Effects of Environmental Cadmium Exposure on the Liver in Korean Adults: Cross-Sectional and Longitudinal Studies.

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life. The liver is a major organ for Cd metabolism, but the toxicity of Cd is unclear. This study sought to determine whether blood Cd (BCd) level (representing recent exposure [months] to Cd) was associated with liver function in Korean adults, both cross-sectionally and longitudinally. The baseline cross-sectional study involved 2,086 adults (male: 908, female: 1,178) in 2010 - 2011, and 503 of them (male: 207, female: 296) were followed up in 2014 - 2015. BCd was measured by graphite-furnace atomic absorption spectrometry, and liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltransferase [GGT]) were determined. Liver damage was defined as an abnormal elevation of more than one liver function index. The geometric mean of BCd (1.07 µg/L) was higher in females than in males (1.16 vs. 0.96 µg/L). Liver function indices increased significantly in a dose-dependent manner according to the BCd levels, except for ALT in males, and were higher in males than in females. BCd level was also associated with the risk of liver damage in both sexes. No significant changes in BCd were observed between baseline and follow-up. The liver function indices in 2014 - 2015 were comparable to those in 2010 - 2011 in males, while ALT and GGT were significantly increased in 2014 - 2015 compared to 2010 - 2011 in females with relatively high BCd. These findings suggest that even a low level of environmental Cd exposure, short- and long-term, may affect liver function, and females appear more susceptible than males.

Epidemiological Characteristics of COVID-19 Outbreak at Fitness Centers in Cheonan, Korea.

BACKGROUND: In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. METHODS: From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. RESULTS: A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. CONCLUSION: The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

Lead, Mercury, and Cadmium Exposure in the Korean General Population.

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0-83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0-4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.

Exome-wide association study identifies genetic polymorphisms of C12orf51, MYL2, and ALDH2 associated with blood lead levels in the general Korean population.

BACKGROUND: Lead (Pb) is a ubiquitous toxic metal present in the environment that poses adverse health effects to humans. Inter-individual variation in blood Pb levels is affected by various factors, including genetic makeup. However, limited data are available on the association between genetic variation and blood Pb levels. The purpose of this study was to identify the genetic markers associated with blood Pb levels in the Korean population. METHODS: The study subjects consisted of 1,483 healthy adults with no history of occupational exposure to Pb. We measured blood Pb levels and calculated probable daily intake of Pb according to dietary data collected using 24-hour recall. We conducted exome-wide association screening using Illumina Human Exome-12v1.2 platform (n = 500) and a replication analysis using VeraCode Goldengate assay (n = 1,483). RESULTS: Among the 244,770 single nucleotide polymorphisms (SNPs) tested, 12 SNPs associated with blood Pb level were identified, with suggestive significance level (P < 1 × 10-4). In the Goldengate assay for replication, three SNPs (C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671) were associated with statistically suggestively significant differences in blood Pb levels. When stratified by drinking status, a potential association of C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 with blood Pb level was observed only in drinkers. A marginally significant gene-environment interaction between ALDH2 rs671 and alcohol consumption was observed in relation to blood Pb levels. The effects of the three suggestively significant SNPs on blood Pb levels was dependent on daily calcium intake amounts. CONCLUSIONS: This exome-wide association study indicated that C12orf51 rs11066280, MYL2 rs12229654, and ALDH2 rs671 polymorphisms are linked to blood Pb levels in the Korean population. Our results suggest that these three SNPs are involved in the determination of Pb levels in Koreans via the regulation of alcohol drinking behavior, and that their negative effects may be compensated by appropriate calcium intake.

Low-Level Environmental Cadmium Exposure Induces Kidney Tubule Damage in the General Population of Korean Adults.

Cadmium (Cd) is the most potent nephrotoxic heavy metal and may affect bone; it also has a long biological half-life in the human body. This study was designed to assess the effect of environmental low-level Cd exposure on kidney function and bone in the general population. The subjects of this cross-sectional study were 1907 healthy Korean adults who had not been exposed to Cd occupationally. We analyzed the concentrations of Cd in the urine, markers of renal tubule damage, such as ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) activity in the urine, calculated the estimated glomerular filtration rate (eGFR) using serum creatinine, and measured bone mineral density (BMD). Also, we analyzed malondialdehyde (MDA) levels in the urine. The geometric mean concentration of Cd in urine was higher in women (1.36 µg/g creatinine) than in men (0.82 µg/g creatinine). Urinary Cd was significantly positively correlated with urinary ß2-MG and NAG activity, whereas it was negatively correlated with eGFR and BMD. The risk of renal tubule damage was significantly associated with urine Cd level, and the association remained significant after controlling for various confounding variables. However, no association was observed between urinary Cd level and glomerular dysfunction or bone damage. The concentration of MDA was increased with urinary Cd level in a dose-dependent manner. These findings suggest that low-level environmental Cd exposure may cause microscopic damage to renal tubules through oxidative stress but might not impair kidney glomeruli or bones.

Molecular characterization of the spike and ORF3 genes of porcine epidemic diarrhea virus in the Philippines.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. In the present study, we analyzed the spike genes and ORF3 genes of seven PEDV strains detected in Philippine pigs in June 2014. There are four major epitope regions in the spike glycoprotein: a CO-26K equivalent (COE) domain, SS2 and SS6 epitopes, and an epitope region recognized by the 2C10 monoclonal antibody. Analysis of Philippine strains revealed amino acid substitutions in the SS6 epitope region (LQDGQVKI to SQSGQVKI) of the S1 domain. Substitutions were also detected in the 2C10 epitope region (GPRLQPY to GPRFQPY) in the cytoplasmic domain. Phylogenetic analysis of the complete spike gene sequences from the seven strains revealed that they clustered within the G2 group but were distantly related to the North American and INDELs clusters. Interestingly, these strains were close to Vietnamese PEDVs on the ORF3 genetic tree and showed high (97.0-97.6 %) sequence identity to ORF3 genes at the nucleotide level.

A novel strain of porcine epidemic diarrhea virus in Vietnamese pigs.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and dehydration in suckling pigs and has caused high rates of death among piglets and substantial economic loss in Vietnam since 2009. To investigate the genotypes of prevailing PEDVs, intestinal and fecal samples from piglets from central and northern Vietnam were collected and analyzed. Phylogenetic analysis of the nucleotide sequences of complete spike genes of PEDVs from Vietnam resulted in the identification of two divergent groups. PEDVs (HUA-PED45 and HUA-PED47) belonged to the G2b group, along with Chinese, US, and Korean strains occurring at the end of 2010, in May 2013 and in November 2013, respectively. Six strains from the Quang Tri region were assigned to the G1b group, along with Chinese and US strains. The Vietnamese PEDVs detected in infected piglets had a nationwide distribution and belonged to the G2b and G1b genotypes.

Reference levels of blood mercury and association with metabolic syndrome in Korean adults.

PURPOSE: Mercury (Hg) is a nonessential and toxic metal that is widely distributed in the environment. This study was performed to estimate the representative blood Hg level, to determine the contributing factors to Hg exposure, and to analyze the association of blood Hg with metabolic syndrome in Korean adults. METHODS: Mercury exposure is assessed by total Hg concentration in blood. A total of 2,114 healthy adults who have not been exposed to Hg occupationally were sampled by the multistaged, sex-, and age-stratified probability method. Information was collected regarding the subjects' demographic characteristics, lifestyles, and past medical history. The participants then underwent physical examination and blood sampling. RESULTS: The geometric mean concentration of Hg in whole blood was 3.90 µg/L, which was significantly influenced by sex, age, smoking, alcoholic consumption, residence area, and seafood intake after adjustment for confounders. Significant increases in body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyceride were observed according to the blood Hg levels after adjustment for covariates. Also, Hg exposure was significantly associated with metabolic syndrome and their components such as obesity and increased fasting glucose. CONCLUSION: The blood Hg level in Korean adults is higher than that in USA and other Western countries, while it is similar to or lower than that in other Asian countries. The blood Hg level is influenced by sociodemographic factors and individual lifestyles including dietary habits. Furthermore, blood Hg is associated with metabolic syndrome, in which Hg exposure may play a role as a possible risk factor for cardiovascular diseases.

Association between urinary arsenic concentration and genetic polymorphisms in Korean adults.

Arsenic (As) is a human carcinogen widely distributed in the environment. This study evaluated the association between the urinary As concentration and single nucleotide polymorphisms (SNPs) in Korean adults to determine the genetic factors related to As concentration. The study included 496 participants for the genome-wide association study (GWAS) and 1483 participants for the candidate gene approach study. Participants were 19 years and older. The concentrations of total As (Tot As) and total As metabolites (Tmet As, the sum of inorganic As and their metabolites; arsenite, arsenate, monomethylarsonic, and dimethylarsinic acid) in the urine were analyzed. The GWAS identified four SNPs (rs1432523, rs3776006, rs11171747, and rs807573) associated with urinary Tot As and four SNPs (rs117605537, rs3776006, rs11171747, and rs148103384) significantly associated with urinary Tmet As concentration (P < 1 × 10-4). The candidate gene study identified two SNPs (PRDX2 rs10427027 and GLRX rs3822751) in genes related to the reduction reaction associated with urinary Tot As and Tmet As. This study suggests that genetic factors may play a role in regulating As metabolism in the human body, affecting both exposure levels and its potential health risks in the general Korean population, even at low exposure levels. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00216-x.

Complete genome analysis of three live attenuated Rinderpest virus vaccine strains derived through serial passages in different culture systems.

The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77, and LA96) were analyzed in order to investigate their genetic variability. These three vaccine strains were all derived from the same virus strain origin (Fusan) through repeated passages in different culture systems. The full genome length of the three strains was 15,882 nucleotides, and the sequence similarity between the three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete strain was greater than that between the Fusan and Kabete strains for the P, V, and C genes. The difference in pathogenicity among these strains might be due to the V gene, which has a positive (>1) selection ratio based on the analysis of synonymous (dS) and nonsynonymous (dN) substitution rates (dN/dS ratio [ω]).

Phylogenetic analysis of porcine astrovirus in domestic pigs and wild boars in South Korea.

Porcine astrovirus (PAstV) belongs to genetically divergent lineages within the genus Mamastrovirus. In this study, 25/129 (19.4 %) domestic pig and 1/146 (0.7 %) wild boar fecal samples tested in South Korea were positive for PAstV. Positive samples were mainly from pigs under 6 weeks old. Bayesian inference (BI) tree analysis for RNA-dependent RNA polymerase (RdRp) and capsid (ORF2) gene sequences, including Mamastrovirus and Avastrovirus, revealed a relatively geographically divergent lineage. The PAstVs of Hungary and America belong to lineage PAstV 4; those of Japan belong to PAstV 1; and those of Canada belong to PAstV 1, 2, 3, and 5, but not to 4. This study revealed that the PAstVs of Korea belong predominantly to lineage PAstV 4 and secondarily to PAstV 2. It was also observed that PAstV infections are widespread in South Korea regardless of the disease state in domestic pigs and in wild boars as well.

Kobuvirus in South Korean black goats.

Kobuviruses have been detected in humans and several animal species, including cattle, swine, sheep, canines, mice, and probably bats. While investigating the possibility of Kobuviruses infecting additional animal host species, we detected kobuvirus in three fecal samples from domestic Korean black goats. In a maximum parsimony tree and a Bayesian tree, the 08KG680 strain fell within the bovine kobuvirus lineage, but the 09KG172 and 10KG056 strains did not fall within any of the known animal kobuvirus lineages. Comparative analysis of the partial nucleotide sequences of the RNA-dependent RNA polymerase (RdRp) gene of the 08KG680 strain also revealed high amino acid sequence identity and a close genetic relationship with bovine kobuvirus, but the amino acid sequences of the other two strains had low similarity to those of known kobuvirus isolates from any animal species. The similarity of the sequence of the 08KG680 strains with the bovine kobuvirus indicate that the infectious may have originated from cattle, but the possible source for remaining strains could not be classified.

Three clusters of bovine kobuvirus isolated in Korea, 2008-2010.

Fecal samples (n = 107) were collected from cattle with ascertained or suspected diarrheal disease on Korean farms during 2008-2010. Of these, 37 samples tested positive for bovine kobuvirus. The 37 positive samples came from 32 cattle that exhibited diarrhea and five cattle that were non-diarrhetic. The majority of the virus-positive feces samples were from calves under 1 month of age (n = 25). Nine of the 37 cattle infected with bovine kobuvirus were confirmed to have a co-infection with other viruses including bovine rotavirus (n = 3), bovine coronavirus (n = 1), bovine viral diarrhea virus (n = 1), and both bovine coronavirus and bovine viral diarrhea virus (n = 4). A neighbor-joining tree grouped 36 of the Korean kobuvirus strains (with the exception of the KB8 strain) into three clusters (G1, G3, and G4), while strains derived from Thailand and Japan (except the U1 strain) were included in the G2 cluster. The results indicated that Korean bovine kobuvirus has diverse lineages regardless of disease status and species.

Environmental Health Studies in the Korean National Industrial Complexes (EHSNIC): Focus-Group Interviews.

This study investigated the social outcomes of the Environmental Health Studies of National Industrial Complex (EHSNIC), which have been conducted by the National Institute of Environmental Research (NIER) in eight National Industrial Complex Areas (NICAs) since 2003. Eighteen sessions of focus-group interviews with 85 people were conducted from October 2016 to January 2017. Interviewees were stakeholders from eight NICAs and included resident representatives, environmental nongovernment organizations, local government officials, and environmental health and safety officers from companies. Interview results were divided into six categories: EHSNIC awareness, EHSNIC outcomes, EHSNIC limitations, EHSNIC continuation, EHSNIC improvement directions, and EHSNIC results use. They were then further indexed into 23 divisions. EHSNIC awareness varied across stakeholders. A major EHSNIC outcome is that a continued result database was established, which was used as a reference for environmental improvements. EHSNIC limitations included no proper healthcare actions taken during the EHSNIC study period, a lack of EHSNIC results disclosure, a failure to reflect local specificity, and a lack of validity in the results. Regarding EHSNIC continuation, all stakeholders said EHSNIC should be conducted continuously. EHSNIC improvement directions included conducting studies tailored to each NICA, identifying correlations between pollutant exposure and disease, increasing the sample size, and performing repeated studies. Regarding EHSNIC results use, respondents wanted to use the results as a reference to relocate residents, ensure distance between NICAs and residential areas, provide healthcare support, develop local government policies, and implement firms' environmental controls. Since EHSNIC aims to identify the health effects of NICAs on residents and take appropriate actions, it should be continued in the future. Even during the study period, it is important to take steps to preventively protect residents' health. EHSNIC also needs to reflect each NICA's characteristics and conduct reliable research based on stakeholder participation and communication.

How Does Low Socioeconomic Status Increase Blood Lead Levelsin KoreanChildren?

Although studies have shown that a low socioeconomic status (SES) is associated with high blood lead levels (BLLs) in children, the mechanism underlying this observation is not well known. To determine how SES influences BLLs via environmental factors in Korean children, we conducted a population-based cross-sectional study of 4744 children aged 5⁻13 years. Questionnaires on sociodemographic information, environmental factors, and food consumption were administered to the children's parents. BLLs in the study subjects were measured.The complete set of hypothesized associations was assessed using regression analysis and structural equation modeling. SES was associated with high BLLs. The total effects of nutritional factors, lead in the air and total length of nearby roads, and agriculture on BLLs were -0.062 (p < 0.001), 0.068 (p = 0.005), and 0.038 (p = 0.035), respectively. The direct effects of playing outdoors and SES on BLLs were 0.113 (p < 0.001) and -0.111 (p < 0.001), respectively. Although playing outdoors had a greater direct effect on BLLs than did SES, the total effect of SES (standardized ß = -0.132, p < 0.001) was greater than that of other sources owing to indirect effects (ß = -0.020, p = 0.004). A low SES was a major risk factor for elevated BLLs via environmental factors.

Health effects of environmental pollution in population living near industrial complex areas in Korea.

Several epidemiological studies have reported an association between environmental pollution and various health conditions in individuals residing in industrial complexes. To evaluate the effects of pollution from industrial complex on human health, we performed a pooled analysis of environmental epidemiologic monitoring data for residents living near national industrial complexes in Korea. The respiratory and allergic symptoms and the prevalence of acute and chronic diseases, including cancer, were used as the outcome variables for health effects. Multiple logistic regression analysis was used to analyze the relationship between exposure to pollution from industrial complexes and health conditions. After adjusting for age, sex, smoking status, occupational exposure, level of education, and body mass index, the residents near the industrial complexes were found to have more respiratory symptoms, such as cough (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06 to 1.31) and sputum production (OR, 1.13; 95% CI, 1.03 to 1.24), and symptoms of atopic dermatitis (OR, 1.10; 95% CI, 1.01 to 1.20). Among residents of the industrial complexes, the prevalence of acute eye disorders was approximately 40% higher (OR, 1.39; 95% CI, 1.04 to 1.84) and the prevalence of lung and uterine cancer was 3.45 times and 1.88 times higher, respectively, than those among residents of the control area. This study showed that residents living in the vicinity of industrial complexes have a high risk of acute and chronic diseases including respiratory and allergic conditions. These results can be used as basic objective data for developing health management measures for individuals residing near industrial complexes.

Effect of dietary patterns on the blood/urine concentration of the selected toxic metals (Cd, Hg, Pb) in Korean children.

This study was aimed to examine the association the blood/urinary concentration of toxic metal (Hg, Pb, and Cd) with children's dietary patterns. This cross-sectional study included 1026 school children aged 8-17 years. Dietary patterns were defined using factor loading scores for 108 foods from a Semi-Quantitative Food Frequency Questionnaire. A high blood Hg level was found in boys with a high score in the 'fish' pattern (p = 0.02), and in girls with a high score in 'fruit' pattern (p = 0.04). The concentration of Pb was related to the 'imprudent' pattern in high school boys (p = 0.02). The effect of the 'vegetable' pattern on high excretion of urinary Cd was observed in low grade elementary (p = 0.04) and middle school students (p < 0.0001), and the effect of the 'fruit' pattern on the urinary Cd was observed in high grade elementary school students (p = 0.02). This study suggests that the concentration of selected toxic metals in blood/urine could be affected by children's dietary pattern.

Mercury Exposure in Association With Decrease of Liver Function in Adults: A Longitudinal Study.

OBJECTIVES: Although mercury (Hg) exposure is known to be neurotoxic in humans, its effects on liver function have been less often reported. The aim of this study was to investigate whether total Hg exposure in Korean adults was associated with elevated serum levels of the liver enzymes aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT). METHODS: We repeatedly examined the levels of total Hg and liver enzymes in the blood of 508 adults during 2010-2011 and 2014-2015. Cross-sectional associations between levels of blood Hg and liver enzymes were analyzed using a generalized linear model, and nonlinear relationships were analyzed using a generalized additive mixed model. Generalized estimating equations were applied to examine longitudinal associations, considering the correlations of individuals measured repeatedly. RESULTS: GGT increased by 11.0% (95% confidence interval [CI], 4.5 to 18.0%) in women and 8.1% (95% CI, -0.5 to 17.4%) in men per doubling of Hg levels, but AST and ALT were not significantly associated with Hg in either men or women. In women who drank more than 2 or 3 times per week, AST, ALT, and GGT levels increased by 10.6% (95% CI, 4.2 to 17.5%), 7.7% (95% CI, 1.1 to 14.7%), and 37.5% (95% CI,15.2 to 64.3%) per doubling of Hg levels, respectively, showing an interaction between blood Hg levels and drinking. CONCLUSIONS: Hg exposure was associated with an elevated serum concentration of GGT. Especially in women who were frequent drinkers, AST, ALT, and GGT showed a significant increase, with a significant synergistic effect of Hg and alcohol consumption.

Antigenic characterization of classical swine fever virus YC11WB isolates from wild boar.

Classical swine fever (CSF), a highly contagious disease that affects domestic pigs and wild boar, has serious economic implications. The present study examined the virulence and transmission of CSF virus strain YC11WB (isolated from a wild boar in 2011) in breeding wild boar. Virulence of strain YC11WB in domestic pigs was also examined. Based on the severe clinical signs and high mortality observed among breeding wild boar, the pathogenicity of strain YC11WB resembled that of typical acute CSF. Surprisingly, in contrast to strain SW03 (isolated from breeding pigs in 2003), strain YC11WB showed both acute and strong virulence in breeding pigs. None of three specific monoclonal antibodies (7F2, 7F83, and 6F65) raised against the B/C domain of the SW03 E2 protein bound to the B/C domain of strain YC11WB due to amino acid mutations (720K→R and 723N→S) in the YC11WB E2 protein. Although strains YC11WB and SW03 belong to subgroup 2.1b, they had different mortality rates in breeding pigs. Thus, if breeding pigs have not developed protective immunity against CSF virus, they may be susceptible to strain YC11WB transmitted by wild boar, resulting in severe economic losses for the pig industry.

Blood lead, parental marital status and the risk of attention-deficit/hyperactivity disorder in elementary school children: A longitudinal study.

The aim of this study was to investigate the blood lead level and parental marital status that might influence the development of attention-deficit/hyperactivity disorder (ADHD) symptoms in school-aged children. The participants in the survey included elementary school children, and they were followed up biennially. The participants' parents or caregivers were administered a questionnaire including ADHD rating scale. Among 2967 who were not suspected to have ADHD at baseline survey, 2195 children who took follow-up test for ADHD were evaluated. The incidence rate of suspected ADHD was 5.0% (107 cases) during the two years of the follow-up period. The geometric mean blood lead level was 1.56µg/dL. Relative risk ratio for ADHD was estimated using logistic regression analysis. After adjustment for potential confounders, ADHD developed more frequently in children with blood lead levels of >2.17µg/dL (highest quartile) (RR 1.552, 95% CI 1.002-2.403) and in children with a single parent (RR 1.805, 95% CI 1.002-3.254). The RR was 3.567 (95% CI 1.595-7.980) in children with relatively high blood lead levels (>2.17µg/dL) from single-parent families, compared with those with low blood lead and a two-parent family. The ADHD risk in association with blood lead level was modified by family status.