notcause adverse reaction was evidenced to be about 20 mg/kg in dogs.
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  • Toshiki NISHIGAKI, Seiki MINAMIDE, Masayuki NAKAZAWA
    1977 Volume 2 Issue 2 Pages 199-212
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    In order to investigate the effect of N-(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-atopic agent, on renal functions, the present experiment was carried out using Wistar male rats. N-5' was given orally at doses of O (control), 200, 400 and 800 mg/kg for 5 weeks. For the purpose of the regression test, four or five animals in each group were kept without drug for 5 weeks after the termination of drug administration. One fatality, which showed an inhibition of body weight gains and a slight increase in water intake, was found only in the animals treated with 800mg/kg. In urinalysis at the 1st and 3rd week of experimental period, a slight increase in urine volume and decreases in specific gravity and electrolytes were found in the animals treated with 800 mg/kg, but not at the 5th week and in the regression test. Abnormalities were not observed in renal concentration test, PSP excretion test, urea nitrogen level in serum and 24hr-endogenous creatinine clearance test. In histopathological examination, no lesions could be seen. On account of these results, N-5' seemed not to have the potential of renal toxicity.
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  • Katsuyuki NAKAJIMA, Satoshi TSUCHIYA, Takashi NAKAJIMA, Kenji HARADA, ...
    1977 Volume 2 Issue 2 Pages 213-225
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Recently the cases of suicides committed by the auto exhaust gas have increased, estimating more than 1, 500 people for a year 1975 in Japan. The representative case of the suicide was reproduced and mice, rats and rabbits were placed inside the car for the gas exposure. In attempt to see which factors play major role in the development of acute poisoning due to inhalation of auto exhaust gas, we investigated toxic states of rats, mice and rabbits induced by the exposure to auto exhaust gas, carbon monoxide and oxygen deficient air. The effect of these gases varied considerably from each other with regard to time period till the loss of righting reflex and respiratory arrest, respiratory and cardiac rate and blood pressure. Auto exhaust gas appeared far more toxic than carbon monoxide per se. The reduction of oxygen concentration increased the toxicity of both carbon monoxide and auto exhaust gas. Furthermore, the carbon monoxide combined with oxygen deficiency produced effects on the constellation of these parameters markedly similar to those of auto exhaust gas. It is estimated that the combination of high carbon monoxide concentration and oxygen deficiency are largely responsible for acute intoxication by auto exhaust gas.
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  • Norihiko KOBAYASHI, Shiro OHMORI, Masao MINEMOTO, Takao GOJO, Sadao NA ...
    1977 Volume 2 Issue 2 Pages 227-237
    Published: April 15, 1977
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Effects of orally given L-glutamine, MMSC1, antacids (magnesium aluminosilicate·CaCO3) or their combination on various experimental gastric or duodenal ulcer and gastric secretion in rats were studied. 1. L-Glutamine at 1, 284mg/kg or MMSCI at 80mg/kg did not inhibit the stress ulcer induced by water-immersion stress (25°C, 20hr), while antacids at 1, 636mg/kg showed a tendency for inhibition of the ulcer. The combination significantly inhibited the development of the ulceration and resulted in a potentiation of the effect caused by each drug alone. 2. L-Glutamine at 427.8mg/kg, MMSCI at 26.7mg/kg or antacids at 545.5mg/kg did not inhibit Shay ulcer (48hr fasting, 12hr ligation). The combination significantly inhibited the ulcer and resulted in a potentiation of the effect caused by each drug, at which time the gastric acidity and the pepsin activity were significantly reduced. 3. L-Glutamine at 427.8mg/kg or antacids at 545.5mg/kg did not inhibit the development of the gastric lesions induced by noradrenaline and serotonin (4hr), while MMSCI at 26.7mg/kg showed inhibition of the ulcer. The combination markedly inhibited the ulcer and resulted in a potentiation of the effect caused by each drug alone. 4. L-Glutamine at 427.8mg/kg inhibited the development of the gastric lesions induced by aspirin in pylorus-ligated animals (7hr), while MMSCI at 26.7mg/kg or antacids at 545.5mg/kg did not inhibit the ulcer at all. The combination markedly inhibited the ulcer and resulted in a potentiation of the effect caused by each drug alone. 5. Consecutive administration of L-glutamine (855.6mg/kg/day), MMSCI (53.4mg/kg/day) or antacids (1, 019mg/kg/day) for 10 days after ulcerative operation showed a significant effect for the healing of gastric ulcer. The combination revealed a significant effect but not d potentiation of the effect caused by each drug alone. 6. Consecutive administration of L-glutamine (427.8mg/kg/day), MMSCI (26.7mg/kg/day) or antacids (545.5mg/kg/day) for 10 days failed to affect the healing of duodenal ulcer, whereas the combination revealed a significant acceleration of the healing and resulted in a potentiation of the effect caused by each drug alone. The dosing by L-glutamine (855.6mg/kg/day), MMSCI (53.4mg/kg/day) or antacids (1, 019mg/kg/day) showed a significant effect for the healing.
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