53 Reproductive and Neurobehavioural Toxicity Studies of Amaranth Administered to Mice in the Diet or in Drinking Water
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TOYOHITO TANAKA, OSAMU TAKAHASHI, SHINSHI OISHI |
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The colour additive amaranth was given in the diet at levels of 0 (control), 0.03, 0.09, and 0.27%, or in drinking water at levels of 0 (control), 0.025, 0.075, and 0.225% from 5 weeks of age in the F0 generation until
weaning of the F1 generation to mice, and selected reproductive and neurobehavioural parameters were
measured. Amaranth produced few adverse effects on either litter size or litter weight and sex ratio at birth.
There were no significant adverse effects of amaranth on the average offspring weight during the lactation
period. In neurobehavioural parameters, swimming direction on postnatal day (PND) 4 and olfactory
orientation on PND 14 were significantly affected in male and female offspring in a dose-related manner in the
diet study. In drinking water study, swimming head angle on PND 4 and olfactory orientation on PND 14 were
significantly affected in both male and female offspring in a dose-related manner. The dose levels of amaranth
in these studies produced some adverse effects on neurobehavioural parameters in mice.
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Food Red No.2, amaranth, reproductive toxicity, behavioural development, mice |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,279-285,2000 |
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54 Subchronic Toxicity of Suprout Suppressant Chlorpropham (CIPC) in Mice
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TOMOKO FUJITANI, YUKIE TADA, AYA FUJII, MIYAKO KIMURA, MASAKO YONEYAMA |
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Subchronic toxicity of chlorpropham (CIPC), a widely used sprout suppressant, was studied in ICR mice. Groups of ten male and ten female mice 5 weeks old were given diet containing 0, 1875, 7500 or 30000 ppm of CIPC for 13 weeks, then were hematologically and pathologically examined. Methemoglobin level were significantly elevated in both sex of the 7500 and 30000 ppm groups. Hemoglobin concentration, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and white blood cell counts in both sex of the 30000 ppm group were significantly increased. Dose-dependent splenomegaly was observed in both sex of the 7500 and 30000 ppm group. Congestion of red pulp, lymphoid atrophy, increased extramedullary hematopoiesis and increased hemosiderin deposition were observed in the spleen of those mice. Mild hepatomegaly was observed in both sex of the 30000 ppm group.
Hepatocellular hypertrophy with eosinophilic granular cytoplasm, sinusoidal dilatation, hemosiderin deposition, extramedullary hematopoiesis and hepatocellular necrosis were observed in the liver of those mice. Hematopoietic cell hyperplasia and hemosiderin deposition were observed in the bone marrow of both sex in the 30000 ppm group. Hemosiderin deposition in renal tubules was observed in both sex of the 30000 ppm group. The results suggested that subchronic administration of CIPC in the diet for 13 weeks was hemotoxic and hepatotoxic in ICR mice.
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chlorpropham, sprout supressant, herbicide, subchronic, hemotoxicity, mice |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,286-291,2000 |
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55 Studies on Antitumor and Antimetastatic Activities of Rokumi-gan in Rats
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KUNIAKI TAYAMA, HIROSHI TAKAHASHI, NORIO YANO, KATSUHIRO YUZAWA, AKEMICHI NAGASAWA, YOSHIMITSU, SAKAMOTO, NAOTO AOKI |
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chinese medicine, Rokumi-gan (Liu-Wei-Wan), antitumor activity, antimetastatic activity, rat bladder tumor |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,292-294,2000 |
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56 Studies of Antitumor Effect of Juzen-taiho-to and the Synergistic Effect with Cisplatin in Rats
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KUNIAKI TAYAMA, YOSHIMITSU SAKAMOTO, NORIO YANO, HIROSHI TAKAHASHI, KATSUHIRO YUZAWA, AKEMICHI NAGASAWA, NOBUTAKA FUKUMORI, YUKIE TADA, SHINOBU HAYASHIDA, NAOTO AOKI |
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chinese medicine, Juzen-taiho-to (Shi-Quan-Da-Bu-Tang), antitumor effect, antimetastatic effect, rat bladder tumor, cisplatin (CDDP) |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,295-300,2000 |
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57 104-Week Feed Studies of Juzen-taiho-to in F344 Rats
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YOSHIMITSU SAKAMOTO, YUKIE TADA, KUNIAKI TAYAMA, AKEMICHI NAGASAWA, NOBUTAKA FUKUMORI, NORIO YANO, KATSUHIRO YUZAWA, HIROSHI TAKAHASHI, TORAO IKEDA, NAOTO AOKI |
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Chronic toxicity of Juzen-taiho-to, a Chinese medicine, in F344 rats was examined. Groups of F344
rats, each consisted of 20 males and 20 females, were fed a pelleted diet containing Juzen-taiho-to at
concentrations of 0 (control), 0.2, 0.8 and 3.2% for 104 weeks. The dose of 0.2% Juzen-taiho-to corresponds to
the therapeutic dose in humans. Following the completion of the experiment, no difference was observed in
survival between the treated and control groups of both sexes. There was no evidence of adverse effects of
the treatment on the body and organ weights, hematology and serum biochemical examination. A variety
of non-neoplastic and neoplastic lesions was observed in all groups, including the controls, but all were
those known to occur spontaneously in F344 rats. No significant increase in the severity and/or incidence
of any lesion was found for either sex in the treated groups. Under the present experimental condition,
there was no evidence of toxic effects and carcinogenicity of Juzen-taiho-to in rats. Additionally, chronic
nephropathy (a spontaneous lesion) was milder in the treated groups than the control groups. This result
suggests that Juzen-taiho-to may retard the progression of chronic nephropathy. |
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Juzen-taiho-to, chinese medicine, F344 rats, 104-week feeding test |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,301-307,2000 |
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58 Effects of Natural Food Additive on Mouse Embryos with the Use of
Whole Embryo Culture Method IV Tea Extracts
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AKIO OGATA, HIROSHI ANDO, YOSHIKAZU KUBO, NAOTO AOKI |
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To study the effects of tea extracts (TE) on mouse embryos, whole embryo culture was carried out. On day 8 of gestation (plag day = day 0), CD-1 (ICR) mouse embryos were explanted and cultured for 48 hrs. Twenty-four hrs after the start of culture, the cultured mouse embryos were directly exposed to the medium containing 0 (control), 31.25, 62.5, 125 µg/ml of TE. Yolk sac diameter, blood circulation in the yolk sac, crown-rump length of the embryo, number of somites, heart beats and the shape of embryos were used as parameters for the development of conceptus including the embryo. No significant difference was observed between the control and the exposed groups on the mean diameter of the yolk sac, the number of somites and the shape of embryos. However, an increased number of embryos with poor developmet of blood circuration in the yolk sac and the decreased mean number of heart beats were noticed in the group given 125 µg/ml TE. An embryo with developmental retardation of the first branchial arch was observed in the group treated with 125 µg TE/ml . These results suggest that a high dose of TE affects the development of mouse embryos, but has no teratogenic effects.
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mouse, whole embryo culture, natural food additive, tea extracts |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,308-310,2000 |
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59 Long Term Toxicity Studies of Lac Color in F344 Rats
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YOSHIMITSU SAKAMOTO, YUKIE TADA, KUNIAKI TAYAMA, AKEMICHI NAGASAWA, NOBUTAKA FUKUMORI, NORIO YANO, KATSUHIRO YUZAWA, HIROSHI TAKAHASHI, TORAO IKEDA, NAOTO AOKI |
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Groups of F344 rats, each consisted of 20 males and 20 females, were fed a pelleted diet containing lac color at concentrations of 0 (control), 0.313, 1.25, 5.0% for 78 weeks. An increase in the absolute and relative organ weight of parotid gland, a major salivary gland, was observed in both sexes of the 5.0% group. In the female 5.0% group, absolute and relative weight of the submaxillary gland was also increased. Dose-related histological changes were observed in the parotid gland and kidney. Histological examination of the parotid gland revealed diffuse hypertrophy of acinar cells. These changes were observed in both males and females of the groups given doses of 1.25% or more. Although mineralization at the cortico-medullary junction in kidney is a spontaneous lesion, increased incidence and enhancement of this lesion by lac color administration were observed. Incidence and severity of this lesion in females were higher than those in males. There were no dose-related changes in clinical signs, mortality, body weights, and food and water consumption in either male or female rats. Except for the salivary glands, changes indicating obvious toxicity of lac color were not observed in organ weights, hematological and serum biochemical examination.
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lac color, food additive, F344 rats, 78-week feed study |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,311-316,2000 |
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60 Ultrastructural Changes of the Parotid Gland in Rats Fed with Lac Color
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NOBUTAKA FUKUMORI, YOSHIMITSU SAKAMOTO, NAOTO AOKI |
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Hypertrophy of the rat parotid gland has been reported in the previous 13-week toxicity test for lac color. Ultrastructural changes in the parotid gland after two-week or four-week feeding with 5% lac color were studied in rats by transmission electron microscopy. In the hypertrophic parotid gland associated with lac color treatment, an increase of zymogen granules was observed in the acinar cells of the terminal portion. The secretory granules within the acinar cells were also enlarged and electron-translucent. The results revealed that the hypertrophy of the parotid gland was associated with ultrastructural abnormalities of secretory granules in the acinar cells.
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lac color, parotid gland, rat, electron microscopic observation |
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Ann.Rep.Tokyo Metr.Res.Lab.P.H., 51,317-322,2000 |