Evaluating the risk of phthalate and non-phthalate plasticizers in dust samples from 100 Japanese houses.

Phthalates are widely used as plasticizer and associated with various health issues. Recently, non-phthalate plasticizers are replacing phthalates; however, the exposure to these substances and the risk in Japan is unclear. In this study, we assessed the concentrations of phthalates, non-phthalate plasticizers, and phthalate degradation products in house dust and determined their respective exposure risks via oral and dermal routes. Twelve phthalates, seven non-phthalate plasticizers, and two degradation products were determined in the house dust obtained from 100 Japanese homes. The median concentration of di(2-ethylhexyl) phthalate (DEHP), accounting for 85 % of the total concentration of phthalates and non-phthalate plasticizers detected in this study, was 2.1 × 103 µg/g of dust. Apart from DEHP, diisononyl phthalate (DINP) and di(2-ethylhexyl) terephthalate (DEHT) were the most abundant in the house dust, accounting for 6.2 % (median: 1.7 × 102 µg/g of dust) and 6.1 % (median: 1.7 × 102 µg/g of dust) of the total concentrations, respectively. DEHP and DEHT concentrations in house dust were higher in apartment and small houses (floor area: ≤30 m2 or 31-60 m2 for DEHP and 31-60 m2 for DEHT) than in detached and large houses (floor area: ≥121 m2). Conversely, di-n-butyl phthalate (DnBP) concentrations were significantly higher in detached and large houses (floor area: ≥121 m2) than in apartment and small houses (floor area: ≤30 m2). The total hazard quotient (HQ), using the maximum concentration in house dust, revealed that oral and dermal exposure to house dust was 1.3 × 10-6-0.11 for adults (all substances) and 1.6 × 10-5-2.2 × 10-2 for preschool children (except for DnBP and DEHP), suggesting no risk. The HQs for DnBP and DEHP exposure via house dust for preschool children using the maximum values were 0.46 and 1.2, and 6.0 × 10-3 and 0.18 using the median values, indicating that risk of DEHP exposure should be exhaustively determined by considering other exposure routes that were not evaluated in this study, such as diet.

Carbon and nitrogen stable isotope ratios of diet of the Japanese and diet-hair offset values.

The stable isotope ratios of carbon and nitrogen (δ13C and δ15N) were measured in composite samples of Japanese food and hair. Three hundred eighty-nine foodstuffs were collected in Tokyo and Gunma Prefecture, Japan, in 2020. The foodstuffs were classified into 15 food categories, prepared as usually consumed, and mixed to make 15 composite samples representing each of the food categories. Similarly prepared samples for foodstuffs collected in 2011 and 2015 were also examined. Composite hair samples were collected from a barber shop in Tokyo and a beauty salon in Gunma in 2019. The δ13C and δ15N values of the food and hair composites were measured by elemental analyzer/isotope ratio mass spectrometry after defatting. The δ13C and δ15N values of the food composite varied from composite to composite and according to year of collection. The whole-diet δ13C values were -21.1, -22.0, and -21.5 ‰ for the 2011, 2015, and 2020 samples, respectively; the δ15N values were 5.0, 4.4, and 4.4 ‰, respectively. Diet-hair offset values of δ13C and δ15N were calculated to be 1.9 and 4.3 ‰ for δ13C and δ15N, respectively. These offset values will be important for dietary analysis and nutritional research using hair isotope ratios.

Exposure levels of organophosphate pesticides in Japanese diapered children: Contributions of exposure-related behaviors and mothers' considerations of food selection and preparation.

Organophosphate (OP) pesticide exposure is a public health issue due to its potential link to neurodevelopmental problems in children. This study aimed to examine the exposure levels of OP pesticides in Japanese toddlers and explore the possible contributions of their exposure-related behaviors and their mothers' considerations of food selection and preparation to their exposure levels to OP pesticides. We recruited diapered children participating in the Japan Environment and Children's Study and collected used disposable diapers from 1037 children between June 2015 and August 2016. Six dialkylphosphates (DAPs) were measured in the urine extracted from the diapers. The geometric means of urinary creatinine (Cr)-unadjusted and Cr-adjusted concentrations of the sum of the six DAPs (ΣDAP) were 120 nmol/L and 243 nmol/g Cr, respectively. A receiver operating characteristic curve analysis for propensity scores of exposure-related factors revealed that discriminatory powers determining whether Cr-unadjusted and Cr-adjusted ΣDAP concentrations exceeded the 95th percentile values were lower for the exposure-related behaviors (areas under the curve, 0.72 and 0.69, respectively) and the mothers' considerations of food selection and preparation (0.55 and 0.57, respectively) than those for the foodstuffs ingested on the survey day (0.75 and 0.81, respectively). Some exposure-related behaviors, namely the use of insecticides, herbicides, and insect repellent sprays, were found to be associated with increased Cr-unadjusted ΣDAP concentrations (odds ratio, 2.0-2.6) via multivariate analysis. In contrast, only the use of a fragrance or deodorant was associated with increased Cr-adjusted ΣDAP concentrations (odds ratio, 2.3). This is the first report on the exposure levels of OP pesticides in a large number of Japanese toddlers. Some household chemical product use was related to OP common metabolite DAP levels. Japanese toddlers were widely exposed to OP pesticide.

Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A).

PURPOSE: Effects of fetal, perinatal and childhood environment on the health of children at birth and during later life have become a topic of concern. The Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A) is an ongoing birth cohort of pregnant women and their children which has been used to provide unique data, as adjunct studies of JECS, on multifaceted potential factors affecting children's health. PARTICIPANTS: The JECS-A is part of the JECS which follows a total of 100 000 pairs of children and their mothers (fathers' participation is optional) across 15 regions in Japan. In JECS-A, of the 8134 pregnant women living in Ichinomiya City and Nagoya City, Japan, a total of 5721 pregnant women and their 5554 children were included. Sociodemographic and psychological data as well as biological specimens were collected from the pregnant women and their spouses (if available) in the cohort during their pregnancy. Information on children included in the JECS-A was collected from their mothers and includes demographic, behavioural, childcare, psychological and psychiatric data. Urine extracted from disposable diapers and anthropometric data were also obtained from the children. FINDINGS TO DATE: A similar distribution trend for age at delivery was confirmed between the pregnant women enrolled in the JECS-A and the national statistics of the relevant areas. However, differences in education level and household income were observed. A total of 5502 children remained in the cohort at 18 months after delivery. Compared with the national statistics, the basic demographics of the children in the cohort represented the population in the study areas. FUTURE PLANS: The enrolled children in the JECS-A will be followed until the age of 13 years. The studies that come from JECS-A will complement JECS and bring novel results with a high level of generalisability.

Blood mercury, lead, cadmium, manganese and selenium levels in pregnant women and their determinants: the Japan Environment and Children's Study (JECS).

The Japan Environment and Children's Study (JECS) is a birth-cohort study of 100,000 mother-child dyads that aims to investigate the effect of the environment on child health and development. Mercury (Hg), lead (Pb), cadmium (Cd), manganese (Mn) and selenium (Se) are considered to be important co-exposures when examining the effect of other chemical substances on child development. The levels of these elements in the blood of 20,000 randomly selected mid/late-term pregnant women from the whole JECS cohort were analysed using inductively coupled plasma-mass spectrometry. The median concentrations (interquartile ranges) for Pb, Hg, Cd, Mn and Se were 0.63 (0.51-0.78) µg dl-1, 3.83 (2.70-5.43) µg l-1, 0.70 (0.52-0.95) µg l-1, 16.1 (13.2-19.6) µg l-1 and 178 (165-192) µg l-1, respectively. Hg and Se correlated positively with each other (Spearman's ρ = 0.287), as did Pb and Cd (ρ = 0.239) and Cd and Mn (ρ = 0.267). The blood Pb levels decreased by 5-10-fold over the past 25 years. The main predictors of the blood levels of each element were fish consumption for Hg, maternal age and non-alcoholic beverage consumption for Pb, maternal age and smoking for Cd, gestational age at sampling for Mn and serum protein levels for Se. These results revealed the historical trends and current predictors of the blood levels of these elements in pregnant Japanese women.

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.

[Exposure Assessment in Japan Environment and Children's Study].

In this review, we present an initial plan for exposure assessment in the Japan Environment and Children's Study (JECS) by focusing on a biomonitoring technique and discuss the challenges encountered when using the biomonitoring technique for exposure measurements. JECS registered 103,099 pregnant mothers and has been following children born to them. Various biological samples were collected from mothers during pregnancy (blood and urine), at birth (blood and hair) and at check-up one month after birth (breast milk). Samples were also collected from children at birth (cord blood) and at check-up one month after birth (hair and blood spot). Those samples will be used to assess maternal and foetal exposures to chemical substances. Measurement reliability, i.e., intraclass correlation coefficient (ICC), and attenuation bias related to low ICCs should be taken into consideration when using the biomonitoring results. Along with the biomonitoring technique, simulation models, pharmacokinetic (PK) models and exposomics techniques are under development in JECS. New analytical techniques include deciduous teeth measurements and -omics analyses. In particular, PK models and sensor technologies are one of the most important methodologies for future JECS exposure analyses. Statistical methods for examining the effects of intercorrelated multiple exposures as well as nondetection data should also be explored.

Estimation of daily intake of arsenolipids in Japan based on a market basket survey.

Arsenolipid concentrations were measured in 17 food composites prepared from 152 food items purchased in Shizuoka city, Japan, to (1) determine the food contributing to daily intake of arsenolipids, and (2) estimate the daily intake of arsenolipids. Analysis of arsenolipids was performed by high performance liquid chromatography-inductively coupled plasma mass spectrometry/electrospray ionization tandem mass spectrometry (HPLC-ICP-MS/ESI-MS-MS). Arsenic containing hydrocarbons (AsHCs), arsenic containing fatty acids (AsFAs), and arsenosugar phospholipids (AsSugPLs) were detected only in "algae" and "fish and shellfish" of the 17 food composites in a concentration range of 4.4-233 ng As/g fresh weight (fw). Two cytotoxic arsenolipids, AsHC332 and AsHC360, were detected in "algae" and "fish and shellfish" in the concentrations range of 33-40 ng As/g fw. The estimated average daily intake of AsHC332 and AsHC360 was ca 3000 and 360 ng As/person/day, or 50 and 6.0 ng As/kg bw/day, respectively. The present study indicated that arsenolipids from "algae" and "fish and shellfish" consumption contributed to the daily intake of toxic AsHCs, though the margin of exposure for the AsHC332 and AsHC360 does not appear to pose a health risk for the general Japanese population.

Exposure assessment of heavy metals in an e-waste processing area in northern Vietnam.

In developing countries, inappropriate recycling of e-waste has resulted in the environmental release of toxicants, including heavy metals, that may have deleterious health effects. In this study, we estimated daily metal intakes in five households in a Vietnamese village located in an e-waste processing area and assessed the health risk posed by exposure to the metals. Garden soil, floor dust, 24-h duplicate diet, and ambient air samples were collected from five households in northern Vietnam in January 2014. All samples were acid-digested, and contents of Cd, Cu, Mn, Pb, Sb, and Zn were measured by using ICP mass spectrometry and ICP atomic emission spectroscopy. In addition, the soil, dust, and diet samples were subjected to an bioaccessibility extraction test to determine bioaccessible metal concentrations. Hazard quotients were estimated from bioaccessible metal concentrations, provisional tolerable weekly intakes, and reference doses. Garden soil and floor dust were estimated to be mainly contributors to daily Pb intake, as indicated by calculations using bioaccessible metal concentrations and the U.S. Environmental Protection Agency soil plus dust ingestion rate. Diet was suggested to contribute significantly to daily Cd, Cu, Mn, Sb, and Zn intake. Estimated metal exposures via inhalation were negligible, as indicated by calculations using International Atomic Energy Agency reference inhalation rates. The maximum hazard quotients were calculated as 0.2 (Cd), 0.09 (Cu), 0.3 (Mn), 0.6 (Pb), 0.2 (Sb), and 0.5 (Zn), on the basis of bioaccessible metal concentrations. The contributions of Cd, Cu, Mn, Sb, and Zn except Pb to potential noncancer risk for adult residents of the five households in the e-waste processing area may be low.

Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects.

Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg-1 day-1 (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL-1. Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.

Quantitative analysis of organophosphate insecticide metabolites in urine extracted from disposable diapers of toddlers in Japan.

BACKGROUND AND AIM: Epidemiological studies linking insecticide exposure to childhood neurodevelopment have been gaining global attention. Despite the rapid development of the central nervous system in early childhood, studies regarding the biological monitoring of insecticide exposure in diapered children are limited. In this study, we aimed to clarify the concentrations of organophosphate (OP) insecticide metabolites in toddler urine extracted from disposable diapers in Japan. METHODS: We recruited diapered children from the Aichi regional subcohort participants of the Japan Environment and Children's Study (JECS) at the time of their 18-month checkup. A total of 116 children wore designated disposable diapers overnight, which were then sent as refrigerated cargo. The urine was extracted from the diapers using acetone and analyzed by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) to determine the concentrations of six dialkyl phosphates (DAPs) (i.e., dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP], diethyl phosphate [DEP], diethyl thiophosphate [DETP], and diethyl dithiophosphate [DEDTP]). DAP absorption into the diapers was quantified to calculate the urinary DAP concentrations. RESULTS: The DAP recovery using the developed method yielded between 54.2% (DEDTP) and 101.4% (DEP). Within-run precision expressed as the relative standard deviation was between 2.4% and 14.7%, and the between-run precision was between 3.1% and 8.5%. A Bland-Altman analysis confirmed the agreement between the results obtained by the developed method and by the measurements for the corresponding urine without diaper absorption. The geometric means (GM) of urinary DMP, DMTP, DMDTP, DEP, DETP, and total DAPs (ΣDAP) were 3.6, 3.9, 0.9, 6.0, 0.6µg/L, and 137.6 nmol/L, respectively. The GM of DEDTP was not calculated due to its low detection rate. CONCLUSIONS: We successfully established a method to measure the DAP concentrations in urine extracted from diapers and this is the first report of these pesticide concentrations in diapered children in Japan.

Urinary inorganic arsenic concentrations and semen quality of male partners of subfertile couples in Tokyo.

Inorganic arsenic (iAs) has been known as a testicular toxicant in experimental rodents. Possible association between iAs exposure and semen quality (semen volume, sperm concentration, and sperm motility) was explored in male partners of couples (n = 42) who visited a gynecology clinic in Tokyo for infertility consultation. Semen parameters were measured according to WHO guideline at the clinic, and urinary iAs and methylarsonic acid (MMA), and dimethylarsinic acid concentrations were determined by liquid chromatography-hydride generation-ICP mass spectrometry. Biological attributes, dietary habits, and exposure levels to other chemicals with known effects on semen parameters were taken into consideration as covariates. Multiple regression analyses and logistic regression analyses did not find iAs exposure as significant contributor to semen parameters. Lower exposure level of subjects (estimated to be 0.5 µg kg(-1) day(-1)) was considered a reason of the absence of adverse effects on semen parameters, which were seen in rodents dosed with 4-7.5 mg kg(-1).

Daily inorganic arsenic intake of the Japanese estimated by a probabilistic approach.

OBJECTIVE: The objective was to estimate the inorganic arsenic (iAs) intake of the general Japanese adult population by a probabilistic approach. METHODS: Bioaccessible iAs concentrations in rice (n=56) and hijiki (n=32), the two food items that are the major iAs sources for the Japanese, were measured by liquid chromatography-ICP mass spectrometry. The concentration in cooked rice was estimated from the measured concentration in a raw rice sample while taking into consideration the loss of iAs during cooking. The iAs concentration in hijiki was measured using soaked hijiki samples. The daily consumption of cooked rice and soaked hijiki was taken from published data. The distribution profile of daily iAs intake was estimated by multiplying the bioaccesible iAs concentration in cooked rice and soaked hijiki samples by the amount of these samples consumed daily, which were randomly extracted according to the respective distributions. This process was repeated 10,000 times. RESULTS: The distribution profiles of iAs concentration in rice and hijiki were normal and log-normal, respectively, and those of the amount of cooked rice and soaked hijiki consumed were beta and log-normal, respectively. The daily bioaccessible iAs intake values were estimated to be 19 and 59 µg/day at 50 and 95 percentile. At 50 percentile iAs intake, the contributions from rice and hijiki were estimated to be equal, whereas the contribution from hijiki increased with the estimated total daily iAs intake. CONCLUSIONS: The iAs intakes of Japanese subjects estimated in previous duplicated portion studies were fairly consistent with the present estimation. Moreover, it was confirmed that the cancer risk derived from dietary iAs intake of the general Japanese population was not negligible.

Inorganic arsenic in the Japanese diet: daily intake and source.

The concentrations of arsenic (As) species in 19 food composites prepared from 159 food items purchased in Shizuoka city, Japan, were determined (1) to estimate total daily intake of inorganic As (InAs) and some organic As species and (2) to determine food contributing to total daily InAs intake. As analysis included extraction of As species with a synthetic gastric juice (0.07 mol/L HCl + 0.01 % pepsin) from food composite and high-performance liquid chromatography-high efficiency photo-oxidation-hydride generation-inductively coupled plasma mass spectrometry. InAs was detected in 9 of 19 food composites at a concentration of 0.423-450 ng As/g fresh-weight. Daily intake of InAs from cereals was greatest (13 µg/person/day) followed by algae (5.7 µg/person/day), and the intake from the two categories constituted 90 % of the total daily InAs intake of adults (21 µg/person/day on a bioaccessible-fraction basis and 24 µg/person/day on a content basis). Analysis of individual food items showed that rice and hijiki contributed virtually 100 % of InAs from cereals and algae, respectively. The present survey indicated that InAs from rice and hijiki consumption contributed to total daily InAs intake and consequently to significant cancer risk of the general Japanese population. Daily intake of some organic forms of As and their contributing food categories was also estimated.

Daily intake of inorganic arsenic and some organic arsenic species of Japanese subjects.

The daily dietary intake of inorganic arsenic (InAs) and some of organic arsenic (OrAs) species of Japanese subjects were estimated by determining the concentrations of As species in two different sets of total diet sample: duplicated diet samples collected from 25 subjects in Japan and a certified reference material with total diet matrix (NIES CRM No. 27 Typical Japanese Diet, TJD). The concentration of InAs and OrAs in diet samples were determined by LC-ICP-MS using a photo-oxidation and hydride generation system. The median intake of InAs for the 25 subjects was 3.8 µg day(-1) (2.0-57 µg day(-1)) and intake of 27 µg day(-1) was estimated from TJD. The median intake of MMA, DMA and TMAsO were <0.18, 1.1 and <0.053 µg day(-1) for the 25 subjects and that of MMA, DMA, AB and TMAsO was estimated to be 3.9, 11, 140 and 5.9 µg day(-1), respectively, based on TJD analysis. On the basis of InAs intakes estimated and the oral slope factor of the US EPA and Health Canada, excess cancer risk was estimated to exceed acceptable level. Cancer risk posed by the dietary InAs of the general Japanese may not be negligible.

Evaluation of bactericidal effects of low-temperature nitrogen gas plasma towards application to short-time sterilization.

To develop a novel low-temperature plasma sterilizer using pure N(2) gas as a plasma source, we evaluated bactericidal ability of a prototype apparatus provided by NGK Insulators. After determination of the sterilizing conditions without the cold spots, the D value of the BI of Geobacillus stearothermophilus endospores on the filter paper was determined as 1.9 min. However, the inactivation efficiency of BI carrying the same endospores on SUS varied to some extent, suggesting that the bactericidal effect might vary by materials of sterilized instruments. Staphylococcus aureus and Escherichia coli were also exposed to the N(2) gas plasma and confirmed to be inactivated within 30 min. Through the evaluation of bactericidal efficiency in a sterilization bag, we concluded that the UV photons in the plasma and the high-voltage pulse to generate the gas plasma were not concerned with the bactericidal effect of the N(2) gas plasma. Bactericidal effect might be exhibited by activated nitrogen atoms or molecular radicals.