Eisei Shikenjo hokoku. Bulletin of National Institute of Hygienic Sciences最新文献

A 28-day oral toxicity test of Phoxim was carried out in male and female Slc: Wistar rats given dose levels of 0, 7.5, 75 and 750 mg/kg/day by gavage. A 14-day recovery test was conducted for animals receiving the 750 mg/kg dose level. There were no deaths with any dose and food consumption and growth were not affected. No specific changes were observed in any of the hematological parameters investigated. At the 750 mg/kg level, significant increases of liver, kidney, and adrenal gland weights were observed in both sexes, which persisted throughout the recovery period. Hepatic lesions with necrosis and swelling of hepatocytes were also observed with the highest dose, but these changes appeared to be reversible because they were no longer present after the recovery period. At doses of 7.5 mg/kg and above, remarkable inhibition of the serum cholinesterase activity was observed in both sexes. This persisting in female rats after the recovery period. Based on these results, the no-observed-effect level (NOEL) was concluded to be less than 7.5 mg/kg/day under the present experimental conditions.

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 191 samples tested, seven were found to inhibit the growth of HIV in vitro. Four of seven have hopeful signs, as the ranges of effective doses of the samples are wide.

To examine toxicities of nitrobenzene as part of the re-evaluation of toxicities of existing chemicals, a 28-day repeat dose toxicity study was performed in male and female F344 rats at dosages of 0, 5, 25 and 125 mg/kg/day of nitrobenzene. All rats in each group consisting of 6 males and 6 females received a daily intragastric administration of this chemical for 28 days. Additional two groups of animals exposed to 0 and 125 mg/kg/day were used for examinations of subsequent recovery for 2 weeks. One female in the 125 mg/kg group died on day 27. Decreased movement, pale skin, gait abnormality and decreases of body weights or their gains were seen in the 125 mg/kg group. Hematology revealed decreases of RBC, Hb and Ht in the 25 and/or 125 mg/kg groups. Blood biochemistry revealed increases of total cholesterol and albumin and decreases of BUN in the 25 and 125 mg/kg groups, and increases of A/G ratio in both sexes and ALT, ALP and total protein in females in the 125 mg/kg group. In the organ weight, increases of the liver, spleen, kidney weight and decreases of the testis and thymus were seen in the 125 mg/kg group. In addition, the increased liver weight was also seen in males receiving 5 mg/kg, and the increased spleen weight in both sexes receiving 25 mg/kg. Histopathology revealed spongiotic changes and brown pigmentation in perivascular region of the cerebellum, increased extramedullary hematopoiesis of the liver, brown pigmentation of renal tubular epithelium and degeneration of seminiferous tubular epithelium and atrophy of seminiferous tubule in the 125 mg/kg group, and congestion, increased brown pigmentation in red pulp and increased extramedullary hematopoiesis of the spleen and increased hematopoiesis of the bone marrow in treated groups. Findings mentioned above disappeared or tended to be decreased during or at the end of the recovery period. Although no effect-dose level was detected in this study, severe anemia and disorder of spermatogenesis and central nervous system which have been reported in the long-term toxicity study could be reconfirmed.

A determination method for total bromine that presents in various chemical forms in foods by gas chromatograph with ECD was investigated. Food samples were ashed with KOH at 600 degrees C for 2h and the residue was dissolved in water and filtered. The filtrate was acidified with sulfuric acid, and potassium permanganate solution was added to the solution. The liberated bromine was reacted with cyclopentanone and the product was extracted with hexane and quantified by gas chromatograph with ECD. Recovery of bromine by this method was more than 80% and the detection limit was lower than that of the conventional method. The total bromide in the samples prepared for the total diet study program was quantified by this method and the total intake of bromine was estimated. The total intake of bromine was 8-12 mg and about 20% of ADI (1 mg/kg/day).

Weight variation and content uniformity tests are both intended to ensure the uniformity of dosage units. In the Japanese Pharmacopoeia, modifications to these tests have been proposed in thirteenth revision with new concepts based on statistical considerations. The points of change are as follows: 1. introduction of a variables requirement, 2. matching of sampling plans of weight variation and content uniformity tests, 3. clarification of conditions for application of content uniformity tests, 4. criterion of quality based on deviation not from the sample mean but from the label claim.

A new approach to standardization of plastic containers for pharmaceuticals in the Pharmacopoeia of Japan (JP) has been proposed, structured into the following three parts: (1) "Plastic Containers for Pharmaceuticals" in the GENERAL INFORMATION section that describes the general requirements and rationales for conformity; (2) "Test Methods for Plastic Containers" in the GENERAL TESTS section that describes various test methods applicable for verifying conformity; (3) Special requirements and/or limit values for special containers such as infusion bags in a MONOGRAPH section. New standards should be designed to cover plastic containers of any shape and volume made of any kind of material.

A 13-week subchronic toxicity study of bisphenol A (BPA) was performed in male and female B6C3F1 mice at dose levels of 0, 0.2, 0.5, 1.0, 2.0 and 4.0% in the diet, to facilitate dose selection for a subsequent carcinogenicity study. Mice were randomly allocated to 6 groups, each consisting of 10 males and 10 females. Two 0.2% group males and two 4.0% group females died during the experimental period. Suppression of body weight gain and increase in food consumption were observed in males and females of the 4.0% groups. Hematological examination revealed decrease in number of erythrocytes, volume of hemoglobin and value of hematocrit in males and females of the groups receiving 1.0% or above, and an increase in number of platelets in males of 4.0% group. Decrease in number of erythrocytes and hematocrit value was also noticed in females of 0.5% group. Histopathologically, cystic dilatation, degeneration or regeneration of renal tublues were found in males and females of 1.0% or higher groups, multinucleated hepatocytes were increased in mice of both sexes treated with any dose of BPA, and fibrous osteodystrophy was observed in males and females of the 4.0% groups. Based on the results of the present study, it was concluded that the maximum tolerance dose (MTD) of BPA is 0.2% in diet, because the dose level of 0.5% proved to exert significant hematological toxicity.

Raw progesterone material was tested for preparation of the "Progesterone Reference Standard (Control 931)". Analytical data obtained were as follows: melting point, 131.6 degrees C; infrared spectrum, the same as that of the JP Progesterone Reference Standard; optical rotation, [alpha]D20 = +181.1 degrees; thin-layer chromatography, no impurity was detected; high-performance liquid chromatography (HPLC), trace amounts of two impurities were detected; loss on drying, 0.23%; assay results, 99.4% by UV spectrophotometry in the JP XII and 100.5% by HPLC. Based on the above findings, the raw material was authorized as the JP Progesterone Reference Standard (Control 931).

Summaries of first drafts of Environmental Health Criteria (EHC), which were circulated for comments by IPCS in the period of 1993 approximately 1994, are presented. EHC drafts on 10 compounds were received in this period.

A 13-week subchronic toxicity study of L-histidine monohydrochloride was performed in male and female F344 rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5.0% in the diet, to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Suppression of body weight gain and decrease in food consumption were observed in males of the 5.0% group along with hematological examination as revealed by increases in hemoglobin volume and hematocrit. Serum biochemical examination demonstrated increased levels of BUN and creatinine in females of the 5.0% group, and increased level of BUN in females of the 1.25% group. Histopathologically, sperm granulomas in the epididymis were found in half of the 5.0% group males. Based on the results of the present study, it was concluded that the MTD of L-histidine monohydrochloride is 2.5% in diet, because the dietary dose level of 5.0% proved to exert significant toxicity reflected in suppression of body weight gain and formation of sperm granulomas.