A critical factor in the evaluation of the risk associated with cutaneous exposure to chemical substances is an information relating to the percutaneous absorption of these substances. Recent developments in the percutaneous absorption of chemical substances in industry, especially organic solvents, are reviewed, and these percutaneous absorption rates in humans and animals exposed in vivo and their excised skin in vitro from vapor and liquid phase are summarized. Evaluations concerning the amounts of percutaneous absorption in vivo of organic solvents in toxicity are discussed by a mathematical model by using the percutaneous absorption coefficient for vapor phase and the percutaneous absorption rate for liquid phase, and recommendations for future research of organic solvents are proposed from the relationship between these chemical-physical properties and these percutaneous absorption rates.

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Mast cells are a major cell type capable of inducing inflammation, in response to various kinds of allergens including so-called environmental substances. The present review introduces recent progress of the function of mast cells in inflammation and the effect of environmental pollunts affecting them, such as NOx, particles of oxidized metals, DDT, ultraviolet irradiation with chemicals, carcinogen and metal ions. Metal ions act on histamine release from mast cells as a stimulator (Cu²⁺, Fe³⁺) or an inhibitor (Zn²⁺, Co²⁺). Zinc ion was inhibitory in the reactions of Ca²⁺ uptake and phospholipid turn over in stimulated mast cells. The mechanism of histamine release from mast cells by a chemical agent was examined by using active oligomer of compound 48/80, a Ca²⁺-dependent IgE type histamine releaser. Binding of oligomer to cell surface receptor induced immediate metabolism of polyphosphoinositide (degradation of PIP₂ and formation of IP₃ and DG) but it was Ca²⁺-independent reaction. Oligomer induced Ca²⁺-dependent accumulation of arachidonic acid into PC, PI and PA, which may be important in the formation of releasing substance and arachidonic acid-originated biological substances. Mast cells may be useful to explore the effect of environmental substances related to inflammation.

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The amounts of homologous series of linear alkylbenzenesulfonates (LAS) in the wastewater treatment plant were measured as free and complex LAS by using methylene blue colorimetry and high-performance liquid chromatography. The concentration of free LAS in the influent was found at levels varying 0.34 to 0.54 mg/l, with an average value of 0.43 mg/l, and complex LAS was found at levels varying 1.7 to 2.4 mg/l, with an average value of 2.0 mg/l. The removing efficiencies in the primary sedimentation tank were 58% for free LAS and 0% for complex LAS, and those in the aeration tank and the secondary sedimentation tank were 16% for free LAS and 87% for complex LAS. There was no clear tendency that both free and complex LAS with longer C chain length were more effectively removed than those with shorter ones in the effluent and the sludge. Free LAS remained in the raw sludge was 73% to the amount (30 kg/d) treated in the primary sedimentation tank, whereas free and complex LAS and in the excess sludge was 2% and 0.06%, respectively, to the amount (9 kg/d for free LAS and 210 kg/d for complex LAS) treated in the aeration tank and the secondary sedimentation tank. The results obtained in this work suggest that free LAS is preferentially removed in the primary sedimentation tank to be in the raw sludge, whereas complex LAS is biodegradated in the aeration tank and the secondary sedimentation tank.

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Dimethyl disulfide (DMDS) formation by bacteria isolated from normal or abnormal activated sludges was examined. Bacteria with high DMDS-forming ability could not be isolated from normal activated sludge. However, when the activated sludge was abnormally conditioned at high biochemical oxygen demand (BOD) loading, bacteria capable of forming DMDS from methionine were isolated.

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A rapid and sensitive method for the simultaneous determination of nicotine and its principal metabolite, cotinine in the urine is described. An Extrelut column extraction procedure was introduced and the quantitative analyses were performed by gas chromatography equipped with a thermionic detector. This method had a good reproducibility and the recovery approximately 100 (93-102) per cent. Urinary and plasma cotinine levels determined by our method were compared with those determined by radioimmunoassay. There was a good correlation between them. There was a highly significant difference in urinary nicotine level, nicotine/creatinine ratio, cotinine level and cotinine/creatinine ratio between nonsmokers and smokers. Cigarettes consumed per day highly correlated with urinary cotinine level and cotinine/creatinine ratio, but not with urinary nicotine level and nicotine/creatinine ratio.

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^<14>C-2-Chloroethyl benzoate (¹⁴C-CEB) was given to animal to investigate its fate in the body, and the following results were observed ; The absorption rate of ¹⁴C-CEB was so fast that a radioactivity in blood was observed 15 min after a single oral administration. Relatively higher distributions of radioactivity were noted in the liver and kidney comparing with other many organs. Almost all radioactivity of dose was excreted only in the urine 12 h after the administration, and its accumulation was not recognized in any region of the body. The rate of distribution to tissues after a cutaneous application was also fast, and the radioactivity was rapidly excreted as well as in the case of oral dosing. The amount of radioactivity transferred into the bile was only 0.8% of the dose 24 h after an intravenous injection. The urinary metabolite corresponding to 99.3% of the radioactivity in the rat urine was identified to be hippuric acid by thin-layer chromatography (TLC) and isotope dilution method. Additionally, p-hydroxybenzoic acid was also detected in the hydrolyzed rat urine.

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The effect of methanol on the activity of hepatic δ-aminolevulinic acid synthetase (ALA synthetase) was investigated in male mice. The activity of ALA synthetase increased with increasing doses of methanol up to 100 mmol per kg of body weight injected intraperitoneally. In both the methanol-treated mice and normal mice, the apparent biological half-life time of the enzyme was about 56 min after the administration of cycloheximide. The increase of the enzyme activity by methanol was significantly inhibited by pretreatment with actinomycin D, an inhibitor of protein synthesis. The apparent Km value of the enzyme for glycine did not change but the V_max value increased in methanol-treated mice. Pretreatment of mice with pyrazole, a potent inhibitor of alcohol dehydrogenase, significantly inhibited the methanol-induced increase of ALA synthetase, whereas pretreatment with either 3-amino-1, 2, 4-triazole or acetanilide, inhibitors of catalase, did not alter the increase of the enzyme activity by methanol. It was concluded that methanol injected to fasted mice induces hepatic ALA synthetase and that the enzyme induction is associated with the oxidation of methanol by alcohol dehydrogenase.

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A high sensitive and selective screening chip for the detection of methamphetamine in the human urine was developed by use of Simon's reagent and silica gel TLC plate. Equal volume of 2% sodium nitroprusside and 5% sodium carbonate solution was thoroughly but carefully sprayed on the plate, and then it was dried at 110°C for 3 h, followed cutting to ca. 3×1.5 cm chip after cooling. The chip could be detected over 10 ng of methamphetamine by color reaction in acetaldehyde gas. Detection ability of the chip stocked in dessicator did not fall at least after 3 months. The analytical method of the sample urine by using this chip was as follows : 5 ml of sample urine was extracted with 2 ml of benzene under basic conditions, and ca. 20 μl of the extract was spotted on the chip, then it was exposed to acetaldehyde gas. Blue color was developed in case of the urine containing methamphetamine over 0.1 μg/ml. The methamphetamine in the extracted solution regarded as positive by this method could be identified by GC-MS after TFA-derivatization. The screening error of this method was about 3%.

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Paraquat (1, 1'-dimethyl-4, 4'-dipyridylium dichloride) was found to give a blue color, when it was spotted on a 1 N NaOH-impregnated paper followed by heating with a hair-dryer. This method is suitable for rapid preliminary detection of paraquat in beverages in the field of forensic chemistry. The detection limit of paraquat was approximately 0.2 μg on a blue spot. Electrophoresis on paper impregnated with 0.1 M sodium phosphate buffer (pH 12) was also found to be useful for confirmation of paraquat.

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The selection of best solvent for extracting cartap from human blood was examined. The experimental procedures were as follows ; One ml of blood sample was added to 0.5 ml of 8% sodium hydroxide solution in a 15 ml test tube. The sample was extracted with 5 ml of cyclohexane by shaking for 3 min, and centrifuged at 3000 rpm for 2 min. The cartap extracted with cyclohexane was derivatized by reacting with 3, 4-dimethyl benzyl chloride. The 3, 4-dimethyl benzyl derivative of cartap was spectrophotometrically measured by using tropaeoline OO as an ion-associating reagent. For the extraction of cartap from blood sample no interference could be observed with the compounds, such as Fe (III), Cu (II), glycine, L-phenylalanine, urea, glucose, lactose.

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The LC₅₀ test method by use of Tubifex was developed for the evaluation of eco-toxicity of chemicals. The change of the observation period, the size of Tubifex or the test temperature affected little the LC₅₀ value of 3, 5-dichlorophenol. Acute toxicity of 20 chemicals was tested at 20°C for 48 h by use of Tubifex of 30-50 mm in length. The test results were compared with the other three biological test methods ; EC₅₀ of activated sludge respiration inhibition test, LC₅₀ of Oryzias latipes (Himedaka ; red killifish) acute toxicity test and EC₅₀ of Tetrahymena pyriformis proliferation inhibition test. A good correspondence was found in each two test method compared, and the regression analysis showed that the sensitivity of the Tubifex test lied between those of activated sludge and O. latipes tests.

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The effects of chelating agents, such as citric acid, ethylendediaminetetraacetic acid (EDTA), L-cysteine and L-leucine, on the inhibition of small intestinal absorption of L-histidine with cadmium in rats were studied. The depressed absorption of L-histidine (1.29 mM) from the small intestine of rats in situ in the presence of cadmium (0.27 mM) was greately restored by the addition of citric acid (10-20 mM) and EDTA (0.5 mM), and moderately by L-cysteine (1.29 mM). In addition, the intestinal accumulation of cadmium was significantly decreased by the addition of citric acid, EDTA and L-cysteine. An in vitro intestinal experiment suggested that the result of complexing of cadmium by the chelating agents, such as citric acid, EDTA and L-cysteine, decreased the accumulation of cadmium in the intestinal tissue and protected the active transport of L-histidine across the rat small intestine.

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