[Toxicity and carcinogenicity studies of musk xylol in B6C3F1 mouse].

Toxicity and carcinogenicity studies of musk xylol were examined in B6C3F1 mice. The LD50 of the chemical was considered to be more than 4000 mg/kg. In the acute toxicity and 14-day repeated-dose oral toxicity studies, tremor was observed in some animals given high doses of the chemical. In the 17-week repeated-dose oral toxicity study, musk xylol was given at dietary dose levels of 0.0375, 0.6%. During the experimental period, almost all mice given 0.3% or more died. There was no difference in the body-weight gain between the treated groups given 0.15% or less and the control group. Histologically, enlargement and irregularity of hepatocyte were found in both sexes given 0.15% or more. Based on the results, the chemical was given at dietary levels of 0 (control), 0.075 or 0.15% for 80 weeks in the carcinogenicity study. Overall tumor incidences in all treated groups of both sexes were significantly higher than those in the respective controls. Combined malignant and benign liver cell tumors increased clearly in both sexes and a significant positive trend for the occurrence of hepatocellular carcinomas was noted in males. Incidences of lung and Harderian gland tumors and lymphomas in treated groups were also slightly higher than those in controls. In addition, incidences and total numbers of malignant tumors increased significantly in treated groups of both sexes, although no dose-relation was evident. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice of both sexes when given at dose-levels of 0.075 or 0.15% in the diet for 80 weeks.


[Usage of chitosan as a pharmaceutical material effectiveness as an additional additives of sodium alginate].

Application of chitosan, a deacetylated compound of chitin obtained from shells of shrimps, was investigated with reference to the pharmaceutical excipient for directly compressed tablets. Several drugs were chosen as model compounds and their in vitro dissolution tests were carried out according to the JP XI dissolution test. When chitosan was used alone as an excipient, immediate-release tablets were obtained, as already reported. But when more than 5% of sodium alginate, 1000 cps, was added as excipient, tablets showed an extended-release property under the present experimental conditions.


[Identification of nutmeg by thin-layer chromatography and its introduction to Japanese standards for non-pharmacopoeial crude drugs].

When nutmeg was extracted with hot methanol and cooled, much precipitate was produced. The colorless crystals, obtained on recrystallization, were identified as trimyristin by spectroscopic means and by direct comparison with the standard. Then, the identification of nutmeg was established by using the same extraction as above and subjecting the precipitate to thin-layer chromatography. This method was newly introduced to the Standards for Non-pharmacopoeial Crude Drugs.


[Recent world-wide advances in irradiation of food and its identification].

Irradiation (ionizing radiation) of various foods is growing in popularity internationally. For example, it is used as a substitute for the use of post-harvest pesticides. This trend has served to intensity research on the identification of irradiated foods. The first Research Co-ordinated Meeting on Analytical Detection Method for Irradiated Foods was held in Poland under the sponsorship of FAO/IAEA in 1990 in order to solve problems related to the international trade of irradiated foods and to ensure their correct labelling in the market. In this review, the world-wide advances in the irradiation of food and its identification are introduced and discussed.


[Determination of thiabendazole (TBZ) in grapefruit].

The officially recognized gas chromatographic method (detector: nitrogen-phosphorus detector) for determination of thiabendazole (TBZ) in grapefruits, tends to give results that are higher than the actual values. This may be due to the fact that more of the TBZ in authentic TBZ solution is adsorbed on the column than TBZ in the sample solutions that contain a lot of impurities. Because of this difficulty, two liquid chromatographic methods were compared. If a fluorescence detector is available, the method of Nakazato et al. (ethyl acetate extraction and ion pair HPLC) is the best for preparation of test solution. When an ultraviolet detector is used, clean-up of the ethyl acetate extract is necessary. By the method of Kitada et al., the retention time of TBZ becomes shorter after injection of many samples. In view of these results, the method of Nakazato et al. is the methods-of-choice for TBZ in grapefruit.


Migration and material tests of some food-contact plastic wares made in Thailand.

Migration and material tests of food-contact plastic wares were carried out in compliance with the Thai Food Act. Sample materials studied were melamine resin, polyethylene, polypropylene, polystyrene, and polyvinyl chloride. Migration levels of phenol, formaldehyde, colors and heavy metals were determined. A test for vinyl chloride monomer in polyvinyl chloride was carried out. Migrant and residual levels in all samples were in compliance with the Act.


[Preliminary screening for antiviral AIDS drugs. II. Report on fiscal year 1989].

Preliminary screening for antiviral AIDS drugs was carried out using three different in vitro assay systems. Among 104 samples tested, six were found to inhibit the growth of HIV in vitro. Four of six were acidic polysaccharides of sea weed origin and one was a well-known anti HIV chemical whose anti-HIV activity has not been reported.


[A study on toxicological information search--an example from a study on food additives].

The information search method for toxicological evaluation of food additives was examined. Both a survey of the existence of critical reviews or specific databases for toxicological evaluation and the performance of preliminary online-search are important for a comprehensive and effective search. Examples of file selection and search scheme examination are reported. The results are considered to be generally applicable to toxicological information search for other groups of chemicals.


[Summaries on the first draft of the EHC monographs in 1990].

The first drafts of the EHC monographs in 1990 were summarized into Japanese. The chemicals consist of hexachlorocyclopentadiene, trichlorfon, fenitrothion, methylparathion, trichloroethane, platinum and selected platinum salts, di(2-ethylhexyl)phthalate, partially halogenated chlorofluorocarbons, methyl ethyl ketone, and propachlor.


[Enhancing effect of L-histidine on the formation of 8-hydroxy-deoxyguanosine induced by hydrogen peroxide in vitro].

Treatment of deoxyguanosine with H2O2 (56 mM) at 37 degrees C for 2 hrs resulted in the formation of 8-hydroxydeoxyguanosine (8-OH-dG). The formation of 8-OH-dG by H2O2 was increased about 3-folds in the presence of 78 microM L-histidine (L-His). The result suggests that oxidative DNA damage induced by H2O2 in vitro might be enhanced by L-His.


[Study on essential metal concentration in the organs of rats (report 2)--lung.liver.kidney.spleen].

The objective of this study was to obtain the normal ranges of essential metals in male and female Slc: Wister rats aged 9 or 11 weeks. Concentration of 10 elements (Ca, Cu, Fe, K, Mg, Mn, Na, P, S and Zn) in the lung, liver, kidney and spleen of rats was determined by inductively coupled argon plasma atomic emission spectrometry (ICP). Each sample was digested with nitric acid and perchloric acid in a sealed double Teflon vessel with polypropylene jacket by heating with a microwave oven. The concentrations of Fe and Mn in the liver were different between males and females. The Fe level in the female was higher than that in the male, and Mn level in male was higher than that in female. The concentration of Fe in the spleen was different by sex and ago. The Fe level in female was 2.3 times higher than that in male, and that in rats of 11 weeks was 1.8 times higher than that of 9 weeks.


[A study on the usefulness of the OECD Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)].

We studied the usefulness of the OECD combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox) using cyclophosphamide (CP), which is well known for its toxicological properties. CP was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague-Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body weight and food consumption were observed in males given 6.7 mg/kg and in all treated females. One, 3 and 12 females died during pregnancy in the groups given 3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group. Leukopenia and anemia were evident in treated males. The thymus and spleen weights were significantly decreased in treated rats. Histopathologically, atrophy of the thymus, spleen and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss and postnatal death of pups were found in treated dams. The body weight of pups from treated dams was significantly lowered. Thus, most of the known toxicological properties of CP regarding systemic toxicity and reproductive/developmental toxicity were clearly demonstrated in this study. Therefore ReproTox can be considered a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume, although teratogenic potential and adverse effects on spermatogenesis and fertility were not detected under the present experimental conditions.


[Cholecalciferol Reference Standard (Control 901) of the National Institute of Hygienic Sciences].

Cholecalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 85.8 degrees C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS of Cholecalciferol; absorptivity at 265 nm E1%lcm = 476; optical rotation [alpha]20D = + 110.1 degrees; no impurities were detected by TLC and HPLC analyses; assay 100.1% by HPLC against the USP RS. Based on the above results, the raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.


[Ergocalciferol Reference Standard (Control 901) of the National Institute of Hygienic Sciences].

Ergocalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 118.4 degrees C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS of ergocalciferol; absorptivity at 265nm E1%lcm = 467; optical rotation [alpha]20D = 103 degrees; no impurities were detected by TLC and HPLC analyses; assay 100.1% by HPLC against the USP RS. Based on the above results, the raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.


[Prednisolone Acetate Reference Standard (Control 901) of the National Institute of Hygienic Sciences].

Prednisolone Acetate Reference Standard (Control 901) for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 236 degrees C (decomposition); IR spectrum was same as that of JP RS of prednisolone acetate; absorptivity at 243 nm E1%lcm = 379; optical rotation [alpha]20D = +113.0 degrees; no impurity was detected by TLC, but a small amount of two impurities was found by HPLC analysis; assay by HPLC against the JP RS 100.2%. Based on the above results, this raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.


[Fluocinolone Acetonide Reference Standard (Control 901) of the National Institute of Hygienic Sciences)].

Fluocinolone Acetonide Reference Standard (Control 901) for the Japanese Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained: melting point 268 degrees C (decomposition); IR spectrum was same as the previous JP RS of Fluocinolone Acetonide; absorptivity at 237nm E1%1lcm = 363; optical rotation [alpha]20D = 105.7 degrees; no impurity was detected by TLC, but two impurities were detected by HPLC analysis; assay by HPLC against the previous JP RS 100.2%. Based on the above results, this raw material was authorized as the Reference Standard of the National Institute of Hygienic Sciences.


[Diclofenamide Reference Standard (Control 891) of National Institute of Hygienic Sciences].

Quality of the raw material of diclofenamide was evaluated for preparation of "Diclofenamide Reference Standard". Analytical results for the sample were as follows: melting point 240 degrees C (decomposition); UV spectrum indicates absorption maxima at 286 and 295 nm and the absorption ratio A286/A295 1.04; IR spectrum is same as that of the USP Reference Standard; no impurity was found by TLC, but a trace of one was found by HPLC analysis; the purity is assumed to be 99.95% by HPLC analysis; loss on drying 0.1%; assay by HPLC against USP Reference Standard 100.2%. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Epitiostanol Reference Standard (Control 891) of National Institute of Hygienic Sciences].

The raw material of epitiostanol was examined for preparation of "Epitiostanol Reference Standard". Analytical results for the sample were as follows: melting point 130.7 degrees C (decomposition); UV spectrum indicates absorption maximum at 263 nm in ethanol; IR spectrum indicates specific absorption at 2920, 1383, 1056 and 590 cm-1; optical rotation [alpha]20D+ 24.4 degrees; no impurity was found by TLC, but a small amount of one was found by HPLC analysis and the purity is assumed to be 99.5%; water content 1.52%. Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Methoxalene Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw material of methoxalene was examined for the preparation of the "Methoxalene Reference Standard". Analytical data obtained were as follows: ultraviolet spectrum, lambda max = 300, 249 and 218 nm; absorbance, E1cm(1%) (300 nm) = 559; infrared spectrum, same as that of USP Reference Standard of Methoxalene; melting point, 148 degrees C; thin-layer chromatography, no impurities were detected until 50 micrograms; high-performance liquid chromatography (HPLC), no impurities were detected, water, 0.04%; assay, 99.9% by absorbance method and 100.4% by the HPLC method in terms of the USP Reference Standard. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Indocyanine Green Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw material of indocyanine green was examined for the preparation of the "Indocyanine green Reference Standard (Control 901)". Analytical data obtained were as follows: ultraviolet and visible spectrum, lambda max = 785, 394, 216 nm; absorbance, E1cm(1%) (785 nm) = 3239; infrared spectrum, same as Indocyanine Green USP Reference Standard; sodium iodide, 4.1%; thin-layer chromatography, no impurities were detected until 100 micrograms; high-performance liquid chromatography, 4 impurities were detected; loss on drying, 1.8%; assay, 103.4% against USP Reference Standard. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Tolnaftate Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw material of tolnaftate was examined for the preparation of the "Tolnaftate Reference Standard". Analytical data obtained were as follows: ultraviolet spectrum, lambda max = 257 nm; absorbance, E1cm1% (257 nm) = 723; infrared spectrum, same as that of USP Reference Standard of Tolnaftate; melting point, 112.1 degrees C; thin-layer chromatography, no impurities were detected until 500 micrograms; high-performance liquid chromatography, no impurities were detected; loss on drying, 0%; water, 0.01%; assay, 100.4% by absorbance method and 100.1% by the HPLC method in terms of the USP Reference Standard. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Retinol Acetate Reference Standard for Thin-layer Chromatography (Control 901) and Retinol Palmitate Reference Standard for Thin-layer Chromatography (Control 901) of National Institute of Hygienic Sciences].

The raw materials of retinol acetate and retinol palmitate were examined for the preparation of the "Retinol Acetate Reference Standard for Thin-layer Chromatography" and "Retinol Palmitate Reference Standard for Thin-layer Chromatography", respectively. Analytical data obtained were as follows: thin-layer chromatography, no impurities were detected in retinol acetate and one impurities was detected in retinol palmitate; The Rf values of retinol acetate and retinol palmitate were consistent with those of Reference Standards (Control 713), respectively; ultraviolet spectrum, lambda max = 326 approximately 327 nm; relative extinction, within the range reported in JPXI; weight variation of capsules, retinol acetate 224.0 +/- 15.5 mg (RSD 6.9%), retinol palmitate 222.0 +/- 13.8 mg (RSD 6.2%); assay, retinol acetate 57000 I.U./g, retinol palmitate 57000 I.U./g. Based on the above results, these raw materials were authorized to be the Reference Standards of the National Institute of Hygienic Sciences.


[Methylergometrine Maleate Reference Standard (Control 891) of National Institute of Hygienic Sciences].

The raw material of methylergometrine maleate was examined for the preparation of the "Methylergometrine Maleate Reference Standard". Analytical data obtained were as follows: melting point, 181.7 degrees C; ultraviolet spectrum, lambda max = 313 nm; absorbance, E1%1cm (313 nm) = 181.3; infrared spectrum, 3406, 2962, 2928, 1645, 1574 cm-1; thin-layer chromatography, 6 impurities were detected; high-performance liquid chromatography, no impurities were detected; loss on drying, 0.02%; optical rotation, [alpha]20D = + 44.04 degrees; assay, 99.5% against Ergometrine Maleate Reference Standard (Control 755). Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Cyclandelate Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw material of cyclandelate was examined for preparation of the "Cyclandelate Reference Standard". Analytical data obtained were as follows: melting point, 60 degrees C; ultraviolet spectrum, lambda max = 252, 258 and 264 nm E1%1cm = 6.1 (252 nm), 7.5 (258 nm), 5.9 (264 nm); infrared spectrum, 3454, 2948, 1730, 1453, 1202, 737, 695 cm-1; thin-layer chromatography, no impurities were detected until 1000 micrograms; high-performance liquid chromatography (HPLC), one impurity was detected, loss on drying, 0.00%. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Potassium Sucrose Octa Sulfate Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw material of potassium sucrose octa sulfate was examined for the preparation of the "Potassium sucrose octa sulfate Reference Standard (Control 901)". Analytical data obtained were as follows: infrared spectrum, 3494, 1642, 1247, 1002, 795, 584 cm-1; high-performance liquid chromatography, 3 impurities were detected; water, 6.2%; assay of sucrose octa sulfate, 99.1%. Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[Riboflavin Reference Standard (Control 891) of National Institute of Hygienic Sciences].

The raw material of riboflavin was examined for the preparation of the "Riboflavin Reference Standard (Control 891)". Analytical data obtained were as follows: melting point, 238.2 degrees C (decomposition); absorbance, E1%1cm = 859 (267 nm), 277 (372 nm), 327 (445 nm); infrared spectrum, same as Riboflavin Reference Standard (Control 872); thin-layer chromatography, 5 impurities were detected; high-performance liquid chromatography, 11 impurities were detected; loss on drying, 0.25%; optical rotation, [alpha]20D = -133.6 degrees; solubility, less than 16 min; assay, 100.1% against Riboflavin Reference Standard (Control 872). Based on the above results, this raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.


[d-Camphor Reference Standard (Control 901) and dl-Camphor Reference Standard (Control 901) of National Institute of Hygienic Sciences].

The raw materials of d-camphor and dl-camphor were examined for the preparation of the "d-Camphor Reference Standard" and "dl-Camphor Reference Standard". Analytical data obtained were as follows: ultraviolet spectrum, lambda max = 257 nm; absorbance, E1%1cm(257 nm) = 723; infrared spectrum, 2956, 1742, 1045 cm-1; optical rotation, [alpha]20D = +42.9 degrees (d-camphor), [alpha]20D = -0.00 degrees (dl-camphor); melting point, 180 degrees C (d-camphor), 179 degrees C (dl-camphor); gas-chromatography, one impurity was detected in d-camphor and four impurities were detected in dl-camphor. Based on the above results, these raw materials were authorized to be the Reference Standards of the National Institute of Hygienic Sciences.


[Estimated production by the official inspection of coal-tar dyes (including dye aluminum lakes) in 1990 based on official inspection figures].

The number of official inspections of coal-tar dyes and their lakes from april in 1990 till march in 1991 was 836 in total. The quantity passed amounted to 238 ton in Japan. The production of color for 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 46.2% in this period.


[Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate (TCEP) applied to female mouse skin].

Tris(2-chloroethyl)phosphate (TCEP), a widely used flame retardant, was tested for its skin chronic toxicity/carcinogenicity using female Slc: ddY mice. TCEP (5 and 50%) dissolved in ethanol was applied to the shaved skin twice a week for 79 weeks. The control group received ethanol under similar condition. In addition, 5 animals in each group were killed at 6 and 12 months and used for the chronic toxicity study. In body weight, food consumption and survival rate, there was no significant difference between the control and treated groups. Spleen weight was decreased in the 50% group. No significant difference in the incidence of tumors and other non-neoplastic lesions of the skin and other organs was found between the control and treated groups. The results indicate that under the conditions of the present study, TCEP has no carcinogenicity and toxicity for the skin.


[Studies on "Erythrosine Standard", Dye Standards of National Institute of Hygienic Sciences].

"Erythrosine Standard (C.I. 45430)", Dye Standards of National Institute of Hygienic Sciences, was prepared. The content of this Dye Standard was determined by the gravimetric method. This content averaged 99.1%. Ultra violet-visible absorption and infrared spectra of the Dye Standard were also determined.


[Studies on "brilliant blue FCF standard", dye standards of National Institute of Hygienic Sciences].

"Brilliant Blue FCF Standard (C.I. 42090)", Dye Standards of National Institute of Hygienic Sciences, was prepared. The content of this Dye Standards was determined by titanium trichloride method. This content averaged 96.3%. Ultra violet-visible absorption and infrared spectra of the Dye Standard were also determined.


[Studies on "Tartrazine Standard", Dye standards of National Institute of Hygienic Sciences].

"Tartrazine Standard (C.I. 19140)", Dye Standards of National Institute of Hygienic Sciences, was prepared. The content of this Dye Standard was determined by the titanium trichloride method. This contents averaged 99.0%. Ultra violet-visible absorption and infrared spectra of the Dye Standard were also determined.


[Studies on "allura red AC standard", dye standards of National Institute of Hygienic Sciences].

"Allura Red AC Standard (C.I. 16035)", Dye Standards of National Institute of Hygienic Sciences was prepared. The content of this Dye Standards was determined by the titanium trichloride method. This content averaged 95.5%. Ultra violet-visible absorption and infrared spectra of the Dye Standard were also determined.


[Acute and subacute toxicity studies of Bis(2,3-dibromopropyl) phosphate magnesium in rat].

Acute and subacute oral toxicity tests of Bis(2,3-dibromopropyl) phosphate magnesium (Bis-BP.Mg) were carried out in Wistar rats. In the acute toxicity test, Bis-BP.Mg suspended in arabic gum was administered orally to a group consisting of 10 male and 10 female rats, and they were observed for 14 days. LD50 values of male and female rats were 283 (253 approximately 314) mg/kg and 261 (219 approximately 310) mg/kg, respectively. As toxic symptoms, eyelid closure, crouching, shivering and staggering gait were observed in the treated groups of both sexes. In gross findings, hypertrophy, discoloration and necrotic change of the liver, and hypertrophy and discoloration of the kidney were observed in the treated groups. In histopathological examination, necrosis, desquamation, large nuclei formation of the tubular epithelium, and tubular dilatation of the kidney and necrosis of the liver cells were observed in the treated groups. In the subacute toxicity test, groups of rats consisting of 5 males and 5 females were fed a commercial diet containing 0, 30, 100, 300 and 1000 ppm Bis-BP.Mg for 45 days. In body weight and food consumption, there were no significant difference between the control and treated groups. Significant increases were observed in the liver and kidney weights of male rats fed 1000 ppm Bis-BP.Mg. Histopathologically, desquamation, swelling, and large nuclei formation of the tubular epithelium and tubular dilatation of the kidney were observed, but they were much less frequent than those in the acute toxicity test. It was concluded that Bis-BP.Mg has apparent renal toxicity.


[Studies on the uptake of 8-anilino-1-naphthalene sulfonate by rat freshly isolated renal cells].

The addition of 8-anilino-1-naphthalene sulfonate (ANS) into rat renal cell suspension caused a rapid increase in fluorescence (Ex. 400 nm, Em. 470 nm). The increase in fluorescence seemed to be composed of two phases. When the cells were disrupted by ultrasonic wave, the fast phase (0-ca 20 sec) increased and the slow phase (after ca 40 sec) disappeared. The rate of increase in the slow phase was dependent on the concentration of ANS and on the ambient temperature. A double reciprocal plot of the rate and the concentration exhibited straight line. It was decreased by bromophenol blue and rose bengal but not by other organic anions like p-aminohippuric acid and several metabolic inhibitors. It seemed that the uptake of ANS into the renal cell is mediated by a carrier which is different from that for p-aminohippuric acid.


[Studies on the teratogenic potential of 2,2'-isobutylidene-bis (4,6-dimethylphenol) in rats].

2,2'-Isobutylidene-bis(4,6-dimethylphenol), an antioxidant, was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 5, 15 or 45 mg/kg body weight during days 7 to 17 of gestation, and the effects of the compound on dams and fetal developments were examined. In the dams at the two higher dose levels of 15 and 45 mg/kg, toxic signs (tremor, startle reflex, salivation, involuntary urination, wheezing and nostril discharge) were observed. Moreover, at the highest dose level, additional toxic signs (lacrimation and vaginal bleeding), suppression in maternal body weight gain and food consumption were observed. However, there was no evidence of an increase in malformations attributable to the treatment with 2,2'-isobutylidene-bis(4,6-dimethyl-phenol) in any of the treated groups. It was concluded that 2,2'-isobutylidene-bis(4,6-dimethylphenol) has no teratogenic effect in rats, though toxic signs were observed in treated dams of the 15 and 45 mg/kg groups.


[Twenty-eight-day repeated dose toxicity test of p-phenetidine in F344 rats].

A twenty-eight-day repeated dose toxicity test of p-phenetidine was carried out in male and female F344 rats at dose levels of 160, 40, 10 or 0 mg/kg/day. Thirty animals of both sexes were divided into 6 groups of equal number. All groups were treated daily by i.g. administration for 28 days, two extra groups of animals at dose levels of 160 and 0 mg/kg being used for investigation of recovery over 14 days. Hematological and urinary examinations revealed decrease in erythrocytes and increased serum reticulocytes and urinary urobilinogen in the 160 and 40 mg/kg groups of both sexes, and methemoglobinemia occurred in the 160 mg/kg group. Increase in spleen weight was noted in the 160 and 40 mg/kg groups. On histopathological examination, hemosiderosis, increased extramedullary hemopoiesis, congestion of the spleen and myeloid hyperplasia of the bone marrow were observed in the 160 and 40 mg/kg groups of both sexes. Repair of these lesions occurred within 14 days after the cessation of administration. Based on these findings, a no-observed-effect level for p-phenetidine would be concluded 10 mg/kg/day.


[Subchronic oral toxicity study of stevioside in F344 rats].

A 13-week subchronic oral toxicity study of stevioside was carried out in F344 rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5% in diet, to determine appropriate dose levels for a 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Between the control and treated groups, there were no differences in body weight gain during the administration period and in food consumption in the later period of the study. LDH on biochemical investigation and single cell necrosis in the liver revealed by histopathological examination were increased in all male treated groups. These were not considered specific changes, because of the lack of any clear dose response, the relatively low severity and the limitation to males. Other parameters that were found to demonstrate significant differences on hematological and biochemical investigations were of minor toxicological significance. From these results, a concentration of 5% in diet was concluded to be a suitable maximum tolerable dose of stevioside for a 2-year carcinogenicity study in rats.


[Dose-response relationship of promotion by phenobarbital in rat two-stage hepatocarcinogenesis].

Investigation of the effect of various doses of phenobarbital (PB) in Experiment I (PB dose levels: 0, 38, 75, 150, 300 or 600 ppm) and Experiment II (PB dose levels: 0, 1, 4 or 16 ppm) given to male F344 rats (20 animals/group) in drinking water for 39 weeks after a single intraperitoneal injection of diethylnitrosamine (DEN) was performed using incidence of hepatic tumors and number or area of enzyme-altered foci as end-point lesions. There were no significant differences in the final body weight changes between DEN-initiated PB treatment (DEN+PB) and DEN-initiated (DEN) groups. Dose-dependent increases in the absolute and relative liver weights and in the incidence of hepatic carcinoma were found in the DEN+PB groups treated with 38 ppm PB or above 75 ppm PB or above, respectively. The numbers or areas of gamma-GTP or GST-P positive foci of the liver were increased in the DEN+PB groups treated with 38 ppm PB or above. Additional investigation of 7-ethoxycoumarin o-deethylase (7-ECDE) induction in Experiment III, 7 groups consisting of 3 animals/group being fed water containing PB (0, 1, 4, 16, 75, 300 or 1200 ppm) for 1 week after the initiation of DEN and a further 7 groups (5 rats/group) receiving the same drinking water without DEN treatment, revealed dose-dependent increases of 7-ECDE in the DEN+PB groups and PB groups treated with 16 ppm PB or above. The present studies indicate that the threshold for promotion by PB is 38 ppm.


[Subchronic oral toxicity study of cyanoguanidine in F344 rats].

A 13-week subchronic oral toxicity study of cyanoguanidine was performed in male and female F344 rats by feeding of CRF1 powder diets containing 0, 1.25, 2.5, 5 and 10% cyanoguanidine to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Inhibition of body weight gain was more marked in both sexes of the 10% group and in females of the 5% group as compared with the control group. Mean food intake in males of the groups treated with 5% or 10% and in females of the 10% group was significantly higher than that in the control group. Serum biochemical investigation revealed a higher level of serum BUN in both sexes of the 10% group. On histopathological examination, toxic changes characterized by the occurrence of intranuclear eosinophilic inclusion bodies in the proximal tubular epithelium of the kidney were observed in both sexes of the 10% group. Similar inclusion bodies were also seen in 2 out of 10 males of the 5% group. From these results, it was concluded that a level of 10% of cyanoguanidine in the diet is unequivocally toxic. A dose level, 5% cyanoguanidine, in the diet might be appropriate as a high dose for a carcinogenicity study.


[Ultrastructural study of the blood-testis barrier in rat by the lanthanum method].

Ultrastructural changes of the testes in 35-week-old WBN/Kob rats were investigated using the lanthanum-tracer method. Tissues were cut and fixed with a solution containing 1% lanthanum and 2% glutaraldehyde in a 0.1 M sodium cacodylate buffer at pH 7.8 and with a solution of 2% osmium and 1% lanthanum in a 0.1 M sodium cacodylate buffer. Ultrathin sections of epoxy resin-embedded specimens were stained with uranyl acetate and lead citrate and observed into a JEM-100CXS JEOL transmission electron microscope. The remnants of each testis were fixed in Bouin's fixative, and observed light-microscopically, where almost all seminiferous tubules in all of the six testes were found to be severely atrophied. Electron microscopically, lanthanum pigments were limited in the Sertoli cell tight junctions of the seminiferous tubules even in the severely atrophied tubules. In conclusion, it is unlikely that the testicular atrophy in WBN/Kob rats is attributable to dysfunction of the blood-testis barrier.


[Twenty-eight day repeated dose toxicity test of m-nitroaniline in F344 rats].

A twenty-eight day repeated oral dose toxicity test of m-nitroaniline (m-NA) was carried out in male and female F344 rats at dose levels of 0, 15, 50 or 170 mg/kg/day. Animals of both sexes were divided into 6 groups, each consisting of 30 animals, 4 groups being used for the 28 days dosing study and the remainder for investigation of subsequent recovery. Inhibition of body weight gain, and induction of cyanosis and methemoglobinemia were observed in the highest dose groups of both sexes, but there were no animal mortalities. Testicular atrophy was evident but there was no effect on the ovaries in the same group. In addition to these findings, hemolytic anemia and increases of liver, spleen and kidney weights were also observed in both sexes in a dose-related fashion. Histologically, the highest dose group showed reduction of spermatogenesis with multinucleated giant cell formation, lipofuscin deposition mainly in the proximal renal tubules, and increases in hemosiderin deposition and extramedullary hematopoiesis in the liver. Dose-related increases in the incidence of hemosiderin deposition in the spleen, erythroid hyperplasia in the bone marrow and swelling of hepatocytes were observed in treated groups. After a 14 day recovery period, these findings were attenuated or had disappeared. Based on these results obtained under the present experimental conditions, it was concluded that m-NA induces hemolytic anemia and exerts testicular toxicity in rats and that the non-observed-effect level of m-NA is less than 15 mg/kg/day.


Stability of vitamin B1 in a commercial multivitamin syrup preparation.

Accelerated stability studies of a commercial vitamin B1 syrup preparation were carried out at 50, 60, 70 and 80 degrees C. The decomposition of vitamin B1 in the preparation followed pseudo-first order reaction kinetics. Apparent decomposition rate constants conformed to the Arrhenius equation. Apparent activation energy and shelf-life at 25 degrees C were estimated to be 24.2 kcal/mol and 3.3 years, respectively.


[Up-dating the references for environmental health criteria for anionic surfactants and preparation of its first draft].

The preparation of a EHC monograph for anionic surfactants was started in 1980. The chemicals consist of linear alkylbenzene sulfonate (LAS), alkyl sulfate (AS) and alkyl alpha-olefin sulfonate (AOS). Although a preliminary draft appeared in 1985, further works were stopped for 5 years. For the development of the preliminary draft, up-dating the references was performed by using on-line JICST data base from 1981 to 1990. The number of literature on LAS was 486. On the other hand the number on AS was about 1/5 that of LAS. In the case of AOS, only 20 literatures were retrieved. The literatures on LAS were many in the research field of environmental science and very few in the toxicology field.


[Improvements of commentary work on the first drafts of the EHC monographs].

The EHC is historically most important among the activities of IPCS which was inaugurated in 1980, and its first draft is being circulated to IPCS contact points throughout the world. Comments and suggestions in improvements to the first draft of the EHC monograph is essential to the sound development of this document. Our suggestions on such improvements are the basis of this report.


[Comparative studies on acute toxicity of glutaraldehyde using young and old rats].

Acute oral toxicity test of glutaraldehyde (GA) was carried out in young (5-6W) and old (57-60W) Wistar/ST rats. Experiment 1: Various doses of GA were administered by gavage. After 30 minutes, the rats showed abnormal gait, then took an abdominal or lateral position after 4 hours. Gross erosion, discoloration and thickening of the glandular stomach mucosa and hyperemia of the liver, intestine and lung were observed in the dead rats. The LD50 values were 283 mg/kg for young rats and 141 mg/kg for old rats. Experiment 2: One half of the LD50 doses (140 mg/kg and 70 mg/kg of GA) were administered to young and old rats by gavage, respectively. Both groups showed a similar toxicity. Organ weights were not changed. In gross findings, erosion, discoloration and thickening of the glandular stomach mucosa were observed on day 1-7, but these damages were recovered by day 14. Histopathologically, atrophy, degeneration, necrosis, hemorrhage, edema and cell infiltration of the glandular stomach mucosa were found on day 1. Recovery from these changes was observed from day 3. Changes in several serum enzyme activities were observed on day 1-3. Therefore, susceptibility to the acute toxic effect of GA was higher in old rats than in young rats. However, no apparent differences were observed in the toxic profiles by GA between young and old rats.


[Survey of radiocesium in domestic mushrooms on the market].

Domestic mushrooms on the market were tested for concentration of radiocesium; cesium-134 and 137 by gamma-ray spectrometer. Cesium-137 was detected in most samples of dried and raw shiitake (Lentinus edodes (Berk.) Sing.). The concentrations were from 6.7 to 73.9 Bq/kg in dried ones and from 1.3 to 6.4 Bq/kg in raw ones. It was not detected in enokitake (Flammulina veltipes (Fr.) Sing.) and shimeji (Lyophyllum aggregatum (Secr.) Kühner and Pleurotus ostreatus (Fr.) Quél.). Cesium-134 was not found in all samples.


[Studies on origin of illicit methamphetamine. I. The relationship of enantiomeric compositions between methamphetamine and its raw material (ephedrine)].

In order to elucidate the relationship of enantiomeric compositions between methamphetamine (MA) and its raw materials, ephedrine (EP) enantiomers, commercial EP samples and MA samples prepared from them were analyzed by HPLC using GITC-prelabeling. The GITC derivatives were separated on ODS column using methanol-water-acetic acid (45:54:1) at a flow rate of 1.2 ml/min for EP and tetrahydrofuran-water-acetic acid (29:70:1) at a flow rate of 1 ml/min for MA. The chromatographic conditions resulted in such a good separation of four EP and two MA enantiomers that 1/1000 enantiomeric impurities could be detected and discriminated from the major enantiomer with good reproducibility. Moreover, it was demonstrated that the asymmetric center at alpha-position of amino group was entirely retained throughout the reductive reaction of the EP samples, and that the MA samples inherited the enantiomeric character from the EP samples used. This method was applied to discriminative analysis of MA samples seized in Japan.


[Development of a database for registration of journals in the library of NIHS].

A database for registration and management of journals in the library of NIHS was developed using dBASE III PLUS software. The database was shown to be useful in searching for journals subscribed in the various divisions of NIHS and for those already expired. Additional data related to accounting on and arrangement of journals will help management of the library.


[Pyridoxine hydrochloride reference standard (Control 911) of the National Institute of Hygienic Sciences].

The raw material of pyridoxine hydrochloride was examined for preparation of the "Pyridoxine Hydrochloride Reference Standard". Analytical data obtained were as follows: loss on drying, 0.00%; pH, 2.87; melting point, 204.6 degrees C (decomposition); infrared spectrum, same as Pyridoxine Hydrochloride Reference Standard (Control 879); thin-layer chromatography, nonimpurities were detected; assay, 100.0% by non-aqueous titration and 100.0% by UV spectrophotometry. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 911).


[Tocopherol reference standard (Control 911) of the National Institute of Hygienic Sciences].

The raw material for tocopherol was tested for preparation of the "Tocopherol Reference Standard (Control 911)". Analytical data obtained were as follows: infrared spectrum, same as Tocopherol Reference Standard (Control 881); absorptivity, E1%1cm (292nm) = 75.5; thin-layer chromatography, no impurities were detected up to 50.0 micrograms; high performance liquid chromatography (HPLC), four impurities were detected; assay, 100.7% by HPLC. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 911).


[Prednisolone reference standard (Control 911) of the National Institute of Hygienic Sciences].

Prednisolone was tested for preparation of the "Prednisolone Reference Standard (Control 911)". The quality of raw material was examined and compared with the previous Reference Standard (Control 872). Analytical data obtained were as follows: loss on drying, 0.10%; melting point, 233.2 degrees C (decomposition); optical rotation, [alpha]20D+98.77 degrees; UV spectrum, lambda max = 243nm; absorptivity, E1%1cm (243nm) = 413.5; IR spectrum, 1711, 1612, 1110, 888cm-1; one impurity was detected by thin-layer chromatography and high-performance liquid chromatography (HPLC), respectively; assay, 100.1% by HPLC. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 911).


[d-Camphor reference standard (Control 911) and dl-Camphor Reference Standard (Control 911) of the National Institute of Hygienic Sciences].

The raw materials of d-camphor and dl-camphor were examined for preparation of the "d-Camphor Reference Standard" and "dl-Camphor Reference Standard". Analytical data obtained were as follows: ultraviolet spectrum, lambda max = 290nm; infrared spectrum, 2958, 1742, 1045cm-1; optical rotation, [alpha]D20 = +42.7 degrees (d-camphor), [alpha]D20 = -0.3 degrees (dl-camphor); melting point, 180 degrees C (d-camphor), 179 degrees C (dl-camphor); gas-chromatography (GC), one impurity was detected in d-camphor and three impurities in dl-camphor; assay, 99.5% (d-camphor), 99.5% (dl-camphor) by GC. Based on the above results, these raw materials were authorized as the Japanese Pharmacopoeia Standard (Control 911).


[Tocopherol acetate reference standard (Control 911) of the National Institute of Hygienic Sciences].

The raw material for tocopherol acetate was tested for preparation of the "Tocopherol Acetate Reference Standard (Control 911)". Analytical data obtained were as follows: infrared spectrum, same as Tocopherol Acetate Reference Standard (Control 881); absorptivity, E1cm1% (284nm) = 43.5; thin-layer chromatography, no impurities were detected up to 50.0 micrograms; high performance liquid chromatography (HPLC), two impurities were detected; assay, 100.3% by HPLC. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Standard (Control 911).


[Quality tests for ibuprofen preparations].

Ibuprofen preparations were tested with a view to checking their quality by physical methods such as determination, disintegration and dissolution tests. These studies were carried out on 48 kinds of commercial ibuprofen preparations. The drug content of each preparation was measured by spectrophotometry (264nm), and the values were in the range of 90-110%. In the disintegration tests of 36 tablets, a few tablets of two preparations failed to disintegrate completely after 60 minutes. However the number of such tablets was within the limit specified in JP. The dissolution test described in the USP monograph was also applied to the 36 tablets, and it was found that 9 tablets failed the test provision that over 70% of the tablets must be dissolved within 30 minutes.


[Studies on the analysis of copper chlorophyll and sodium copper chlorophyllin in imported foods].

The analysis of copper chlorophyll (CuCh) and sodium copper chlorophyllin (CuCh-Na) in imported foods was carried out. Standards of CuCh and CuCh-Na were examined by ultraviolet and visible spectrophotometer. CuCh gave absorption maximum around 650 nm, while CuCh-Na gave around 630 nm. Imported sweets and liqueurs were homogenized and extracted with ethyl acetate. These extracts also gave absorption maxima absorbance around 650 nm or 630 nm. The results suggested that a distinction between CuCh and CuCh-Na in foods was possible by spectrophotometry. Visible spectrophotometric quantitation was also tried. However the estimated levels of CuCh or CuCh-Na in the samples by this method did not meet with those by atomic absorption spectrometry.


[Estimated production of coal-tar dyes (including dye aluminum lakes) based on official inspections in 1991].

The total number of official inspection of coal-tar dyes and their lakes from April in 1991 to March 1992 was 835. The quantity which passed inspection amounted to 240 tons in Japan. The official production of color dyes each month in summarised in Table 1 and that by various manufacturers in Table 2. The food coal-tar dye produced in the largest quantity was Food Yellow No. 4, occupying 44.6% of the total during this period.


[Studies on "new coccine standard" for the dye standard of the National Institute of Hygienic Sciences].

The "New Coccine Standard (C.I. 16255)" for the Dye Standard of the National Institute of Hygienic Sciences was prepared. The content of this Dye Standard determined by the titanium trichloride method was 97.5% on the average. The ultraviolet-visible absorption and infrared spectra of the Dye Standard were also measured.


[Studies on "acid red standard" for the dye standard of the National Institute of Hygienic Sciences].

The "Acid Red Standard (C.I. 45100)" for the Dye Standard of the National Institute of Hygienic Sciences was prepared. The content of this Dye Standard determined by the titanium trichloride method was 96.4% on the average. The ultraviolet-visible absorption and infrared spectra of the Dye Standard were also measured.


[Studies on "indigo carmine standard" for the dye standard of the National Institute of Hygienic Sciences].

The "Indigo Carmine Standard (C.I. 73015)" for the Dye Standard of the National Institute of Hygienic Sciences was prepared. The content of this Dye Standard determined by the titanium trichloride method was 97.0% on the average. The ultraviolet-visible absorption and infrared spectra of the Dye Standard were also measured.


[Analytical results of post-harvest pesticides in citrus fruits and fruits juices by GC-MS (SIM) and HPLC with fluorescent detector].

Determination of 6 kinds of post-harvest pesticides (DP, OPP, TBZ, 2,4-D, Imazalil and Benomyl) in citrus fruits and fruits juices was carried out by GC-MS (SIM) and HPLC with fluorescent detector. DP for 16 samples, OPP for 27 samples, TBZ for 12 samples, 2,4-D for 10 samples, imazalil for 20 samples and Benomyl for 4 samples were detected in total 32 samples.


Determination of organophosphorus pesticides in imported foods by FPD-GC and GC-MS.

Organophosphorus pesticides in 47 agricultural products imported at the Yokohama and Kobe Quarantine Station in 1990 were determined by FPD-GC and identified by GC-MS. Chlorpyrifosmethyl, malathion and fenitrothion were found in wheat (0.03-0.69 ppm), chlorpyrifosmethyl and fenitrothion in soy bean (0.02-1.03 ppm), chlorpyrifosmethyl in cherry (0.12-0.17 ppm), chlorpyrifosmethyl in pumpkin (0.07-0.15 ppm), chlorpyrifosmethyl and malathion in corn (0.15-1.38 ppm).


[Studies on reinforcing effects of methylephedrine, caffeine and their mixture with intravenous-self administration in rhesus monkeys].

The reinforcing effects of methylephedrine hydrochloride (ME), anhydrous caffeine (CA) and their mixture (ME+CA) were studied by the intravenous cross self-administration experiment and by the progressive ratio experiment in four male rhesus monkeys each. In the intravenous cross self-administration experiment, ME, CA and ME+CA were found to have reinforcing effects. Self-administration rates above the level of cocaine, a typical reinforcing drug, were not observed in ME or CA alone, but observed in their mixture (120 + 126 micrograms/kg/inj.: M dose or 480 + 504 micrograms/kg/inj.: H dose). The minimum reinforcing doses were 120 micrograms/kg/inj. (M dose) for ME, 126 micrograms/kg/inj.: (M dose) for CA, and ME 30 micrograms+CA 32 micrograms/kg/inj. (L dose) for the mixture. Vomiting was observed during the session in monkeys which showed higher self-administration rates of ME and the mixture, and decreases in the rates were observed in these animals on the next day. One animal at H dose of the mixture, which showed a high self-administration rate on both the 1st and 2nd days, died after the end of the session on the 2nd day. In the progressive ratio experiment, the final ratios at 120 micrograms/kg/inj. of ME, 126 micrograms/kg/inj. of CA and the mixture of ME 120 micrograms/CA 126 micrograms/kg/inj. were almost equal to or less than that of saline (negative control). Thus, these drugs didn't show reinforcing effects at the above levels. However, a reinforcing effect was observed in three out of four monkeys administered 1920 micrograms/kg/inj. of ME, 2016 micrograms/kg/inj. of CA, and the mixture of ME 1920 and CA 2016 micrograms/kg/inj.(ABSTRACT TRUNCATED AT 250 WORDS)


[Studies on the teratogenic potential of p-tert-butylphenolformaldehyde resin in rats].

p-tert-Butylphenolformaldehyde resin, an adhesive, was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 250, 500 and 1000 mg/kg body weight during days 7 to 17 of gestation, and the effects of the compound on dams and fetal developments were examined. No changes in general conditions, maternal body weight, food consumption, numbers of corpora lutea and implantation ratio were observed. There was no evidence of an increase in fetal death or of malformation attributable to the treatment with p-tert-butylphenolformaldehyde resin in any of dose levels examined. It was concluded that p-tert-butylphenolformaldehyde resin has no teratogenic effect in rats.


[Twenty-eight day repeated dose toxicity test of dihepthyl phthalate in F344 rats].

A twenty-eight day repeated oral dose toxicity test of dihepthyl phthalate (DHP) was carried out in male and female F344 rats at the dose levels of 0, 0.2, 1 and 5 g/kg/day. All rats in each group, consisting of 5 males and 5 females, received a daily intragastric administration of DHP for 28 days. Additional two groups of animals exposed to dose levels of 0 and 5 g/kg were used for investigation of subsequent recovery for 2 weeks. No animals died during the administration period. Inhibition of body weight gain was observed in both sexes of the 5 g/kg group. Blood biochemistry revealed significant increases in albumin and A/G ratio in males of the groups treated with 0.2 g/kg or more, and in albumin and total protein in females treated with 1 g/kg or more. In the 5 g/kg group, BUN, GOT, GPT, ALP and Zn was increased in males, and GOT in females. The increases in GOT, GPT and ALP were also observed in males of the 1 g/kg group. Increases in liver and kidney weights were noted in both sexes treated with 1 g/kg or more and in males of the 5 g/kg group, respectively. Testicular weight was decreased in the 5 g/kg group. On histopathological examination, swelling and necrosis of hepatocytes were found in males of the 1 and 5 g/kg groups. Males of the 5 g/kg group showed atrophy of the seminiferous tubules accompanied with loss of spermatogenesis. In the recovery group, similar changes were detected in the testis, but some of the seminiferous tubules showed slight regenerative changes.(ABSTRACT TRUNCATED AT 250 WORDS)


[Twenty-eight-day repeated dose toxicity test of pentaerythritol in F344 rats].

A twenty-eight-day repeated dose toxicity test of pentaerythritol at dose levels of 1000 or 0 mg/kg/day was carried out in male and female F344 rats. Thirteen animals of each sex were divided into 2 groups with 7 rats receiving pentaerythritol treatment and 6 rats served saline as control. All groups received an i.g. administration daily for 28 days. As to serum biochemical and hematological examinations, there were no serious differences between the pentaerythritol-treated rats and the control rats. On histopathological examination, no specific changes were observed in the pentaerythritol-treated rats. Based on these results, the no-observed-effect level of pentaerythritol can be concluded to be more than 1000 mg/kg/day.


[Studies on cell proliferation activities in acute toxic lesions in the liver and pancreas of hamsters treated with N-nitrosobis(2-oxopropyl)amine].

Histopathology and cell proliferation activities in acute toxic lesions in the liver and pancreas of female Syrian hamsters given a S.C. injection of N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 100 mg/kg, were investigated. Histologically, at one day after administration, hypertrophy and focal necrosis of the hepatocytes were observed, whereas no remarkable changes were seen in the pancreas. At 7 days after administration, when diffuse hypertrophy, vacuolation and necrosis of the hepatocytes, and atypical hyperplasia of the bile duct were seen in the liver, hyperplasia of the pancreatic duct and focal necrosis and vacuolation of the acinar cells were noticed in the pancreas. Immunohistochemistry for both 5-bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) revealed remarkable increases of cell proliferation activities in the target cells for BOP toxicity, especially at 7 days after BOP treatment. Meanwhile, the number per nucleus of silver-stained proteins related to nucleolar organizer regions (AgNOR) was significantly increased in the target cells at both 1 and 7 days after BOP treatment. Thus, in the present study, it was suggested that acute toxic changes in the liver of hamsters treated with BOP precedes those in the pancreas. The speculation that AgNOR may be an indicator recognizing earlier alterations on acute BOP toxicity remains to be examined.


[13-week subchronic toxicity study of 1,1-bis(t-butylperoxy) 3,3,5-trimethyl cyclohexane in mice].

A 13-week subchronic toxicity study of 1,1-bis(t-butylperoxy)3,3,5-trimethyl cyclohexane (TMCH) was performed in male and female B6C3F1 mice by feeding a CRF-1 powder diet containing 0, 0.5, 1.0, 2.0 and 4.0% TMCH, to determine the maximum tolerable dose (MTD) for subsequent carcinogenicity study. Mice were randomly divided into 5 groups, each consisting of 10 males and 10 females. Eight animals of both sexes in the 4.0% TMCH group died during the early administration period. Suppression of body weight gains was marked in both sexes of the 4.0% and 2.0% TMCH groups as compared with the control group. The mean food consumption in all groups treated with TMCH was lower than that in the control group in a dose-related manner. Hematological examination revealed decreases in the number of erythrocytes, volume of hemoglobin, and values for hematocrit and mean corpuscular volume (MCV) in both sexes of the 4.0% and 2.0% TMCH groups. The relative liver weights of all groups treated with TMCH increased in a dose-related manner, whereas both absolute and relative spleen weights decreased in a dose-dependent manner. Histopathologically, swelling of the hepatocytes was found centrilobularly or diffusely in both sexes of the 1.0, 2.0 and 4.0% TMCH groups, and decrease of the hematopoietic cells in the bone marrow was observed in both sexes of the 2.0 and 4.0% TMCH groups. In addition, atrophy of red pulp and white pulp of the spleen was found in both sexes of the 2% and 4% TMCH groups.(ABSTRACT TRUNCATED AT 250 WORDS)


[A study of the relationships between exposure periods and no-effect doses in repeated dose toxicity tests].

In the risk assessment of chemicals to humans, it is a very important step to determine no-observed-adverse-effect-levels (NOAEL) or lowest-observed-adverse-effect-levels (LOAEL) from animal experiments. Recently, short-term screening tests, such as 28-day repeated dose toxicity test, are carried out in accordance with the regulative guidelines for the safety evaluation of chemicals. However, many problems still remain in the risk assessment to human based on short-term toxicity studies. For this reason, we studied the relationships between the exposure periods and NOAELs or LOAELs in repeated dose toxicity tests using available test results of 18 halogenated compounds. The ratios between each NOAEL or LOAEL of short-term tests (14, 28 days, 13 weeks and 6 month) and those of long-term tests (longer than one year) were calculated on the basis of same animal species, route and toxic effect. From this study, it was considered that exposures above 13 weeks were needed to satisfy the present safety factor considerations for setting an acceptable daily intake (ADI).


[Flower bud differentiation and development of opium poppy (Papaver somniferum L.) II. Effects of daylength and temperature].

We investigated the effect of daylength (from 9 to 15 hours) and cultivation temperature (from about 13 to 25 degrees C) on flower bud differentiation of three strains of Papaver somniferum L. cv. Ikkanshu, which have been cultivated in Nayoro (Hokkaido), Tsukuba (Central Honshu) and Nagasaki (Kyushu) for the last a few decades. 1. The experiment on the effect of daylength on flowering revealed that the longer the photoperiod was, the earlier flowering occurred. 2. Flower bud differentiation was observed at temperatures of 20 degrees C or less but never at 25 degrees C, and it was more quickly induced at lower temperatures. Furthermore, we also found that the optimum temperature for flower bud development following differentiation was 20 degrees C. From these findings, we reached the conclusion that this species has thermosensitivity. 3. Flower bud differentiation clearly occurred later in the Nayoro strain than in the Nagasaki strain or the Tsukuba strain. This seems to indicate that the Nayoro strain is a different ecological type from other strains. 4. When we compared the size and dry weight of the capsules, which are known to be closely related to opium yield, the capsules of the Nagasaki and Tsukuba strains were considerably smaller and lighter than those of the Nayoro strain. This is attributable to the fact that flower bud differentiation occurred at an early stage before the achievement of sufficient vegetative growth in the Nagasaki and Tsukuba strains.


[Fungi isolated from diseased medicinal plants].

One hundred and forty-four fungal isolates were obtained from diseased Paeonia albiflora Pall. var. trichocarpa Bung., Astragalus membranaceus Bung., Lithospermum erythrorhizon Sieb. et Zucc., Ledebouriella seseloides Wolff and Bupleurum falcatum L. which were collected in the test field of Tsukuba Medicinal Plant Research Station, National Institute of Hygienic Sciences. Most of them were identified into 15 genera containing 8 species. Fungal species presumed to be pathogens of the host plants were as follows: Cladosporium paeoniae, Pestalotia paeoniicola, Glomerella cingulata, Hainesia lythri, Guignardia sp. and Alternaria sp. from P. albiflora, Fusarium spp., Rhizoctonia spp. and Neocosmospora vasinfecta from A. membranaceus, Colletotrichum gloeosporioides from L. erythrorhizon, Rhizoctonia sp., Fusarium spp., Phoma sp. and Pyrenochaeta sp. from L. seseloides, and Fusarium sp., Alternaria alternata, Phyllosticta sp., Phoma sp., Phomopsis sp. and C. gloeosporioides from B. falcatum. Roots of B. falcatum were found to be parasitized by Meloidogyne sp.


[Studies on the identification of psychotropic substances. VIII. Preparation and various analytical data of reference standard of some stimulants, amfepramone, cathinone, N-ethylamphetamine, fenethylline, fenproporex and mefenorex].

The Reference Standards for amfepramone, cathinone, N-ethylamphetamine, fenethylline, fenproporex and mefenorex were prepared. Their purities determined by HPLC were more than 99.5%. For the identification and determination of these six drugs, their analytical data were measured and discussed by TLC, UV, IR, HPLC, GC/MS and NMR.


The metabolism of 1,6-dinitropyrene in rat hepatocytes.

This paper reports investigations using hepatocytes to study the metabolism and DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6-dinitropyrene is not believed to be mutagenic per se, metabolites were synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive and therefore the effect of oxygen on the metabolic pattern and DNA binding was investigated by comparing results from aerobic and anaerobic conditions. The binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased by 15% in the presence of oxygen. Although there was little difference in the rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference in the metabolic pattern. Under anaerobic conditions there was an increase in the level of the terminal reduction product 1-amino-6-nitropyrene.


[Preparation of the first draft of environmental health criteria for acetonitrile: production process of the draft].

Acetonitrile is a high-polarity aprotic organic solvent used in DNA synthesizers, HPLC, and electrochemistry. In addition, it is used larger amounts at petrochemical companies and pharmaceutical firms. Preparation of an Environmental Health Criteria (EHC) monograph for acetonitrile was started in 1986, and its first draft except the environmental section was completed on June 21, 1991. The environmental section has been prepared by Dr. S. Dobson (ITE/UK). The first draft was circulated to EHC Contact Points for comment in March 1992.


[Determination of nicarbazin in imported chicken].

The confirmation and quantitative analysis of nicarbazin (NCZ) in imported chickens were made by high performance liquid chromatography equipped with a photodiode array detector. The results showed that 1 out of 7 chicken samples contained over 30 ng/g of NCZ. The concentrations of NCZ varied from 10 to 120 ng/g according to the parts of the NCZ positive chicken samples.


[Food hygienic indexes on biodegradable polymers].

Current specifications for food packaging made of polyolefine plastics were applied to biodegradable plastics. No lead and cadmium were detected in any biodegradable plastic samples with the exception of bacterial cellulose, which contained trace amounts of lead and cadmium. Potassium permanganate consumption amount was less than the current specification level for polyofines. Sugars leached from bacterial cellulose was 22 +/- 1 microgram per 100 cm2 as glucose, and amino acids leached from poly-gamma-methylglutamate films was 8 +/- 3 micrograms per 100 cm2 as glutamic acid.


[Migration test of lead and cadmium from plastic wares in contact with food].

Release of lead and cadmium from plastic tableware was examined. Samples were treated with 2 ml of 4% acetic acid or 0.1N HCl per cm2 of the surface area at 60 degrees C or 95 degrees C for 30 min. No migration of lead and cadmium from samples containing up to 391 ppm lead or 6863 ppm cadmium was observed.


[Determination of volatile substances and leachable components in polystyrene food contact wares].

Material and migration tests of food-contact plastic wares made of polystyrene were carried out. The average concentration of volatile substances (sum of toluene, ethylbenzene, isopropylbenzene, n -propylbenzene, and styrene) in materials was 861 +/- 692 ppm. Styrene was observed in 95% of 19 samples. alpha-Methylstyrene, which is one of the material compounds of polystyrene, was detected in one sample. Release of volatile substances into n-heptane was not observed at the detection limits of 0.1 ppm.


[Preliminary screening for antiviral AIDS drugs. III. Report on fiscal year 1990].

Preliminary screening for antiviral AIDS drugs has been carried out using three different in vitro assay systems. Among 106 samples tested, five were found to inhibit the growth of HIV in vitro. Two of five have a hopeful sign, as the range of effective doses of the samples is wide.


[First drafts of environmental health criteria circulated for comments by IPCS in 1991-1992].

Summaries of first drafts of Environmental Health Criteria (EHC), which were circulated for comments by IPCS in the period of 1991-1992, were presented. EHC drafts on 14 compounds and one methodology were received in this period.


[Problems and their solutions in preparation of environmental health criteria documents of IPCS].

Problems and solutions in preparing Environmental Health Criteria (EHC) documents for IPCS (International Programme on Chemical Safety) are summarized. Selection of target chemicals, information search, appointment of appropriate drafters, selection and evaluation of data, use of proprietary data, scientific and English editing, organization of international expert meetings, coordination and secretarial works were the important factors in the preparation of EHCs. The elucidation of the process of risk assessment of chemicals in the EHC preparation will be helpful in preparing other criteria documents.


[Study of the effects of some prophylactic measures and radiological contamination in Poland after the Czernobyl accident; Introduction to the research program MZ-XVII].

An aim of the introduction is to remained the scale of radiological contamination in Poland after the accident in the Czernobyl Power Station, the evaluation of findings which led to prophylactic administration of potassium iodide first in part of Poland and later Country-wide. The introduction gives also the history of Research Programme MZ-XVII and its implementation in several regions of Poland. The main aims of the Programme were: 1. Estimation of radioiodine dose accumulated in thyroids of children, youths and adults who lived in different parts of Poland and evaluation whether these doses could lead to the development of thyroid disorders. 2. Evaluation of thyroid function in those exposed to radioiodine in different trimesters of preneonatal life, who were born euthyroid and who were given potassium iodine in first days of life. 3. Evaluation of efficacy of single dose of potassium iodide and estimation of possible intrathyroid and extrathyroid side-effects after prophylactic iodide administration. The foundations of the Programme and Centers involved in its implementation are also specified.


[Epidemiologic foundation for population studies of program MZ-XVII].

Epidemiological foundation included: aim of studies, knowledge about epidemiology of thyroid disorders in Poland, evaluation of radioiodine dose accumulated in thyroids of inhabitants of different age living in different par of Poland, information about relative diet iodine deficiency in different parts of Poland and identification of research teams (manpower) capable to carry on population studies. The final identification of epidemiological foundation was proceeded by pilot studies performed in 4 different regions of Poland. Finally it was decided that population studies would be performed in so called Regions of 6 different University Medical Schools (Białystok, Kraków, Lódź, Poznań, Szczecin, Wrocław). The sample will be selected randomly on the base of information from the voting lists (random selection of vovoidoship, then towns and villages, then streets and number of houses, then number of flats. All living in selected flat or house during Czernobyl accident and born between January 1974 and December 1985 (children) and between January 1926 and December 1973 (adults) will be considered "the sample". In all cases the sample will be examined by means of unified questionnaire and protocol of medical and laboratory examination. The same kits (of the same producers) will be used to evaluate serum TSH, T4, T3 and thyroid autoantibodies. The data obtained will be evaluated by unified computerized system. Separate studies involved the sample of newborns exposed to radioiodine during last trimester of pregnancy, found to be euthyroid and given potassium iodide in first days of life. Separate system was also used to investigate effect of radioiodine and of prophylactic dose of potassium iodide in those with past history of thyroid disorders.


[An information system for analyzing the need for examining certain aspects of radiologic contamination caused by the Czernobyl catastrophe].

In this paper we briefly report a set of programming tools designed to support the analysis of some aspects of radiological contamination caused by Tchernobyl catastrophe. First of all a system for data storing is characterized; after mentioning basic data structures, two mutations of this system are described (one version for data collected during a pilot study and the second for the main investigation). Next the problems of data analysis are discussed. Again we distinguish between pilot and main analysis. A simple query language is introduced and the procedures for coding some variables are mentioned. Lastly the problems and difficulties arising during the whole analysis are specified.


[Evaluation of equivalent body burden in the thyroid for the people of Poland on results of 131I absorption after the disaster in Czernobyl. Determination of thyroid blockade with potassium iodide].

An assessment of effectiveness of the administering of single dose of stable iodine in Poland on the reduction of 131I doses in thyroid has been performed. 5-compartment model of metabolism of iodine developed by Johnson has been used to evaluate predicted levels of stable iodine and 131I content in thyroid and commitment dose equivalent H50 for different doses of stable iodine and various age and sex group population. The measured values of 131I concentration in air and in milk and standard values for milk and food consumption and inhalation rate as well as metabolic parameters were used. Theoretical calculations showed that administering of stable iodine on 1986-04-28, 1986-04-29, 1986-04-30 and 1986-05-01 could have reduced committed dose equivalent H50 form ingestion with inhalation pathway by about 44%, 40%, 26%, 12% respectively. On the basis of measured 131I activity in the thyroid for inhabitants from different districts in Poland (1400 measurement) committed dose equivalents were determined and analysis of radiation hazard from 131I were performed. In the most contaminated regions of Poland average H50 doses for children 1-5 and 5-10 years old are close to 50 mSv (permissible level for population) and maximal doses exceed this limit four times. These maximal doses occurred for about from 5% inhabitants from these area. In the moderate and low contaminated regions of Poland the average doses are fivefold and tenfold less respectively.


[Chronicled report on the period from May 1 to September 27, 1989. Discussion of risk factors].

The Institute of Mother and Child was invited in 1988 by professor J. Nauman to his Chernobyl program, so as to inspect children born after Chernobyl accident, particularly these born in first days following the accident dated 26 april 1986. The central part of Poland is covered with screening for congenital PKU and hypothyroidism therefore all children had estimated TSH-spot levels between 3rd and 5th day of life. So as to control the present state of general health and thyroid state in the study group a questionnaire with a letter to parents explaining the aim of the inquiry was sent to the parents (see addenda). About 14000 letters were send from which around 12000 responses were returned to the Institute. From informations received this way we draw the preliminary conclusion that no significant damage in health of these children or their siblings can be found. About 20% of the mothers admitted taking the Lugol solution in a last day of pregnancy. However it should be taken into account that these data were collected 2 years after the accident and are not fully reliable. In the period 1989-1990 a group of 1912 children (938 boys and 974 girls) was called to the Department of Endocrinology of the Institute and inspected. The age was from 2.9 to 4.2 years. All children had screening TSH-spot test result negative (below 30 microIU/ml). General health state The general health state of the children inspected was good. Only 33 of them (1.7%) had various congenital malformations what is not different from general population of polish children. Mental development was in 1897 cases normal, in 15 cases IQ was decreased and the score varied from 75 to 80 according the Brunet-Lezine scale. Average physical development was normal. Body height evaluated in standard deviation score (SDS) was as follows: SDS = 0.0 in 359; SDS = +0.9 +/- 0.6 in 906 and SDS = -0.5 +/- 0.3 in 647 cases. Thyroid state At 1904 inspected and analytically estimated children the thyroid function was normal. Only in 8 cases (0.8%) a goiter was found with euthyroid state. Analytical data were as follows: total T4 serum level = 111.8 + 43.1 nmol/l (50.4-171.9), ref. value: 50.1-170.0 nmol/l; total T3 serum level = 2.5 +/- 0.4 nmol/l (ref. value 1.9-3.6); TSH serum level 4.4 +/- 2.6 uIU/ml. Trace amounts of antithyroid membrane antibodies were found at 12 children (0.63%) of the group in serum diluted 1:250.(ABSTRACT TRUNCATED AT 400 WORDS)


[Results of studies on the effect of radiologic contamination after the Czernobyl catastrophe and prophylactic iodine on thyroid morphology and function of inhabitants of North-East Poland].

The results of the investigations of radioactive contamination after the Chernobyl catastrophe and subsequent iodine prophylaxis on the thyroid gland function and morphology in Northeast Poland. The aim of the study was to determine whether kalium iodine in one dose during radioactive contamination in Poland limited the radioactive dose in the thyroid gland and if significant disadvantageous side-effects in the intrathyroid and extrathyroid occurred. Additionally during the studies we tried to determine if radioactive iodine contamination which occurred in the region of the Medical Academy in Białystok caused an increase in thyroid disease. It is interesting to note the different results obtained after radioactive contamination with the results from the investigations in this same territory in 1983-1985. In 1983-1985, before the Chernobyl catastrophe, 6,921 persons in Northeast Poland were investigated. In 1986-1988, immediately after the disaster 4,010 persons were investigated. The main study according to grant No MZ-XVII was carried out in three provinces: Białystok, Suwałki and Olsztyn. In this investigation 10,011 persons born before April 26, 1986 and after January 1, 1936 participated, 5,789 townspeople and 4,222 villagers, 3,987 children up to 16 years of age it the time of the disaster 1,973 boys and 2,009 girls; 6,024 adults 2,509 men and 3,516 women were drawn from a register. Committed doses to the thyroid in the investigated region were one of the highest in Poland and depended on age group and were depended on time of prophylaxis non proportional. Iodine prophylaxis was provided mainly with one dose of Lugol solution about 90%, 95% children and 30% adults took iodine. The majority of the population (53.3%-74%) were given iodine in April. From May 1st to 5th 23.0-43.4% received iodine, but after May 5th very few persons. Iodine was well tolerated, but Lugol Solution was better tolerated than other kinds of iodine. Only 241 (4.4%) cases had side effects, mainly vomiting (143), symptoms such as stomach ache, diarrhea, dyspnoe, skinrash etc. in lesser numbers. 12% (29 persons) were seen by a physician. In the investigated population were 200 pregnant women aged 19-40 years of which the majority (177) delivered full term healthy babies. Only 1 interrupted pregnancy and 7 had spontaneous abortion. Changes in the thyroid were noticed by 187 persons (2.3%-11.7%) most of which were enlargement of the thyroid, but only a few were confirmed by a physician. In the studied population from 1989 to 1990 over 30% of the population had struma.(ABSTRACT TRUNCATED AT 400 WORDS)


[Study on consequences of radioactive iodine pollution and iodine prophylaxis after the Czernobyl accident in the Krakow region].

Program of investigations of effects of radiation and iodine prophylaxis undertaken after Czarnobyl accident in Kraków region had to be modified due to goiter endemy in this region. These modifications included: 1) Division of the region into 3 areas (voivodship Nowy Sacz, urban voivodship Kraków and area of Kielce and Swietokrzyskie mountains). 2) Study on iodine uptake in food and urinary secretion. 3) Examination of iodine level in drinking water, add an attempt of calculation of radiation dose absorbed by thyroid. Characterization of selected areas, principles of selection of study groups are presented as well as organizational details and methods of data collection.


[Evaluation of iodine levels in daily dietary intake and urine of persons participating in epidemiological studies in the Krakow macro-region after the disaster in Czernobyl and level of iodine in drinking water of that region].

Following the Czernobyl accident, an epidemiologic study was undertaken in which the daily iodine intake was estimated in 15% of the population studied. Iodine excretion was measured in single morning urine specimens. The iodine content was also assessed in the water form wells and in cow-milk at farms in randomly chosen villages in the region of Krynica and Nowy Sacz. On the basis of a 24-hour diet recall, the mass of each food product consumed daily was estimated for 483 persons in the Kraków voivodship (14.4% of the total population) and for 397 persons in the Nowy Sacz voivodship (15.8% of the total population). Using this data, the nutrient content of the daily diet was calculated for each studied individual. Measurements of iodine content in water and cow-milk show relatively lower iodine levels in the Nowy Sacz voivodship. The estimated value of the iodine content in milk (5.5 micrograms/100 g of milk) was considered in the estimates of the chemical composition of the daily diet of the inhabitants of this region. The mean values of the daily energy as well as the protein and calcium consumption in all subpopulations grouped with respect to domicile, age and sex, fell within the recommended daily allowances for these groups. The iodine content, while widely scattered, concentrated around low values. The median values of the iodine content in children of age 3-10 years, age 10-16 years and in adults, were 66%, 48% and 25-40% of the recommended daily allowances, respectively. No particular differences in the food intakes were observed between inhabitants of Kraków and Nowy Sacz voivodships. Nor were significant differences found in the urine iodine excretion in groups of these regions. The low iodine content in the daily food intake may be an essential factor in the ethiology of the increasing number of thyroid goiter.


[Epidemiologic studies after the disaster in Czernobyl in the population of children in the Krakow region].

In 1989-1990 the epidemiologic studies about the impact of of Czarnobyl events on the health of children in Kraków and Nowy Sacz region were performed. The morphologic and functional changes of thyroid gland in children were estimated. Almost 90% of children in both districts received the iodine preparations for prophylactic reason. The mean time of intake was between 5-10 days following the Czarnobyl explosion. There were no relationship between the dose of iodine absorbed during prophylactic action and incidence of goiter. The prevalence of goiter amounted to 34.8-47.6% in boys and girls consecutively in Kraków district and 53.8-70.5% in Nowy Sacz. No hormonal changes in T3, T4 and TSH serum concentration were found in children with goiter and those without goiter. The complications after iodine intake were transient and seen only in a small number of children.


[Results of epidemiologic studies performed after the disaster in Czernobyl among the adult part of the population in the region of Krakow].

Epidemiologic studies following the Czernobyl accident were performed in region Kraków, including Kraków, Nowy Sacz and Kielce district. 1426 males and 2495 females were selected according to the random sample on the whole population of Kraków and Nowy Sacz, as well as in some selected areas in Swietokrzyski Mountains, and in Kielcecity. The aim of the study was to assess the results of the prophylaxis with Kalium iodine after the radiation and the incidence of the goiter in the population. It was stated, that 19.2% of the population in Kraków district, 16.9% in Nowy Sacz and 20% in Kielce received the prophylactic dosis of K.J. 80% took mainly the Lugol solution, between May, the 1st and 5th, 1986. Among 18 of person showing side effects like gastrointestinal disturbances, 16 were of female sex. Goiter incidence according to WHO classification was 50.7%, 67.3% and 49.9% in Kraków, Nowy Sacz and Kielce respectively. The difference between the incidence of goiter in males and females was 1:3. In women it was rather Ist and IInd degree of goiter, in men OB and Ist. Nodules of thyroid gland in the rural region of Kraków, Nowy Sacz and Kielce were seen in women in 10.8%, 1.7%, add 12.3% consecutively. Hormonal studies i.e T3, T4, TSH serum concentration showed normal results in all groups studied. TSH concentration was the highest in the group OB. The microsomal and antithyroglobulin antibodies level was the same independently on the prophylactic dosis of Lugol solution. The high incidence of thyroid diseases not related to the accident was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


[Influence of radioactive contamination and iodine prophylaxis after the Czernobyl disaster on thyroid morphology and function of the Poznan region].

The radioactive contamination of Poznań Region was recognized after Chernobyl accident as average. The predicted values of minimal (inhalation) and maximal (inhalation and ingestion) committed dose equivalent to the thyroid varied from 2.5 (min) to 24.7 (max) mSv in different groups of adults and children. To follow up the results of iodine prophylaxis and some aspects of possible thyroid gland morphological and functional changes 11086 persons were carefully investigated clinically and biochemically. Among these 11086 persons were 42.6% males and 57.4% females both adults from 17 till 40 year and children up do 16 years. The following parameters were reviewed: pregnancy, time of residence in the region, thyroid abnormalities, family history concerning thyroid diseases, iodine intake in April and May 1986 with possible side effects, changes in the thyroid size observed before and after 1986, degree and kind of thyroid enlargement, serum concentration of T3, T4, TSH, ATMA and ATG titre and finally the effectiveness of thyroid blockade at 24, 48 and 72 h after ingestion of Lugol's solution. Side effects of the ingestion of potassium iodide from 30-70 mg were observed in 153 cases, 36 of them consulted medical doctors but in no case the side effects (dominated by vomiting) threatened the life. In the investigated group were 144 pregnant women. Majority, because 88% of them delivered the baby on or after time and 6.9% before time, 4.9% of natural abortions were noted but non artificial. In the group of children thyroid gland abnormalities before 1986 were reported in 3 cases in 23 after 1986 it is after Chernobyl accident. This information is interesting but needs more precise analysis of different dependencies occurring. The data obtained indicated the existence in Poznań. Region the goiter endemy because 27.5% of investigated children and adults had goiter classified as grades O-B, I, II and III. The elevation or diminution of T3 values were noted in 1164 cases, for T4 in 418 cases and for TSH in 1412 cases. The presence of antimembrane and antithyroglobulin antibodies were observed in 303 cases. All persons with changes observed in thyroid morphology and function are periodically controlled and the results will be published separately. The investigations performed and results presented concern the early aspects of radioactive contamination and effects of iodine prophylaxis. The answer regarding late effects including thyroid cancer needs further multi year studies for which the clinical material investigated in different parts of Poland and well documented should be used as model group for further periodical studies.


[Effectiveness of iodine prophylaxis and frequency of thyroid enlargement (thyroid goiter) and clinical diagnosis of thyroid diseases in inhabitants of the Szczecin region after the Czernobyl accident].

The study, supported by program MZ-XVII, was carried on 4567 inhabitants of the area of Szczecin (2350 females and 2217 males). The population was chosen randomly, according to a simple drawing scheme. All subjects were clinically examined using standardised questionnaires. In 3468 persons (including 1807 girls and women, 1661 boys and men) apart form clinical examination, the assessment of thyrotropin, thyroxine and triiodothyronine in serum and frequency of antithyroglobulin antibodies and antithyroid membrane antibodies were evaluated. The data indicate that 94% of children in Szczecin's region received the prophylactic dose of iodine, mostly between the 1st and the 5th of May 1986. Only 17% of the adults received iodine. The most common preparation was Lugol solution given in a single dose. Among all persons who received iodine, only in 5% of subjects the side effects were noted (mostly in children), including symptoms of gastrointestinal tract (vomiting, abdomen pain) and occasionally intrathyroid side effects (thyroid pains). In examined population the high frequency of thyroid enlargement, mainly in women (up to 43-44% at the age group 30-50 years) was found. The frequency of clinical diagnosis of thyroid disease was higher in women than in man (most often the diffuse goiter, rarely the nodular goiter). The frequency of thyroid enlargement and clinical diagnosis of thyroid disease was not dependent on prophylactic iodine intake. The iodine prophylaxis did not influence on thyroid hormones and TSH serum levels and on frequency of antithyroid antibodies.


[Data from the Wrocław region about thyroid diseases and use of prophylactic iodine after the reactor accident in Czernobyl].

The radiological contamination of Wrocław Region after Czernobyl accident was evaluated as moderate. In the frame of Research Programme MZ-XVII 4310 persons (2012 men and 2298 women) were randomly selected and investigated. Among them were 1525 children up to 16 years old. 925 children and 854 adults took potassium iodide; only minority in April but majority between May 1st and May 5th. Side effects was rare phenomenon seen in about 5% of those who ingested potassium iodide and in majority of cases was very mild (with rash and vomiting as most common clinical symptoms). Only 13 persons with side effects have visited physicians. Among 955 women aged 19-40 years 71 were pregnant in May 1986. 55 of them delivered on time, 3 before time. Average health state of newborns was 9.1 according to Apgar scale. 10 women have had spontaneous abortion and 3 decided to terminate pregnancy in first 6 weeks. The physical examination revealed the presence of diffuse goiter in 384 persons and of nodular goiter in 23 persons. In majority of cases the goiter was small, OB or I. according to WHO classification.


[Effects of prophylactic doses of potassium iodide on the course of thyroid diseases (1986-1990) diagnosed due to the atomic accident at Czernobyl in adult patients at the outpatient endocrinologic hospital clinic in Lodz].

2521 patients of the Lódź Outpatient Endocrinological Clinic (2290 females, 231 males; inhabitants of the central region of Poland Lódź City, Lódź Metropolitan Area, Piotrków, Płock, Sieradz, Skierniewice and Włocławek Provinces in which committed dose equivalent to the thyroid was between 2.7-7.0 mSv [min.-max.] in Skierniewice Province and 4.6-11.7 mSv in Płock Province) were included in the study. The patients were divided into 5 groups: I--persons who did not take the protective dose of potassium iodide (KI) after Chernobyl Nuclear Power Plant accident and did not received any treatment with thyroid preparations or hormones at that time (n = 1282), II--patients who receive KI, once or several times (n = 774), III--patients who took orally iodine tincture or other iodine-containing preparations for the above purposes (n-37), IV--patients who took tablets of Thyroideum (Polfa) Thyroideum siccum (dry thyroid extract), once or several times, as a prophylactic action (n = 79), V--patients who were in the course of continuous treatment with Thyreoideum or thyroid hormones at the time of Chernobyl accident (n = 349). The analysis was performed for all the patients jointly, as well as separately for: either sex, three age groups (18-30, 31-55, 56-70 yrs) and 7 administrative areas specified above. All the patients were subjected into complex clinical examination, serum TSH, T3, T4 concentrations, anti-thyroid membrane antibodies (ATMA) and antithyroglobulin antibodies (ATg) titres, as well as ultrasound, scintigraphy, and fine needle aspiration biopsy of the thyroid (the last two according to indications) included. The patients were also examined by means of a special questionnaire (Patient's Inquiry Sheet), which was subsequently submitted to computer analysis. All the doctors' diagnoses from 1986 (17 different diagnoses) and 1990 (27 different diagnoses), as well as the course of diseases, were verified with use of a specially prepared IBM PC/AT computer program ChernStat.(ABSTRACT TRUNCATED AT 400 WORDS)


[Laboratory tests: level of T3, T4, TSH and antithyroid gland autoantibodies in the Polish population].

In 1986-1990 epidemiologic studies on the thyroid diseases frequency in the polish population were undertaken. During this studies the serum levels of TSH, T4, T3 and autoantibodies were estimated in more than 30 thousand people. TSH was estimated in 30749, T4 in 30928, T3 in 30621 and autoantibodies in 31265 randomly chosen people in 5 districts. We have arbitrarily established the normal range for TSH to be between 0.4-3.8 microIU/ml, for T4 4.4-12.5 micrograms% and for T3 0.9-1.95 ng/ml. The tested group has been divide in 4 subgroup: girls and boys from 1 to 15 years of age the year of the Chernobyl accident, men and women from 15 to 50 years of age at the date of the accident. TSH values in the normal range were found in 85 to 92% of the tested population, depending on the subgroup. T4 vales in the normal range were found in 85 to 92% of the tested groups. T3 vales in the normal range were found in 86 to 93% of the tested groups. The absence of any kind of autoantibodies was established in 89.7% of the tested population. TSH values was above the normal range (above 3.8 microIU/ml) in 3.4% of boys, 4.3% girls, 3.2% men and 3.8% women. TSH vales below the normal range (less the 0.4 microIU/ml) were found in 4.3% boys, 5.0% girls, 10% men and 11.2% women. T4 values above the normal range (higher then 12.5 micrograms%) were found in 12.9% boys, 12.6% girls, 4.6% men and 5.9% women.(ABSTRACT TRUNCATED AT 250 WORDS)


[Results of studies performed with the MZ-XVII program on a national scale; summary and conclusions].

MOST IMPORTANT OBSERVATIONS: (FROM COUNTRY-WIDE POPULATION STUDIES) 1. In some voivodships localized in south-east and north-east parts of Poland thyroids of young children would, without protective measures, accumulate more then 60 MsV of radioiodine, thus exceeding intervention level settled for the country. 2. Thyroid function of newborns exposed to radioiodine during neonatal life was normal and frequency of neonatal hypothyroidism similar to that seen in years before Czernobyl accident. 3. Potassium iodide administrated to newborns in some of them profuced transient rise of TSH (Wolff-Chaikoff phenomenon), thus suggesting, that ki dose settled for newborns could be to high. 4. Thyroid radioiodine dose accumulated in thyroids of older children, teenagers and adults was in majority of regions well below the dose of 50 MsV. 5. The frequency of non-toxic diffuse goiter, especially in traditional endemic goiter area was found to be high, but is also relatively high in others regions of Poland and seems to depend on iodine deficiency or relative iodine deficiency. 6. The frequency of other thyroid disorders is within the limit reported in countries with relative iodine deficiency. 7. More than 95% of children and teenagers took protective, single dose of potassium iodide (about 10 millions). 8. Approximately 27% of adults took protective dose of potassium iodide (about 7 millions). 9. Organization of protective action in 11 north-east and south-east voivodoships was good about 75% of all obtain ki solution within 24 hours. In the rest of the country where protective action was ordered april 30, in afternoon hrs only about 25% obtained ki the same day and the rest during next 48-72 hrs. 10. The fact that prior to the protective action limited number of children was given iodine alcohol solution permitted for external use speaks about the fear and panic observed in Poland in first days after Czernobyl accident. 11. Extrathyroidal side-effects after ki administration appeared in about 5% were usually light or moderate and in majority of cases disappearing without medical assistance. Vomiting was most commonly seen side-effect in young children, thus suggesting that either dose, or the chemical form of the drug for this group of age was unproper. 12. Intrathyroidal side-effects of single dose of ki was rare phenomenon seen mostly in newborns, very young children and some adults with history of thyroid disease in the past. 13. Its possible that even small dose of radioiodine accumulated in thyroid produce immunological response leading to the appearance of thyroid antibodies in blood serum.


[Analysis of early results of combined treatment with glucocorticoids and telecobalt therapy for Graves' disease ophthalmopathy].

Early results of combined use of glucocorticoid administration and irradiation with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy associated with Graves' disease have been analyzed in a group of 33 patients including 28 women and 5 men of age between 25 and 66 years (mean age 47.3 years). The combined therapy was a modification of the original method of Bartalena et al. which consisted in the gradual increase of the initial dose of glucocorticoids and prolongation of the period of administration of the drug. The ophthalmic lesions were assessed by thorough ophthalmologic examination and classified according to Werner. The ophthalmopathy index was calculated according to Donaldson. Satisfactory results of treatment have been obtained in 32 patients, with 9 patients being completely relieved from any objective or subjective ophthalmic symptoms (very good results), and 23 patients having still small afflictions originating from the soft tissues of the eye socket, exophthalmos, diplopia during marginal vision and a decreased visual acuity (good results). The clinical recovery was mostly connected with the improvement in the condition of soft tissues of the eye socket, cornea and external ocular muscles and, to a smaller extent, exophthalmos which persisted to some degree and acuity of vision not always attaining normal values. In one person the results of treatment were unsatisfactory despite some improvement. Very good and good results obtained in 97% of patients indicate that the administration of glucocorticoids combined with the irradiation of retrobulbar tissues with radioactive cobalt can now be regarded as the most effective method of treatment of the progressive oedematous-infiltrative ophthalmopathy.