Neonicotinoid insecticides (NEOs) are widely used in agriculture as foliar and seed treatments, for indoor and outdoor insect control, home gardening and pet products. The aim of this study is to develop and validate a simple method for quantitation of urinary NEO metabolites, 6-chloronicotinic acid (6CN), 2-chloro-1,3-thiazole-5-carboxylic acid (2CTCA) and 3-furoic acid (3FA) for biomonitoring of NEO exposure. The sensitivity and reliability of our method were examined in this study. Two mL urine was pipetted into a test tube, and 50 ?L H2SO4 (5 mol/L) and I.S. solution (10 mg/L isotope labeled 3PBA) were added for deconjugation procedure. After incubation at 86 oC for 2 hours, the solution was loaded into preconditioned SPE cartridge (Bond Elut Plexa PCX, Agilent Technologies). After the wash by 500 ?L formic acid solution (2%), the SPE cartridge was dried under vacuum for 3 min and eluted with 500 ?L methanol. The eluate was divided into two equal volumes in test tubes. These eluates were dried up with N2 gass, and the residues were resolved with 250 ?L acetonitrile in one test tube for 6CN and 2CTCA or with 250 ?L toluene in another test tube for 3FA. After derivatization using 40 ?L N,O-bis (trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane, each of 1 ?L sample was separately analyzed by gas chromatography-mass spectrometry. The regression equations ranging from 0.6 to 10 ?g/L were y=0.013x+0.0015 (r2=0.999) for 6CN, y=0.0054x+0.0002 (r2=0.999) for 2CTCA and y=0.0048x+0.0013 (r2=0.997) for 3FA. Our present method is simple, sensitive and reliable for the determination of urinary 6CN, 2CTCA and 3FA, i.e. lower limit of detection (0.1 ?g/L for each metabolites) compared with previous reports with satisfactory intra- and inter-day accuracy and precision (variability less than 12.3 %, R.S.D). This is the first report about determination of 2CTCA and 3FA in urine to the best of our knowledge.
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.
Particle stimulated chemiluminescence (CL) production by human polymorphonuclear leucocytes (PMN) has been utilized to evaluate the pathogenicity of mineral and glass fibers with the understanding that reactive oxygen metabolites (ROM) production as measured by CL is etiopathogenically related to fiber toxicity. In the present study to investigate the specific pathogenic role of fiber number and dimensions, CL production from PMN exposed to anthophyllite asbestos mineral and glass fiber samples milled for different time periods was measured. Almost all the fibrous particles in the glass fiber sample were destroyed after milling for 30 minutes. With anthophyllite, the total number of fibrous particles remained almost constant for up to 240 minutes of milling, although the size of fibrous particles was reduced. CL produced by the same mass of glass fiber was elevated after milling for 15 minutes, but then declined when the milling time was further increased. Similarly, with anthophyllite, the production of CL was elevated at the first period of milling for 30 minutes, but then declined at the longer milling times. The level of CL produced was not correlated to the total number of fibrous particles, for both the glass fiber and the anthophyllite samples. Likewise for the glass fiber and anthophyllite samples, no specific range of fiber dimension was correlated to the peak hight CL production. These findings indicate that neither the total number, nor the specific range of fiber dimension solely determines CL production. As a consequence, it may be concluded that other physiochemical factors, such as the surface reactive characteristics of milled fibers, may be more closely related to CL production by PMN.
This article presents not only a brief overview of birth cohort studies focusing on environmental health in which the associations between health and environment were examined, but also a tentative plan to apply epidemiological data to benchmark dose calculation. According to the preceding studies, the checkpoints to be scrutinized when a result is not consistent with those of other researchers are as follows: (1) whether the study included all crucial confounders, (2) whether it included any exposure marker or confounder with a U-shaped dose-response curve, (3) whether the outcome measure was conducted by two or more examiners that might lead to measurement bias, (4) whether such examiners picked up information about exposure levels of the subjects before measuring the endpoints, and (5) whether subjects with different genetic factors were included in the analysis. In addition, (6) researchers conducting a children's study on developmental effects due to toxic substances must keep in mind that the impact of prenatal methylmercury exposure, independent of postnatal exposure, may continue for at least seven years. (7) When an environmental health research emphasizes to be population-based study, the levels of exposure to environmental chemical substances in developed countries with strict environmental regulations may be too low to examine a dose-response relationship for critical dose estimation. Such risk assessment should be carried out among the subjects with a wide range of exposure levels.
The most severe effects of methylmercury (MeHg) exposure to child development are thought to develop through exposure during fetal life and childhood. However, the comparison of neurodevelopmental effects by prenatal and postnatal MeHg exposure (PreMeHg and PostMeHg, respectively) remains unclear. We aimed to investigate the associations between neurodevelopmental indicators and PreMeHg or PostMeHg. The participants were 134 children in the first grade of elementary schools aged 7–8 years from the Kinan region, an area with high consumption of MeHg-rich whales and tunas in Japan. We measured MeHg levels in preserved umbilical cord tissues and total mercury (T-Hg) levels in children’s hair to estimate PreMeHg and PostMeHg levels, respectively. Neuropsychological (intelligence quotient, Boston Naming Test, and reading tests) and neurophysiological (brainstem auditory evoked potential [BAEP], visual evoked potentials [VEP], and color vision) studies were performed to evaluate neurodevelopmental status. Multiple regression analyses were conducted according to sex. The geometric mean MeHg levels in preserved umbilical cord tissues and T-Hg levels in children’s hair were 0.11 µg/g and 2.94 µg/g, respectively. Neither PreMeHg nor PostMeHg was related to neuropsychological indicators. Positive associations between MeHg exposure and neurophysiological results were observed only in boys. PreMeHg was positively associated with N145 latency in VEP (β: 12.01, 95% confidence interval [CI]: 0.648, 23.38). PreMeHg or PostMeHg was significantly associated with the III–V interpeak intervals in BAEP (β [95% CI] = 0.142 [0.041, 0.243] and 0.159 [0.052, 0.265], respectively). After adjusting for PreMeHg, the significant positive correlation between PostMeHg and BAEP latencies disappeared. In conclusion, auditory and visual circuits might be more affected by PreMeHg than by PostMeHg only in boys. Further studies are needed to investigate the balance in the body between MeHg and selenium or docosahexaenoic acid with protective effects against MeHg toxicity during the fetal period or childhood according to sex.
Urinary pyrethroid (PYR) metabolites such as 3-phenoxybenzoic acid (3PBA) and chrysanthemumdicarboxylic acid (CDCA) have been used as the most sensitive biomarker for PYR exposure. The purpose of this study was to reveal the distribution of urinary PYR metabolite concentrations in Japanese workers. Urine samples were collected in both summer and winter seasons from 260 Japanese adults who worked as food distributors (FD, n=92), apple farmers (AF, n=144) or pest control operators (PCO, n=24). FD is regarded as a representative population exposed to PYRs at environmental background levels. 3PBA and CDCA were measured by gas chromatography-mass spectrometry. Logarithmically transformed PYR metabolites were used for all statistical analyses. High detection frequencies of CDCA and 3PBA were observed in both seasons (more than 92%). The geometric mean values (GSD) of 3PBA in summer and winter were 0.7 (2.3) and 0.5 (2.5) for FD, 0.9 (2.7) and 0.4 (3.1) for AF, and 2.6 (2.9) and 1.8 (3.1) ?g/g creatinine for PCO, respectively. Those of CDCA were 0.33 (3.9) and 0.13 (3.1) for FD, 0.30 (4.1) and 0.21 (3.0) for AF, and 0.56 (3.4) and 0.26 (2.9) ?g/g creatinine for PCO, respectively. Significant seasonal differences (summer > winter) in both metabolites were found in all the groups except for 3PBA in PCO (p<0.05), suggesting that PYR exposure level in summer might be higher than in winter regardless of occupations. Concentrations of 3PBA in PCO were significantly higher than those in other groups in both seasons. On the other hand, differences of urinary CDCA concentrations were not found among the three groups, indicating that there was no occupation-related exposure to PYR, which are metabolized into CDCA, in AF and PCO. Results of our preliminary analysis about the relationship between urinary CDCA and indoor use of its parent compound PYR in FD indicates the possibility that one of PYR exposure sources in general populations may be vapor of PYR insecticides used for mosquito and fly control.
Mercury is a global pollutant that affects the health of both humans and ecosystems. This Special Issue collects three review papers and six research articles that report on the latest findings on the mechanisms of mercury toxicology and its impacts on environmental health. This collection of papers provides useful, new information on the mechanisms of mercury toxicity and methods of improving the risk assessment of mercury exposure.
The benchmark dose (BMD) is defined as the dose that corresponds to a specific change in an adverse response compared to the response in unexposed subjects, and the lower 95% confidence limit is termed the benchmark dose level (BMDL). In this study, the threshold of daily ethanol intake affecting blood pressure was calculated by both the BMD approach and multiple logistic regression analysis to clarify the relation between the BMDL and no‐observed‐adverse‐effect level (NOAEL). Systolic and diastolic blood pressures (SBP and DBP) and daily ethanol intake were explored in 1,100 Japanese salesmen. The SBP and DBP were positively related to daily ethanol intake ( p < 0.001) when adjusting for possible confounders such as age, body mass index, and smoking status. The adjusted risk for hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg) increased significantly when daily ethanol intake exceeded 60 g/day, and the categorical dose of interest was 60.1–90 g/day. The BMDL and BMD of ethanol intake for increased SBP and DBP were estimated to be approximately 60 and 75 g/day, respectively. These findings suggest that the BMDL and BMD correspond to the NOAEL and lowest‐observed‐adverse‐effect level, respectively, if the sample number of clinical data is large enough to confirm the dose‐response association.
