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

A 13-week oral toxicity study of gardenia blue was performed in male and female F344 rats at the dose levels of 5.0, 2.5, 1.25, 0.6 and 0% in the diet, to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No groups showed decreases in body weight gain and food intake, and all animals survived until the end of the experiment. A dose-dependent decrease in number of platelets was observed in females treated with gardenia blue in hematological examination, but not in males. No histopathological change, relating to the treatment, in megakaryocyte which is the progenitor cell of platelets was observed in the treated-females. Serum biochemistry revealed increases in GOT and GPT in both sexes treated with the 5.0% and 2.5% gardenia blue, as compared to the control value. However, these were not considered to be specific changes because of lack of any clear dose response. In addition, no histopathological changes indicating obvious toxicity of gardenia blue were observed in the liver of both sexes treated with gardenia blue. Based on these data, the MTD of gardenia blue for both sexes in F344 rats was considered to be 5.0% or more in the diet.

We have been surveying toxic substances in food and foodstuffs and carrying out a total diet study on the intakes of various substances since 1979 in cooperation with local public institutes in Japan. In this paper, we report the daily intakes of mercury, PCB and arsenic from foods, and the relation between the concentrations of these substance in fish and the fish body weight. The intakes of mercury and arsenic were 6.9-11.0 micrograms/ man/day and 120-230 micrograms/man/day, respectively. The intakes of these substances remained on a stable level from 1979 to 1994. On the other hand, the intake of PCB decreased from 3.1 micrograms/man/day in 1979 to 0.9 microgram/man/day in 1994. Most of the intakes of mercury, PCB and arsenic were derived from the diet group "fish and shellfish". The level of mercury in fish increased with increasing fish body weight. For PCB and arsenic, there was no correlation between these concentrations in fish and the fish body weight, except that mackerel and croaker show a higher concentration of PCB when they are small. Arsenic shows almost a constant level in each fish regardless of their body weight.

A structure-based pharmaceutical database for drug interactions has been developed. This database is based on the ISIS/Desktop and the Microsoft Access relational database system for Windows. Data of Japanese accepted name, molecular formula, molecular weight, CAS registry number, therapeutic category index code, structural formula, Japan ethical drugs code, side effects information, drug interactions information were taken from "Japanese Accepted Names for Pharmaceuticals 1992", "Drugs in Japan Ethical Drugs 1993" and "Drug Intelligence Reinforce".

A restriction endonuclases (ENase) designated EcoO44I was purified without non specific nucleases from enteropathogenic Escherichia coli O44 Hiromi strain of affected human origin. The yield was 1, 100 units/g of wet cells. The EcoO44I ENase recognized and cleaved the specific sequence of 5'-GGTCTC-3' (1/5) as was the case with Eco31I or BsaI ENase. Because of the stability and high yield, EcoO44I would be useful for recombinant DNA technology after isolation of EcoO44-positive, avirulent mutant strains of E. coli O44 Hiromi.

The ability of high performance anion exchange chromatography (HPAEC) with pulsed amperometric detection was studied for evaluation of carbohydrate moieties of erythropoietin (EPO) products. The N-linked oligosaccharides were released from EPO by the treatment with N-glycosidase F. HPAEC analysis of oligosaccharide standards revealed that elution time of sialylated oligosaccharides were dependent on the number of sialic acid, which contributed to the activity of EPO. Using HPAEC, N-linked oligosaccharides of two kinds of recombinant human EPO (rhEPO) produced in chinese hamster ovary (CHO) cells and baby hamster kidney (BHK) cells were compared. The HPAEC profiles of oligosaccharides of these EPO products indicated that there were some differences in the carbohydrate moieties between CHO rh-EPO and BHK rh-EPO. In conclusion, HPAEC method is useful to evaluate the quality of EPO products.

Carbon monoxide in imported tilapia was determined with a gas chromatograph equipped with a molecular sieve 13x column (2.3 m), a methanizer and a FID for the inspection of imported food. The concentration of carbon monoxide in the sample, which was vacuum packed and suspected to be treated with carbon monoxide, was 16 x 10 micrograms/kg in fish meat, and 37 x 10(3) microliters/l in the bubble in the package. On the other hand, carbon monoxide in the reference, which was vacuum packed but was not treated with carbon monoxide, was 10 micrograms/kg in fish meat and 76 microliters/l in the bubble in the package. Carbon monoxide was less than 4 micrograms/kg in two vacuum packed fish meat of tilapia sold in a market in Tokyo. From these results, the suspected sample was concluded to be treated with carbon monoxide for color fixating of protoheme in fish meat.

The raw material for cholecalciferol was tested for preparation of the "Cholecalciferol Reference Standard (Control 941)". Analytical data obtained were as follows: melting point, 88.5 degrees C; UV and infrared spectra, the same as those for JP Cholecalciferol Reference Standard (Control 923), respectively; specific absorbance at 265 nm E1%1cm = 471; optical rotation, [alpha]20D = +107.3 degrees; thin-layer chromatography and high-performance liquid chromatography (HPLC), no impurities were detected, respectively; assay, 101.3% by HPLC. Based on the above results, the candidate raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).

The raw material of ulinastatin was examined for preparation of the "Ulinastatin Reference standard". The candidate material was evaluated in collaboration with one domestic laboratory, and the potency of trypsin inhibiting activity was determined to be 3500 unit/vial. Other analytical data obtained were as follows: UV maximum absorption was observed at 276 nm, the molecular weight was estimated to be about 66000 +/- 5000 by gel filtration method. Maximum variance of material contents in 10 vials was 6.52% by means of the weight variation test in JP XII. Based on the above results, this raw material was authorized to be the first "Ulinastatin Reference Standard" of the National Institute of Health Sciences.

A 13-week subchronic toxicity study of josamycin was performed in male and female F344 rats to determine the maximum tolerable dose (MTD) for subsequent investigation of the carcinogenicity. As animals refused to take diet containing 5.0% josamycin in our preliminary study, dose levels in the present study were determined as 0, 0.16, 0.32, 0.63, 125 and 2.5% in diet. Rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animal died during the administration period and no group showed significant changes in body weight gain. Definite toxicity of josamycin was not noted in hematological and serum biochemical examinations. Histopathological examinations revealed no particular findings related to josamycin administration except cecal enlargement in the 1.25 and 2.5% groups. based on the results of the present study, it was concluded that the MTD of josamycin in 2.5% in diet, because the dietary dose level of 2.5% proved to exert no significant toxicological signs.

The number of official inspection of coal-tar dyes and their lakes from April in 1994 till March in 1995 were 635 in total. The quantity which passed inspection amounted to 186 ton in Japan. The production of color in each month was summarised in Table 1, and by each producing company in Table 2. The food coal-tar dye produced in the largest quantity was Food Yellow No.4, occupying 40.7% in this period.