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

An information system for chemical safety has been developed on the National Institute of Health Sciences (NIHS) Information and Computing Infrastructure. The system is based on client server systems on the local area network (LAN) connected to the Internet. A wide range of safety information for chemicals including foods, food additives, household goods, industrial chemicals and environmental pollutants were collected and put on the World Wide Web (WWW) server and the database management system, Sybase. In addition to original information contents, the System has links to many useful Web sites so that it functions as a global hub for chemical safety information.

The raw material of tocopherol acetate was tested for the preparation of the "Tocopherol Acetate Reference Standard (Control 941)". Analytical data obtained were as follows: infrared spectrum, the same as that of the Tocopherol Acetate Reference Standard (Control 919); specific absorbance, E1(1%)cm (284nm) = 44.5; thin-layer chromatography, no impurities were detected until 50.0 micrograms; high-performance liquid chromatography (HPLC), 2-3 impurities were detected and the amount was estimated to be about 1%; assay by HPLC, 100.8%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).

Preliminary screening of antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 246 samples of different origin tested, six were shown to inhibit the growth of HIV in vitro. Two of the positive samples have hopeful signs, as the ranges of effective doses are wider than those of most of positive samples which had been found by us.

We describe the information and computing infrastructure in National Institute of Health Sciences, which were constructed until May, 1996. The in house computer network and computing facilities for common usage in NIHS have been developed under the initiative of Division of Chem-Bio Informatics since 1989. The present LAN (Local Area Network) consists of coaxial cables and optic fibers which are connected by a LAN Switch. The LAN is connected to the Internet via IMnet, the inter ministry network back bone of the Science and Technology Agency. Various types of workstations and personal computers such as SUN WS, Silicon Graphics WS, IBM WS & PC, Macintosh, and NEC PC are connected to the LAN. This computing network environment which we named NICI (NIHS Information and Computing Infrastructure) not only provides network communications but also facilitates advanced computating systems for chemical safety research at NIHS as a COE.

Teratogenicity of magnesium chloride hexahydrate (MgCl2.6H2O) was examined in rats. Magnesium chloride hexahydrate dissolved in distilled water was given to pregnant Wistar rats by gavage once a day from day 6 through 15 of pregnancy at doses of 0, 200, 400 and 800 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Magnesium chloride hexahydrate caused no increased incidences of fetal malformation, and no toxic signs in the pregnant rats and the fetuses. It was concluded that magnesium chloride hexahydrate has no teratogenicity in rats when given by gavage. The no observed adverse effect level was estimated to be over 800 mg/kg/day for both pregnant rats and rat fetuses.

The raw material of betamethasone was tested for preparation of the "Betamethasone Reference Standard (Control 951)". Analytical data obtained were as follows: loss on drying, 0.0%; infrared spectrum, the same as that of the JP Betamethasone Reference Standard (Control 845); thin-layer chromatography, no impurity was detected; high-performance liquid chromatography (HPLC), two kinds of impurities were detected and the total amount was estimated to be 0.16 +/- 0.01% (n = 3); assay, 100.0% by HPLC. Based on the above results, the raw material was authorized as the JP Betamethasone Reference Standard (Control 951).

Bioequivalence tests in Japan are now under the improvement according to the WHO guidance. This article describes the desirable assessment of bioequivalence where the use of discriminatory subjects, application of confidence interval methods, logarithmic transformation of pharmacokinetic data are recommended. The role of dissolution tests in bioequivalence assessment is also discussed.

Enzyme activities in serum from experimental animals had been assayed by HITACHI 7150 Automatic Analyzer using K factors for calibration. Because K factor is derived from a molar extinction coefficient and, reagent and sample volumes for each assay system, it is a constant value in usual assay. As an alternative calibration method, a human standard serum, which is commercially available and well-controlled, is presently used in the same assay system because of some difficulties in supply. Four serum enzymes of human, rat, dog and monkey sera were determined by the above two methods. All values calibrated by human standard serum were approx. 10% higher than that using K factors. These small differences are allowable because data calibrated by human standard serum can be compared with previous data given by K factors.

In order to investigate whether goitrogens and liver enzyme-inducers modify the tumorigenesis in the liver or lung, 6-week old male F344 rats were given single subcutaneous injection of DHPN, and starting one week later received water containing goitrogens, namely sulfadimethoxine (SDM), propylthiouracil (PTU) and potassium thiocyanate (KSCN), or an enzyme-inducer, phenobarbital (PB), for 19 weeks ad libitum. Although the number of GST-P positive foci in the liver was significantly increased in the PB group as compared to the control group, there were no significant fluctuations in the SDM, PTU and PB groups. With respect to the lung, it is suggested that SDM, KSCN and PB may enhance the lung tumorigenesis, since the multiplicities of hyperplasias of alveolar epithelia were increased in groups treated with these compounds.

The components in a commercial natural food additive "Grapefruit seed extract" and the ethanol extract of grapefruit seeds were analyzed by HPLC and LC/MS. The HPLC chromatogram of the commercial grapefruit seed extract was quite different from that of the ethanol extract of grapefruit seeds. Three main peaks were observed in the chromatogram of the commercial grapefruit seed extract. By comparison of the retention times and the absorption spectra with those of authentic samples, two peaks were ascribed to methyl-p-hydroxybenzoate and 2,4,4'-trichloro-2'-hydroxydiphenylether (triclosan). Triclosan was also identified by LC/MS by using the negative electrospray ionization method.