UDP-glucuronosyltransferase (UGT) catalyzes a transfer of glucuronic acid from UDP-glucuronic acid to various endogenous and exogenous compounds and is located in the endoplasmic reticulum of liver and other tissues. Glucuronidation is a major detoxication reaction and provides great effects on the metabolism, disposition and excretion of pharmacologically and toxicologically active compounds. There are several UGT isoenzymes with different and overlapping substrate specificities and under different regulation. During the last decade, there has been a dramatical increase in the understanding of the structure and function of UGT isoenzymes especially through the recombinant DNA technology. This review concentrates on the recent developments in the research on glucuronidation and deals with purification, cloning, gene structure, deficiency, chromosomal location and function of UGT isoenzymes and glucuronides as active metabolites.

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Rain samples were collected at Tokyo, Japan, during 11 periods of precipitation from October, 1989 to September, 1990. Five volatile halogenated hydrocarbons in the rain samples were determined by an automated purge trap/on-column cryofocusing method using capillary gas chromatography with ⁶³Ni-ECD. The levels of volatile halogenated hydrocarbons during the above period were averaged as 261 ng/l for chloroform, 369 ng/l for 1, 1, 1-trichloroethane, 46 ng/l for carbon tetrachloride, 136 ng/l for 1, 1, 2-trichloroethylene and 99 ng/l for 1, 1, 2, 2-tetrachloroethylene. The levels determined in this study were compared with those of other reports. The levels of volatile halogenated hydrocarbons in Tokyo rain showed seasonal fluctuations, presumably because of climatic factors such as atmospheric temperature and other factors such as reaction with OH radical. In some cases, the level of all determined compounds decreased with time-series during an event, which might be due to a wash-out effect. Some compounds with high solubility in water showed rapid decrease, which leads to a certain selectivity of this effect. The scavenging effect of volatile halogenated hydrocarbons by a rain event could be traced by the simultaneous analysis of ambient air and rainwater.

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A chemical carcinogen, ethyl carbamate (urethane), has been shown to be a contaminant of various alcoholic beverages. The condition of ethyl carbamate formation from cyanide via cyanate and the method of its prevention method with a cyanide metabolizing enzyme, bovine liver rhodanese, were studied using a model solution of alcoholic beverage. Ethyl carbamate was not formed from thiocyanate or cyanuric acid, but from cyanate ; it was also formed from cyanide in the presence of diacetyl or cupric ion. The formation from cyanate was accelerated in higher temperature and at lower pH, but was prevented by di- or tribasic acid. 2-Aminobenzoic acid inhibite the formation from cyanate, cyanide, urea and carbamoyl phosphate, and these results suggest that cyanate is the genuine intermediate of ethyl carbamate formation from cyanide, urea and carbamoyl phosphate, Sulfite which is used for an antioxidant in wine did not inhibit the ethyl carbamate formation. In addition, the formation of ethyl carbamate from cyanide with diacetyl was inhibited one-fifth by pretreatment with rhodanese, at neutral pH range.

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We investigated the mutagenicity of rubber additives used in tire and tire extracts. Thiuram and dithiocarbamate type rubber vulcanization accelerators showed mutagenic activity in Salmonella typhimurium TA100 and some tires contain these additives, whereas no significant mutagenic activity was found in the tire extracts. These results suggested that the mutagenic activity of accelerators might be inhibited by other tire components such as the activators or the antioxidants. This paper describes the effects of activators and antioxidants on the mutagenic activity of accelerators. N-Isopropyl-N'-phenyl-p-phenylenediamine (IPPD), widely used as an antioxidant, inhibited the mutagenic activity of thiuram and dithiocarbamate type accelerators when added together. On the other hand, addition of UV irradiated IPPD to these accelerators resulted in no inhibitory effect on the mutagenic activity of these accelerators. Activators had no effect on the mutagenic activity of these accelerators. In order to confirm interaction between accelerators and antioxidants, tire extracts were separated into fractions corresponding to these additives by silica gel column chromatography and each fraction was subjected to the Ames test. The accelerator (Zn-DMDTC) fraction had mutagenic activity while the antioxidant (IPPD) fraction was non-mutagenic. These observations demonstrated that IPPD inhibits or reduces the mutagenic activity of thiuram and dithiocarbamate type accelerators when they are combined such as in tire processing.

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A method for the simultaneous determination of 1, 1, 1-trichloroethane (TCE) and 1, 4-dioxane (DO) in household aerosol products by gas chromatography (GC) was developed. For the determination of TCE and DO using the headspace method, an aerosol product sample was propelled in 50 ml beaker. Two grams of the propelled solution was weighed in a 125 ml vial, and 20 ml of methanol and 2.0 ml of 1, 2-dichloropropane as an internal standard were added. The vial was incubated more than 60 minutes at 30°C, 200 μl of the headspace gas was injected to a GC. When the DO chromatogram was subjected to interference from kerosene in the sample, the subsequent water extraction method was employed for the determination of DO. Two grams of the propelled sample solution, to which 20 ml of hexane was added, was extracted with water (30, 20, 20, 20 ml). The aqueous layer, after addition of 20 g of sodium chloride, was re-extracted with ethyl ether (40, 20, 20 ml). The organic layer was dried, and the volume was made to 100 ml, and aliquot of the solution was injected to a GC. A fused silica capillary column was used as the GC column. By this method, 270 commercial aerosol products were analyzed, and TCE was detected in 48 products in the range of 5-88%, half of which were water proofing agent products. DO was detected in 39 products, in all of which TCE was detected. The range of DO concentration was 0.17-2.25%. The water extraction method was employed for 23 products in 270. A good correlation between the contents of DO and TCE in the samples was observed. This correlation suggested that TCE containing 3% of DO was extensively used for manufacturing aerosol products.

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This study presents a new technique for confirmation opium or powdered opium by detection of a characteristic ingredient of meconic acid in the sample. Meconic acid could be simply purified from the opium or powdered opium sample by offering water-extracts of the sample to a treatment with a Sep-Pak NH₂ cartridge. This purification procedure leads to a high yield of trimethyl derivative of meconic acid with diazomethane.

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The inhibitory effects of twenty-five commercial detergents on the oxygen uptake rate (OUR) of activated sludge (AS) were investigated by the use of the oxygen electrode method. The commercial detergents are used for many application, such as laundry detergents (Sample No. 11-13), dish-washing detergents (Sample No. 21-25), household cleaners (Sample No. 31-39), fabric softeners (Sample No. 41-42), bleaching agents (Sample No. 51-54) and scouring cleansers (Sample No. 61-62). The IC₅₀ values of the commercial detergents tested here were measured to be 670-2100, 720-2900, 660-22000, >25000, 1800-2300 and >2500 or >25000 mg/l, respectively, for No. 11-13, No. 21-25, No. 31-39, No. 41-42, No. 51-54 and No. 61-62. Surfactant is one of the major compounds in commercial detergents, and the IC₅₀ values of the surfactants of LAS, SDS, AE, AOS, AES, AO, sodium palmitate, sodium laurate and sodium oleate were 250, 190, >2500, 150, 530, 100, >2500, 410 and >2500 mg/l, respectively. On the other hand, the builders such as sodium silicate, sodium carbonate, sodium sulfate, enzyme and fluorescent agents had little adverse effect on the OUR of AS. Therefore, it was revealed that the major inhibitory compounds in commercial detergents were not builders but surfactants.

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2, 7-Diaminophenazine (2, 7-diNH₂-Pz) formed from m-phenylenediamine (PD) by hydrogen peroxide (H₂O₂) oxidation was extremely mutagenic in Salmonella typhimurium strain TA98 with a mammalian metabolic activation system (S9 mix). In order to evaluate the modulating effect of phenol derivatives and iron (II) sulfate on H₂O₂ oxidation of m-PD, m-PD and mixtures of m-PD and phenol derivatives (m-PD/phenols) were treated with 3% H₂O₂ in the presence or absence of iron (II) sulfate and their mutagenicity was tested using strain TA98 with S9 mix. The total mutagenicity, which was calculated from the yields of oxidized mixtures (i.e. ethyl acetate extract) and their mutagenicity, decreased remarkably by the addition of iron (II) sulfate into the H₂O₂ oxidation system. Since the yields of 2, 7-diNH₂-Pz and ethyl acetate extract decreased more in a H₂O₂-iron (II) sulfate oxidation system than those in a H₂O₂ oxidation system, the reduction of the total mutagenicity was presumed to be due to the accelerated polymerization of m-PD by iron (II) sulfate added. Furthermore, the modulating effect of 5 kinds of metal chelates on the mutagenicity of 2, 7-diNH₂-Pz and on the H₂O₂ oxidation of m-PD was evaluated. All tested metal chelates reduced the mutagenic response of 2, 7-diNH₂-Pz in strain TA98 with S9 mix, and the strongest inhibitory effect was observed in the case using hemin. The amount of free 2, 7-diNH₂-Pz in the mixture solution of 2, 7-diNH₂-Pz and metal chelates was correlated to the mutagenic potency of the mixture. It was suggested that the mutagenic inhibitory effect of metal chelates depend on the complex formation of metal chelates with 2, 7-diNH₂-Pz. The addition of metal chelates into the H₂O₂ oxidation system of m-PD significantly decreased the amount of free 2, 7-diNH₂-Pz in the reaction mixture. The reduction of the yield of 2, 7-diNH₂-Pz was assumed to be based on the polymerization of m-PD by metal chelates as catalyst and formation of complex with 2, 7-diNH₂-Pz and metal chelates.

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A high-performance liquid chromatographic method for the analyses of 10 kinds of corticosteroids, i.e., prednisolone, cortisone, 6α-methylprednisolone, betamethasone, dexamethasone, triamcinolone acetonide, fluorometholone, hydrocortisone acetate, cortisone acetate and dexamethazone acetate and 3 kinds of anabolic agents, i.e., β-estradiol, testosterone and progesterone in health food was developed. These hormones were extracted with acetonitrile in an ultrasonic bath. The crude extract was purified and fractionated into two parts, i.e., corticosteroids and β-estradiol fraction and testosterone and progesterone fraction, by solid phase extraction using a Sep Pak C₁₈ and a BAKERBOND spe NH₂. Each fraction was chromatographed on a Nucleosil 100-5C₁₈ column with acetonitrile-water-0.2M phosphate buffer pH 3.0 (38 : 57 : 5) for corticosteroids and β-estradiol fraction and (50 : 47 : 3) for testosterone and progesterone fraction. Detection was achieved with a UV monitor set at 230 nm and 250 nm for corticosteroids and β-estradiol fraction and at 245 nm for testosterone and progesterone fraction. The recoveries from powdered terrapin, powdered viper, powdered royal jelly and shark extract fortified with the standard mixture at level of 0.2 μg/g each were 39.4-105.6% for corticosteroids and 67.2-95.4% for anabolic agents. Each hormone in health food at level as low as 0.02 μg/g was determined by the proposed method.

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In order to elucidate the biological effect of LaCl₃·7H₂O, a 28-day repeated oral administration test was conducted in Slc : Wistar rats of each sex by gavage at doses of 0, 40, 200 or 1000 mg/kg/day with the pair feeding group. Two more groups (0 mg/kg, 100 mg/kg) of both sexes were appended as 14-day recovery groups after the 28-day administration. Body weight and food consumption were measured, and hematological, serum-biochemical and histopathological examination were performed. The concentrations of lanthanum and essential elements in organs were determined by ICP-MS or ICP-AES. The number of eosinophilic leucocytes increased in rats of both sexes dose-dependently. At a dose of 1000 mg/kg, hyperkeratosis in the forestomach of both sexes, eosinophilic leucocyte infiltration in the submucosa of the stomach of both sexes, erosion and dilatation of acinus of the glandular stomach in males, and swelling of the glandular stomach epithelium in females were found. These results suggest that lanthanum is irritant to the stomach mucosa. At doses higher than 200 mg/kg, a significant decrease of the serum cholinesterase activity was observed only in females. The serum transaminase activity increased in both sexes at a dose of 1000 mg/kg. This finding is suggestive of hepatotoxicity, although there were no histopathological changes of the liver. Lanthanum was accumulated in the liver, kidney, spleen and femur in a dose-dependent manner. The accumulation of lanthanum in the liver was the highest and higher level was found in the liver of female than of male. The sex-dependent differences were demonstrated in terms of the irritating reaction of the stomach mucosa, the reduction of the serum cholinesterase activity and the accumulation of lanthanum in the liver. The all over data make it clear that lanthanum was absorbed through the digestive tract. Dose-dependent decreases of iron concentrations in the liver, kidney and spleen, and those of barium and strontium concentrations in the femur were observed in both sexes.

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Solid-phase extraction of acephate in natural water was studied using ODS-cartridge. 250 ml of sample water to which 25 g of ammonium sulfate was added was passed through the cartridge at a flow rate of 10 ml/min. The cartridge was dried with dry air. Acephate was eluted with 10 ml of methanol. After removing the solvent from the eluate, 1 ml of acetone was added to the residue and determined by gas chromatograph with a flame thermionic detector. The recovery of acephate added to river water was in the range of 84-90%. The coefficient of variation was less than 7%. The limit of detection was 1 μg/l. By the proposed method, the concentration of acephate in river and lake waters, which were used for water supply in Ibaraki, was determined through the year. No acephate were detected in any water samples.

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A method for the determination of pesticides by gas chromatograph/mass spectrometry (GC/MS) using internal standards was developed. A GC/MS type HP-5980 equipped with a SIM detector and a 0.25 mm i.d.×30 m glass capillary column cross-linked with 0.1 μm of 100% dimethyl polysiloxane (DB-1) was mainly used. The internal standards used as retention index standards of GC were n-alkylbis (trifluoromethyl) phosphine sulfides [(CF₃)₂-PS-(CH₂)_nCH₃]. The mass spectrum of each compound (n=9, 11, 13, 15, 17 and 19) showed strong fragment ion peaks at m/z M⁺-69 and M⁺-101, and these peaks were used for the monitoring of fragment ions. The results of experiments with 32 pesticides showed the coefficents of variations (CV%) of pesticides of 2.1-16.6% with internal standards and 4.2-29.2% without internal standards at 0.2-0.5 ng of pesticides. The values for 2.0 ng of pesticides were 0.5-9.1%, and 5.3-14.0% with and without internal standards, respectively. This method using internal standards provides good reproducibility in the analysis of pesticides.

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A simultaneous analysis for thiuram, iprodione and bensulide in environmental water was performed by the procedures including solid-phase extraction and high performance liquid chromatography (HPLC). To 1000 ml of sample water, two grams of ethylenediamine tetraascetic acid disodium dihydrate (EDTA·2Na·2H₂O) was added. The sample solution was passed through Sep-Pak ENVtC₁₈ cartridge which was previously washed with acetonitrile containing 50 mM EDTA·2 Na. The cartridge was washed with acetonitrile-H₂O (3 : 7) and the sample was eluted with acetonitrile. The eluant was analysed by HPLC on a column of C₁₈-bonded silica gel (Nucleosil 120-5C18) with acetonitrile-methanol (60 : 40) as mobile phase. The recoveries of thiuram, iprodione and bensulide added to environmental waters were 91-96%, 101-105% and 100-104%, respectively. Addition of EDTA·2Na to the sample water was effective for analysing thiuram.

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In Japan, several phenethylamine derivatives such as mescaline and 3, 4-methylenedioxyamphetamine, which are hallucinogens were appointed to narcotics in 1989 and 1990. Reference standards of phenethylamine derivatives are required for their forensic chemical analyses. Present study was intended to synthesize phenethylamine derivatives from benzaldehyde derivatives by a novel route improving the yield. Five narcotic phenethylamine derivatives, mescaline hydrochloride, p-methoxyamphetamine hydrochloride (PMA), 3, 4-methylenedioxyamphetamine hydrochloride (MDA), 2, 5-dimethoxyamphetamine hydrochloride (DMA), 3, 4, 5-trimethoxyamphetamine hydrochloride (TMA) and their β-hydroxy derivatives that can be their raw materials were obtained. The methods were as follows 1) Nitroalcohols were obtained by a condensation of nitroalkane and benzaldehydes using sodium methoxide as a catalyst. 2) The nitroalcohols were acetylated with acetic anhydride. 3) The acetyl derivatives were converted into nitro-olefins by elimination of acetic acid. 4) Phenethylamine derivatives were synthesized from nitro-olefins by catalytic reduction using palladium on carbon in an autoclave. 5) In the same way, β-hydroxyphenethylamine derivatives were synthesized from nitroalcohols.

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