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

Liver tumor-promoting effects of anthelminthic agents, febantel (Feb), fenbendazole (Fen) or oxfendazole (Oxf), were investigated in a rodent 2-stage carcinogenesis model. Five-week-old male F344 rats were initiated with or without diethylnitrosamine (DEN) and one week later given diet containing Fen (3600, 1800, 600, 200 or 70 ppm), Feb (2000, 1000, 500 or 100 ppm) or Oxf (500, 250, 100 or 10 ppm) for 8 weeks. Induction of CYP1A1/2 was observed in treated groups of DEN + Feb and DEN + Oxf groups, and its induction was most marked in DEN + Oxf groups. CYP2B1 and CYP4AI were also induced in these treated groups. The number or area of Cx32 positive spots per hepatocyte was significantly decreased in treated groups except for DEN + Oxf 100 ppm group, as compared to DEN alone group. GST-P positive foci was significantly increased in DEN + Fen groups treated with 1800 ppm or more, DEN + Feb groups treated with 1000 ppm Feb or more and DEN + Oxf groups treated with 250 ppm Oxf or more. These results suggest that these three compounds have liver tumor promotion effects and the promoting action in Oxf is most strong among them.

The raw material of dl-camphor was examined for the preparation of the "dl-Camphor Reference Standard". Analytical data obtained are as follows: ultraviolet spectrum, lambda max = 290 nm; infrared spectrum, the same as that of the present JP Camphor Reference Standard; melting point, 179.6 degrees C; purity test by gas-chromatography (GC), three kinds of impurities were detected; assay by GC, 99.0%. Based on the above results, the candidate raw material was authorized as the JP Reference Standard (Control 951).

We developed the system of the guide for the drug and the relevant information by using the database on the Internet. We set up a site of drug information (Drug Info Guide). This system enabled pharmaceutical and medical staff to easily access the latest drug information. Further, we attempted to promote the exchange of the information regarding the safety and the efficacy of drugs among them.

Somatropin material was examined for preparation of the "Somatropin Reference Standard". The candidate material was evaluated by a domestic collaborative study in which eight laboratories participated. The protein content was determined to be 4.5 mg/Vial based on amino acid analysis. Because of the possibility of application as a chemical reference standard for assay by the HPLC method, a physico-chemical evaluation of the candidate material was also performed. By SE-HPLC, the content of polymer, dimer were determined to be 0.54%, 0.98%, respectively. By RP-HPLC, the early peak area ascribed to desamido and sulfoxide form was 1.07% of the total peak area. And for informational data, the potency of the candidate material, being estimated by three different biological methods, weight gain assay, tibia test and adiposeconversion assay is 14.8 IU/vial. Based on the above results, the candidate was authorized as the Somatropin Reference Standard of the National Institute of Health Sciences.

The raw material for Fast Green FCF was tested for preparation of the "Fast Green FCF Standard (C.I. 42053)". Analytical data obtained were as follows: paper chromatography, only one spot is observed; arsenic content, 0.38 microgram/g; chloride content, 0.11%; sulfate content, 3.30%; heavy metals, lead, 8.0 micrograms/g, manganese, 28.1 micrograms/g, and chromium, 1.6 micrograms/g; infrared spectra, 1575 cm-1, 1169 cm-1, and 1033 cm-1; loss on drying, 2.39%; assay, 93.0% by the titanium trichloride titration. Based on the above results, the raw material was authorized as the Dye Standard of National Institute of Health Sciences.

The shelf-life estimates of pharmaceutical products obtained by matrixing are compared with those obtained by ordinary analysis, using stability data generated by the Monte Carlo method. The effect of the variation in stability due to different packaging and formulations on the shelf-life estimates is described. Analysis of variance is proposed for the evaluation of shelf-life estimates obtained by matrixing. The relationship between the power of the test and the significance level is discussed as well as the effect of assay error on the power of test.

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 138 samples tested, two were found to inhibit the growth of HIV in vitro. Neither of the positive samples has hopeful signs, as the ranges of effective doses of the samples are very narrow.

The Concise International Chemical Assessment Document or CICAD is a new chemical safety document series. It was launched by the IPCS in 1995, based on the decision of the International Forum on Chemical Safety in 1994, to internationally assess safety of 500 additional chemicals by the year 2000. The strategy to achieve this ambitious goal is to internationalize existing national assessment documents by rearranging contents of them into a standardized format, succinctly describing critical data, and adding international assessment process so as to be prepared efficiently, concisely and reliably. Critical review of document drafts by competent experts and input from countries including developing ones is required in the preparation. The author wishes to establish a framework to develop national reviews of chemical risk assessment domestically, while cooperating with this international programme.

Summaries of first draft of Environmental Health Criteria (EHC), which were circulated for comments by IPCS in the period of 1995-1996, are presented. EHC drafts on 9 compounds were received in this period.