Miwako Dakeishi

Long-term consequences of arsenic poisoning during infancy due to contaminated milk powder

Arsenic toxicity is a global health problem affecting many millions of people. The main source of exposure is drinking water contaminated by natural geological sources. Current risk assessment is based on the recognized carcinogenicity of arsenic, but neurotoxic risks have been overlooked. In 1955, an outbreak of arsenic poisoning occurred among Japanese infants, with more than 100 deaths. The source was contaminated milk powder produced by the Morinaga company. Detailed accounts of the Morinaga dried milk poisoning were published in Japanese only, and an overview of this poisoning incident and its long-term consequences is therefore presented. From analyses available, the arsenic concentration in milk made from the Morinaga milk powder is calculated to be about 4–7 mg/L, corresponding to daily doses slightly above 500 μg/kg body weight. Lower exposures would result from using diluted milk. Clinical poisoning cases occurred after a few weeks of exposure, with a total dose of about 60 mg. This experience provides clear-cut evidence for hazard assessment of the developmental neurotoxicity. At the present time, more than 600 surviving victims, now in their 50s, have been reported to suffer from severe sequelae, such as mental retardation, neurological diseases, and other disabilities. Along with more recent epidemiological studies of children with environmental arsenic exposures, the data amply demonstrate the need to consider neurotoxicity as a key concern in risk assessment of inorganic arsenic exposure.

Lead Toxicity: Does the Critical Level of Lead Resulting in Adverse Effects Differ between Adults and Children?

Lead Toxicity: Does the Critical Level of Lead Resulting in Adverse Effects Differ between Adults and Children?: Katsuyuki Murata, et al. Department of Environmental Health Sciences, Akita University School of Medicine

Assessment of DNA Damage in Japanese Nurses Handling Antineoplastic Drugs by the Comet Assay

Assessment of DNA Damage in Japanese Nurses Handling Antineoplastic Drugs by the Comet Assay: Makiko Sasaki, et al. Department of Environmental Health Sciences, Akita University School of Medicine—To clarify genotoxic effects of occupational exposure to antineoplastic drugs in Japan, we examined DNA damage, assessed by the comet assay, in 121 female nurses and 46 female clerks working at three hospitals in the northeast of Japan. The comet assay is considered to be a sensitive and rapid method for DNA strand break detection in individual cells, and tail length and tail moment are used as the comet parameters. Concerning the basal characteristics, the 46 control subjects had higher rates of smoking and coffee‐drinking habits and lower hemoglobin than the 121 nurses (p<0.05). The log‐transformed tail length in the nurses was significantly longer than that in the control subjects after adjusting for possible covariates such as age and smoking habit (p<0.05). Also, the log‐transformed tail length was significantly longer, in the 57 nurses who had handled antineoplastic drugs in the last six months, than that in the 46 control subjects (p<0.05); but, no significant difference in tail length or tail moment was seen between the two nurse groups with and without experience of handling hazardous drugs (p>0.05). These results suggest that Japanese nurses who have worked at hospitals using antineoplastic drugs may have a potential risk of DNA damage. To minimize this risk in Japan, use of biological safety cabinet and appropriate protective equipments, in addition to staff education and training, should be implemented in the healthcare environment.

Cardiac autonomic imbalance in female nurses with shift work

The pathophysiology underlying the shift work-related cardiovascular disease is still poorly understood. The chronic effects of shift work on cardiac autonomic functions were assessed in 47 hospital nurses working under a rotating three-shift system (shift nurses) and 36 public health nurses without shift work (non-shift nurses). The heart rate variability, %LF and %HF (i.e., proportions of sympathetic and vagal activities, respectively), and LF/HF ratio were calculated from the electrocardiographic RR intervals by using autoregressive spectral analysis, and heart rate-corrected QT interval (QTc and QT index) was also measured. The LF/HF ratio, %LF, and QT index were significantly larger in the shift nurses than in the non-shift nurses; also, the power spectral density of HF (PSD(HF)) was significantly decreased in the shift nurses. There was a significant, inverse correlation between the corrected QT interval and PSD(HF) in the non-shift nurses, but not in the shift nurses. It is suggested that shift work in female nurses may cause a sympathodominant state due to depressed vagal tones. Also, a pathophysiology of shift work-related cardiovascular disease, derived from the present and previous findings, may be characterized by the attenuation of the inverse association between the corrected QT interval and vagal activity observed in non-shift workers.

Effects of hair treatment on hair mercury-The best biomarker of methylmercury exposure?

ObjectivesExposure misclassification is a major obstacle to obtain accurate dose-response relationships. In order to solve this problem, the impact of hair treatment on total mercury in hair was assessed in Japanese women.MethodsA cross-sectional study was carried out among 327 women at age 24–49 years to determine hair mercury levels and estimate daily mercury intakes from seafood by using a food frequency questionnaire.ResultsHair mercury levels in the women and daily mercury intake ranged from 0.11 to 6.86 (median 1.63) μg/g and from 0.77 to 144.9 (median 15.0) μg/day, respectively. The hair mercury was positively correlated with the daily mercury intake (p<0.001). When the women were divided into two subgroups based on artificial hair-waving, hair coloring/dyeing, residence (non-fishing and fishing areas), and working status, a significant difference in the hair mercury level was observed between the women with and without artificial hair-waving only (p<0.001). The multiple regression analysis showed that the log-transformed hair mercury level was significantly related to the log-transformed daily mercury intake (standardized regression coefficient βs=0.307) and artificial hair-waving (βs=−0.276); but not to hair coloring/dyeing, residence, working status or age. Permanent hair treatment was estimated to reduce total mercury in hair by approximately 30%, after adjusting for daily mercury intake and other possible factors.ConclusionsThese findings suggest that hair mercury is not the best biomarker of methylmercury exposure when a study population includes women with artificial hair-waving.

Critical Dose of Lead Affecting δ-Aminolevulinic Acid Levels

Critical Dose of Lead Affecting δ‐Aminolevulinic Acid Levels: Katsuyuki Murata, et al. Akita University School of Medicine—To estimate the critical dose of the association between the blood lead concentration (BPb) and δ‐aminolevulinic acid (ALA) levels, ALA levels in plasma (ALA‐P), blood (ALA‐B), and urine (ALA‐U), and the activity of δaminolevulinic acid dehydratase (ALAD) were determined in 186 Japanese lead workers, aged 18– 62 yr, with BPb levels of 2.1–62.9 µg/dl. For this purpose, the benchmark dose (BMD) method, recently used in the environmental health field in place of the no‐observed‐adverse‐effect level, was introduced into this study. The BMD was defined as the BPb level that resulted in an increased probability of abnormal change in ALA‐related parameters by an excess risk (BMR) of 5% in exposed workers i.e., from P0 (abnormal probability of 5% in unexposed workers) to P0+BMR for exposed workers at the BMD. ALA‐related parameters were significantly correlated with BPb. The BMDs computed from the 186 workers, after controlling for age, were 15.3–20.9 µg/dl for ALA levels, and 2.9 µg/dl for ALAD; likewise, the BMDs from the 154 workers with BPb levels of less than 40 µg/dl were 3.3– 8.8 µg/dl for ALA levels, and 2.7 µg/dl for ALAD. Since the cutoff value of ALA‐P, computed from the latter workers, seems to be closer to the upper normal limit in unexposed adults than does that from the former workers, it is suggested that the critical dose of BPb causing the increased levels of ALA is below 10 µg/dl. Such critical doses are necessary to promote preventive activities of adverse effects of lead.

Benchmark Dose of Lead Inducing Anemia at the Workplace

To estimate the critical dose of lead inducing anemia in humans, the effects of lead on hemoglobin (Hb) and hematocrit (Hct) levels and red blood cell (RBC) count were examined in 388 male lead-exposed workers with blood lead (BPb) levels of 0.05-5.5 (mean 1.3) micromol/L by using the benchmark dose (BMD) approach. The BPb level was significantly related to Hb (regression coefficient beta=-0.276), RBC (beta=-11.35), and Hct (beta=-0.563) among the workers (p < 0.001) when controlling for age and working status. The average BPb levels were significantly higher in the workers with anemia (1.85 micromol/L), based on the WHO criteria, than in those without anemia (1.26 micromol/L). The benchmark dose levels of BPb (i.e., lower 95% confidence limits of BMD), calculated from the K-power model set at an abnormal probability of 5% in unexposed workers and an excess risk of 5% in exposed workers were estimated to be 0.94 micromol/L (19.5 microg/dl) for Hb, 0.94 micromol/L (19.4 microg/dl) for RBC, and 1.43 micromol/L (29.6 microg/dl) for Hct. These findings suggest that reduction in hematopoietic indicators may be initiated at BPbs below the level currently considered without effect.

Effects of Shift Work on Autonomic and Neuromotor Functions in Female Nurses

Effects of Shift Work on Autonomic and Neuromotor Functions in Female Nurses: Noriko Ishii, et al. Division of Environmental Health Sciences, Department of Social Medicine, Akita University School of Medicine—Thirty‐seven nurses with shift work, working under a rotating three‐shift system, and 37 nurses without shift work, having worked during the daytime for one or more years prior to this study, were examined to assess the effects of shift work on cardiac autonomic and neuromotor functions. Their ages ranged from 25 to 58 yr. The electrocardiographic (ECG) R‐R interval variability, %LF and %HF (i.e., proportions of sympathetic and parasympathetic activities, respectively), and LF/HF ratio were computed by means of autoregressive spectral and component analyses. The %LF and LF/ HF ratio were significantly larger in the nurses with shift work than in those without shift work, although there was no significant difference in the heart rate‐corrected QT interval on ECG between them. And, hand‐ear coordination differed significantly between the nurses with shift work and those without. Despite the presence of potential selection bias, it is suggested that shift work in nurses may cause not only a long‐term sympathodominant state but also some neuromotor impairment.

ASSOCIATION OF ALCOHOL DEHYDROGENASE 2 AND ALDEHYDE DEHYDROGENASE 2 GENOTYPES WITH FASTING PLASMA GLUCOSE LEVELS IN JAPANESE MALE AND FEMALE WORKERS

AIMS The objective was to clarify the effect of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) genotypes on the diabetic risk in Japanese workers. METHODS At the time of mandatory health checkup, the ADH2 and ALDH2 genotypes, as well as fasting plasma glucose (FPG) levels, body mass index (BMI), smoking habit, and weekly alcohol intake, were examined in 492 men and 183 women working at motor vehicle dealerships. RESULTS In using two-way analysis of variance to manipulate ADH2 and ALDH2 genotypes and alcohol intake (>70 g/week for men and >35 g/week for women), the FPG level after the adjustment for age, BMI, smoking habit, and another genotype was significantly higher in the men with ADH2*1/1 genotype than in those with the other genotypes, but there was no significant difference in the FPG level between the men with and without ALDH2*1/1 genotype. In contrast, the women with ALDH2*1/1 genotype had significantly lower FPG levels than those with the other genotypes, but there was no significant difference in the FPG level between the women with and without ADH2*1/1 genotype. Also, a significant interaction between ethanol intake and ALDH2 genotypes was seen only in the women. CONCLUSIONS These findings suggest that genotypes of ADH2 and ALDH2 can modify the diabetic risk, irrespective of amounts of alcohol consumed. Also, there may be sex differences in the effect of these enzyme genotypes on glucose metabolism.

Effects of mixed organic solvents on neuromotor functions among workers in Buddhist altar manufacturing factories.

Effects of Mixed Organic Solvents on Neuromotor Functions among Workers in Buddhist Altar Manufacturing Factories: Toyoto Iwata, et al. Department of Environmental Health Sciences, Akita University School of Medicine—To clarify the neuromotor effects of long‐term exposure to mixed organic solvents, postural sway and tremor were measured in 62 solvent workers of four Buddhist altar manufacturing factories who had worked for 1–46 (mean 12) yr. By using the passive gas sampler, 8‐h time‐weighted average concentrations in the workers were estimated to be 0.02–8.7 ppm for toluene, 0.02–7.7 ppm for xylene, 0.02–5.5 ppm for styrene and 0.02–40.5 ppm for n‐hexane. Sagittal sway and sway area of the posturography with eyes closed were significantly larger in the solvent workers than in 35 age‐matched controls (p<0.05), and there was a significant difference in Romberg quotient of sagittal sway between the two groups (p<0.05). Also, tremor intensities at 1.0–5.9 Hz, 6.0–9.9 Hz and 10.0–13.9 Hz with the right hand, and at 6.0–9.9 Hz with the left hand were significantly stronger in the solvent workers than in the controls. Among the solvent workers, transversal and sagittal sways with eyes open and tremor intensity at 10.0–13.9 Hz were significantly related to toluene exposure (p<0.05), which may have been due to the acute effects of such solvents. These findings suggest that long‐term exposure to mixed organic solvents may impair neuromotor functions as measured by postural sway and tremor.