Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study.

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects.

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

Teenage and young adult pregnancy and depression: findings from the Japan environment and children's study.

Teenage pregnancy increases the threat of depression because of its many factors. Pregnancy during young adulthood may also have several risk factors for depression compared to older pregnancies. However, data on depression in young adult pregnancies are lacking. This study investigated the association between teenage and young adult pregnancy and depression. Data from the Japan Environment and Children's study was used as a nationwide multicenter prospective cohort study. A multivariate logistic regression was performed to investigate the association between age groups (14-19, 20-24, 25-29, 30-34, ≥ 35 years) and depression, adjusted for behavioral and sociodemographic characteristics. Depression was assessed using the Kessler Psychological Distress Scale. In total, 96,808 pregnant women responded to the questionnaire. Teenage (14-19 years) and young adult (20-24 years) pregnancy were associated with an increased risk of depression compared to older pregnancy (≥ 35 years) (teenage: OR 4.28, 95% confidence interval, CI [3.24-5.64]; young adult: OR 3.00, 95% CI [2.64-3.41]). After adjusting for covariates, the magnitude of the risk of depression was attenuated. However, teenage and young adult pregnancy remained at a significantly increased risk of depression compared to older pregnancy (teenage: OR 2.38, 95% CI [1.77-3.21]; young adult: OR 2.14, 95% CI [1.87-2.46]). Our findings indicate that teenage and young adults' pregnancy are at an increased risk of depression compared to older pregnancy. These findings suggest prioritizing teenage and young pregnant women for prevention and interventions related to depression.

Quantitative Measurement of Phthalate Exposure Biomarker Levels in Diaper-Extracted Urine of Japanese Toddlers and Cumulative Risk Assessment: An Adjunct Study of JECS Birth Cohort.

Phthalate exposure monitoring and risk assessment in non-toilet-trained children are rarely reported. This adjunct study of the Japan Environment and Children's Study assessed cumulative health risks in 1.5-year-old toddlers in the Aichi regional subcohort by biomonitoring 16 urinary metabolites of eight phthalate plasticizers. Overnight urine was extracted from toddlers' diapers (n = 1077), and metabolites were quantified using ultraperformance liquid chromatography coupled with tandem mass spectrometry. The analyses' quality was assured by running quality control samples. The highest geometric mean concentration was found for mono-(2-ethyl-5-carboxypentyl) phthalate, followed by mono-isobutyl phthalate (23 and 21 µg/L, respectively). Di-2-ethylhexyl phthalate (DEHP) and di-butyl phthalate exhibited higher risks [hazard quotient (HQ) > 1] than the cutoff level in a small proportion of toddlers; 8 and 14% of toddlers were at cumulative risk of multiple phthalates beyond the cutoff level [hazard index, (HI) > 1], based on the tolerable daily intake of the European Food Safety Authority and the United States Environmental Protection Agency Reference Dose. HI > 1 for antiandrogenicity in creatinine-unadjusted and -adjusted estimations were exhibited by 36 and 23% of the children, respectively. Thus, identifying exposure sources and mitigating exposure are necessary for risk management. Additionally, continuous exposure assessment and evaluation of health outcomes, especially antiandrogenic effects, are warranted.

Residue levels of organophosphate pesticides and dialkylphosphates in agricultural products in Japan.

High urinary levels of dialkylphosphates (DAPs), which are common structures of organophosphate pesticides (OPs), have been associated with several adverse health outcomes in human biomonitoring studies. Previous studies have indicated that dietary OP exposure and ingestion of environmentally degraded DAP, which is inactive with acetylcholinesterase, can lead to an increase in urinary DAP levels in the general population. However, the specific food sources contributing to the intake of OPs and DAPs have not been identified. In this study, we analyzed the levels of OPs and preformed DAPs in various food items. DAP levels were markedly high in certain fruits, such as persimmon, apple juice, kiwi, and mandarin. In contrast, only moderate levels of OPs were detected in these foods. Furthermore, the levels of OPs and DAPs were positively associated with vegetables, whereas no such association was observed in fruits. Increased consumption of certain fruits presumably leads to a marked increase in urinary DAP levels in individuals despite limited exposure to OPs, resulting in reduced reliability of urinary DAPs as a marker of OP exposure. Therefore, the possible effects of dietary habits and the resulting intake of preformed DAPs should be considered when interpreting biomonitoring data of urinary DAPs. Additionally, DAP levels in most organic foods were much lower than those in conventional foods, suggesting that the reduction in urinary DAPs by organic diet intervention may be mainly attributed to the reduced intake of preformed DAPs rather than reduced exposure to OPs. Therefore, urinary DAP levels may not be suitable indicators for evaluating ingested OP exposure.

Association between whole blood metallic elements concentrations and gestational diabetes mellitus in Japanese women: The Japan environment and Children's study.

BACKGROUND: Exposure to several metallic elements has been suggested as a risk factor for gestational diabetes mellitus (GDM), but inconsistent findings have been reported. This study aimed to examine the association between the maternal whole blood concentration of metallic elements (Hg, Pb, Cd, Mn, and Se) and GDM using the dataset of the Japan Environment and Children's Study (JECS), a nationwide birth cohort study, which was designed to examine the adverse effects of pre/post-natal exposure to hazardous environment. METHODS: The data of 78,964 pregnant women who were participants of JECS were used. Blood samples were collected from the pregnant women at second/third trimester of gestation. We employed logistic regression analysis, quantile g-computation (QGC) and a distributed lag nonlinear model (DLNM) to examine the association between the blood concentration of metallic elements and the risk of GDM. RESULTS: The prevalence of GDM was 2.1%. In the logistic regression analyses, maternal blood Hg was associated with an increased risk of GDM. In QGC analysis, although metallic elements mixtures were not related to an increased risk of GDM, Hg (52.6%) may be the main contributor. According to the results of DLNM, for maternal exposure to Hg, 4.99 ng/g was identified as its susceptible minimum window for elevated risk of GDM. CONCLUSIONS: Our findings highlighted an association between Hg exposure and an increased risk of GDM. Studies of the underlying mechanisms and potential contributing factors, including fish intake, of this association are warranted.

Study Design and Participants' Profile in the Sub-Cohort Study in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles. METHODS: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. RESULTS: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. CONCLUSION: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Relations of mold, stove, and fragrance products on childhood wheezing and asthma: A prospective cohort study from the Japan Environment and Children's Study.

This prospective cohort study aimed to examine the associations between mold growth, type of stoves, and fragrance materials and early childhood wheezing and asthma, using data from the Japan Environment and Children's Study. Mold growth at home, usage of kerosene/gas stove, wood stove/fireplace, and air freshener/deodorizer were surveyed using a questionnaire at 1.5-year-old, and childhood wheezing and doctor-diagnosed asthma during the previous year were obtained using a 3-year-old questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between exposure to childhood wheezing and asthma. A total of 60 529 children were included in the analysis. In multivariate analyses, mold growth and wood stove/fireplace had significantly higher odds ratios (ORs) for wheezing (mold growth: 1.13; 95% CI, 1.06-1.22; wood stove/fireplace: 1.23; 95% CI, 1.03-1.46). All four exposures had no significant ORs for childhood doctor-diagnosed asthma; however, in the supplemental analysis of northern regions, wood stove/fireplace had a significantly higher OR for asthma. Mold growth and wood stove/fireplace had significant associations with childhood wheezing in the northern regions. Mold elimination in the dwellings and use of clean heating (no air pollution emissions) should be taken into consideration to prevent and improve childhood wheezing and asthma.

Increased serum anti-CYP2E1 IgG autoantibody levels may be involved in the pathogenesis of occupational trichloroethylene hypersensitivity syndrome: a case-control study.

Occupational exposure to trichloroethylene (TCE) causes a systemic skin disorder with hepatitis known as TCE hypersensitivity syndrome (TCE-HS). Human Leukocyte Antigen (HLA)-B*13:01 is its susceptibility factor; however, the immunological pathogenesis of TCE-HS remains unknown. We herein examined the hypothesis that autoantibodies to CYP2E1 are primarily involved in TCE-HS. A case-control study of 80 TCE-HS patients, 186 TCE-tolerant controls (TCE-TC), and 71 TCE-nonexposed controls (TCE-nonEC) was conducted to measure their serum anti-CYP2E1 antibody (IgG) levels. The effects of TCE exposure indices, such as 8-h time-weighted-average (TWA) airborne concentrations, urinary metabolite concentrations, and TCE usage duration; sex; smoking and drinking habits; and alanine aminotransferase (ALT) levels on the antibody levels were also analyzed in the two control groups. There were significant differences in anti-CYP2E1 antibody levels among the three groups: TCE-TC > TCE-HS patients > TCE-nonEC. Antibody levels were not different between HLA-B*13:01 carriers and noncarriers in TCE-HS patients and TCE-TC. The serum CYP2E1 measurement suggested increased immunocomplex levels only in patients with TCE-HS. Multiple regression analysis for the two control groups showed that the antibody levels were significantly higher by the TCE exposure. Women had higher antibody levels than men; however, smoking, drinking, and ALT levels did not affect the anti-CYP2E1 antibody levels. Anti-CYP2E1 antibodies were elevated at concentrations lower than the TWA concentration of 2.5 ppm for TCE exposure. Since HLA-B*13:01 polymorphism was not involved in the autoantibody levels, the possible mechanism underlying the pathogenesis of TCE-HS is that TCE exposure induces anti-CYP2E1 autoantibody production, and HLA-B*13:01 is involved in the development of TCE-HS.

Simultaneous quantification of pyrethroid metabolites in urine of non-toilet-trained children in Japan.

BACKGROUND: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year. METHODS: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer. RESULTS: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH2-FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH2-FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60). CONCLUSIONS: This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.

Relationship between delivery with anesthesia and postpartum depression: The Japan Environment and Children's Study (JECS).

BACKGROUND: Postpartum depression is one of the most commonly experienced psychological disorders for women after childbirth, usually occurring within one year. This study aimed to clarify whether women with delivery with anesthesia, including epidural analgesia, spinal-epidural analgesia, and paracervical block, had a decreased risk of postpartum depression after giving birth in Japan. METHODS: The Japan Environment and Children's Study (JECS) was a prospective cohort study that enrolled registered fetal records (n = 104,065) in 15 regions nationwide in Japan. Binomial logistic regression analyses were performed to calculate the adjusted odd ratios (aORs) for the association between mode of delivery with or without anesthesia and postpartum depression at one-, six- and twelve-months after childbirth. RESULTS: At six months after childbirth, vaginal delivery with anesthesia was associated with a higher risk of postpartum depression (aOR: 1.233, 95% confidence interval: 1.079-1.409), compared with vaginal delivery without analgesia. Nevertheless, the risk dropped off one year after delivery. Among the pregnant women who requested delivery with anesthesia, 5.1% had a positive Kessler-6 scale (K6) score for depression before the first trimester (p < 0.001), which was significantly higher than the proportions in the vaginal delivery without analgesia (3.5%). CONCLUSIONS: Our data suggested that the risk of postpartum depression at six months after childbirth tended to be increased after vaginal delivery with anesthesia, compared with vaginal delivery without analgesia. Requests for delivery with anesthesia continue to be relatively uncommon in Japan, and women who make such requests might be more likely to experience postpartum depressive symptoms because of underlying maternal environmental statuses.

Indoor volatile organic compounds exposures and risk of childhood acute leukemia: a case-control study in shanghai.

A case-control study was conducted to investigate the relationship between indoor air pollution and childhood acute leukemia (AL) in Shanghai. 97 cases and 148 gender-, age-, and residence-matched controls were included. Indoor air pollution was evaluated by questionnaires and quantitative measurement including 14 volatile organic compounds (VOCs) and nitrogen dioxide (NO2) in the homes of the two groups. The levels of individual VOCs, VOC families, TVOC (sum of the concentrations of the individual VOCs) and NO2 were compared between the two groups. Exposure to styrene and butyl alcohol were associated with an increased risk of childhood AL (styrene: odds ratio (OR)=2.33, 95% confidence interval (CI): 1.07-5.07; butyl alcohol: OR = 2.51, 95%CI: 1.19-5.28); 4th quartile of chlorinated hydrocarbons (OR = 2.52, 95%CI: 1.02-6.26) and 3rd quartile of TVOC (OR = 4.03, 95%CI: 1.06-6.81) had significant higher ORs for childhood AL compared with that in the lowest quartiles. Elevated levels of individual VOCs, VOC families and TVOC were also associated with self-reported risk factors. Our findings suggest that VOCs exposure was associated with an elevated risk of childhood AL, underscore that more attention should be paid to indoor air pollution as a risk factor of childhood AL.

Increased risk of occupational trichloroethylene hypersensitivity syndrome at exposure levels higher than 15 mg/L of urinary trichloroacetic acid, regardless of whether the patients had the HLA-B*13:01 allele.

Occupational trichloroethylene (TCE) exposure can cause hypersensitivity syndrome (TCE-HS). The human leukocyte antigen (HLA)-B*13:01 is reportedly an important allele involved in TCE-HS onset. However, the threshold exposure level causing TCE-HS in relation to HLA-B*13:01 remains unknown. We conducted a case-control study comprising 37 TCE-HS patients and 97 age- and sex-matched TCE-tolerant controls from the Han Chinese population. Urine and blood of patients were collected on the first day of hospitalization, and those of controls were collected at the end of their shifts. Urinary trichloroacetic acid (TCA) was measured as an exposure marker, and end-of-shift levels in the patients were estimated using the biological half-life of 83.7 h. HLA-B genotype was identified using DNA from blood. Crude odds ratios (ORs) for TCE-HS in the groups with urinary TCA concentration >15 mg/L to ≤50 mg/L and of >50 mg/L were 21.9 [95% confidence interval (CI) 4.2-114.1] and 27.6 (6.1-125.8), respectively, when the group with urinary TCA ≤15 mg/L was used as a reference. The frequency of HLA-B*13:01, the most common allele in the patients, was 62.2% (23/37), which was significantly higher than 17.5% (17/97) in the TCE-tolerant controls, with a crude OR of 8.4 (3.1-22.6). The mutually-adjusted ORs for urinary TCA >15 to ≤50 mg/L, >50 mg/L, and for HLA-B*13:01 were 33.4 (4.1-270.8), 34.0 (5.3-217.1), and 11.0 (2.4-50.7), respectively. In conclusion, reduction of TCE exposure to ≤15 mg/L is required for TCE-HS prevention because urinary TCA concentration >15 mg/L showed increased risk of TCE-HS, regardless of whether the patients had the HLA-B*13:01 allele.

Effects of long working hours and shift work during pregnancy on obstetric and perinatal outcomes: A large prospective cohort study-Japan Environment and Children's Study.

BACKGROUND: The work patterns of pregnant women may be related to adverse obstetric and perinatal outcomes. This study aimed to clarify the effects of weekly working time according to frequencies of night shifts during pregnancy on adverse outcomes in Japan. METHODS: The Japan Environment and Children's Study, a prospective cohort study, was conducted in 15 regions nationwide in Japan. The study population included pregnant women with singleton pregnancies (n = 99 744). The mothers' working hours and frequencies of night shifts during the first and the second/third trimesters were assessed using a self-administered questionnaire. Outcome data were collected from medical transcripts. RESULTS: Compared with nonworking women, women who worked during pregnancy had significantly increased adjusted odds ratios (aORs) of threatened miscarriage (maximum aOR: 1.47, 95% confidence interval [95% CI]: 1.26-1.73) and of threatened preterm labor (maximum aOR: 1.63, 95% CI: 1.41-1.87). Increased aORs were observed for hypertensive disorders of pregnancy (maximum aOR: 2.02, 95% CI: 1.39-2.93) in women working ≥36 hours per week with night shifts, for vacuum/forceps delivery (maximum aOR: 1.34, 95% CI: 1.22-1.48) at ≥36 hours with or without night shifts, and for small-for-gestational-age babies (aOR: 1.32, 95% CI: 1.10-1.59) at ≥46 hours with night shifts. In contrast, lower aORs were observed for gestational diabetes and meconium-stained amniotic fluid in women working without night shifts. CONCLUSIONS: Work during pregnancy slightly increased the risks of threatened miscarriage and threatened preterm labor. Long working hours increased the risks of hypertensive disorders of pregnancy, vacuum/forceps delivery, and small-for-gestational-age babies.

Optimization and validation of a highly sensitive method for determining glyphosate in human urine by solid-phase extraction and liquid chromatography with tandem mass spectrometry: a methodological study.

BACKGROUND: Glyphosate and its salt formulations are nonselective herbicides that have been extensively used worldwide, both for residential and agricultural purposes. The possible carcinogenicity and teratogenicity of glyphosate remain to be elucidated. We developed a sensitive and high-throughput analytical method for urinary glyphosate using liquid chromatography-tandem mass spectrometry with the aim of contributing to glyphosate exposure assessment in epidemiological studies. METHODS: After urine dilution (creatinine matching dilution to 0.05 g creatinine/L), glyphosate was extracted using two types of solid phase extraction columns (SCX and NH2) with automated sample preparation instruments. The eluate was dried and dissolved in the mobile phase, followed by liquid chromatography-tandem mass spectrometry analysis. The optimized method was applied to urine samples obtained from 54 Japanese adults and children. RESULTS: The results from the validation study demonstrated good recoveries (91.0-99.6%), within- and between-run precisions (< 15%), low detection limits (0.1 µg/L), and lower limit of quantification (0.3 µg/L). The detection frequency and median concentration of the urinary glyphosate in Japanese subjects were 59% and 0.25 µg/L (0.34 µg/g creatinine). CONCLUSIONS: Our reliable determination method was successful in measuring urinary glyphosate concentration. Moreover, this is the first biomonitoring report of urinary glyphosate levels in the Japanese general population.

Association between maternal blood cadmium and lead concentrations and gestational diabetes mellitus in the Japan Environment and Children's Study.

PURPOSE: To examine the association between elevated blood cadmium (Cd) and lead (Pb) concentrations and increased risk of gestational diabetes mellitus (GDM). METHODS: This cross-sectional study included pregnant women (n = 16,955) enrolled in the Japan Environment and Children's Study. Concentrations of Cd and Pb in blood samples collected at 22-28 weeks' gestation were measured by inductively coupled plasma mass spectrometry. GDM was diagnosed according to the 2011 Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists criteria. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis. RESULTS: Blood Cd and Pb concentrations were slightly higher among women with GDM than among those without GDM; however, these differences were not statistically significant. Elevated blood Cd and Pb concentrations were not associated with increased GDM risk in the nulliparous group (Cd OR 0.76; 95% CI 0.28-2.08 for high vs low category; Pb OR 2.51; 95% CI 0.72-8.72) or the parous group (Cd OR 0.64; 95% CI 0.29-1.44; Pb OR 0.31; 95% CI 0.04-2.29). CONCLUSIONS: This study demonstrates that Cd and Pb exposure, in the range of blood levels observed, has no significant relationship with the development of GDM. Further prospective studies would be valuable to confirm these findings.

Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: a review.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) has been widely used in the manufacture of polyvinyl chloride-containing products such as medical and consumer goods. Humans can easily be exposed to it because DEHP is ubiquitous in the environment. Recent research on the adverse effects of DEHP has focused on reproductive and developmental toxicity in rodents and/or humans. DEHP is a representative of the peroxisome proliferators. Therefore, peroxisome proliferator-activated receptor alpha (PPARα)-dependent pathways are the expected mode of action of several kinds of DEHP-induced toxicities. In this review, we summarize DEHP kinetics and its mechanisms of carcinogenicity and reproductive and developmental toxicity in relation to PPARα. Additionally, we give an overview of the impacts of science policy on exposure sources.

Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.

BACKGROUND: Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan. METHODS: Urine samples were collected from 62 non-smoking pregnant women (12-22 weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2 weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses. RESULTS: For all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points. CONCLUSION: This study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.

For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate.

In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a "super-aging" society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.

A sensitive and efficient procedure for the high-throughput determination of nine urinary metabolites of pyrethroids by GC-MS/MS and its application in a sample of Japanese children.

Four pyrethroids (PYRs), metofluthrin, profluthrin, tefluthrin, and transfluthrin, which were newly developed and have relatively high vapor activity at ambient temperature, are now playing a key role in safely controlling insects in our daily lives. We developed a sensitive and high-throughput determination method for urinary metabolites derived from the newly developed PYR, e.g., 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), 2,3,5,6-tetrafluorobenzyl alcohol (FB-Al), and other PYR metabolites such as trans-chrysanthemumdicarboxylic acid (trans-CDCA) and 3-phenoxybenzoic acid (3PBA). After high temperature acid hydrolysis of 2 mL urine sample in 24-deep well plate, the PYR metabolites were extracted by semi-automated liquid-liquid extraction with tert-butyl methyl ether. N,O-Bis (trimethylsilyl) trifluoroacetamide containing 1% trimethylchlorosilane or 1,1,1,3,3,3-hexafluoroisopropanol were used for the derivatization of PYR metabolites, and the derivatized metabolites were analyzed separately by GC-MS/MS equipped with dual injector system (DB-5MS and mid- to high-polarity phase Rtx-65 columns). The derivatization and evaporation conditions were mainly optimized for improving sensitivity and reproducibility. The mean within-run day precisions were less than 18.4% (relative standard deviation, %RSD) with low detection limits ranging from 0.01 µg/L for HOCH2-FB-Al to 0.06 µg/L for trans-CDCA. This method was successfully applied to urine samples obtained from 50 3-year-old children with high detection frequencies (e.g., 82% for HOCH2-FB-Al and 84% for FB-Al). This method may be a pivotal tool for developing risk assessment from PYR exposure in the general population.