Chlorine-containing cyclic pentapeptide (Cl-peptide) is one of the hepatotoxic and hepatocarcinogenic metabolites of Penicillium islandicum Sopp. The sc LD<50> values of Cl-peptide for mice, rats and guinea-pigs were all in the range of 0.5 mg/kg, while the po LD<50> values for mice and rats were around 5mg/kg. The newborn mice were less susceptible than the adults. The acutely intoxicated mice and rats showed a marked elevation of serum transaminases and a transient increment followed by a marked decline of blood glucose level. The liver of animals pretreated with the toxin showed marked declines of glycogen and microsomal protein and an increase of cyclic AMP content. Tracer experiments revealed a preferencial accumulation of the toxin in the liver of mice and an excretion through feces. Correlation between the hepatotoxicity and the hepato-accumulation of the cyclic peptide was discussed.
Mice were exposed to toluene vapor at 1, 10, 100 and 1, 000ppm for six hours daily over a period of 20 days. Observations were made on the animals' wheel-turning activity during exposure and on the findings of peripheral blood and the bone marrow. In wheel-turning activity, all exposed groups showed less cumulative rounds than the control group. The group of 1 ppm ten days after exposure and the other exposed groups 6 to 8 days after exposure tended to show less rounds than the control group. Regarding peripheral blood findings, the groups of 100 ppm and 1, 000 ppm showed a decrease in red cell count. Each group of 10, 100 and 1, 000 ppm showed a decrease in thrombocyte count. All exposed groups showed an increase in white cell count in the midway of experiments and afterwards showed a recovery except the group of 1, 000 ppm. Regarding the bone marrow, the group of 1, 000 ppm showed a trend of hypoplasia and no other exposed groups showed remarkable changes. From the above findings of peripheral blood and the bone marrow, the extent of disturbances in toluene exposure seemed slighter than that in benzene exposure. It was revealed, however, that exposure to as low as 1 to 100 ppm of toluene influenced mice's spontaneous activity. In Japan, from an industrial health view point, 100 ppm has been recommended to be allowable limits for toluene in workplace air. The present authors' experimental data advocate still lower allowable limit.
An animal experiment with rats was carried out to determine the effects of simultaneous administration of Cd and Zn on the accumulation of Cd in organs during long-term exposure. The diet for Group I contained 50ppm Cd and that for Group II contained 50ppm Cd and 500ppm Zn. Group III was the control group. One-half of the animals in each group were sacrificed after 6 weeks of exposure and the other half after 13 weeks of exposure. Cd, Zn, and Cu concentrations in the liver and the right kidney and Ca concentration in the femur were analyzed. The left kidney was examined histopathologically. The increase of body weight in Group II diminished in the 4th and 5th weeks of exposure, but returned to the normal rate by the 12th week. The average renal Cd concentration of Group I was significantly higher than that of Group II, but no differences was found for that in the liver. Zn accumulation in the liver and the kidney was increased by administration of Cd and it did not depend on the concentration of Zn in diet. No significant intergroup differences were found for Ca concentration in the femur. Cu accumulation in the exposed groups showed a marked increase in the kidney and slight decrease in the liver. Although significant histopathological changes were not observed in the kidney of the exposed groups, some unfavorable influence of Zn on the renal toxicity of Cd was suggested. From these results, it is concluded that Cd accumulation in organs is not influenced by the simultaneous administration of Zn, but Zn concentration increases in the liver and the kidney with Cd exposure.
The toxic effects of 13 food dyes were studied on Artemia salina larvae. It was found that xanthene dyes containing halogen atoms in their molecules were more toxic, Phloxin and Rose Bengal containing chlorine especially toxic, than the other groups of food dyes. The effect of food dyes on leucine aminopeptidase and lactate dehydrogenase activities in Artemia salina was studied in order to investigate the mechanism of the toxicity. It was shown that lactate dehydrogenase activity was inhibited completely by Phloxin and Rose Bengal, and that leucine aminopeptidase activity was not inhibited by these dyes in contrast to the remarkable inhibition of that in Paramecium caudatum by these dyes. These results and some kinetic experiments described later suggested that the property of leucine aminopeptidase from Paramecium caudatum was different from that of Artemia salina. The effect of food dyes on lactate dehydrogenase activity was also studied in vitro and the mechanism of the toxicity was discussed in relation to the anaerobic metabolism in Artemia salina.
Cell lysis and changes of shape were examined to elucidate the effects of injections on rat erythrocytes. Hemolysis did not occur within the range of pH 5.5-8.0 and 160-700 mOsm/kg in a period of 2 hrs at 37°C. Clear change of shape were not observed within the range of pH 7.0-8.0 and 280-300 mOsm/kg in a period of 2 hrs at 37°C by a scanning electron microstopy. Benzyl alcohol, ethyl alcohol and propylene glycol showed strong hemolytic activity at the concentration, regularly contained in injections. Benzyl alcohol produced internalization of erythrocytes ; however clear morphological change was not observed with ethyl alcohol or propylene glycol. The effects of other drugs or ingredients in injections were also examined.
The increasing scope of government regulation is leading to a vastly expanded market for chemical flame retardants. Their toxicological and biological properties, however, have not been investigated sufficiently. In general the animal experiments which have been the routine method for the evaluation of toxic effect of chemicals take a long time and much money. From the above-described viewpoint, we examined in this report the cytotoxicity of some flame retardants on various cultured mammalian cells and investigated its usefulness as a simple, rapid and relatively inexpensive screening method. The results obtained were as follows; 1) The cytotoxic degree caused by several flame retardants on HeLa cells correlated fairly well to the oral acute toxicity (LD<50>) on mice or rats. Enlargement of the cell and nucleus sizes and appearance of polynuclear cells were the characteristic changes by morphological examination. 2) Similar effect was observed on other cell lines tested, except on DL 1 cell lines which were more sensitive to some of the tested flame retardants. 3) Examination on the primary cultured cells from liver, kidney, brain and muscle showed that there was no marked difference among their susceptibility. In addition, the applicability and usefulness of the cytotoxicity experiments using cultured mammalian cells were discussed.
"Malti" is a commercial sweet material which contains maltitol in a concentration of more than 75 per cent. Groups of male and female Wistar rats were maintained on diets containing "Malti" in concentrations of 3% and 10% for one and a half years (78 weeks), in order to study long-term toxicity with special reference to carcinogenicity. During the experiment, no unusual signs were observed among the test rats. Growth and food consumption data revealed no Malti-related differences. Hematologic parameters and clinical blood chemistry data showed no significant differences except for a lowering of serum cholesterol level in all Malti groups. Pathologic and patho-histologic examinations revealed no diffinite abnormalities. Carcinogenit activity was also negative.