We investigated mechanisms of oxidative DNA damage caused by carcinogenic metal compounds. Chromate (VI), nickel (II), cobalt (II), iron (III)-nitrilotriacetate and copper (II) induced DNA damage generating active oxygen species in the presence of hydrogen peroxide (H₂O₂). DNA damage was enhanced by endogenous reductants such as ascorbate, NADH and glutathione. An indirect mechanism of carcinogenesis by lead was studied using δ-aminolevulinic acid, which caused DNA damage in the presence of Cu (II). On the basis of these findings, we reviewed the mechanism of metal carcinogenesis mediated by active oxygen species. We also studied a mechanism of DNA damage induced by the interaction of metal ions and "non-mutagenic" carcinogens. Benzoquinone and its derivatives such as metabolites of benzene, o-phenylphenol, pentachlorophenol and p-dichlorobenzene caused Cu (II)-dependent DNA damage via H₂O₂ generation through a redox cycle of benzoquinone derivatives which required NADH for reduction. Tryptophan metabolites and caffeic acid induced Cu (II)-mediated DNA damage through H₂O₂ formation, which was enhanced by preincubation with Mn (II). It can be concluded that most of "non-mutagenic" carcinogens generate H₂O₂, which causes metal-dependent DNA damage.

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The influence of diet on the subacute toxicity of methylmercury (MeHg) was investigated using C57BL/6N male mice, each fed a 24.8% protein diet (normal protein diet, NPD), a 7.5% protein diet (low protein diet, LPD) or LPD supplemented by methionine and cystine to NPD level (amino acid supplemented diet, ASD). When MeHg was consecutively administered to each group of mice (20 μmol/kg per day), median survival times were 11, 18 and 30 d in ASD-, LPD- and NPD-fed mice, respectively. Toxic symptoms including ataxia and loss of body weight were in that order. Hg accumulation rate in brain was faster in LPD-fed mice than in NPD-fed mice, and was further enhanced in ASD-fed mice. The fact that Hg in plasma low molecular weight (LMW) fraction was in the order of ASD->LPD->NPD-fed mice, would be one reason for the difference in the brain Hg accumulation. Hg levels in liver, blood and plasma showed a monotonous increase, and their terminal Hg levels were similar in the three groups. Renal Hg levels increased rapidly and almost never changed from the 7th d in the three groups. Urinary excretion of Hg in LPD-fed mice was markedly lower than in NPD-fed mice throughout the experimental period ; that in ASD-fed mice, which was the highest at least for the first few days, began to decline earliest. No difference was observed in fecal Hg levels during the early part of the experiment. Our results suggest that diet is an important factor determining the susceptibility to subacute MeHg toxicity, and that accelerated Hg accumulation rate in the brain caused by diet would result in higher susceptibility to subacute MeHg toxicity.

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With the aim of revaluating short-time hygienic hand disinfection in general wards, the efficacy of chlorhexidine gluconate (CHG) and povidone-iodine (PVI) was studied using the glove-juice procedure. In addition, the in vitro bactericidal activity of these antiseptics against 9 different bacterial strains was studied. Test groups of volunteers who disinfected their hands in a basin containing an aqueous solution of either 0.2% CHG or 0.2% PVI showed significantly inferior disinfection efficacy when compared to test groups which applied detergent solutions containing 4% CHG or 7.5% PVI directly onto their palms, scrubbed their hands, and washed the disinfectant away with running water, or to test groups which disinfected their hands by rubbing them with 0.2% CHG in 80% ethanol or 0.5% PVI in 80% ethanol. In addition, for the test groups which used CHG preparations (4% CHG in detergent, 0.2% CHG in 80% ethanol, or 0.2% aqueous CHG), the disinfection efficacy was maintained, even at 90 min after disinfection, as well as immediately after disinfection. However, for the test groups which used PVI preparations (7.5% PVI in detergent, 0.5% PVI in 80% ethanol, or 0.2% aqueous PVI), the disinfection efficacy at 90 min after disinfection was distinctly reduced. Furthermore, it became evident from the results of the in vitro bactericidal activity study that, compared to CHG, the bactericidal efficacy of PVI is reduced to a large extent in the presence of organic matter. These study results showed that the efficacy of CHG is superior to PVI, even in short-time hygienic hand disinfection.

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Individual adsorption characteristics of β-carotene and triolein on attapulgite and sepiolite were compared in order to elucidate how triolein inhibits the adsorption of β-carotene. Adsorption rate of triolein on attapulgite and sepiolite was twice that of β-carotene at the very beginning of adsorption. Adsorption isotherms of β-carotene and triolein were well expressed by the Langmuir equation. Maximum adsorption amount of triolein was larger than that of β-carotene. β-Carotene and triolein were chemically and physically, respectively adsorbed on the weak acid sites which are distributed on the surface of adsorbent.

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For the investigation of the safty evaluation of antimicrobial and deodorant agents, a new method for the analysis of fungicides in household products was developed and examined. N-(Fluorodichloromethylthio) phthalimide (FPI) and N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio) sulfamide (dichlofluanide) in commercial household products (miticidal finished products, household paints and fungicidal spray product) were determined by capillary gas chromatography using a flame photometric detector (FPD). A successfully cleaned up preparation using the difference in liquid-liquid partition behaviour and a florisil cartrige column has been developed for the determination. The recoveries of FPI and dichlofluanide added to miticidal finished products at the amount of 20 μg were 72-81% (FPI) and 75-80% (dichlofluanide) on the average, respectively. And the recoveries of FPI and dichlofluanide added to paints at the amount of 2000 μg were 98-106% (FPI) and 96-106% (dichlofluanide) on the average, respectively. FPI was detected in 2 out of 8 brands of miticidal finished products by this proporsal method. A large amount of dichlofluanide (over 10000 μg/g) was detected one out of 6 brands of household paints by this proporsal method.

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As a part of toxicological evaluation study on combined sulfite, we have prepared four kinds of sulfite adducts (89-98% yield) by the reaction of free sulfite with food ingredients (acetaldehyde, pyruvic acid, glucose, arabinose). These products were characterized by IR, NMR, FAB-MS measurements. The results of NMR analysis revealed that sulfite is bound to carbonyl group. In addition, sugar sulfite adducts were shown to exist in open-chain forms. All of the sulfite adducts were found to be pure by FAB-MS and elemental analysis. Their stability in water was examined and found to be stable at pH 2.0 for 2 h (37°C).

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DNA strand breakage activity and mutagenicity of the product (s) formed by a reaction of thiamine and nitrite under simulated gastric conditions were examined. A reaction mixture of thiamine and nitrite at pH 3 induced DNA single-strand breaks when incubated with a supercoiled plasmid DNA at pH 7.4 and 37°C. Product (s) from thiamine and nitrite were found mutagenic to Salmonella typhimurium TA100 strain without metabolic activation. The number of His⁺ revertant colonies was 1200/10-μmol eq of thiamine. Hence, thiamine is an undesirable precursor of DNA strand breakage and mutagenic substance (s) when mixed with nitrite.

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When certain mutagenic anti-cancer medicines are used for cancer therapy, secondary production of cancer by the medicines themselves is feared. Certain bio-antimutagenic substances may decrease secondary cancer induction without interfering with the effectiveness of the anti-cancer therapies. The bio-antimutagenic effects of cobaltous chloride, gallic acid, taurine and isethionate on the anti-cancer medicines chlorambucil and methotrexate were investigated using the Drosophila melanogaster wing spot test. Cobaltous chloride reduced the mutagenicity of methotrexate, but not chlorambucil. Gallic acid reduced the mutagenicity of both medicines. Taurine and isethionate also reduced the mutagenicity of methotrexate.

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A simple method for the simultaneous determination of pantothenyl alcohol (PA) and pantothenyl ethyl ether (PE) in cosmetics by high performance liquid chromatography has been developed. Samples (cosmetics) containing PA and PE were dissolved with chloroform (CHCl₃). The samples including PA and PE were passed through Bondelute SI^[○!R] cartrige. After washing the cartrige with CHCl₃, PA and PE were eluted with methanol (MeOH). The optimum condition for the separation of PA and PE in cosmetics were as follows : column, TSK gel ODS 80 T_s (4.6 mm i.d.×150 mm) ; mobile phase, CH₃CN-MeOH-H₂O (15 : 10 : 75), 0.5 ml/min ; column temperature, 40°C ; detection wavelength, 210 nm. Recoveries of PA and PE from 7 cosmetics were more than 90%. Determination limits of PA and PE were 10 μg/g and 5 μg/g, respectively.

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In order to further investigate the genotoxic effects of Sophorae Flos, Astragali Radix and Eucommiae Cortex which are reported to induce mutagenicity in Ames test, a chromosome aberration study of the water extracts of these crude drugs was carried out using cultured Chinese hamster lung cells. Sophorae Flos did not induce chromosomal aberrations in either direct method or S9 Mix method. In the S9 Mix method, Astragali Radix at a dose of 1.25 mg/ml modestly increased the incidence of aberrant cells (16%). Eucommiae Cortex was strongly clastogenic to the cells and dramatically elevated the incidence of aberrant cells (98%) at a concentration of 4.55 mg/ml in the direct method. These results suggest that Astragali Radix and Eucommiae Cortex may be genotoxic to mammalian cells

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Organochlorine pesticides as well as synthetic antibacterialagents in cattle meats were extracted with acetonitrile, and the extract was divided into two parts for the individual clean-up. One part of the extract was cleaned up by silica gel column chromatography, and determined by electron capture detecter-gas chromatography (ECD-GC) for organochlorine pesticides. Another part of the extract was cleaned up by washing with n-hexane in the case of edible meats, or by solid phase extraction with Sep-pak Alumina N or tC₁₈ mini column in the case of edible viscera, and determined by HPLC with a UV detector for the synthetic antibacterialagents. Recoveries of 7 organochlorine pesticides in edible meats spiked at 0.1 ppm were 54.3-104.6%, and recoveries of 13 antibacterialagents in edible viscera spiked at 0.4 ppm were 59.1-105.3%. Confirmation of nicarbazin (NCZ) in chicken, trimethoprim (TMP) spiked in pork by GC-MS were studied.

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