Effect of Neonicotinoid Pesticides on Japanese Water Systems: Review with Focus on Reproductive Toxicity.

Neonicotinoid pesticides (NPs) are neurotoxic substances. They are highly effective as insecticides owing to their water solubility, permeability, and long-lasting activity. These molecules are structurally similar to nicotine and act as nicotinic acetylcholine receptor agonists. The administration of NPs to experimental animals reportedly causes neuromuscular and reproductive disorders. Moreover, recently reported problems caused by NPs include damage to land-dwelling creatures (such as mammals and birds), hydrobiology, and ecosystems. This review summarizes the recent reports on NP concentrations detected in river systems in several Japanese regions. These values were lower than the environmental standard values; however, seasonal variations were observed. Furthermore, reports on NP-induced testicular and ovarian toxicity were examined, revealing that the mechanism of injury is mainly driven by oxidative stress. The use of NPs is declining worldwide, except in Japan; therefore, continuous monitoring remains necessary.

Association between telomere length in human umbilical cord tissues and polychlorinated biphenyls in maternal and cord serum.

Environmental exposure to persistent organic pollutants during pregnancy has potential adverse health effects on the fetus. One of the environmental pollutants is polychlorinated biphenyl (PCB). Earlier, we reported the presence of PCBs in fetal tissues such as the umbilical cord. Telomere length (TL) is a biomarker of aging because it shortens with each cell division. According to the Developmental Origins of Health and Disease hypothesis, fetal exposure to environmental pollutants during pregnancy affects the occurrence of non-communicable diseases in later life. In the current study, we investigated the association between cord tissue TL and serum levels of PCBs. The subjects were 114 mother-child pairs participating in a birth cohort study, the Chiba Study of Mother and Child Health (C-MACH). Maternal serum was collected during pregnancy, and cord serum and tissue were obtained at birth. TL was assessed by qPCR using genomic DNA extracted from the cord tissue. Maternal and cord serum PCB congener levels were assessed using gas chromatography and negative ion chemical ionization qMS. In male fetuses, serum levels of PCB74 in the cord blood were significantly associated with TL following covariate adjustment, but no significant association was found in female fetuses. These data suggest that the TL of the umbilical cord is affected by fetal exposure to PCBs.

Association between Total and Individual PCB Congener Levels in Maternal Serum and Birth Weight of Newborns: Results from the Chiba Study of Mother and Child Health Using Weighted Quantile Sum Regression.

Maternal exposure to polychlorinated biphenyls (PCBs) during pregnancy is associated with a low birth weight; however, the congener-specific effects of PCB congeners are not well defined. In this study, we used maternal serum samples from the Chiba Study of Mother and Child Health (C-MACH) cohort, collected at 32 weeks of gestational age, to analyze the effects of PCB congener exposure on birth weight by examining the relationship between newborn birth weight and individual PCB congener levels in maternal serum (n = 291). The median total PCB level in the serum of mothers of male and female newborns at approximately 32 weeks of gestation was 39 and 37 ng g-1 lipid wt, respectively. The effect of the total PCB levels and the effects of PCB congener mixtures were analyzed using a linear regression model and a generalized weighted quantile sum regression model (gWQS). The birth weight of newborns was significantly associated with maternal exposure to PCB mixtures in the gWQS model. The results suggest that exposure to PCB mixtures results in low newborn birth weight. However, specific impacts of individual PCB congeners could not be related to newborn birth weight.

Assessment of Personal Relaxation in Indoor-Air Environments: Study in Real Full-Scale Laboratory Houses.

The relationship between chemical concentrations in indoor air and the human sense of comfort and relaxation have been reported. We investigated the effect of the sum of volatile organic compounds (ΣVOCs; sum of 79 VOCs) on the level of relaxation in two laboratory houses with almost identical interior and exterior appearances. The electroencephalogram (EEG) was monitored to evaluate the degree of personal relaxation objectively. The experiments were conducted in laboratory houses (LH) A and B with lower and higher levels of ΣVOCs, respectively. A total of 168 healthy volunteers participated, who each performed the task for 20 min, followed by a 10-min break, and EEG was measured during the break. Simultaneously as subjective evaluations, the participants were asked to fill a questionnaire regarding the intensity of odor and preference for the air quality in each LH. The subjective evaluation showed a significant association between ΣVOCs and participants' relaxation (OR: 2.86, 95%CI: 1.24-6.61), and the objective evaluation indicated that the participants were more relaxed in the LH with lower levels of ΣVOCs than that with higher levels (OR: 3.03, 95%CI: 1.23-7.50). Therefore, the reduction of ΣVOCs and odors in indoor air would have an effect, which is the promotion of relaxation.

Association between sum of volatile organic compounds and occurrence of building-related symptoms in humans: A study in real full-scale laboratory houses.

It is well known that the indoor environment, particularly indoor air quality (IAQ), has significant effects on building-related symptoms (BRSs) in humans, such as irritation of mucosal membranes, headaches, and allergies, such as asthma and atopic dermatitis. In 2017, Chiba University launched the "Chemiless Town Project Phase 3" to investigate the relationship between IAQ and human health. Two laboratory houses (LHs) were built on a university campus in which the interiors and exteriors were similar, but the levels of indoor air volatile organic compounds (VOCs) were different. A total of 141 participants evaluated IAQ using their sensory perception. There was a significant relationship between differences in VOC levels and BRSs occurrence (OR: 6.89, 95% CI: 1.40-33.98). It was suggested that people with a medical history of allergies (OR: 5.73, 95% CI: 1.12-29.32) and those with a high sensitivity to chemicals (OR: 8.82, 95% CI: 1.16-67.16) tended to experience BRSs. Thus, when buildings are constructed, people with a history of allergies or with a sensitivity to chemicals may be at high risk to BRSs, and it is important to pay attention to IAQ to prevent BRSs.

Concentrations of Formic Acid, Acetic Acid, and Ammonia in Newly Constructed Houses.

Herein, the concentrations of formic acid, acetic acid, and ammonia in samples of indoor air for 47 new houses were measured two weeks after completion. The houses were fabricated with light-gauge steel structures. The measurements were performed in living rooms and bedrooms without furniture and outdoors. Air samples were analyzed using ion chromatography. The mean values were 28 (living room), 30 (bedroom), and 20 µg m-3 (outdoor air) for formic acid; 166 (living room), 151 (bedroom), and 51 µg m-3 (outdoor air) for acetic acid; and 73 (living room), 76 (bedroom), and 21 µg m-3 (outdoor air) for ammonia. The total values of the three substances accounted for 39.4-40.7% of the sum of chemical compound values. The analyzed compounds were indicated by two principal components (PC), PC1 (30.1%) and PC2 (9%), with 39.1% total variance. Formic acid, acetic acid, and ammonia were positively aligned with PC1 and negatively aligned with PC2. Factors such as room temperature, aldehydes, and phthalates were positively aligned with PC1 and negatively aligned with PC2. Furthermore, concentrations of formic acid, acetic acid, and ammonia were significantly and positively correlated with room temperature (p < 0.05).

Prevalence and risk factors of pre-sick building syndrome: characteristics of indoor environmental and individual factors.

BACKGROUND: With the aim to prevent sick building syndrome and worsening of allergic symptoms, primarily resulting from the indoor environment, the relationships among people's residential environment in recent years, their lifestyle habits, their awareness, and their symptoms were investigated using an online survey. METHODS: In the survey, respondents experiencing symptoms specific to sick building syndrome, although they were not diagnosed with sick building syndrome, were categorized in the pre-sick building syndrome group. The relationships among individual characteristics, residential environment, and individual awareness were analyzed. RESULTS: Results showed that the prevalence of pre-sick building syndrome was high among young (aged 20-29 years) population of both sexes. In addition, "condensation," "moisture," "musty odors" in the house, and the "use of deodorant and fragrance" were all significantly associated with pre-sick building syndrome. Conversely, there was no significant association with recently built "wooden" houses that are highly airtight and have thermal insulation. CONCLUSIONS: Efficient "ventilation" plans and "ventilation" improvement and air conditioning systems to prevent mold and condensation in rooms are necessary to maintain a good, indoor environment that is beneficial for health. Efforts should also be made to encourage individuals to regularly clean and effectively ventilate their homes.

Indoor Air Quality Analysis of Newly Built Houses.

Recently, people have become increasingly aware of potential health issues related to indoor environments. In this study, we measure the concentrations of various volatile organic compounds, carbonyl compounds, and semi-volatile organic compounds, as well as the ventilation rates, in 49 new houses with light-gauge steel structures one week after completion. The proper indoor air quality of new residential environments can be ensured by characterizing people's exposure to certain chemicals and assessing future risks. Our results show that the concentrations of the measured compounds were lower than the guideline values set by the Ministry of Health, Labour and Welfare of Japan, and would continue to decrease. However, we observed that unregulated compounds, assumed to be substitutes for regulated solvents, contributed substantially to the total volatile organic compounds. To reduce indoor chemical exposure risks, the concentrations of these unregulated compounds should also be minimized. In addition, their sources need to be identified, and manufacture and use must be monitored. We believe it is important to select low-emission building materials for reducing residents' exposure to indoor chemicals.

An Altered DNA Methylation Status in the Human Umbilical Cord Is Correlated with Maternal Exposure to Polychlorinated Biphenyls.

Maternal exposure to polychlorinated biphenyls (PCBs) results in abnormal fetal development, possibly because of epigenetic alterations. However, the association between PCB levels in cord serum with fetal DNA methylation status in cord tissue is unclear. This study aims to identify alterations in DNA methylation in cord tissue potentially associated with PCB levels in cord serum from a birth cohort in Chiba, Japan (male neonates = 32, female neonates = 43). Methylation array analysis identified five sites for female neonates (cg09878117, cg06154002, cg06289566, cg12838902, cg01083397) and one site for male neonates (cg13368805) that demonstrated a change in the methylation degree. This result was validated by pyrosequencing analysis, showing that cg06154002 (tudor domain containing 9: TDRD9) in cord tissue from female neonates is significantly correlated with total PCB levels in cord serum. These results indicate that exposure to PCBs may alter TDRD9 methylation levels, although this hypothesis requires further validation using data obtained from female neonates. However, since the present cohort is small, further studies with larger cohorts are required to obtain more data on the effects of PCB exposure and to identify corresponding biomarkers.

The relationship of maternal PCB, toxic, and essential trace element exposure levels with birth weight and head circumference in Chiba, Japan.

Maternal exposure to high levels of persistent organic pollutants (POPs) and trace elements is an important concern for fetal growth. In our previous study, we showed the polychlorinated biphenyl (PCB) levels in maternal serum from the Chiba Study of Mother and Child Health (C-MACH) cohort and their relationships between PCB levels in cord serum with birth weight of newborn. Various reports on the relationship between chemical exposure and birth status have been published; however, studies that analyze the effects of both PCB and metal exposure together in one cohort are still limited. In this study, we aimed to determine the relationship of maternal serum levels of PCBs and toxic and essential trace elements [mercury (Hg), manganese (Mn), selenium (Se), and cadmium (Cd)], with birth weight and head circumference, in the C-MACH cohort. The median concentration of total PCBs in maternal serum around 32 gestational weeks (n = 62) was 360 pg g-1 wet wt (41 ng g-1 lipid wt). The levels of Hg, Mn, Se, and Cd in maternal serum were 0.89, 0.84, 100, and 0.024 ng g-1, respectively. In this study, the Bayesian linear model determined the relationships of the birth weight and head circumference with combinations of PCB levels, toxic and essential trace elements, and questionnaire data. We found that PCB concentrations in maternal serum were weakly and negatively related to birth weight, whereas trace elements were not associated with birth weight. Serum PCB and Mn levels were negatively associated with head circumference, whereas other trace elements were not associated with head circumference. These results showed that maternal exposure to PCBs may be related to birth weight and head circumference, while maternal exposure to Mn is related to head circumference, even when adjusted based on the exposure levels of other contaminants, and maternal and fetal characteristics. Therefore, our findings indicate that maternal exposure to PCBs and Mn might be negatively related with birth weight and head circumference.

Alterations in urinary metabolomic profiles due to lead exposure from a lead-acid battery recycling site.

Lead poisoning is considered a public health threat, particularly in developing countries. Health problems from Pb exposure occur in many parts of the world, especially near Pb mines, Pb smelters, and used lead-acid battery (ULAB) recycling plants. In this study, we analyzed the urine metabolome of residents in a village located near a ULAB recycling facility to investigate the biological effects of Pb exposure (ULAB: n = 44, Reference: n = 51). Lasso linear regression models were moderately predictive of blood Pb levels, as evaluated by a training set (R2 = 0.813) and against an external test set (R2EXT = 0.647). In lasso logistic regression models, areas under receiver operating characteristic curves, as measured by 5-fold cross-validation (AUCCV = 0.871) and against an external test set (AUCEXT = 0.917), indicated accurate classification of urine samples from the affected village and from a reference site. Ten candidate biomarkers identified at false discovery rates of <0.05 were associated with ATP-binding cassette (ABC) transporters, possibly related to the disruption of small-molecule transport in the kidney; amino acid, porphyrin, and chlorophyll metabolism; and the heme biosynthetic pathway. Collectively, the results suggest that lead Pb is related to the health effects in individuals residing in ULAB site by alteration of these biological pathways.

Fetal exposure markers of dioxins and dioxin-like PCBs.

Fetal exposure to polychlorinated biphenyls (PCBs), polychlorinated-p-dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have been associated with a number of adverse health outcomes. Although the placenta acts as a barrier between the mother and the fetus, these contaminants transfer through the placenta exposing the fetus. Several studies have investigated placental transfer, but few have assessed the co-variation among these contaminants. Maternal blood, cord blood, and cord tissue were collected from 41 Japanese mother-infant pairs and analyzed for dioxin-like PCBs and PCDD/Fs. Hierarchical cluster analysis followed by principal component analysis were used to assess the co-variation. Two stable clusters of dioxin-like PCBs were found in maternal and cord blood. One cluster of low/medium chlorinated dioxin-like PCBs was present in all three matrices with 2,3',4,4',5-PeCB(#118) and 3,3',4,4',5-PeCB(#126) explaining the majority of the clusters' variances. Medium/high chlorinated dioxin-like PCBs clustered in maternal blood and cord blood but not in cord tissue. 2,3,4,4',5-PeCB(#114) and 2,3,3',4,4',5,5'-HpCB(#189) explained the majority of the clusters' variances. There was a substantial correlation between the sum of dioxin-like PCBs and total PCDD/F in all three matrices. The sum of the four suggested PCBs plus 3,3',4,4'-TeCB(#77) correlated well with total PCDD/F in all three matrices. Apart from the dioxin-like PCBs, little co-variation existed among the studied contaminants. The five PCBs can be used as fetal exposure markers for dioxin and dioxin-like PCBs in maternal and cord blood respectively. In cord tissue, more higher chlorinated dioxin-like PCBs need to be measured as well.

Maternal-fetal transfer rates of PCBs, OCPs, PBDEs, and dioxin-like compounds predicted through quantitative structure-activity relationship modeling.

The present study aims to predict the maternal-fetal transfer rates of the polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), and dioxin-like compounds using a quantitative structure-activity relationship model. The relation between the maternal-fetal transfer rate and the contaminants' physicochemical properties was investigated by multiple linear regression (MLR), partial least square regression (PLS), and random forest regression (RF). The 10-fold cross-validation technique estimated low predictive performances for both MLR and PLS models (R 2CV = 0.425 ± 0.0964 for MLR and R 2CV = 0.492 ± 0.115 for PLS) and is in agreement with an external test (R 2pred = 0.129 for MLR and R 2pred = 0.123 for PLS). In contrast, the RF model exhibits good predictive performance, estimated through 10-fold cross-validation (R 2CV = 0.566 ± 0.0885) and an external test set (R 2pred = 0.519). Molecular weight and polarity were selected in all models as important parameters that may predict the ability of a molecule to cross the placenta to the fetus.

Dietary Habits and Cooking Methods Could Reduce Avoidable Exposure to PCBs in Maternal and Cord Sera.

Polychlorinated biphenyls (PCBs), like other persistent organic pollutants, are accumulating throughout the food chain and pose health threats to humans, especially children and foetuses. There is no protocol for reducing the contamination levels of the PCBs in humans. This study identified food items and cooking methods that reduce serum PCB levels by analysing data collected from the Chiba Study of Mother and Child Health. The sample size was 194 subjects. Serum PCB levels were measured using gas chromatography-electron capture negative ionization quadrupole mass spectrometry. Information on dietary habits was obtained from a brief diet history questionnaire that included questions about food items and cooking methods. Food items were categorized into food groups, and nutrient levels were calculated based on food item consumption. Principal component analysis and lasso regression were used as statistical methods. The analyses of food items and nutrients suggested that food items rich in dietary fibre reduce avoidable exposure to PCBs, as could grilling and deep frying of food, which could reduce avoidable exposure to serum PCBs in mothers and foetuses. (174 words).

For a healthier future: a virtuous cycle for reducing exposure to persistent organic pollutants.

In the modern society, people are exposed to various pollutants during their lifetime. Worldwide, the status of children's health has changed in recent decades. Some studies have attempted to identify the causes of these changes and whether they relate to pollutant exposure; however, such attempts have faced major challenges because human life is complex, involving many social and environmental factors. Several long-term cohort studies are being conducted to determine the relationship between diseases and social and environmental factors in children. Even before we establish complete proof of adverse effects, we should attempt to decrease risk to future generations by adopting precautionary principles. Environmental exposure to persistent organic pollutants can be reduced throughout the stages of life-the fetal period, newborn and infant periods, childhood, adolescence and adulthood (preconception) by individuals as well as by society as a whole. Through reducing environmental exposure to pollutants, adverse health effects can also be reduced, which will contribute to healthier future generations. Here, we suggest a virtuous cycle for improving the health of future generations through reduced exposure to persistent pollutants.

Assessment of questionnaire-based PCB exposure focused on food frequency in birth cohorts in Japan.

We investigated the relationship between food frequency questionnaire (FFQ) responses and serum polychlorinated biphenyl (PCB) levels of mothers and fathers recruited from the Chiba Regional Center, which is one of the 15 regional centers of the Japan Environment and Children's Study (mothers: n = 1477, fathers: n = 219). The expected PCB values were estimated from the participants' FFQ answers and medical records (age, body mass index and number of deliveries). Based on the stepwise forward selection results of Bayesian regression models, age and fish and egg consumption were positively associated with PCB concentrations and a number of deliveries were negatively associated with PCB concentrations in mothers, whereas only age was positively associated with PCB concentrations in fathers.These findings indicated that the estimation of daily dietary intake may be useful for the prediction of PCB concentration for mothers.

Chiba study of Mother and Children's Health (C-MACH): cohort study with omics analyses.

PURPOSE: Recent epidemiological studies have shown that environmental factors during the fetal period to early childhood might affect the risk of non-communicable diseases in adulthood. This is referred to as the developmental origins of health and disease (DOHaD) concept. The Chiba study of Mother and Children's Health (C-MACH) is a birth cohort study based on the DOHaD hypothesis and involves multiomics analysis. This study aims to explore the effects of genetic and environmental factors--particularly the fetal environment and postbirth living environment--on children's health, and to identify potential biomarkers for these effects. PARTICIPANTS: The C-MACH consists of three hospital-based cohorts. The study participants are pregnant women at <13 weeks gestation. Women who underwent an examination in one of the three hospitals received an explanation of the study. The participants consented to completing questionnaire surveys and the collection and storage of biological and house/environmental samples. Participants were provided unique study numbers. All of the data and biological specimens will be stored in the Chiba University Center for Preventive Medical Sciences and Chiba University Center for Preventive Medical Sciences BioBank, respectively. FINDINGS TO DATE: Consent to participate was obtained from 433 women. Of these women, 376 women completed questionnaires in the early gestational period. The mean age was 32.5 (4.4) years. The mean body mass index (BMI) was 21.1 (3.0) kg/m(2). Before pregnancy, 72.3% of the women had a BMI of 18.5-24.9 kg/m(2). During early pregnancy, 5.0% of the participants smoked. FUTURE PLANS: Primary outcomes are allergy, obesity, endocrine and metabolic disorders, and developmental disorders. Genome-level, metabolome-level, umbilical cord DNA methylation (epigenome), gut microbiota and environmental chemical exposure variables will be evaluated. We will analyse the relationships between the outcomes and analytical variables.

Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure.

Polychlorinated biphenyl levels in the blood of Japanese individuals ranging from infants to over 80 years of age.

Individuals' exposure to various persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), and its adverse health effects have been a cause of concern. We measured blood PCB concentrations from samples taken from 507 Japanese individuals ranging from infants to those over 80 years of age. The blood PCB levels increased with age for both male (Spearman's r = 0.69, p < 0.001) and female (Spearman's r = 0.70, p < 0.001) participants. Adult men and nulliparous women showed similar increases with age. However, the PCB levels of multiparous women were lower than those of nulliparous women in their thirties (p = 0.005), probably because the PCBs were transferred from the mothers to their children during pregnancy and lactation. Among infants (<2 years of age), some had as high levels of accumulated PCB levels as those in adults >30 years of age. In some cases, the PCB levels were over 0.8 ng/g wet weight, similar to levels observed in adults over 50 years of age. In the future, it will be necessary to do research on the health of the children who are exposed by high concentration level of POPs.

The influence of environmental exposure to formaldehyde in nasal mucosa of medical students during cadaver dissection.

BACKGROUND: Environmental exposure to formaldehyde is commonly associated with clinical symptoms such as mucosal irritation and olfactory disorders. However, the impact of such exposure on the development of mucosal inflammation and its outcome has not been carefully evaluated. METHODS: The observational non-comparative study was planned. The study population consisted of group of 41 medical students who had signed up for a cadaver dissection course as part of their gross anatomy teaching at the school of medicine Chiba University in Japan. During such dissection course, the students are exposed to variable levels of environmental formaldehyde routinely employed for the preservation the cadavers. The subjects were evaluated by a detailed medical examination. We measured their serum IgE levels. In addition, an olfaction test and nasal mucosal sensitivity to histamine was serially determined, immediately before and after the course and 6 months after the completion of the course. RESULTS: Olfactory abnormalities were observed in 13/41 (32%) subjects and increased nasal mucosal hypersensitivity to histamine was observed in 17/41 (41%) during and immediately after completion of the course. These subjects had evidence of preexisting allergic rhinitis. 6/41 (15%) other students with no prior evidence of allergic rhinitis also exhibited formaldehyde associated clinical symptoms during the dissecting course. However, the symptoms disappeared upon completion of the course in all subjects studied. CONCLUSIONS: Temporary abnormalities in the olfaction test and increased nasal mucosal hypersensitivity to histamine were observed in a few students with preexisting allergic rhinitis after environmental exposure of high concentrations of formaldehyde. These effects appeared to be transient.