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

Immunotoxicity is the detrimental effects of xenobiotics on immune functions of hosts, which result in enhanced susceptibility to infectious agents and tumours. A variety of environmental chemicals, such as pharmaceuticals, food additives, contaminating chemicals in food and drinking water, pesticides, and airborne chemicals, have been reported to exert immunotoxic effects on experimental animals and humans. In this paper, the mechanisms of immune responses, the effects of typical immunotoxic chemicals on the immune systems, and the methods for detecting immunotoxicity were described. In addition, the strategies and guidelines for immunotoxicity assessment were briefly outlined and discussed.

Three kinds of the candidate raw material for protamine sulfate was tested for preparation of the "Protamine Sulfate Reference Standard (Control 941)". The candidates were evaluated by physicochemical tests and anti-heparin tests. Analytical data were summarized in Table 1. Based on the above results, the best one having the highest anti-heparin activity was selected and authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).

The raw material for betamethasone valerate was tested for preparation of the "Betamethasone Valerate Reference Standard (Control 941)". Analytical data obtained were as follows: melting point, 194.3 degrees C (decomposition); UV and infrared spectra, the same as those for JP Betamethasone Valerate Reference Standard (Control 844); optical rotation, [alpha]20D = +79.4 degrees; thin-layer chromatography and high-performance liquid chromatography (HPLC), no impurities were detected; assay, 100.0% by HPLC. Based on the above results, the candidate material was authorized as the JP Betamethasone Valerate Reference Standard (Control 941).

The raw material of berberine hydrochloride was examined for preparation of the "Berberine Hydrochloride Reference Standard". The candidate material was evaluated physico-chemically by a collaborative study in which five laboratories participated. Analytical data obtained were as follows: UV spectrum, lambda max = 228, 263, 345, and 421 nm and specific absorbance E1%1cm at each lambda max = 814, 794, 722, and 160, respectively; IR spectrum, specific absorption wave numbers at 2845, 1633, 1568, and 1506 cm-1; thin-layer chromatography, some laboratories detected a trace amount of one or two spot and others not detected; high-performance liquid chromatography, 2-5 impurities were detected and the amount of any impurities were estimated to be less than 0.05% and the total amount less than 0.2%. Based on the above results, the candidate material was authorized as the Berberine Hydorochloride Reference Standard of National Institute of Health Sciences.

We performed comparative studies to determine an acute toxicity of microsomal Ca(2+)ATPase inhibitor, 2,5-di(tert-butyl)-1,4-hydroquinone (DTBHQ) and its related analog, mono(tert-butyl)-1,4-hydroquinone (MTBHQ), which are both used as antioxodants. Wistar rats, 5 weeks old, male and female, were used. By a single dose of oral administration, DTBHQ-induced LD50 values (obtained by Lorke method) in male and female rats were estimated 295.1 and 234.4 mg/kg BW, respectively, whereas each LD50 value for MTBHQ was 711.6 and 400.0 mg/kg BW, respectively. MTBHQ-induced deaths occurred from 8 to 20 minutes after administration, however, DTBHQ-induced deaths occurred more delayed from 1 to 5 days after administration. The observed toxic signs of DTBHQ included diarrhea (jelly like), prone position, lacrimation, salivation and abnormal gait (such as reluctance to walk, limping). Localized purpura and loss of the tail (perhaps as a result of necrosis) were also observed. In comparison, MTBHQ elicited prone position, panting, staggering gait and spastic gait. Without loss of the tail montioned above, dead and sacrified rats showed no remarkable changes in macroscopic examination due to exposure to both compounds.

Enzyme preparations are medicine which prepared from natural and biotechnological enzymes or modified enzymes. The catalytic ability of the preparations display the efficacy of a medicine, and its chemical substance is protein. From these characteristics, the quality of enzyme preparations has to be evaluated at viewpoints what distinguish from synthetic drugs. Quality of enzyme preparations should be evaluated and assured from the following viewpoints: 1) definition of enzyme source, 2) identification of function for catalyst and substance as protein, 3) purity for functional enzyme protein, 4) biochemical evidence that justifies pharmacological action, 5) safety, and 6) contents.

International Programme on Chemical Safety (IPCS), an international collaboration in safety evaluation of chemicals, initiated a programme called Joint Meeting on Pesticides or JMP, last autumn. The JMP is an activity contributing to harmonizing evaluation procedures and saving expertise and financial resources, having several unique features. First, the outputs of the scientific evaluations and data covering all major areas related to pesticide safety in one JMP meeting can be applied to the areas of food safety, occupational health, and environmental protection. Second, succinct presentation of the outputs of reliable evaluations in a tabular form, supported by detailed information in the Environmental Health Criteria documents help people in countries, especially those in developing ones, understand the evaluations and rely on them in establishing their guidelines on pesticide safety. This format of the JMP report is a good example for short assessment reviews on chemicals (Concise International Assessment Document) which will be prepared by an international cooperation project based on Agenda 21 decisions.

The raw material of glycyrrhitinic acid was examined for preparation of the "Glycyrrhitinic Acid Reference Standard". The candidate material was evaluated physico-chemically by a collaborative study in which five laboratories participated. Analytical data obtained were as follows: UV spectrum, lambda max = 251 nm and specific absorbance E1%1cm (EtOH) at the lambda max = 145; IR spectrum, specific absorption numbers were at 1719, 1654, 1216, and 1170 cm-1; thin-layer chromatography, some laboratories detected a trace amount of one spot and others not detected; high-performance liquid chromatography, 2-6 impurities were detected and the amount of any impurities were estimated to be less than 0.2% and the total amount less than 0.5%. Based on the above results, the candidate material was authorized as the Glycyrrhitinic Acid Reference Standard of National Institute of Health Sciences.

Dr. Mitsuo Watanabe has offered many suggestions and points to be considered on the Japanese Pharmacopeia. His points of the matter include the nomenclature of reagents. Issues on electrodes and volumetric standard solutions to be used in nonaqueous potentiometric titrations are also involved, as well as the justification of a method for quantitative determination and analytical method validation. His concerns have prompted studies and careful surveys of these vital points to consider investigating that the nomenclature of reagents should be directed to prencipally follow the rules of IUPAC. Consideration has also been given to an issue of nonaqueous potentiometric titration, where problems many frequently be found with liquid junction between the electrode and the solution under titration. To work out the issue, investigations have started of an alternative technique characterized in using a platinum (or silver) electrode and a glass electrode as an indicator electrode and a reference electrode, respectively, without any liquid junction. For any titration system in question that can be regarded as nonaqueous titration from viewpoints of analytical chemistry. It has been suggested the use of any volumetric standard solutions of aqueous system should generally be avoided. Other points received consideration include sampling procedures for testing, interpretation of results from quantitation, and analytical method validation.

The raw material for ergocalciferol was tested for preparation of the "Ergocalciferol Reference Standard (Control 941)". Analytical data obtained were as follows: melting point, 117.6 degrees C; UV and infrared spectra, the same as those for JP Cholecalciferol Reference Standard; specific absorbance, E1%1cm = 458 (265 nm); thin-layer chromatography and high-performance liquid chromatography (HPLC), no impurities were detected, respectively; assay, 100.6% by HPLC. Based on the above results, the candidate raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).