Haruhiko Sakurai

Mutagenic activity of selenium compounds

The mutagenicities of selenate (SeO2/4-) and selenite (SeO2/3-) were determined by two bacterial assay systems: Kadas rec-assay and Amess Salmonella test. In both assays, these compounds were found to be weak mutagens. In the Salmonella test, selenate (0.05 revertants/nmole) and selenite (0.2 revertants/nmole) gave rise to base-pair substitution.

Comparative evaluation of four urinary tubular dysfunction markers, with special references to the effects of aging and correction for creatinine concentration

Comparative evaluation was made on alpha(1)-microglobulin (alpha(1)-MG), beta(2)-microglobulin (beta(2)-MG), retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG), as a marker of renal tubular dysfunction after environmental exposure to cadmium (Cd), with special references to the effects of aging and correction for creatinine concentration. For this purpose, a previously established database of 817 never-smoking Japanese women (at the ages of 20 to 74 years) on hematological [hemoglobin, serum ferritin (FE), etc.] and urinary parameters [alpha(1)-MG, beta(2)-MG, creatinine (cr), and a specific gravity] was revisited. For the present analysis, the database was supplemented by the data on RBP and NAG in urine. The exposure of the women to Cd was such that the geometric mean Cd in urine was 1.3 microg/g cr. Among the four tubular dysfunction markers, NAG showed the closest correlation with Cd, followed by alpha(1)-MG and then beta(2)-MG, and RBP was least so although the correlations were all statistically significant. The observed values of the markers gave the best results, whereas correction for a urine specific gravity gave poorer correlation, and it was the worst when correction for creatinine concentration was applied. Age was the most influential confounding factor. The effect of age appeared to be attributable at least in part to the fact that both creatinine and, to a lesser extent, the specific gravity decreased as a function of age. Iron deficiency anemia of sub-clinical degree as observed among the women did not affect any of the four tubular dysfunction markers. In conclusion, NAG and alpha(1)-MG, rather beta(2)-MG or RBP, are more sensitive to detect Cd-induced tubular dysfunction in mass screening. The use of uncorrected observed values of the markers rather than traditional creatinine-corrected values is recommended when comparison covers people of a wide range of ages.

Bias induced by the use of creatinine-corrected values in evaluation of β2-microgloblin levels

The present study was initiated to examine if the correction for creatinine (CR or cr) is the best approach among the three methods of correction for CR, correction for a specific gravity (SG or sg) and the use of observed values in managing difference in urine density. For this purpose, a database previously developed on 10,753 adult women in 10 non-polluted areas in Japan was re-visited for information on age, urinary levels of Cd, Mg, Ca, Zn, beta(2)-MG, and creatinine, and urine specific gravity as well as smoking habits. Never-smoking women with various urine density counted 8975 cases (the various urine density group). From these cases, 7081 cases with adequate urine density (i.e. 0.5 g/l < or = CR < or = 3.0 g/l and 1.010 < or = SG < or = 1.030) were selected (the adequate urine density group). When a beta(2)-MG level of 400 microg/g CR or 400 microg/l was taken as a cut-off value for beta(2)-MG-uria, both the prevalence of beta(2)-MG(cr)-uria [i.e. cases with beta(2)-MG (as corrected for CR) in excess of 400 microg/g cr] and that of beta(2)-MG(sg)-uria increased as a function of the decrease in Cd(cr) or Cd(sg). The prevalence of beta(2)-MG(ob)-uria also varied as a function of CR and SG, especially of CR, but its range of variation was smaller than the corresponding changes in beta(2)-MG(cr)-uria prevalence. A noteworthy advantage for the use of observed values over that of SG-corrected values was the minimum effect of age. In over-all evaluation, therefore, the recommended approach appeared to be the use of non-corrected observed values (after selection of urine samples for adequate urine density if desired) or correction for SG, rather than correction for CR.

Uptake of cadmium in meals from the digestive tract of young non-smoking Japanese female volunteers.

Uptake of Cadmium in Meals from the Digestive Tract of Young Non‐smoking Japanese Female Volunteers: Yuriko Kikuchi, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University

Effect of lead on cardiac parasympathetic function

SummaryA cross-sectional survey was performed on 172 male, lead exposed workers to clarify the effects of lead on the cardiac autonomic nervous system expressed as the decrease of R-R interval variation on an electrocardiogram and to obviate the dose-effect relationship between blood-lead level (Pb-B) and the degree of the decrease. For 132 workers who were exposed to lead for more than one year and whose Pb-B levels were relatively stable (Pb-B variation less than 20 μg/dl during recent one year), a significant dose-related decrease of R-R interval variation during deep breathing was observed. Age-adjusted R-R interval variation during deep breathing in those whose Pb-B were 30 μg/dl or above was significantly decreased compared with those whose Pb-B levels were 20 μg/dl or below. This decrease was observed more clearly in younger workers. These results suggest that an effect on autonomic nervous system expressed as decrease of R-R interval variation during deep breathing might be one of the earliest effects of lead exposure.

Biological response and subjective symptoms in low level lead exposure.

Workers occupationally exposed to lead in the air of up to 60μg/cu m were examined for blood lead (Pb-B), urinary δ-aminolevulinic acid (ALA), erythrocyte ALA dehydrase (ALAD), hemoglobin, hematocrit, red blood cell count, and subjective symptoms. The Pb-B and ALAD showed consistent increases and decreases, respectively, corresponding with the levels of Pb exposure, while other tests revealed no association with Pb. The range of Pb exposure as expressed by Pb-B was up to 50μg/100 gm. Subjective symptoms and urinary ALA are not likely to be increased at the Pb-B level of about 50μg/100 gm and less.

Cross sectional observation of the effects of carbon disulphide on the nervous system, endocrine system, and subjective symptoms in rayon manufacturing workers

OBJECTIVES: A prospective cohort study was initiated to clarify whether the current level of exposure to carbon disulphide (CS2) is low enough to prevent occurrence of subclinical health impairments or to ameliorate health effects due to past high exposure. This paper describes the effects of exposure to CS2 on the nervous and endocrine systems, and the subjective symptoms in a baseline observation. METHODS: The effects were evaluated of CS2 on the median nerve conduction velocity, neurobehavioural and psychological tests, and subjective symptoms related to solvents in 432 male workers exposed to CS2 and 402 reference workers from 11 rayon factories in Japan. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS2 was either dichotomised or categorised into three groups by job type. RESULTS: Reductions were observed in motor (-1.9 m/s) and sensory (-0.91 m/s for orthodromic and -1.1 m/s for antidromic) nerve conduction velocities in the workers exposed to CS2 at the spinning and refining processes. Small but significant increases were found in self rated depression scale score and decrease in digit span (backward) in the workers exposed to CS2. Of 54 subjective symptoms many were increased--namely, heavy feeling in the head, light headedness, fainting after suddenly standing up, tremor, dullness, and increased sensitivity of skin in the extremities, reduced grasping power, reduced sexual desire, and increased rough skin. The endocrinological indicator--the concentration of glycosylated haemoglobin--was also increased in the workers exposed to CS2. CONCLUSIONS: Subclinical effects on the nervous system and on glucose metabolism were found in the workers exposed to CS2. One interpretation is that relatively higher exposure to CS2 in the past may induce these, but the effects are still not entirely ameliorated under the current exposure to CS2. Another possibility is that the current exposure to CS2 may cause these positive findings. A follow up observation is necessary to clarify these questions.

Evidence on n -acetyltransferase Allele-associated Metabolism of Hydrazine in Japanese Workers

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Increased urinary beta 2-microglobulin in cadmium exposure: dose-effect relationship and biological significance of beta 2-microglobulin.

A study on the general population from both cadmium-polluted and control areas and on cadmium alloy workers indicates that beta 2-MG in urine is very closely correlated with aging, but it indicates an association with cadmium exposure. However, the age factor is stronger than cadmium exposre in both polluted and control areas among persons without clinical proteinuria. On the other hand, cadmium exposure is most likely correlated with beta 2-MG even in nonpolluted areas. Thus it seems that there is no noneffect level of cadmium dose in affecting the elevation of beta 2-MG in urine. beta 2-MG in serum indicated a very close correlation with cadmium in blood among cadmium alloy workers. This may suggest that an increase of beta 2-MG in both blood and urine in an early stage of cadmium exposure is caused by the increased level of beta 2-MG in blood, which may be a result of stimulation due to cadmium, but not necessarily by the clinical dysfunction of reabsorption of beta 2-MG in the renal.

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers.

OBJECTIVE: A prospective cohort study was designed to clarify the relations between occupational exposure to carbon disulphide (CS2) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. METHODS: Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS2 was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n = 422). About a quarter of the urine samples were > 5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aorta, stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Roses questionnaire. Information on potential confounding factors was collected by self administered questionnaire. RESULTS: Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS2 (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. CONCLUSIONS: Significant effects of CS2 on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.