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

Raw human chorionic gonadotrophin material was examined for preparation of the "Human Chorionic Gonadotrophin Reference Standard (Control 941)". The candidate material was assayed against the 3rd International Standard by the rat ovarian weight method. The potency of the new standard was defined as 1180 international units per ampoule as the result of 18 assays in four collaborative laboratories.

N-(Fluorodichloromethylthio)phthalimide (Fluor-folpet) has been widely used as an anti-mold and anti-bacterial agent. In this study, 28 days repeated-dose oral toxicity study of fluor-folpet was carried out in Slc:Wistar rats. An oral toxicity study for fluor-folpet, the twenty-eight days test, repeated-dose, oral administration, was performed as follows: Five week-old rats, male and female, 10 rats, each/group, were treated with intragastric administration of fluor-folpet with a dose of 0 (1% Sodium CMC, control), 20, 80 and 320 mg/kg, body weight. Recovery test, for 14 days after the last treatment, was examined for the control and the 320 mg/kg groups. The 320 mg/kg groups, both males and females, showed significantly reduced their body-weight gain compared with the control group. In the 320 mg/kg group, five out of 20 male rats and four out of 20 female rats died from dyspnea during the treatment period. In the female rats in the 320 mg/kg group, serum ChE level was decreased to 50% of control level and gamma-GT was increased in a dose-dependent manner, but these serum levels recovered after 14 days non-treatment period. No histopathological change, relating to the treatment, in liver was observed. Increased weight of the kidney and vacuolation in renal tubules were found in both sexes of 320 mg/kg group. Hyperkeratosis and hyperplasia of the stomach epithelium were observed at the dose more than 80 mg/kg in male, and more than 20 mg/kg in female. A supplemental study, repeated-dose, oral administration in rats carried out to examine the dyspnea revealed that severe acute toxic damages in epithelium of nasal cavity and meatus nasopharyngeus were induced by intragastric administration of fluor-folpet. Fluor-folpet is shown to be cytotoxic. In conclusion, the no-observed-effect level (NOEL) for fluor-folpet was not found under the experimental conditions employed in this repeated-dose toxicity study.

Teratogenicity of stevioside was examined in rats. Stevioside 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, 250, 500 and 1000 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Stevioside caused no increased incidences of fetal malformation, and no toxic signs in the pregnant rats and the fetuses. It was concluded that stevioside has no teratogenicity in rats when given by gavage. The no observable adverse effect level was estimated to be over 1000 mg/kg/day for both pregnant rats and rat fetuses.

To clarify whether bromodichloromethane (BDCM)-induced cholangiofibrosis progresses to cholangiocarcinoma, further morphological examinations were performed on the livers obtained from our previous experiment. The livers of Wistar rats fed diet containing 2200, 550, 140 or 0 ppm of microencapsulated BDCM up to 24 months were examined at months 6, 12, 18, and 24. The liver sections were stained with H-E, PAS and Azan, and were subjected to immunostaining using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody for determination of the PCNA labeling index of bile duct epithelia, as well as silver staining for nucleolar organizer regions (AgNORs). At month 6, the severity of hyperplasia of atypical bile duct epithelia in the 2200 ppm group was marked, their PCNA labeling index being highest (68.5). The number of bile ducts gradually decreased, and the severity of fibrosis became more marked, with prolongation of the treatment. The PCNA labeling index in hyperplastic bile ducts in this group also decreased to 31.5 at month 24. The number of AgNORs in the nuclei of bile duct epithelia in the 2200 ppm group was highest at month 6, but decreased thereafter. The present study suggests that the possibility of the progression from cholangiofibrosis to neoplastic lesions is extremelly low.

In order to characterize the toxicity of iron lactate, a 26-week feeding study was performed in male and female F344 rats. Animals were divided into 2 groups, and given diet containing iron lactate at concentration of 0 or 2%. No animals died during the administration period. Body weight gain was suppressed in both sexes of the 2% group compared with the 0% group. Hematologically, anemia was observed in male of the 2% group. Serum alkaline phosphatase decreased in both sexes of the 2% group. The spleen weight of both sexes and kidney weight of females were higher in the 2% group than in the 0% group. Lipid peroxide increased not only in the liver and the kidney homogenates of treated males and females, but also in the serum of treated females. Histopathologically, iron deposition was observed in the liver, the kidney and the spleen of treated males and females, and in the intestine of treated females. The present results indicate that the iron lactate administration caused iron deposition in the liver and the other several organs, resulting in lipid peroxidation in these organs.

Polyvinylpolypyrroridone (PVPP) has been used in many countries for removing polyphenols in beer and wine, and was permitted as a food additive in Japan in April 1995. Prior to this approval of the compound, we studied procedures for identifying PVPP and its water soluble substances by colorimetry and infrared (IR) spectrometry for the establishment of the specification.

The migration of lead and cadmium from lacquered tableware was investigated. Seven samples of bowls and five samples of chopsticks were purchased on the market. The migration test was carried out with 4% acetic acid at 60 degrees C for 30 min. Lead and cadmium in the test solution was determined by flameless atomic absorption spectrometry. Release of lead was 3.4 and 4.4 ppb from two samples and release of cadmium was 1.3 ppb from one sample. Those samples were chopsticks coated with natural lacquer and colored with pattern. No other samples released lead and cadmium. Evapolation residue was less than 13 ppm in all samples.

Summaries of first drafts of Environmental Health Criteria (EHC), which were circulated for comments by IPCS in the period of 1994-1995, are presented. EHC drafts on 10 compounds were received in this period.

New guidelines on the establishment of quality specifications and analytical methods for a new drug application were notified from the Evaluation Division of the Pharmaceutical Affairs Bureau, Ministry of Health and Welfare, on September, 1994. General policies as well as an impurity test, drug release, and the uniformity of dosage unit are discussed from the viewpoint of international harmonization and technical advancement.

Herbal medicines, as the major remedy in traditional medical systems, have been used in medical practice and made a great contribution to maintaining human health. WHO is fully aware of the importance of herbal medicines of the health of many people throughout the world, and then WHO reported 3 kinds of guideline for herbal medicines. U.S.A. has the new bill for dietary supplement included herbal medicines, and been discussed the harmonizing North American Herbal Regulation.