Dioxins levels in human blood after implementation of measures against dioxin exposure in Japan

Background: Over the past few decades, the Japanese Ministry of the Environment has been biomonitoring dioxins in the general Japanese population and, in response to public concerns, has taken measures to reduce dioxin exposure. The objectives of this study were to assess the current dioxin dietary intake and corresponding body burden in the Japanese and compare Japanese dioxin data from 2011 to 2016 and 2002–2010 surveys. We also examined the relationship between blood dioxins and health parameters/clinical biomarkers. Methods: From 2011 to 2016, cross-sectional dioxin surveys were conducted on 490 Japanese (242 males and 248 females, aged 49.9 ± 7.6 years) from 15 Japanese prefectures. Blood (n = 490) and food samples (n = 90) were measured for 29 dioxin congeners including polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) using gas chromatography coupled with high-resolution mass spectrometry. Using the 2006 World Health Organization toxic equivalence factors, the toxic equivalents (TEQs) were calculated. Clinical biomarkers and anthropometric parameters were also measured and information on lifestyle behaviours collected. Data imputations were applied to account for blood dioxins below the detection limit. Results: The median (95% confidence interval or CI) blood levels and dioxin dietary intake was respectively 9.4 (8.8–9.9) pg TEQ/g lipid and 0.3 (0.2–0.4) pg TEQ/kg body weight/day. The median blood dioxin level in the 2011–2016 survey was found to have decreased by 41.3% compared to the 2002–2010 surveys. Participants who were older were found to be more likely to have higher dioxin levels. Blood dioxins were also significantly associated with body mass index, triglycerides, docosahexaenoic acid, eicosapentaenoic acid, and dihomo-gamma-linoleic acid levels in blood. Furthermore, associations between blood dioxin and dietary dioxin intake were evident in the unadjusted models. However, after adjusting for confounders, blood dioxins were not found to be associated with dietary dioxin intake. Conclusions: Blood dioxin levels declined over the past decade. This study showed that the measures and actions undertaken in Japan have possibly contributed to these reductions in the body burden of dioxins in the Japanese population

The association between temperature variability and cause-specific mortality: Evidence from 47 Japanese prefectures during 1972–2015

BackgroundIn the context of climate change, extreme temperature events are known to be associated with increased mortality risk. However, data about the mortality risk related to temperature variability (TV) accounting for both intra- and inter-day variations in temperature are limited.ObjectivesThe present study aims to quantify the associations between TV and cause-specific mortality in Japan, evaluate whether the effects of TV are modified by prefecture-level characteristics and examine the temporal trend in mortality risk of TV.MethodsData on daily all-cause and 11 cause-specific mortality and meteorological variables in 47 Japanese prefectures from 1972 to 2015 were collected. TV was defined as the standard deviation of daily minimum and maximum temperatures during exposure days. A quasi-Poisson regression model combined with a distributed lag non-linear model was firstly applied to assess the prefecture-specific mortality effects of TV, adjusting for potential confounders. The pooled effects of TV at the national level were then obtained via a meta-analysis through the restricted maximum-likelihood estimation. Potential effect modification by prefecture characteristics was firstly examined using a meta-regression analysis, and the joint modification of season and humidity was then evaluated after including product terms in two-stage analyses. Finally, the temporal trend in TV effects was evaluated by a random-effect meta regression model after obtaining the prefecture-year-specific effects.ResultsTV had significant adverse effects on all-cause and cause-specific mortality. The effects of TV were more detrimental to those with asthma and senility. In general, the estimates of mortality risk increased with longer exposure days. A 1 °C increase in TV at 0–7 days of exposure was associated with a 0.9% (95% confidence intervals: 0.82%–0.98%) increase in all-cause mortality. All-cause mortality risk of TV showed a decreasing trend during our study period. TV effects were larger in densely populated prefectures and on warm and humid days.ConclusionsTV-related death is a significant issue in Japan that requires effective interventions

In utero and Lactational Exposure to Acetamiprid Induces Abnormalities in Socio-Sexual and Anxiety-Related Behaviors of Male Mice

Neonicotinoid, a widely-used pesticide group designed to selectively bind to insect nicotinic acetylcholine receptors, were considered to be relatively safe for mammalian species. However, it has been found to activate vertebrate nicotinic acetylcholine receptors than ever anticipated, and could be toxic to the mammalian brain. In the present study, we evaluated the developmental neurotoxicity of acetamiprid (ACE), one of the most-widely used neonicotinoid, in C57BL/6J mice whose mothers were administered ACE via gavage at doses of either 0 mg/kg (control), 1.0 mg/kg (low-dose) or 10.0 mg/kg (high-dose) from gestational day 6 to lactation day 21. As possible endpoints, a battery of behavior tests, socio-sexual and anxiety-related behaviors, as well as testosterone level and the number of vasopressin-immunoreactive cells in the paraventricular nucleus of the hypothalamus were examined. In addition, behavioral flexibility was assessed for mice in a group-housed environment using an IntelliCage, a fully automated mouse behavioral analysis system. In adult male mice exposed to ACE at both low and high doses, significant reduction of anxiety level was found in the light-dark transition test. Males in the low-dose group also showed a significant increase in sexual and aggressive behaviors. In contrast, neither the anxiety nor the sexual behavior of females was altered. No impairments in testosterone level, the number of vasopressin-immunoreactive cells, and behavioral flexibility were detected in either sex. These results suggest the possibility that in utero and lactational ACE exposure interferes with the development of the neural circuits required for executing socio-sexual and anxiety-related behaviors in male mice specifically

Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy : a multicenter, investigator‑blinded, randomized, parallel group controlled trial (PACI Study) : protocol for a randomized controlled trial

Background: Atopic dermatitis is the first clinical manifestation of the atopic march, with the highest incidence in the first year of life. Those affected often go on to develop other allergic diseases including food allergy, asthma, and allergic rhinitis. Recent evidence suggests that sensitization to foods may occur through a defective skin barrier which is common in atopic dermatitis in early life. We hypothesize that therapeutic aggressive intervention to treat new onset atopic dermatitis may prevent the development of later allergen sensitization, and associated food allergy, asthma, and allergic rhinitis. Methods: This study is a multi-center, pragmatic, two-parallel group, assessor-blind, superiority, individually randomized controlled trial. Atopic dermatitis infants (N = 650) 7–13 weeks old who develop an itchy rash within the previous 28 days are randomly assigned to the aggressive treatment or the conventional treatment in a 1:1 ratio. The primary outcome is oral food challenge-proven IgE-mediated hen’s egg allergy at the age of 28 weeks. Discussion: This is a novel pragmatic RCT study to examine the efficacy of early aggressive treatment for atopic dermatitis to prevent later food allergy. If our hypothesis is correct, we hope that such a strategy might impact on disease prevention in countries where food allergy is common, and that our results might reduce the frequency and associated costs of all food allergies as well as hens egg food allergy. Long-term follow and other similar studies will help to determine whether such a strategy will reduce the burden of other allergic diseases such as asthma and allergic rhinitis

Analysis of PFOA in dosed CD-1 mice. Part 2: Disposition of PFOA in tissues and fluids from pregnant and lactating mice and their pups

Previous studies in mice with multiple gestational exposures to perfluorooctanoic acid (PFOA) demonstrate numerous dose dependent growth and developmental effects which appeared to worsen if offspring exposed in utero nursed from PFOA-exposed dams. To evaluate the disposition of PFOA in the pregnant and lactating dam and her offspring, time-pregnant CD-1 mice received a single 0, 0.1, 1, or 5 mg PFOA/kg BW dose (n = 25/dose group) by gavage on gestation day 17. Maternal and pup fluids and tissues were collected over time. Pups exhibited significantly higher serum PFOA concentrations than their respective dams, and their body burden increased after birth until at least postnatal day 8, regardless of dose. The distribution of milk:serum PFOA varied by dose and time, but was typically in excess of 0.20. These data suggest that milk is a substantial PFOA exposure route in mice and should be considered in risk assessment modeling designs for this compound

A new approach for measuring the muon anomalous magnetic moment and electric dipole moment

This paper introduces a new approach to measure the muon magnetic moment anomaly a?? = (g - 2)/2 and the muon electric dipole moment (EDM) d?? at the J-PARC muon facility. The goal of our experiment is to measure a?? and d?? using an independent method with a factor of 10 lower muon momentum, and a factor of 20 smaller diameter storage-ring solenoid compared with previous and ongoing muon g - 2 experiments with unprecedented quality of the storage magnetic field. Additional significant differences from the present experimental method include a factor of 1000 smaller transverse emittance of the muon beam (reaccelerated thermal muon beam), its efficient vertical injection into the solenoid, and tracking each decay positron from muon decay to obtain its momentum vector. The precision goal for a?? is a statistical uncertainty of 450 parts per billion (ppb), similar to the present experimental uncertainty, and a systematic uncertainty less than 70 ppb. The goal for EDM is a sensitivity of 1.5 ?? 10-21 ecm

Periconceptional maternal diet quality influences blood heavy metal concentrations and their effect on low birth weight: the Japan Environment and Children’s Study

Background: Both poor maternal nutrition and toxic heavy metal exposure influence foetal growth and development. However, whether consumption of a variety of healthy foods modifies the association between prenatal heavy metal exposure and foetal growth is unknown. Objective: We examined whether long-term maternal diet quality in periconception modifies the associations between maternal circulating concentrations of heavy metals and foetal growth. Design: Data of 72,317 Japanese women who delivered singleton infants was extracted from the Japan Environment and Children’s Study. Maternal diet over a 1-year before the first trimester of pregnancy was assessed using a validated food frequency questionnaire, and overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Maternal whole-blood concentrations of mercury (Hg), lead (Pb) and cadmium (Cd) were measured during the second/third trimester of pregnancy. Bayesian inference of multiple linear regression analysis was performed to evaluate the relationships between maternal diet quality and the blood concentrations of heavy metals; Bayesian logistic regression was used to analyse the risk of low birth weight (LBW; <2,500 g). Results: After controlling for confounders, a high maternal balanced diet score was associated with low concentrations of blood Pb and Cd and high Hg. While all heavy metals assessed were positively associated with LBW risk, a higher maternal balanced diet score was negatively associated with LBW risk. A high-quality maternal diet attenuated the effect of Pb on LBW, an effect that was more marked at high blood Pb concentrations. Conclusion: A high-quality, ‘well-balanced’ diet prior to conception may reduce exposure to some heavy metals and mitigate the elevated risk of LBW associated with prenatal Pb exposure in Japanese mother–child pairs