Increased urinary excretion of δ-aminolevulinic acid (ALA) is an early biological sign of toxic lead absorption. Therefore, its determination is a very useful screening test for the periodical examination of workers exposed to lead. Previously, we developed a simplified method for determining urinary ALA without ion-exchange column. This method is based on two findings: (a) ALA-pyrrole is extractable with ethyl acetate to be separated from other Ehrlich-positive substances such as urea, and (b) the ALA-pyrrole can form a complex with the modified Ehrlich's reagent in ethyl acetate. In the present study, using this method, we determined urinary ALA of healthy adult men and estimated the normal levels for ALA. The results are as follows: (1) The urinary ALA concentration obtained from the spot urine samples of 299 workers (age: mean=37.1 years range=20-56 years) with no history of occupational lead exposure was 2.39±0.87 mg/liter (mean and standard deviation), with upper limit of 4.10 mg/liter for 95%-confidence interval. (2) The distribution of ALA in the normal spot urine was not log-normal, but normal. (3) No significant difference between the excretion level of urinary ALA and the age was observed.

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1) Two cases of aplastic anemia were found among over-glaze decoration workers in potteries. They had used solvents containing benzene for treating liquid gold (a kind of pigment) or for wiping off the varnish (an adhesive for printing transfer papers). So, the relationship between aplastic anemia of the two cases and their benzene exposure were investigated. Case 1: a 49 year-old man who had been exposed to benzene occasionally for one or two months in 1967 and four hours a day for five months from October, 1971 to February, 1972. He had been in good health before he began to complain of headache in March, 1972. His health conditions acutely worsened and he was admitted to a hospital with a diagnosis of aplastic anemia on March 13, 1972 (Table 1). His severe anemia remitted six months after admission (Fig. 1). The solvent used by him contained 90% of benzene and 10% of toluene. He had used 50 to 100 ml of the solvent a day. It was estimated from the working conditions investigated in the similar factories that he might have been exposed to benzene continuously at about 0.5 ppm and intermittently even at 7.5 to 30 ppm or more. Case 2: a 60 year-old woman who had been exposed to benzene nine hours a day from 1952 to the spring of 1967. She had often complained of nausea, vomiting, fever and pollakisuria since the summer of 1968, and she was admitted to a hospital in March, 1969. She was diagnosed as aplastic anemia at that time (Table 2). She died three months after her admission in spite of medical treatment (Fig. 2). The autopsy revealed that her bone marrow was hypoplastic. She had daily used about 125 ml of the solvent containing benzene. It was estimated from the working conditions investigated in the similar factories that she might have been exposed to 7.5 to 30 ppm or more of benzene almost continuously throughout her working time. Judging from the relationship of the clinical course and the benzene exposure in the two cases, and from the results of other reports on the benzene poisoning (Table 5), it could be considered that aplastic anemia in both cases was caused by benzene. 2) The working conditions, especially benzene exposure, were investigated in six over-glaze decoration factories. Factories A and B were investigated in March, 1977, and factories C, D, E and F in July, 1977. It was revealed that benzene had been used in all the factories (Table 3), which were poorly ventilated. Above 150 ppm of benzene were detected close to the respiratory zone of a worker in factory B (Table 4, Fig. 5). Benzene above 25 ppm (the ceiling value of MAC recommended by the Japan Association of Industrial Health) were often detected in other factories too (Fig. 4). Total phenol in the urine were colorimetrically determined after the indophenol reaction with Gibbs' reagent in 16 workers usually exposed to benzene, six workers occasionally entering into the workrooms where benzene was used and eight students as the control (Fig. 6). Concentrations of total phenol in the urine of the usually exposed workers had a tendency to be higher in the evening (after work) than in the morning (before work). The concentrations of total phenol in the morning urine of the usually exposed workers were significantly higher than those of the students and had a tendency to be higher than those of the occasionally exposed workers. The concentrations of total phenol in the evening urine of the usually exposed workers were significantly higher than those of the occasionally exposed workers. These results showed that benzene had been actually inhaled by the workers. 3) It was made clear that benzene had been used up to very recent time in over-glaze decoration factories and that the ventilation of the factories were not satisfactory. Benzene is rarely used as a solvent in industries in Japan because it has strictly been restricted by law to use it as a solvent. But benzene had been used exceptionally until recently in over-glaze decoration factories, becaus

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Arsenite (As³⁺), arsenate (As⁵⁺), methylarsonic acid (MAA) and dimethylarsinic acid (DMAA) levels in organs and tissues were sequentially determined during the period between 10 minutes and 120 days after oral administration of arsenic trioxide to rats. Male Wistar rats were used as experimental animals, divided into groups each of 5 animals, and given a solution of arsenic trioxide (20 mg/kg as As) orally only once. For the determination of arsenic levels in organs, tissues and blood, these specimens were pretreated with 0.5 N sodium hydroxide solution under heating, while for the determination of arsenic levels in the urine, no pretreatment was made of urine specimens. The arsenic compounds in the samples were reduced, vaporized and isolated by a modification of Braman's method, and determined by the atomic absorption spectrophotometry. 1) Arsenic compound levels in the blood When the rats were given arsenic trioxide, the total arsenic level in the blood began to increase rapidly 6 hours after administration, reaching a peak of about 200 times the control level on the 2nd day, and remained as high as about 47 times the control level even on the 120th day. On the 2nd day, not less than 99% of the total arsenic in the blood was made up of DMAA, the major portion of which was found in the red cells. At this stage, the amount of DMAA in the red cells was presumed to correspond to not less than 60% of the administered dose of arsenic trioxide. The markedly high DMAA level in the blood may be considered as being due to the species specificity of rats. 2) Arsenic compound levels in the liver, kidneys, spleen, lungs, muscle, and brain When the animals were given arsenic trioxide, chiefly As⁵⁺ and also As³⁺ increased in organs and tissues within 6 hours. The increases in these inorganic arsenic compounds were striking in the liver and kidneys in particular. On the 1st or 2nd day, the inorganic arsenic compounds decreased gradually, while the methylated arsenic compounds, chiefly DMAA, increased markedly. The spleen and lungs were the organs where DMAA had accumulated at especially high levels, reaching a peak on the 2nd day. On the 120th day, the level of this compound in the lungs still remained as high as 15 times the control level, and that in the spleen, as high as 10 times the control level. 3) Arsenic compound levels in the skin and hair The total arsenic levels in the skin were low, compared with those in the other organs and tissues. When the levels were classed by the chemical form of arsenic, the increased As⁵⁺ was characteristic. The total arsenic level in the hair began to increase on the 7th day, reaching a peak on the 10th day, but tended to decrease on the 30th day. The total arsenic levels in the hair were characterized by the increased As⁵⁺, which was 75 times the control level on the 10th day and about 5 times the control level on the 120th day. 4) Excretion of the arsenic compounds into the urine and feces When the animals were treated with arsenic trioxide, the largest urinary output of arsenic occurred on the 1st day, then decreasing slowly. As³⁺ was demonstrated in the urine at high levels on the 1st-3rd day, which was the same as the characteristic finding following the ingestion of arsenic trioxide in a human experiment. On the 2nd day and later stages, the output of DMAA was the largest of the outputs of 4 chemical forms of arsenic. As⁵⁺ accounted for the largest part of the fecal output of arsenic, followed by MAA, and the outputs of DMAA and As³⁺ were very small.

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