Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study.

This study aimed to reveal a new dimension of allergy profiles in the general population by using machine learning to explore complex relationships among various cytokines/chemokines and allergic diseases (asthma and atopic dermatitis; AD). We examined the symptoms related to asthma and AD and the plasma levels of 72 cytokines/chemokines obtained from a general population of 161 children at 6 years of age who participated in a pilot birth cohort study of the Japan Environment and Children's Study (JECS). The children whose signs and symptoms fulfilled the criteria of AD, which are mostly based on questionnaire including past symptoms, tended to have higher levels of the two chemokine ligands, CCL17 and CCL27, which are used for diagnosis of AD. On the other hand, another AD-related chemokine CCL22 level in plasma was higher only in children with visible flexural eczema, which is one of AD diagnostic criteria but was judged on the same day of blood examination unlike other criteria. Here, we also developed an innovative method of machine learning for elucidating the complex cytokine/chemokine milieu related to symptoms of allergic diseases by using clustering analysis based on the random forest dissimilarity measure that relies on artificial intelligence (AI) technique. To our surprise, the majority of children showing at least any asthma-related symptoms during the last month were divided by AI into the two clusters, either cluster-2 having elevated levels of IL-33 (related to eosinophil activation) or cluster-3 having elevated levels of CXCL7/NAP2 (related to neutrophil activation), among the total three clusters. Future studies will clarify better approach for allergic diseases by endotype classification.

Augmentation of cadmium-induced oxidative cytotoxicity by pioglitazone in renal tubular epithelial cells.

The aim of this study was to examine whether a peroxisome proliferator-activated receptor (PPAR)-γ agonist could affect cadmium (Cd)-induced cytotoxicity via the increased expression of megalin, one of the uptake pathways, using renal epithelial LLC-PK1 cells. The treatment with 1 µM Cd for 24 h was not cytotoxic; however, when the cells were pretreated with 0.1 µM pioglitazone for 12 h and then exposed to 1 µM Cd for 24 h, significant accumulation of Cd and cytotoxicity were detected, with an increase in megalin mRNA expression. In addition, pretreatment with pioglitazone significantly increased the Cd-induced generation of hydrogen peroxide and cell apoptosis. The augmented Cd-induced cytotoxicity and apoptosis on preincubation with pioglitazone were inhibited by prior treatment with GW 9662 (PPAR-γ antagonist). These findings suggest that a PPAR-γ agonist could augment Cd-induced oxidative injury and cell apoptosis, possibly dependent on the expression level of the uptake pathway.

Oral exposure to lead for Japanese children and pregnant women, estimated using duplicate food portions and house dust analyses.

BACKGROUND: Lead is a toxic metal abundant in the environment. Consumption of food contaminated at low levels of lead, especially by small children and pregnant women, raises a health concern. METHODS: Duplicated food portions and drinking water were collected over 3 days from 88 children and 87 pregnant women in Shimotsuke, Tochigi, Japan. Participants were recruited in this study between January 2014 and October 2015. Dust was also collected from their homes. Lead concentrations were measured and consequent oral lead exposure levels were estimated for this population at high risk to environmental toxicants. Lead concentrations of peripheral and cord blood, taken from children and pregnant women, and were also analyzed. RESULTS: Lead concentrations in food, drinking water, and house dust were low in general. Oral lead exposure to lead was higher for children (Mean ± SEM; 5.21 ± 0.30 µg/kg BW/week) than in pregnant women (1.47 ± 0.13 µg/kg BW/week). Food and house dust were main sources of lead contamination, but the contribution of house dust widely varied. Means ± SEM of peripheral and cord blood lead concentrations were 0.69 ± 0.04 µg/dL and 0.54 ± 0.05 µg/dL, respectively for pregnant women and 1.30 ± 0.07 µg/dL (peripheral only) in children. We detect no correlation between smoking situations and blood lead concentration in pregnant women. CONCLUSION: We conclude that oral lead exposure levels for Japanese children and pregnant women were generally low, with higher concentrations and exposure for children than for pregnant women. More efforts are necessary to clarify the sources of lead contamination and reduce lead exposure of the population at high risk even in Japan.

Regional differences in infant 25-Hydroxyvitamin D: Pilot study of the Japan Environment and Children's Study.

BACKGROUND: In recent years, a resurgence in the number of infants with vitamin D deficiency has been noted. In addition to seasonal differences in exposure to ultraviolet (UV) rays, regional differences in dietary habits and lifestyles may affect susceptibility to vitamin D deficiency. No studies have been conducted, however, on infants in multiple regions of Japan to determine the extent of differences in vitamin D status. METHODS: 25-Hydroxyvitamin D (25OHD) was measured on radioimmunoassay in 126 infants aged 2-4 years, who participated in the Pilot Study of the Japan Environment and Children's Study (JECS) by the Ministry of Environment of Japan. A multiple regression model with 25OHD level as the outcome variable, and season and region as explanatory variables, was generated. RESULTS: Both region and season during which infants participated in this study significantly affected 25OHD level (P = 0.0087 and <0.0001, respectively; Wald test). Reflecting decreased exposure to UV rays, infants who were examined in winter had lower 25OHD than those examined in summer. Infants from both Fukuoka Prefecture (33°N) and Kumamoto Prefecture (32°N), however, had lower 25OHD than those from Tochigi Prefecture (36°N), contrary to expectations given the extent of UV exposure. CONCLUSIONS: Regional differences in daily habits and/or environmental factors affect 25OHD level in Japanese infants. The JECS is expected to identify those factors to provide guidance on preventing infantile vitamin D deficiency.

Relieving pain and distress during venipuncture: Pilot study of the Japan Environment and Children's Study (JECS).

Pain management for needle-related procedures is poor in Japan. In many countries the use of lidocaine/prilocaine cream for the relief of pain associated with venipuncture has been approved. In children, a psychological approach has also been shown to be effective in reducing pain with venipuncture. We developed a multidisciplinary procedure that combines a cream (2.5% lidocaine and 2.5% prilocaine) and pharmacological approaches such as preparation, education, positioning and distraction. We evaluated the feasibility and acceptability of the procedure for young children. Among 132 pediatric participants, 58.3% did not cry during venipuncture. According to caregiver questionnaire, 71.9% felt that the multidisciplinary procedure eliminated the fear of needle-related procedures in the children; 90.9% were satisfied with it and 75.8% thought it should be applied to all children undergoing venipuncture. The present results suggest that the multidisciplinary procedure is feasible, acceptable and suitable for use in children undergoing venipuncture.

Biomonitoring of mercury, cadmium, and lead exposure in Japanese children: a cross-sectional study.

OBJECTIVES: To measure current Hg, Cd, and Pb exposure in Japanese children, and to estimate dietary intakes of foods responsible for high body burden. METHODS: Blood, hair, and urine samples were collected from 9 to 10-year-old 229 children in Asahikawa and measured for Hg, Cd, and Pb in these matrices. Diet history questionnaire was used to estimate intake of marine foods and other food items. Hg level was measured by cold vapor atomic absorption spectrometry. Cd and Pb levels were determined with inductively coupled plasma mass spectrometry. RESULTS: Geometric mean (GM) of blood Hg, Cd, and Pb was 4.55 µg/L, 0.34 µg/L, and 0.96 µg/dL, respectively. Urinary Cd level was 0.34 µg/g creatinine (GM) and hair Hg was 1.31 µg/g (GM). Approximately one-third (35%) of blood samples had Hg level above the U.S. EPA reference dose (RfD; 5.8 µg/L). Hair Hg level exceeded U.S. EPA RfD (1.2 µg/g) in 59 % samples. Children in the upper quartile of blood Hg level had significantly higher intake of large predatory fish species compared to those in the lower quartile of blood Hg. CONCLUSIONS: Those with high blood Hg level may be explained by more frequent intake of big predatory fish. Cd and Pb exposure is generally low among Japanese children. As no safety margin exists for Pb exposure and high exposure to MeHg is noted in Japanese population; periodic biomonitoring and potential health risk assessment should continue in high-risk populations, notably among children.

Suppression of erythropoietin induction by diethylstilbestrol in rats.

Diethylstilbestrol is an estrogenic endocrine disrupter that has diverse health effects in humans. Bisphenol A is another estrogen-like chemical with possible similar effects to diethylstilbestrol, which has been increasingly used for industry to lead to globally widespread human exposure to it. Hematopoiesis is another of their possible targets, since estrogen suppresses erythropoietin induction to induce anemia. The aim of this study was to clarify the effects of diethylstilbestrol and bisphenol A on erythropoietin induction in rats. We observed the effects of one-shot subcutaneous injection of diethylstilbestrol or bisphenol A on hypoxia-, bleeding-, and cobalt-stimulated erythropoietin induction within 24 h and the hematological outcomes after repeated subcutaneous injection of diethylstilbestrol three times a week for 1 month in rats. Diethylstilbestrol at 10-1,000 µg/kg suppressed stimulus-elevated levels of plasma erythropoietin and its renal mRNA induction. In contrast, bisphenol A at 1,000 µg/kg did not suppress plasma erythropoietin elevated by any stimuli. Repeated injection of diethylstilbestrol at 1,000 µg/kg to rats for 1 month induced an anemic trend due to decelerated erythropoiesis through the insufficient production of erythropoietin, mimicking the effects of estradiol. In conclusion, diethylstilbestrol has a suppressive effect on erythropoietin induction, leading to deceleration of erythropoiesis and the development of anemia.

Rationale and study design of the Japan environment and children's study (JECS).

BACKGROUND: There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children's Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children's health and development. METHODS/DESIGN: Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS' priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. DISCUSSION: Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.

Microplastics in the Asia-Pacific Region in the Plasticene Era: Exposures and Health Risks.

Within the broader Anthropocene Epoch resides the Plasticene Era, where humans are subjected pervasively to nano- and microplastics (NMPs). Human's widespread exposure with NMPs occurs through the air we breathe, water we drink, and food we eat. NMP sources are wide and varied; atmospheric NMPs are largely attributed to fibres from car tyres and synthetic clothing, while particles from food packaging, personal care products, and plastic manufacturing contribute significantly to food and water contamination. NMPs have become inherent within the human body and have been found in every organ. As such, the evidence base around adverse health effects is fragmented but growing. This article presents a mini-review and report of sessions presented about NMPs at the 19th International Conference of the Pacific Basin Consortium for Environment and Health, held on Jeju Island, in 2022. Abundant evidence of substantial exposure to NMPs in the Asia-Pacific region has been exhibited. Addressing this issue necessitates the collaboration of policymakers, manufacturers, and researchers to develop safer alternatives and implement mitigation and remediation strategies. The ongoing development of a new United Nations-led global plastic treaty presents a crucial opportunity that must be acted on and not be compromised.

Burden of skin lesions of arsenicosis at higher exposure through groundwater of taluka Gambat district Khairpur, Pakistan: a cross-sectional survey.

Prior surveys conducted have found higher proportion of arsenic-contaminated wells in villages along river Indus in Pakistan. This study aims to determine the prevalence of arsenicosis skin lesions among population exposed to higher exposure in taluka Gambat district Khairpur in Sindh. The cross-sectional survey was conducted from August 2008 to January 2009 among 610 households. A total of 707 water sources (hand pumps/wells) were tested from the villages of union councils of Agra and Jado Wahan for arsenic levels with Quick rapid arsenic field test kits. A total of 110 households exposed to arsenic levels >50 ppb were identified. Case screening for arsenic skin lesions was performed for 610 individuals residing in these 110 high-risk households. Information regarding household and socio-demographic characteristics, height and weight measurements and arsenic exposure assessment were collected. Physical examinations by trained physicians were carried out to diagnose the arsenic skin lesions. After data cleaning, 534 individuals from all age groups were included in the final analysis which had complete exposure and outcome information. Overall prevalence of arsenicosis skin lesions was 13.5 % (72 cases). Of the 534 individuals, 490 (91.8 %) were exposed to arsenic levels of ≥100 ppb in drinking water (8.2 % to >50-99 ppb, 58.6 % to 100-299 ppb, 14.6 % to 300-399 ppb and 18 % to ≥400 ppb). Prevalence rate (per 100 population) of arsenicosis was highest at arsenic levels of 100-199 ppb (15.2 cases) followed by ≥400 ppb (13.5 cases) and 300-399 (12.8 cases). Prevalence rate was higher among females (15.2) compared to males (11.3). Our study reports arsenicosis burden due to exposure to higher arsenic levels in drinking water in Pakistan. Exposure to very high levels of arsenic in drinking water calls for urgent action along river Indus. Prevalence of skin lesions increases with increasing arsenic levels in drinking groundwater. Provision of arsenic-free drinking water is essential to avoid current and future burden of arsenicosis in Pakistan.

[Allergy and immunotoxicology in preventive and clinical medicine from theory to practice: Occupational allergy and isocyanate-induced asthma].

Genetic and environmental factors and their interactions cause diseases and deteriorate health (Genetic and Environmental Interaction). Exposure to environmental factors plays a major role in the deterioration of health in the workplace.Occupational asthma (OA) is a common disorder in the workplace. Approaches to OA are well described and discussed in "Japanese Guideline for Diagnosis and Management of Occupational Allergic Diseases" by the Japanese Society of Occupational and Environmental Allergy. According to the guideline, OA and work-aggravated asthma comprise work-related asthma, and OA can be further divided into two disease entities: sensitizer-induced OA and irritant-induced OA. The guidelines also describe diagnostic and therapeutic strategies for OA. Since a definitive diagnosis of OA requires a comprehensive decision based on a detailed interview on clinical symptoms related to employment status and clinical tests, including inhalation tests of suspected substances as needed, the possibility of OA should be considered as the first step toward diagnosis of the patient. Otherwise, OA may not be diagnosed. Therapeutic strategies include exposure avoidance, environmental arrangements in the workplace, utilization of social resources for workers, and conventional pharmacotherapy for asthma.Artificially synthesized small compounds are used in various industries and can cause allergies. For example, isocyanates are small compounds in the -NCO group, which have been toxicologically studied. It was later shown that isocyanate could cause various nontoxic adverse health effects, including allergic reactions. Since small agents with low molecular weights bind to proteins, detecting their specific immunoglobulin E (IgE) antibodies targeting small compounds is generally difficult. In contrast, isocyanate-specific IgE antibodies are detectable in individuals with isocyanate allergies.Suspecting OA is essential in cases exposed to newly synthesized compounds, or to those that are already known but applied to new uses, which can be better understood and predicted by studying the health effects of isocyanates.Academic interest in various issues related to allergies, immunology, and toxicology in the workplace includes clinical medicine, epidemiology, and epigenetics related to environmental exposure. Further advanced research in these areas is necessary and promising.

Lung function decrement with arsenic exposure to drinking groundwater along River Indus: a comparative cross-sectional study.

This study was designed to determine the association between chronic arsenic exposure through drinking groundwater and decrement in lung function, particularly among individuals who do not have signs of arsenic lesions, among an adult population. This was a comparative cross-sectional study conducted during the months of January to March 2009. One hundred participants ≥15 years of age in each group, i.e. exposed (≥100 µg/l) and unexposed (≤10 µg/l) to arsenic, determined by testing drinking water samples (using portable kits), were compared for effects on lung function using spirometry. A structured and validated questionnaire was administered. Examination for arsenic skin lesions was also done. There was a decline in the mean adjusted FEV1 of 154.3 ml (95% CI: -324.7, 16.0; p = 0.076), in mean adjusted FVC of 221.9 ml (95% CI: -419.5, -24.3; p = 0.028), and in FEV1/FVC ratio of 2.0 (95% CI: -25.3, 29.4; p = 0.884) among participants who were exposed to arsenic compared to those unexposed. A separate model comprising a total of 160 participants, 60 exposed to arsenic concentrations ≥250 µg/l and 100 unexposed at arsenic concentrations of ≤10 µg/l, showed a decrement in mean adjusted FEV1 of 226.4 ml (95% CI: -430.4, -22.4; p = 0.030), in mean adjusted FVC of 354.8 ml (95% CI: -583.6, -126.0; p = 0.003), and in FEV1/FVC ratio of 9.9 (95% CI: -21.8, 41.6; p = 0.539) among participants who were exposed to arsenic in drinking groundwater. This study demonstrated that decrement in lung function is associated with chronic exposure to arsenic in drinking groundwater, occurring independently, and even before any manifestation, of arsenic skin lesions or respiratory symptoms. The study also demonstrated a dose-response effect of arsenic exposure and lung function decrement.

Lead In Food And Its Correlation With Blood Lead Levels Among Pregnant Women Of Sindh, Pakistan.

BACKGROUND: With increasing control of lead (Pb) in gasoline, food has emerged as an important secondary pathway for Pb exposure globally. This study assessed Pb levels in food duplicates and blood. Furthermore, it assessed the correlation of Pb in food duplicates and blood Pb levels with common food items taken by pregnant women of Sindh, Pakistan. METHODS: A cross-sectional study was conducted from August 2014 to November 2015, in urban (Karachi) and rural (Gambat, Khairpur) area of Sindh-Pakistan. A total of 103 venous blood samples (Karachi = 63 and Gambat = 40) of pregnant women were measured for blood Pb levels at the time of delivery. One month post-delivery, food frequency questionnaire (FFQ) was administered and three-day food duplicates (same number of cooked portions of food eaten by women) were collected. Food duplicates were analysed for Pb levels. Multivariable linear regression was conducted to identify the frequency of food items which contribute to blood and food Pb levels of pregnant women, separately. RESULTS: With 90% confidence interval, chapati (local flat bread) (ß=0.20, p<0.001), boiled rice (ß=0.35, p<0.001), cooked root vegetables (ß= 0.16, p=0.03), fried savory items (ß=0.15, p=0.03), sweet snacks (ß=0.13, p=0.08) were positively associated with elevated mother blood Pb levels. While cream biscuits (ß =-0.14, p=0.04), lassi (blend of yogurt, water and spices) (ß= -0.31, p<0.01), market milk desserts (ß=-0.22, p<0.001), fish (ß= -0.16, p=0.02), soft drinks (ß= -0.19, p=0.01) and supari/gutka (betel-nut) (ß=-0.13, p= 0.06) were negatively associated with mother Pb levels. Tetra-pak market juices (ß= 0.30, p<0.001) and cooked root vegetables (ß=0.19, p=0.05) were positively associated with mother food Pb levels, at 90% CI. CONCLUSIONS: Bread, boiled rice, fried savoury items, sweet snacks and cooked root vegetables were contributing to blood Pb levels of pregnant women in Pakistan. These food items may be contaminated with Pb during processing, packaging and storage. Inverse relation of Supari/gutka and soft drinks with blood Pb levels may be due its overall reduction in absorption capacity of the gut for nutrients. Objective individual food item analysis for Pb is warranted for further intervention.

Latest status of cadmium accumulation and its effects on kidneys, bone, and erythropoiesis in inhabitants of the formerly cadmium-polluted Jinzu River Basin in Toyama, Japan, after restoration of rice paddies.

PURPOSE: The cadmium-polluted Jinzu River Basin in Toyama, Japan, where nephropathy and itai-itai disease were endemic among resident farmers decades ago, has been almost completely restored. The aim of this study is to investigate whether inhabitants there would still exhibit cadmium accumulation and its effects on kidneys, bones, and erythropoiesis. METHODS: We performed a cross-sectional study of 150 subjects from the polluted area and 144 controls from the same prefecture. Participants included female inhabitants from 34 to 74 years of age who underwent examinations to gather anthropometrical and medical information, obtain rice, blood and urine samples, and measure bone mineral density. RESULTS: Cadmium concentration in rice from the polluted area was lower than the level in the control area. Blood and urinary cadmium and urinary ß(2)-microglobulin levels were higher in subjects from the polluted area than controls, and the urinary ß(2)-microglobulin was independently affected by urinary cadmium. Bone mineral density did not differ between the two areas, but it was affected by renal tubular function in subjects from the polluted area. Serum bone alkaline phosphatase was lower in subjects from the polluted area compared to controls. We detected three cases of cadmium nephropathy among the subjects. One of them suffered from a renal anemia type of itai-itai disease. CONCLUSION: Inhabitants in the formerly polluted area still had high cadmium accumulations and showed a characteristic natural history of chronic cadmium toxicity, indicating that the risk remains for developing nephropathy or itai-itai disease in the future.

A longitudinal study of trends in blood dioxins and dioxin-like compounds levels in residents from two locations in Japan during 2002-2006.

To investigate the recent changes in background exposure to dioxin-related compounds, the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dl-PCBs) in the blood of individual residents in Japan were repeatedly examined. Twenty-six subjects (mean age, 52.7 +/- 1.8) from District A and 23 subjects (mean age, 56.1 +/- 1.2) from District B were longitudinally analyzed from 2002 to 2006. District A is a rural area in Osaka prefecture, and District B is an urban area in Saitama prefecture. For the longitudinal analysis of these concentrations, we used the generalized estimating equation (GEE). The PCDD + PCDF concentrations decreased significantly between 2002 and 2006 (p < 0.0001), but the concentrations of dl-PCBs declined to a smaller degree over the 5-year period. A time x body mass index (BMI) interaction suggests that the reduction rate of blood PCDDs + PCDFs and dl-PCB concentrations in subjects with a BMI greater than the 75th percentile is lower than that of subjects with a BMI less than the 75th percentile from 2002 to 2004 over the 5-year period. From other reports on the dietary intake of PCDDs, PCDFs, and dl-PCBs in Japan, the total amount of daily dioxin intake decreased, but the percentage of dl-PCBs increased yearly in the first half of the 2000s. The reason for the difference in the 5-year change in blood concentrations between PCDDs +PCDFs and dl-PCBs may be explained by the yearly change in the dietary dioxin intake.

Association between lifestyle habits and bone mineral density in Japanese juveniles.

OBJECTIVES: We explored the relationship between bone mineral density (BMD) and lifestyle in juveniles to identify factors leading to higher peak bone mass and prevention of osteoporosis in later life. METHODS: Juveniles (1,364 students: 770 boys and 594 girls, aged 6-18 years) attending school in Hokkaido prefecture, Japan, were asked to complete a brief self-administered diet history questionnaire for 10-year-olds (BDHQ10y) providing information about personal history, lifestyle, and intake of nutritional elements. In addition, BMD and grip strength were measured. We analyzed the relationship between BMD and lifestyle factors. RESULTS: The difference in BMD for boys was larger among the junior and senior high school groups. The difference in BMD for girls was larger among older elementary and later school children. Anthropometric variables and grip strength were strongly correlated with BMD. Having a nap-time routine was significantly correlated with BMD, but sleep time and sports club activities were not. BMD among juveniles who attained secondary sexual characteristics was significantly higher than that of juveniles of the same age who had not attained these characteristics. Calcium intake was significantly lower in senior high school students compared with other grades. Consumption of milk by senior high school boys and junior high school girls was weakly correlated with BMD. CONCLUSIONS: Our findings encourage educational interventions to counsel students to avoid weight loss and calcium deficiency. This effective intervention should begin before the higher elementary school, when juveniles have the greatest likelihood for preventing lower peak bone mass and osteoporosis.

Concentration of folic acid (FA) in serum of Japanese pregnant women.

Objectives Exposure to inorganic arsenic (iAs) is a world-wide health concern. We reported that Japanese children and pregnant women are exposed to moderate levels of iAs through food. Reducing iAs contamination from foods of high iAs is an important issue unique in Japan. Integrated iAs is methylated to less toxic organic forms, and S-adenosyl-L-methyonine (SAM), a common methyl-donor of DNA and histones, is utilized in this process. Chronic consumption of SAM by iAs metabolism due to exposure to iAs might alter the epigenetic modification of genome. The SAM biosynthesis pathway is dependent on folate cycle, and it is possible that ingestion of sufficient folic acid (FA) is protective to iAs induced toxicity. Methods In the course of our cross-sectional body burden analyses of Pb and iAs in Japanese children and pregnant women, termed "PbAs study", FA concentration in serum of 104 pregnant women was measured. Results Mean (±SEM) of serum FA concentration was 15.8 ± 1.3 (ng/mL). There are significant number of people showing very high FA (>30 ng/ mL), and large fraction of them were taking supplements daily. Conclusions These results suggested that level of FA ingestion of Japanese pregnant women is high for supporting normal fetal development.

Exposure Assessment of Cadmium in Female Farmers in Cadmium-Polluted Areas in Northern Japan.

Akita prefecture is located in the northern part of Japan and has many cadmium-polluted areas. We herein performed an exposure assessment of cadmium in 712 and 432 female farmers in two adjacent cadmium-polluted areas (A and B, respectively), who underwent local health examinations from 2001-2004. We measured cadmium concentrations in 100 food items collected from local markets in 2003. We then multiplied the intake of each food item by its cadmium concentration in each subject to assess cadmium intake from food and summed cadmium intake from all food items to obtain the total cadmium intake. Median cadmium intake levels in areas A and B were 55.7 and 47.8 µg/day, respectively, which were both higher than that of the general population and were attributed to local agricultural products, particularly rice. We also calculated weekly cadmium intake per body weight and compared it to the previous provisional tolerable weekly intake reported by the Joint FAO (Food and Agriculture Organization)/WHO (World Health Organization) expert committee on food additives or current tolerable weekly intake in Japan of 7 µg/kg BW/week. Medians in areas A and B were 7.2 and 6.0 µg/kg BW/week, respectively. Similar estimated values were also obtained by the Monte Carlo simulation. These results demonstrated that the cadmium exposure levels among the farmers were high enough to be approximately the tolerable weekly intake.

Contribution of house dust contamination towards lead exposure among children in Karachi, Pakistan.

Lead exposure is associated with impaired neurodevelopment among children. House dust is recognized as one of the important secondary sources of lead exposure in children. We assessed the relationship between lead contamination in house dust and blood lead level in Pakistani children. We investigated lead contamination in house dust samples collected from 59 houses in Karachi, Pakistan. The lead content of house dust in Pakistan was relatively higher than that reported in previous studies. Weekly lead intakes from house dust were considerably higher among Pakistani children. In Pakistani children, 12% (7 of 58) showed lead intake values greater than the previous Provisional Tolerable Weekly Intake of lead. A correlation (Pearson's correlation = 0.37) was found between weekly lead intake from house dust and blood lead level in Pakistani children. In addition, blood lead levels were significantly higher in children with high lead intakes than in children with low and medium lead intakes. Thus, house dust is an important source of lead exposure in Pakistani children.