We improved the method for determining urinary δ-aminolevulinic acid (ALA) by HPLC-fluorometer after pre-column derivatization with acetylacetone and formaldehyde, and a stable ALA derivative was obtained without any effect from various urinary components as demonstrated by the complete recovery of ALA (100.9±5.5%, n=85) from the urine samples. The modified procedure was as follows: Twenty μl of urine sample, 5 ml of acetylacetone solution (acetylacetone/ethanol/distilled water containing 4 g/l of NaCl; 15/10/75), and 0.45 ml of 9.3% formaldehyde solution were mixed and boiled for 15 min. The fluorescent derivative of ALA was separated and analyzed by HPLC with the fluorometer at Ex 246 nm and Em 458 nm. Using a gradient program, the retention time of the ALA derivative was 7.3 min and the analysis could be repeated at 13 min intervals. Concentrations of ALA in urine samples measured by this method were significantly correlated with those measured by the Mauzerall-Granick (M-G) method (n=85, r=0.993, p<0.001). The values obtained by our method were, however, lower than those obtained by the M-G method. Urinary ALA concentrations of 40 non-lead workers ranged from 0.1 to 2.3 mg/g creatinine with the mean±SD of 1.1±0.4 mg/g creatinine as measured by the present method.

View full abstract

The effects of Breslow's seven health practices on health were examined. The Todai Health Index (THI), a questionnaire for self-evaluation of physical and mental health, was applied to male workers of a private company as well as their wives. The subjects resided in the suburbs of Tokyo and the average ages of the males and females were 41.5 and 38.4 years, respectively. Statistical results were obtained using Mann-Whitney U-test, analysis of covariance, and Hayashi's quantification theory I.
A statistically significant decrease in the THI scale scores among subjects observing six or more health practices when compared with those observing three or less was demonstrated in vague complaints and irritability in males, and in respiration in females. In males, the THI scale scores of vague complaints, respiration, and the mouth and anus significantly decreased by sleeping well. Those of irritability and irregularity of life decreased by not smoking and those of vague complaints and irritability decreased by not eating between meals. In females, the THI scale scores of vague complaints, eye and skin, and the mouth and anus significantly decreased by exercising regularly. Those of irregularity of life decreased by not smoking. Those of respiration decreased by good weight control. Those of respiration and the mouth and anus decreased by not eating between meals. Exercising regularly in females was a good predictor of vague complaints using multi-variate analysis adjusted for age.
Subjective evaluation of health improved by Breslow's recommended health practices.

View full abstract

[in Japanese]

View full abstract

We investigated the background levels of total mercury in blood and urine samples from Japanese subjects without occupational exposure to mercury vapor.
Blood and urine specimens were decomposed in sealed Teflon containers, and total mercury concentration was measured by reductive vaporization-gold amalgam capture-atomic absorption spectrophotometry.
The mean total mercury concentration in the blood of 56 women aged 34-65 was 18.2±9.9 ng/ml (range 3.9-56.8 ng/ml).
The mean total mercury concentration in the urine of 130 men aged 22-39 was 2.33±1.50 μg/l (range 0.27-10.26 μg/l). The mean total mercury concentration in urine adjusted by specific gravity was 2.19±1.15 μg/l (range 0.68-7.68 μg/l), and that adjusted by creatinine was 1.51±0.68 μg/g creatinine (range 0.39-4.21 μg/g creatinine).
These concentrations did not differ greatly from those reported from Europe and Japan. In expressing the total mercury concentration in urine, the creatinine-adjusted range between the minimum and maximum values was smaller than the range adjusted by specific gravity.

View full abstract

To date the evaluation of chemically-induced neurotoxic effects on humans has been dependent mostly on electrophysiological measurements, neurobehavioral tests and biological exposure assessment. However, recently attempts have been made to develop biochemical parameters in peripheral body fluids which can be easily obtained from humans and which can represent markers for the same parameters in nervous tissue. The approach of this kind is logically based on the following facts: 1) Blood cells (e. g., platelets and lymphocytes) possess some characteristics of monoaminergic neurons such as the existence of storage vesicles of monoamines, membrane neurotransmitter receptors, high affinity uptake sites and neurotransmitter-related metabolizing enzymes. 2) Leakage of nerve-specific markers from nervous tissue to peripheral body fluids may occur following damages of target neuronal cells or macromolecules. 3) Quantitative and/or qualitative alterations of peripheral biochemical markers (e. g. neurotransmitter receptors) can be induced by the regulation mechanisms of neuronal, endocrinal and immunal interactions when the nervous functions are perturbed by various exogenous or endogenous factors. Erythrocyte acetyl cholinesterase (AChE), free erythrocyte protoporphyrin (FEP), lymphocyte neurotoxicity target enzyme (NTE), blood aminolevulinic acid dehydratase (ALA-D), and carboxyhemoglobin (CO-Hb) are well-known peripheral markers of the effects induced by organophosphates (AChE, NTE), lead (FEP, ALA-D) and carbon monoxide (CO-Hb). Many studies have been made on the effects of organic solvents, heavy metals and pesticides on neurotransmission parameters in blood cells such as neurotransmitter uptake, receptor binding and enzyme activity. This paper summarizes the present knowledge on the development and clinical applications of some peripheral biochemical markers such as neurotransmission parameters in blood cells and neuronal or glial cell marker proteins in CSF, blood and urine. The role of these peripheral biochemical markers in the assessment of environmental chemically-induced human neurotoxicity is also discussed.

View full abstract

Utility of multivariate analysis in evaluating the values of laboratory tests on the basis of intra-individual variations (IV) was studied. Periodic health examination on workers has many clinical laboratory tests and these values are generally evaluated in comparison with “normal ranges.” Recently it has been ascertained that the individual normal ranges were narrower than the populational normal ranges. Although the values of an individual should be estimated with normal ranges of the individual, it is almost impossible to determine the normal ranges from only one or two health examinations conducted per annum at the place of work. The author in his study could easily determine IV with a method using Mahalanobis' distance on a basis of populational normal range. In this method, if many values of a person in the tests vary in several years, the distance becomes larger, and if a value in a test falls outside the normal limit, it also becomes larger. This method makes it possible to detect not only an “abnormal” value out of the normal range but also a large value out of IV. To examine the practical validity of the method, the data of 24 employees (males, 45 to 65 years old) from 3 periodic health examinations and those of 20 persons (males, 48 to 71 years old) from 3 to 6 medical checkups were analyzed with regard to 11 items. It was found that 33 out of 44 persons were abnormal in one or more items and that 10 abnormal persons had large IV. They would be missed in the judgement with the use of only “normal ranges.” As the distances were computed by a portable computer with a basic program, the method can be easily used in a small place of work. It is considered that this new method is effective and valuable not only as the screening procedure but also in the evaluation of IV.

View full abstract

Based on a longitudinal questionnaire survey of 11, 121 subjects (males aged 30-59, engaged in various occupations snd firms), this study examined the relationships of the baseline psychosocial work environment and personal health practices to mental disorders which occurred during an 18-month follow-up period.
The onset of mental disorders during the follow-up period was assumed to be the time when the subject reported to have received medical treatment for the first time due to mental disorder. The psychosocial factors of the work environment were conceptually constructed from two aspects of working conditions and occupational stress. Working conditions were assessed by actual working hours, frequencies of late night work (10 p.m.-5 a.m.), and role in the organization. Occupational stress was measured by psychological work overload and job characteristics (job demands, decision latitude). Various factors associated with positive health behavior were examined through an index based on six variables, that is, supper time, exercise, smoking, alcohol consumption, sleep and weight. Multiple logistic analysis showed that both psychological work overload and late night work have a significant independent effect on the onset of mental disorders after controlling for other variables.

View full abstract

With the revision made to the Regulation on the Prevention of Organic Solvent Poisoning in June 30, 1989, analysis of urine must be made for metabolites as a part of the health examination of workers exposed to xylene, N, N-dimethylformamide, styrene, 1, 1, 1-trichloroethane, tetrachloroethylene, trichloroethylene, toluene, and n-hexane. In accordance with this Regulation, health examinations were conducted at eight factories of five chemical manufactures in 1990. This report presents the results obtained for 1, 073 workers as compiled by the Committee of Industrial Health of the Japan Urea and Ammonium Sulfate Industry Association.
1) The results of data analysis have shown that workers whose urine was collected when they had been exposed to an imperceptible degree to organic solvent or who underwent urine collection during an unknown period of time after exposure numbered 615 or 57.3% of all the workers.
2) Workers whose urine was collected within about 5 hours after exposure numbered 458 (42.7%). The metabolite concentrations in these workers were significantly lower than the BEI values.
3) It may be concluded from the results that workers were exposed to organic solvents to an extremely small extent during organic solvent handling operations at chemical industry factories which maintain good control over toxic materials.

View full abstract

The medical examination of workers exposed to lead was conducted as part of the activity of the Occupational Safety and Health Center (OSHC) Project in the Philippines (JICA Project).
The subjects of the medical examination were 21 male and 193 female workers of a semiconductor plant (abbreviated A company), 59 male and 6 female workers of a refrigerator manufacture (B company); 199 male workers of a storage battery manufacturer (C company); and 107 male and 6 female workers of a lead smelter (D company). Among the examination items were questions regarding occupational history, subjective complaints and objective signs, determination of blood lead levels, urine deltaaminolevulinic acid levels, and examination for anemia. The survey was conducted from June to September in 1990.
The following results were obtained:
1) The mean age of the workers ranged from 21.8 to 33.8 years. Those of companies A and B were younger than those of companies C and D. The mean employment duration of males at C company was 10.7 yr, and the longest among the four companies. That in both sexes for A company was 1.8 yr and the shortest among the above mentioned companies.
2) The blood lead geometric mean levels of compamies C and D showed the highest concentration. The level in males of C company was 64.5 μg/dl and that of D company was 80.8 μg/dl. The level in females of A company was 9.9 μg/dl and the lowest in concentration. The urine deltaaminolevulinic acid geometric mean levels were less than 6.0 mg/l in the four companies. There was no company having hemoglobin mean values less than 14.0 g/dl in males or less than 12.0 g/dl in females.
3) The proportion of blood lead levels of 60 μg/dl or more was 67.3% in males of C company, and 89.7% in males and 16.7% in females of D company. The proportion of urine deltaaminolevulinic acid levels of 6 mg/l or more was 1.0% in females of A company, 20.1% in males of C company, and 43.0% in males of D company. The proportion of hemoglobin values less than 14.0 g/dl in males or less than 12.0 g/dl in females was 4.7% in females of A company, 1.7% in males of B company, 3.5% in males of C company, and 12.1% in males of D company.
4) The symptoms having a prevalence of more than 10% in males were easy fatigability and malaise for A company; irritability, joint pains, muscle pains and paraesthesia for B company; all items for C company; and easy fatigability, malaise, irritability, sleep disorder, joint pains, muscle pains, abdominal discomfort and paraesthesia for D company. Those in females were easy fatigability, malaise, irritability, sleep disorder, joint pains, and muscle pains for A company.
5) A relationship between the prevalence of symptoms and blood lead levels was observed. In males. there were significant group differences in the symptoms of easy fatigability, malaise, irritability, sleep disturbance, joint pains, muscle pains, abdominal colic, abdominal discomfort, constipation/diarrhea and paralysis/paresis of the extensor muscles (p<0.05 or p<0.01). With some exceptions, a trend of increasing prevalence with increasing blood lead level was observed. There were no significant differences in females.
6) In males having a blood lead level less than 40 μg/dl, there were significantly positive correlations between age and duration of employment and between blood lead level and duration of employment (p<0.001); and in females, there were significantly positive correlations between age and duration of employment and between blood lead level and hemoglobin values (p<0.05). In males having a blood lead level more than 40 μg/dl, there were significantly positive correlations between age and duration of employment and between blood lead level and urine deltaaminolevulinic acid level (p<0.001)

View full abstract

In Japan “the Regulation on the Prevention of Lead Poisoning” and “the Regulation on the Prevention of Organic Solvent Poisoning” were partially amended in 1989 to introduce biological monitoring in the special medical examinations of workers exposed to lead and 8 organic solvents (toluene, xylene, styrene, N, N-dimethylformamide, n-hexane, tetrachloroethylene, 1, 1, 1-trichloroethane, trichloroethylene).
Since many companies entrust these medical examinations to the Occupational Health Organizations (OHOs), a survey of OHOs which collect blood and urine samples for biological monitoring was made in August 1992, to ascertain the actual status of their activities from April of 1991 to March of 1992.
The following findings were obtained through this survey.
1) One hundred and eighty-six OHOs collected 129, 996 blood samples to measure the concentration of lead, and the median number of samples collected per organization was 356.
2) Thirty-nine OHOs (21.0%; Group A) measured all samples in their own laboratories. The number of samples measured was 55, 462 (42.7%). However, 133 OHOs (71.5%; Group B) entrusted the measurement of all samples to registered laboratories.
3) The median number of samples collected by OHOs in Group A was 1, 121, and the median number of Group B was 211.
4) One hundred and eighty-three OHOs collected 126, 915 urine samples to measure the concentration of δ-aminolevulinic acid and the median number of samples collected per organization was 358.
5) The blood samples as well as the urine samples were divided into three groups according to the levels of lead or δ-aminolevulinic acid concentration. The concentration is relatively low in Group 1 and relatively high in Group 3. The cut-off values for this classification are legally set in the Regulation on the Prevention of Lead Poisoning. The frequency of each group was as follows: lead (Group 1; 93.8%, Group 2; 4.9%, Group 3; 1.3%), δ-aminolevulinic acid (Group 1; 96.8%, Group 2; 3.1%, Group 3; 0.2%).
6) Two hundred and six OHOs collected 615, 148 urine samples to measure the concentration of metabolites of organic solvents. The number of samples collected for measurement of metabolites of toluene was 274, 265, which was largest in number and the number of samples was smallest for N, N-dimethylformamide (10, 353).
7) The number of OHOs which collected the urine samples for measurement of metabolites of toluene was 199 (96.6%), which was largest among 8 organic solvents. In the case of N, N-dimethylformamide, which was smallest in number, 117 OHOs (56.8%) collected the urine samples.
8) Seventeen OHOs (8.3%) measured all the urine samples of organic solvents in their own laboratories, but 169 (82.0%) OHOs entrusted the measurement of all samples to registered loboratories.
9) The urine samples were also divided into three groups according to the levels of the metabolites. The cut-off values for this classification are legally established by the Regulation on the Prevention of Organic Solvent Poisoning. The frequency of Group 1 was high in n-hexane (98.3%) and xylene (98.2%), and the lowest in styrene (87.3%). The frequency of Group 3 was the highest in styrene (3.0%) and the lowest in xylene and n-hexane (0.2%).

View full abstract