髙口 倖暉

Semi-volatile organic compounds (SVOCs), such as phthalates and organophosphate flame retardants (OPFRs), are used in plastic products and electrical and electronic applications as plasticisers or flame retardants. There has been a growing concern that exposure to SVOCs can have an adverse impact on human health. Several large-scale epidemiological studies employ the sampling of house dust using household vacuum cleaners as the standard method. However, in this method, house dust samples might be contaminated by flame retardants and plasticisers because of the presence of these chemicals in the plastic materials of cleaners. Therefore, this study aimed to develop a low-cost, easy-to-distribute sampling method to collect house dust using a mop and analyse OPFRs, phthalate esters, and alternative plasticisers in house dust. Our findings show that the proposed mop sampling method can be easily distributable and lower contamination from a sampling tool. Moreover, the proposed house dust sampling method is extremely useful for a large-scale survey such as a cohort study.

The indoor environment, particularly indoor air quality (IAQ), is significantly associated with building-related symptoms (BRSs) in humans. In our previous studies, we demonstrated a significant relationship between BRSs and indoor chemical concentrations. In Japan, the Ministry of Health, Labor, and Welfare (MHLW) guideline recommends an air quality target of 13 volatile organic compounds (VOCs) and a provisional target of 400 μg/m3 for total VOCs (TVOC). The objective of this study was to determine the relationship between TVOC levels and the risk of BRSs using the Japanese provisional target TVOC level of 400 μg/m3. The relationship between odor intensity and BRSs while the TVOC levels were under 400 μg/m3 was also examined. The study was conducted in a laboratory house (LH) on the campus of Chiba University from 2017-2019. The study included 149 participants who spent 60 minutes in the LH. The participants were asked to evaluate the IAQ of the LH. A significant relationship between the risk of BRSs and the provisional target TVOC level was observed (odds ratio: 2.94, 95% confidence interval: 1.18-7.35). Furthermore, a significant relationship between odor intensity and risk of BRSs in spaces with TVOC levels less than 400 μg/m3 was detected (odds ratio: 6.06, 95% confidence interval: 1.21-30.44). In conclusion, the risk of BRSs is significantly lower in spaces with low TVOC levels and low odor intensity. Reducing the concentration of airborne chemicals and odor intensity may improve IAQ and prevent BRSs.

In this study, we analyzed serum samples of pet cats from Thailand and estimated the contribution to organohalogen compounds (OHCs) exposure through cat food and house dust intake. BDE-209 was predominant in cat sera and accounted for 76% of all polybrominated diphenyl ethers (PBDEs). Decabromodiphenyl ether (BDE-209) is a major contaminant in dry cat food and house dust, which has been estimated to be a source of exposure for Thai pet cats. BDE-209 is a major contaminant of OHCs in dry cat food and house dust, which was estimated to be a source of exposure for Thai pet cats. On the other hand, the level of contamination by PCBs was lower than in other countries. Analysis of pet foods suggested that BDE-209 in pet cat serum was attributable to the consumption of dry cat food. On the other hand, house dust also contained high concentrations of BDE-209. Thus, high levels of BDE-209 in pet cat sera can be attributed to the consumption of dry cat food and house dust. These results suggest that pet cats are routinely exposed to non-negligible levels of OHCs.

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.

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 ofmucosalmembranes, 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 inwhich 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. (C) 2020 The Authors. Published by Elsevier B.V.

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 mu g m(-3) (outdoor air) for formic acid; 166 (living room), 151 (bedroom), and 51 mu g m(-3) (outdoor air) for acetic acid; and 73 (living room), 76 (bedroom), and 21 mu g 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).

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus jamiliaris) and male cats (Fells silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism. (C) 2019 Elsevier B.V. All rights reserved.

Canis lupus familiaris (domestic dog) possess a high capacity to metabolize higher-chlorinated polychlorinated biphenyls (PCBs) to thyroid hormone (TH)-like hydroxylated PCB metabolites (OH-PCBs). As a result, the brain could be at high risk of toxicity caused by OH-PCBs. To evaluate the effect of OH-PCBs on dog brain, we analyzed OH-PCB levels in the brain and the metabolome of the frontal cortex following exposure to a mixture of PCBs (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187, and 202). 4-OH-CB202 and 4-OH-CB107 were major OH-PCBs in the brain of PCB-exposed dogs. These OH-PCBs were associated with metabolites involved in urea cycle, proline-related compounds, and purine, pyrimidine, glutathione, and amino-acid metabolism in dog brain. Moreover, adenosine triphosphate levels in the PCBs exposure group were significantly lower than in the control group. These results suggest that OH-PCB exposure is associated with a disruption in TH homeostasis, generation of reactive oxygen species, and/or disruption of oxidative phosphorylation (OXPHOS) in brain cells. Among them, OXPHOS disturbance could be associated with both disruptions in cellular amino-acid metabolism and urea cycle. Therefore, an OXPHOS activity assay was performed to evaluate the disruption of OXPHOS by OH-PCBs. The results indicated that 4-OH-CB107 inhibits the function of Complexes III, IV, and V of the electron transport chain, suggesting that 4-OH-CB107 inhibit these complexes in OXPHOS. The neurotoxic effects of PCB exposure may be mediated through mitochondrial toxicity of OH-PCBs in the brain.

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical. Next-generation RNA sequencing analysis revealed changes in the expression of genes involved in the circadian rhythm and fatty acid metabolism, such as nuclear receptor subfamily 1, group D, member 1, aryl hydrocarbon receptor nuclear translocator-like protein 1, cryptochrome circadian clock 1, and enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase, in 4-OH-CB107-treated rats. In addition, biochemical analysis of the plasma revealed a dose-dependent increase in the leucine aminopeptidase, indicating the onset of liver damage. These results suggest that OH-PCB exposure may induce liver injury as well as disrupt the circadian rhythm and peroxisome proliferator-activated receptor-related fatty acid metabolism.

Thyroid hormones (THs), which mainly consist of 3, 3', 5-triiodo-L-thyronine (T3) and L-thyroxine (T4), play a critical role in regulating biological processes such as growth and metabolism in various animal species. Thus, accurate measurement of T3 and T4, especially physiologically active free (protein-unbound) forms, in serum/plasma is needed for the evaluation of TH homeostasis. However, such high-precision determination of free THs is lacking for non-human species. The present study aimed to develop a highly sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of six free THs in serum/plasma, which is applicable to not only humans but also non-human species. Two different physical separation steps, ultrafiltration (UF) and equilibrium dialysis (ED), were examined to obtain the free TH fraction. Several experimental conditions were carefully optimized and validated for UF or ED using the commercially available bovine serum. As a result, UF at 1100 x g and 37 degrees C for 30 min with a 30 kDa ultrafiltration device (Centrifree YM-30, Millipore) yielded excellent precision (CV: <10%). The optimized ED step also yielded high precision (CV: <10%) and the measurement values were approximately equal to those of UF, but at least 16h were required to reach equilibrium. Thus, UF combined with LC-MS/MS was finally chosen, in terms of the time needed for the measurement. Acceptable accuracy (recovery: 70%-110%) and intra- and inter-day precision (CV: <10% and <12%, respectively) were obtained, when triplicate analyses in three different days were conducted using the bovine serum. The developed analytical method was successfully applied to the determination of free THs in serum/plasma samples of humans, cats, and dogs. Furthermore, comparison with free T4 concentrations measured by a common immunoassay method evidently indicated that the ultrafiltration-LC-MS/MS method developed in this study can increase the specificity and accuracy of TH measurement. (C) 2018 Elsevier B.V. All rights reserved.

The adverse effects of elevated polybrominated diphenyl ether (PBDE) levels, reported in the blood of domestic dogs and cats, are considered to be of great concern. However, the tissue distribution of PBDEs and their derivatives in these animals is poorly understood. This study determined the concentrations and profiles of PBDEs, hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs), and 2,4,6-tribromophenol (2,4,6-tri-BPh) in the blood, livers, bile, and brains of dogs and cats in Japan. Higher tissue concentrations of PBDEs were found in cats, with the dominant congener being BDE209. BDE207 was also predominant in cat tissues, indicating that BDE207 was formed via BDE209 debromination. BDE47 was the dominant congener in dog bile, implying a species-specific excretory capacity of the liver. OH-PBDE and MeO-PBDE concentrations were several orders of magnitude higher in cat tissues, with the dominant congener being 6OH-BDE47, possibly owing to their intake of naturally occurring MeO-PBDEs in food, MeO-PBDE demethylation in the liver, and lack of UDP-glucuronosyltransferase, UGT1A6. Relatively high concentrations of BDE209, BDE207, 6OH-BDE47, 2'MeO-BDE68, and 2,4,6-tri-BPh were found in cat brains, suggesting a passage through the blood brain barrier. Thus, cats in Japan might be at a high risk from PBDEs and their derivatives, particularly BDE209 and 6OH-BDE47.