Urinary concentrations of environmental phenol among pregnant women in the Japan Environment and Children's Study.

Humans are exposed to various bisphenols, alkylphenols and nitrophenols through dietary intake, food packaging and container materials, indoor and outdoor air/dust. This study aimed to evaluate exposure of Japanese pregnant women to environmental phenols by measuring target compounds in urine samples. From a cohort of the Japan Environment and Children's Study, 4577 pregnant women were selected. Bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), para-nitrophenol (PNP), 3-methyl-4-nitrophenol (PNMC), branched 4-nonylphenol (4-NP), linear 4-nonylphenol and 4-tert-octylphenol (4-t-OP) were analysed using a high-performance liquid chromatograph coupled to a triple-quadrupole mass spectrometer. The urinary metabolite data were combined with a questionnaire to examine the determinants of phenol exposure by machine learning. The estimated daily intake (EDI) and hazard quotient (HQ) of BPA were calculated. PNP (68.2%) and BPA (71.5%) had the highest detection frequencies, with median concentrations of 0.76 and 0.46 µg/g creatinine, respectively. PNMC, BPS, BPF and 4-NP were determined in 24.9%, 11.9%, 1.3% and 0.4% of samples, respectively, whereas BPAF (0.02%) and 4-t-OP (0.02%) were only determined in a few samples. The PNP concentrations measured in this study were comparable with those reported in previous studies, whereas the BPA concentrations were lower than those reported previously worldwide. The EDI of BPA was 0.014 µg/kg body weight/day. Compared with the tolerable daily intake set by the German Federal Institute for Risk Assessment, the median (95th percentile) HQ was 0.044 (0.2). This indicates that the observed levels of BPA exposure pose a negligible health risk to Japanese pregnant women. Determinants of bisphenol and nitrophenol exposure could not be identified by analysing the questionnaire solely, suggesting that biological measurement is necessary to assess exposure of pregnant women to bisphenols and nitrophenols. This is the first study to report environmental phenol exposure of Japanese pregnant women on a nationwide scale.

Association between maternal urinary neonicotinoid concentrations and child development in the Japan Environment and Children's Study.

BACKGROUND: Recent studies have reported the effect of neonicotinoid (NEO) exposures on development in human. However, information about the risk of childhood development delays due to NEO exposures is limited. OBJECTIVES: The study aimed to examine the association between NEO exposure and child development up to 4 years of age using data of the Japan Environment and Children's Study. METHODS: The study employed urinary NEO and metabolite concentrations in the first and second or third trimesters; the Japanese translation of the Ages and Stages Questionnaire (third edition; J-ASQ-3) scores on developmental delay in five domains, namely communication, gross motor skills, fine motor skills, problem solving, and personal-social characteristics from 6 months to 4 years of age; and self-reported questionnaire data. The associations between urinary NEO concentrations and J-ASQ-3 results were analysed using the treed distributed lag mixture model. A total of 8538 participants were included in statistical analyses. RESULTS: The determination rates of urinary acetamiprid-N-desmethyl (dm-ACE), clothianidin (CLO), dinotefuran (DIN) and thiamethoxam (THX) were greater than 50%. Median urinary dm-ACE, CLO, DIN and THX concentrations were 0.34, 0.14, 0.22 and 0.05 ng/ml, respectively, in samples collected during gestational weeks < 23, and 0.28, 0.12, 0.18 and 0.04 ng/ml, respectively, in those collected during gestational weeks ≥ 23. The binomial scores divided by the cut-off values of the J-ASQ were used in the treed distributed lag mixture model. The highest percentage for a domain with a value less than the cut-off value was 'problem solving' at 6 months of age among all the J-ASQ-3 scores (10.5%). There was no statistically significant association between maternal urinary dm-ACE, CLO, DIN and THX concentrations during pregnancy and the J-ASQ-3 results up to 4 years of age. Objective assessment of child development in different populations may be warranted to confirm our findings.

Corrigendum to ``A simultaneous, high-throughput and sensitive method for analysing 13 neonicotinoids and metabolites in urine using a liquid chromatography-tandem mass spectrometry'' [MethodsX 10 (2023) 102129].

[This corrects the article DOI: 10.1016/j.mex.2023.102129.].

A simultaneous, high-throughput and sensitive method for analysing 13 neonicotinoids and metabolites in urine using a liquid chromatography-tandem mass spectrometry.

A simultaneous, high-throughput and sensitive method for analysing nine neonicotinoid pesticides (NEOs) and four metabolites (NEOms) in urine using a liquid chromatography-tandem mass spectrometry (LC-MSMS) was developed. The method detection limit (MDL) and lowest concentration minimum reporting limit (LCMRL) of the nine NEOs were 0.0013-0.048 ng/ml and 0.0050-0.17 ng/ml, respectively. The MDL and LCMRL of the four NEOms were 0.0052-0.52 ng/ml and 0.011-1.6 ng/ml, respectively. Intermediate precision for the nine NEOs and four NEOms was 7.5-12.5% and 7.4-10.9%, respectively. Accuracy for the nine NEOs and four NEOms was 3.83-5.60% and 3.01-29.2%, respectively. The developed method was applied to analyse urine samples collected from participants of a large-scale birth cohort study, namely, the Japan Environment and Children's Study (JECS). •The NEO and NEOm concentrations in 100 µl urine samples were analysed using a highly sensitive LC-MSMS.•Automated solid phase extraction in a 96-well plate was utilised to achieve high-throughput analysis.•Intermediate precision and accuracy were less than 12.5% and 94.8-99.1%, respectively.

Short-term association of air pollution with lung cancer mortality in Osaka, Japan.

Long-term air pollution exposure has been linked to increased lung cancer mortality. However, little is known about whether day-to-day fluctuations in air pollution levels are in relation to lung cancer mortality, particularly in low-exposure settings. This study aimed to evaluate the short-term associations between air pollution and lung cancer mortality. Daily data on lung cancer mortality, fine particulate matter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and weather conditions were collected from Osaka Prefecture, Japan, from 2010 to 2014. Generalized linear models were combined with quasi-Poisson regression were applied to evaluate the associations between each air pollutant and lung cancer mortality after adjusting for potential confounders. Mean (standard deviation) concentrations of PM2.5, NO2, SO2, and CO were 16.7 (8.6) µg/m3, 36.8 (14.2) µg/m3, 11.1 (4.0) µg/m3, and 0.51 (0.16) mg/m3, respectively. Interquartile range increases in concentrations of PM2.5, NO2, SO2, and CO (2-d moving average) were associated with 2.65% (95% confidence intervals [CIs]: 0.96%-4.37%), 4.28% (95% CIs: 2.24%-6.36%), 3.35% (95% CIs: 1.03%-5.73%), and 4.60% (95% CIs: 2.19%-7.05%) increased risk of lung cancer mortality, respectively. Stratified analyses showed that the associations were strongest in the older population and men. Exposure‒response curves showed a continuously increasing mortality risk from lung cancer with elevation of air pollution levels, without discernible thresholds. In summary, we found evidence of increased lung cancer mortality in relation to short-term elevations in ambient air pollution. These findings may merit further research to better understand this issue.

Assessment of Alcohol Exposure From Alcohol-Based Disinfectants Among Premature Infants in Neonatal Incubators in Japan.

Importance: The risk of premature infants in neonatal incubators exposed to evaporated alcohol from alcohol-based disinfectants (ABDs) is unknown. Objective: To assess alcohol concentrations in the peripheral blood of premature infants and neonatal incubators. Design, Setting, and Participants: A quality improvement study comparing 2 different populations before and after introduction of ABD practice (ABD-PRAC) was conducted in a neonatal intensive care unit of a single tertiary hospital in Japan. Participants included premature infants who were born before 34 weeks of gestational age and received medical care in neonatal incubators. The study consisted of 3 periods: (1) September 1, 2020, to August 1, 2021 (prospective observation of pre-ABD-PRAC, (2) August 2 to August 22, 2021 (introduction of ABD-PRAC to medical staff and parents in the neonatal intensive care unit), and (3) August 23, 2021, to March 31, 2022 (prospective observation of post-ABD-PRAC). No follow-up studies were initiated. Interventions: An ABD-PRAC that aimed to reduce alcohol evaporation from ABDs inside neonatal incubators was instituted: (1) place alcohol preps in the incubator just before use and remove them from the incubator as soon as possible and (2) withhold placing hands into the incubators until 60 seconds after using ABDs for disinfection (applied only to family members). Main Outcomes and Measures: Blood alcohol concentration and evaporated alcohol concentrations in neonatal incubators. Results: Disinfectant practice was assessed among 28 infants during the pre-ABD-PRAC (17 infants [10 girls]; median gestational age at birth, 29.4 [IQR, 26.3-30.3] weeks) and post-ABD-PRAC (11 infants [3 girls]; median gestational age at birth, 30.0 [IQR, 25.3-32.2] weeks) study periods. The median blood alcohol concentration was 7.0 (IQR, 5.4-9.3) mg/dL pre-ABD-PRAC and 4.2 (IQR, 2.5-7.2) mg/dL post-ABD-PRAC. The median evaporated alcohol concentration inside neonatal incubators during pre-ABD-PRAC during the day was 23.6 (IQR, 15.9-36.5) ppm and, at night, was 13.2 (IQR, 8.9-19.4) ppm; during post-ABD-PRAC, the concentration was 9.4 (IQR, 6.0-16.0) ppm during the day and 5.7 (IQR, 3.6-9.7) ppm at night. The introduction of ABD-PRAC at 22 weeks' corrected gestational age was associated with a lower blood alcohol concentration in premature infants: regression coefficient value, -8.3 (95% CI, -12.0 to -4.7). Conclusions and Relevance: In this study, alcohol evaporated from ABDs was absorbed by premature infants in neonatal incubators. The findings suggest that introduction of ABD-PRAC was associated with lower alcohol concentrations in neonatal incubators and in the blood of premature infants.

Population attributable fraction of risk factors for low birth weight in the Japan Environment and Children's Study.

BACKGROUND: Low birth weight (LBW), which is considered a birth weight of <2500  g, poses significant health problems for children. However, population attributable fraction (PAF) of risk factors for LBW have not been well studied. OBJECTIVE: We aimed to re-evaluate associations between risk factors for LBW reported in previous studies that used the Japan Environment and Children's Study (JECS) data, and to estimate the magnitude of risk using PAF. METHODS: Data including 91,559 mother-child dyads were obtained from JECS. Risk factors identified by previous studies that used JECS data were used to calculate odds ratios for LBW using a Bayesian logistic regression model. Based on calculated odds ratios, the PAF was calculated. RESULTS: Parity, history of adenomyosis, hypertension disorder of pregnancy, maternal age at birth, prepregnancy body mass index, gestational weight gain (GWG), maternal smoking and lead (Pb) exposure were all significantly associated with LBW. The sum of the PAF of all factors was 79.4 %, with the largest PAF among single risk factors being GWG (16.5 %); the environmental portion of the PAF (Pb exposure, 14.6 % + maternal smoking, 12.1 %) surpassed the PAF of GWG. CONCLUSION: Our findings suggest that the number of births classified as LBW can be reduced by approximately 27% if Pb exposure is reduced to the lowest quartile and maternal smoking is eliminated. Further investigations are needed to identify unknown risk factors for LBW.

Optimal method for determining the intraclass correlation coefficients of urinary biomarkers such as dialkylphosphates from imputed data.

Urinary biomarkers are commonly used in epidemiological studies as surrogates or indicators of exposure to chemical substances. Evaluating the reliability of a biomarker is highly important because use of an unreliable marker may lead to misclassification and attenuation bias, resulting in flawed interpretations and conclusions. Although intraclass correlation coefficient (ICC) is regarded as a typical index of test reliability, methods for determining the ICCs of urinary biomarkers have not been standardised, and different methods have been used. This study evaluated different imputation methods for left-censored data, i.e., four imputation or one substitution methods, before calculating ICCs, and at the same time mathematically assessed the impact of the left-censoring proportion on the estimated ICCs. Biomarkers of exposure to organophosphate pesticides, i.e., dialkylphosphates, were used as an example. The Gibbs sampler-based left-censored missing value imputation approach had the best performance for imputation of values below reporting limits, with lower values on Kolmogorov-Smirnov test statistics than other imputation/substitution methods, i.e., a univariate distribution fitting approach, multiple imputation by chained equation, a bootstrap expectation-maximisation algorithm approach, and a single value substitution. In all imputation methods, however, ICCs decreased as censoring rates increased. We propose a method to estimate true ICCs based on mathematical estimation.

Association between Heated Tobacco Product Use during Pregnancy and Fetal Growth in Japan: A Nationwide Web-Based Survey.

Combustible cigarette smoking impacts fetal growth during pregnancy. However, the risk associated with heated tobacco products (HTPs) remains unclear. This nationwide cross-sectional study investigated whether HTP use during pregnancy is associated with small for gestational age (SGA) outcomes among 5647 post-delivery women with singleton pregnancies, which were divided into four groups: lifetime never-smokers, former smokers before pregnancy, and current smokers for each of the tobacco products during pregnancy (sole HTP and sole combustion smokers). Information on the prevalence of SGA, defined as birth weight and height below the 10th percentile, was retrieved from the Maternal and Child Health Handbooks of post-delivery women. Using logistic regression, the association between sole HTP smokers during pregnancy and SGA, adjusted for covariates, with lifetime never-smokers as reference, was investigated. The prevalence was: current sole HTP smokers during pregnancy, 1.8% (102/5647); and SGA, 2.9% (164/5647). Sole HTP smokers during pregnancy had a higher prevalence of SGA (5.9% [6/102] vs. 2.7% [111/4144]) with an adjusted odds ratio (OR) of 2.50 (95% confidence interval [CI], 1.03-6.05) than lifetime never-smokers. Among sole combustion smokers, the adjusted OR for SGA was 1.95 (95% CI, 0.81-4.67). In Japan, HTP smoking during pregnancy may be associated with an increased risk for SGA.

Association between Haematological Parameters and Exposure to a Mixture of Organophosphate and Neonicotinoid Insecticides among Male Farmworkers in Northern Thailand.

Exposure to insecticides may result in various health problems. This study investigated the association between haematological parameters and exposure to a mixture of organophosphate (OP) and neonicotinoid (NEO) insecticides among male farmworkers in Fang district, Chiang Mai province, northern Thailand. Concentrations of urinary dialkylphosphates, non-specific metabolites of OPs, and NEOs and their metabolites and haematological parameters were measured in 143 male farmworkers. The Bayesian kernel machine regression model was employed to evaluate the associations. Exposure to a mixture of insecticides was significantly associated with the mean corpuscular haemoglobin concentration (MCHC) when the concentrations of all the compounds and their metabolites were at the 60th percentile or higher compared with the 50th percentile. Furthermore, exposure to clothianidin (CLO) showed a decreasing association with MCHC when all the other insecticides were at their mean concentrations. CLO was the most likely compound to reduce MCHC, and this was confirmed by sensitivity analysis. These findings suggest that exposure to NEO insecticides, especially CLO, affects the haematological status relating to haemoglobin parameters.

Urinary Metabolites of Organophosphate Pesticides among Pregnant Women Participating in the Japan Environment and Children's Study (JECS).

Organophosphate pesticides (OPPs) exhibit neurodevelopmental toxicity. To evaluate the effect of prenatal exposure to OPPs in the Japan Environment and Children's Study, a nationally representative birth cohort study, 4575 maternal urine samples were analysed for six OPP metabolites, i.e., dialkylphosphates (DAPs). This study aimed to investigate predictors of urinary DAPs using machine learning approaches and to assess the cumulative risk based on relative potency factors among Japanese pregnant women. The median creatinine-normalised urinary concentrations (interquartile ranges) of dimethylphosphate, dimethylthiophosphate and diethylphosphate, which had a detection rate of 50% or higher, were 3.53 (1.91-6.78), 4.09 (1.66-10.8) and 3.28 (1.88-5.98) µg/g-creatinine, respectively. Possible predictors of urinary DAP concentrations were the month of urine sampling, consumption of apple and maternal body mass index. When fenitrothion was used as an index chemical for cumulative risk assessment, 0.36% of participants exceeded the lower 95% confidence limit of the benchmark dose10.

Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand.

Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors; however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18-40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography-tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.

Indoor air quality of 5,000 households and its determinants. Part A: Particulate matter (PM2.5 and PM10-2.5) concentrations in the Japan Environment and Children's Study.

Exposure to particulate matter (PM) is one of the important risk factors for morbidity and mortality. Although PM concentrations have been assessed using air quality monitoring stations or modelling, few studies have measured indoor PM in large-scale birth cohorts. The Japan Environment and Children's Study (JECS) measured indoor and outdoor air quality in approximately 5000 households when the participating children were aged 1.5 and 3 years. PM was collected using portable pumps for 7 days (total of 24 h), inside and outside each home. Prediction models for indoor PM concentrations were built using data collected at age 1.5 years and post-validated against data collected at age 3 years. Median indoor/outdoor PM2.5 and PM10-2.5 concentrations at age 1.5 years [3 years] were 12.9/12.7 [12.5/11.3] µg/m3 and 5.0/6.3 [5.1/6.1] µg/m3, respectively. Random forest regression analysis found that the major predictors of indoor PM2.5 were indoor PM10-2.5, outdoor PM2.5, indoor smoking, observable smoke and indoor/outdoor temperature. Indoor PM2.5, outdoor PM10-2.5, indoor humidity and opening room windows were important predictors of indoor PM10-2.5 concentrations. Indoor benzene, acetaldehyde, ozone and nitrogen dioxide concentrations were also found to predict indoor PM2.5 and PM10-2.5 concentrations, possibly due to the formation of secondary organic aerosols. These findings demonstrate the importance of reducing outdoor PM concentrations, avoiding indoor smoking, using air cleaner in applicable and diminishing sources of VOCs that could form secondary organic aerosols, and the resulting models can be used to predict indoor PM concentrations for the rest of the JECS cohort.

Indoor air quality of 5,000 households and its determinants. Part B: Volatile organic compounds and inorganic gaseous pollutants in the Japan Environment and Children's study.

Volatile organic compounds (VOCs) are major indoor air pollutants. Quantification of indoor concentrations of VOCs and identification of factors associated with these concentrations can help manage indoor air quality. This study measured the concentrations of VOCs and inorganic gaseous pollutants in around 5000 households in Japan and utilised a random forest model to estimate these concentrations and identify important determinants. The homes of 5017 randomly selected participants in the Japan Environment and Children's Study (JECS) were visited twice, when the children were aged 1.5 and 3 years. Twelve VOCs and inorganic gaseous pollutants were measured during 7 days by passive samplers. Various factors in these households, including household appliances, building characteristics, cooking styles, use of consumer products, renovation, pets, personal behaviours and ventilation were recorded. A random forest model with recursive feature elimination was utilised to identify factors predictive of VOCs and inorganic gaseous pollutants. Toluene, formaldehyde and acetaldehyde were the dominant indoor VOCs. The 95th percentiles of indoor p-dichlorobenzene concentrations at 1.5 and 3 years were 67 µg/m3 and 71 µg/m3, respectively. Random forest models with coefficients of determination ranging from 0.34 to 0.76 outperformed the traditional linear regression models. Factors associated with indoor VOC and inorganic gaseous pollutant concentrations included their outdoor concentrations, indoor and outdoor temperature and relative humidity, month of the year, hours windows were open, kerosene heater use and times of operation and building age. The results provided basic descriptions of indoor VOCs and inorganic gaseous pollutants in Japan and identified several determinants of these concentrations. These determinants should be considered to maintain indoor air quality. These results can be used in epidemiological assessments of the effects of VOCs and inorganic gaseous pollutants on health in children.

Exposure to heavy metals modifies optimal gestational weight gain: A large nationally representative cohort of the Japan Environment and Children's Study.

Clinical guidelines including those set by the US Institute of Medicine, have based optimal gestational weight gain (GWG) on maternal pre-pregnancy body mass index (BMI), but have not considered the role of environmental toxicants such as heavy metals that can disrupt these processes. This study designed to determine optimal GWG ranges in women grouped according to BMI, and to assess whether blood concentrations of heavy metals alter the relationships between GWG and outcomes. A total of 103,060 participants in the Japan Environment and Children's Study recruited between 2011 and 2014 were followed until their children reached 3 years of age. Outcomes included 1 min Apgar score <7, caesarean delivery, childhood obesity, gestational diabetes, pregnancy-induced hypertension, low birth weight, large for gestational age, macrosomia, operative vaginal delivery, postpartum weight retention, preterm birth and small for gestational age. The optimal GWG ranges were determined using multivariate logistic regression models. Stratified analyses were performed to determine optimal GWG ranges according to quartiles of heavy metals. Optimal GWGs for underweight, normal weight and overweight women were found to be 10.0 to <14.0 kg, 6.0 to <12.0 kg and 4.0 to <8.0 kg, respectively. However, the benefits of optimal GWG were attenuated in women exposed to high concentrations of mercury (Hg), lead (Pb) and cadmium (Cd). Despite being within optimal GWG, underweight women with Hg > 5.21 ng/g and overweight women with Hg 3.67-5.21 ng/g, Pb > 7.31 ng/g and Cd > 0.66 ng/g had null effects. Heavy metals can modify the associations between GWG and outcomes, particularly for underweight and overweight women. Because of the complex interactions of environmental toxicants with pre-pregnancy BMI, GWG and adverse outcomes, GWG guidelines should be interpreted cautiously. Environmental toxicants may influence the determination of a clinical guideline.

Characteristics of Exposure of Reproductive-Age Farmworkers in Chiang Mai Province, Thailand, to Organophosphate and Neonicotinoid Insecticides: A Pilot Study.

Exposure to insecticides containing organophosphate (OP) and neonicotinoid (NEO) compounds has been associated with adverse reproductive health outcomes. This study characterized and identified predictors of exposure to OP and NEO among 100 reproductive-age farmworkers from two intensive farming areas in Chiang Mai Province, Thailand, including 50 each from the Fang (FA) and Chom Thong (CT) districts. OP exposure was determined by measuring the urinary concentrations of six dialkylphosphates (DAPs), whereas NEO exposure was determined by measuring the urinary concentrations of NEO compounds and their metabolites (NEO/m). The most frequently detected OPs were diethylphosphate (DEP) and diethylthiophosphate (DETP), with DETP having the highest geometric mean (GM) concentration, 8.9 µg/g-creatinine. The most frequently detected NEO/m were N-desmethyl-acetamiprid (N-dm-ACE), imidacloprid (IMI), and thiamethoxam (THX), with IMI having the highest GM concentration, 8.7 µg/g-creatinine. Consumption of well water was the predominant determinant of OP and NEO exposure in this population. In addition to encouraging workers to use personal protective equipment, exposure of farmworkers to these compounds may be reduced by nation-wide monitoring agricultural insecticides and other pesticides in community drinking water resources.

Determination of Urinary Cotinine Cut-Off Concentrations for Pregnant Women in the Japan Environment and Children's Study (JECS).

Few studies have assessed the accuracy of self-reported questionnaires to determine smoking habits relative to urinary biomarkers. This study investigated urinary cotinine cut-off concentrations distinguishing active, passive and non-smokers among pregnant women who participated in the Japan Environment and Children's Study, a nationwide birth cohort study. Pregnant participants with measured urinary cotinine concentrations (UCCs) and who completed self-reported questionnaires on smoking status were included (n = 89,895). The cut-off values (COVs) for active and passive smokers were calculated by fitting mixed normal distribution functions to UCCs. The sensitivity and specificity of the questionnaires were subsequently evaluated. The median (interquartile range) UCC was 0.24 (0.083-0.96) µg/g-creatinine, with the detection rate of 89%. The COV for distinguishing active smokers from passive and non-smokers was 36.8 µg/g-creatinine. When this COV was considered to represent the true condition, the questionnaire had a sensitivity of 0.523, a specificity of 0.998, a positive predictive value (PPV) of 0.967 and a negative predictive value (NPV) of 0.957. The COV for distinguishing passive smokers from non-smokers was 0.31 µg/g-creatinine, with the questionnaire having a sensitivity of 0.222, a specificity of 0.977, a PPV of 0.868 and an NPV of 0.644. As many as 78% of passive smokers might be misclassified as non-smokers.

Health Risk Assessment and Source Apportionment of Mercury, Lead, Cadmium, Selenium, and Manganese in Japanese Women: An Adjunct Study to the Japan Environment and Children's Study.

Toxic element pollution is a serious global health concern that has been attracting considerable research. In this study, we elucidated the major routes of exposure to three toxic elements (mercury, cadmium, and lead) and two essential elements (manganese and selenium) through diet, soil, house dust, and indoor air and assessed the potential health risks from these elements on women from the coastal area of Miyagi prefecture, Japan. Twenty-four-hour duplicate diet, house dust, soil, and indoor air samples were collected from 37 participants. Cd, Pb, Mn, and Se concentrations were measured using inductively coupled plasma mass spectrometry, and Hg concentrations using cold vapor atomic absorption spectrometry. We found that soil and house dust were the primary reservoirs of these elements. Diet contributed most strongly to the daily intake of these elements, with mean values of 0.72, 0.25, 0.054, 47, and 0.94 µg/kg/day for Hg, Cd, Pb, Mn, and Se, respectively. The mean hazard quotient of Hg was 1.53, indicating a high potential health risk from Hg exposure in daily lives. The intakes of other elements were below the tolerable limits. Future studies with a larger sample size are warranted to confirm our findings.

Poly- and perfluoroalkyl substances in maternal serum: Method development and application in Pilot Study of the Japan Environment and Children's Study.

Poly- and perfluoroalkyl substances (PFAS) have been investigated in a number of cohort studies due to concern over their adverse health effects. The aim of this study was to develop a reliable, high throughput and cost-effective analytical method for a broad range of PFAS in human serum. Protein precipitation, automatic solid phase extraction (SPE) pre-treatment and column-switching LC-MS/MS were employed. The optimised and validated method was then used to analyse the levels of 28 PFAS in 339 maternal serum samples from Pilot Study of the Japan Environment and Children's Study. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnA) and perfluorooctane sulphonic acid (PFOS) were detected in all 339 samples at median (range) concentrations of 1.9 (0.46-15), 1.5 (0.32-10), 1.3 (0.25-4.5) and 3.7 (0.43-15) ng/ml, respectively. These levels are comparable to those reported in previous studies using samples collected from various parts of the world. With a few exceptions, the remainder of the PFAS examined had lower detection rates but were found at concentrations similar to those reported in previous studies. The sensitivity and throughput ability of the method developed here are sufficient for its application in a large-scale biomonitoring study.

The association between gestational use of personal care products and neonatal urological abnormality at birth: The Japan Environment and Children's Study.

Congenital anomalies of the kidney and urinary tract (CAKUT) include a broad group of birth defects. Exposure to endocrine disrupting chemicals (EDCs) is suspected to be one of the risk factors for CAKUT, and the use of personal care products (PCPs) is a source of EDC exposure. Therefore, this study aimed to investigate the relationship between CAKUT and the use of PCPs in a large birth cohort study. Data from 86,899 pregnant women included in the Japan Environment and Children's Study (JECS), an ongoing nationwide project, were analyzed. The prevalence of CAKUT in newborns was 0.25 % and almost 90 % of subjects used PCPs during mid-late pregnancy. No association was found between CAKUT and PCP use in a model adjusted for the following covariates: maternal age at delivery. The result was persistent after rigorous sensitivity analyses.