2Phthalates are widely used as plasticizers in numerous products. However, there has been some concern 3 about the various effects they may have on human health. Thus, household phthalate levels are an important 4 public health issue. While many studies have assessed phthalate levels in house dust, the association of these 5 levels with building characteristics has scarcely been examined. The present study investigated phthalate 6 levels in house dust samples collected from the living areas of homes, and examined associations between 7 these phthalate levels and the interior materials. Dust was collected from two portions of the living area: 8 floor dust from the entire floor surface, and multi-surface dust from objects more than 35 cm above the floor. 9The levels of seven phthalates were measured using gas chromatography/mass spectrometry in selective ion 10 monitoring mode. Phthalate levels were higher in multi-surface dust than in floor dust. Among floor dust 11 samples, those from dwellings with compressed wooden flooring had significantly higher levels of di-iso-

The Hokkaido Study on Environment and Children’s Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

1Although an association between exposure to phthalates in house dust and childhood asthma 2 or allergies has been reported in recent years, there have been no reports of these associations 3 focusing on both adults and children. We aimed to investigate the relationships between phthalate 4 levels in Japanese dwellings and the prevalence of asthma and allergies in both children and adult 5 inhabitants in a cross-sectional study. The levels of seven phthalates in floor dust and multi-6 surface dust in 156 single-family homes were measured. According to a self-reported 7 questionnaire, the prevalence of bronchial asthma, allergic rhinitis, allergic conjunctivitis, and 8 atopic dermatitis in the 2 years preceding the study was 4.7%, 18.6%, 7.6%, and 10.3%, 9respectively. After evaluating the interaction effects of age and exposure categories with 10 generalized liner mixed models, interaction effects were obtained for DiNP and bronchial asthma 11 in adults (P interaction =0.028) and for DMP and allergic rhinitis in children (P interaction =0.015). 12Although not statistically significant, children had higher ORs of allergic rhinitis for DiNP, 13 allergic conjunctivitis for DEHP, and atopic dermatitis for DiBP and BBzP than adults, and liner 14 associations were observed (P trend <0.05). On the other hand, adults had a higher OR for atopic 15 dermatitis and DEHP compared to children. No significant associations were found in phthalates 16 levels collected from multi-surfaces. This study suggests that the levels of DMP, DEHP, DiBP, 17and BBzP in floor dust were associated with the prevalence of allergic rhinitis, conjunctivitis, and 18 atopic dermatitis in children, and children are more vulnerable to phthalate exposure via 19 household floor dust than are adults. The results from this study were shown by cross-sectional 20 nature of the analyses and elaborate assessments for metabolism of phthalates were not considered. 21Further studies are needed to advance our understanding of phthalate toxicity. 22 (Asher et al., 2006). In fact, the increase in the prevalence of asthma and 3 allergies in adults as well as in children has gained attention during recent years (WHO, 2005). 4Various reviews have focused on the associations between increasing asthma and allergies and 5 indoor environmental factors such as house dust mite allergens, environmental tobacco smoke, 6 mould, pets, and nitrogen dioxide. Thus, the indoor environment may have contributed to the 7 increase in asthma and allergies. One of the reasons for increasing asthma and allergies are 8 phthalates. Phthalates have been used as plasticisers for various plastic products, such as toys, 9 food containers, furniture, personal care products, medical devices, and paints. And humans are 10 exposed to phthalates throughout their lifetime, beginning in foetal stages. Due to their hand-to-11 mouth behaviour and eating without hand washing after playing, assessing the exposure of 12 children to dust contaminated with SVOCs is regarded as an important issue (...

1We measured urinary phthalate metabolites, including di-n-butyl phthalate (DnBP), di-isobutyl 2 phthalate, benzyl butyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP), from 178 school-3 aged children and their 284 family members using gas chromatography-mass spectrometry, and we 4 calculated daily phthalate intakes. The highest median levels of phthalate metabolites were for 5 mono-isobutyl phthalate in all participants except schoolchildren, where the highest levels were for 6 mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Comparing the schoolchildren with their parents, 7 the schoolchildren had significantly higher urinary metabolites for MEOHP, mono-(2-ethyl-5-8 carboxypentyl) phthalate, and ΣDEHP. Regarding daily intakes, the schoolchildren had significantly 9 higher daily intakes of DnBP, BBzP, and ΣDEHP. All phthalate metabolite and sums of metabolite 10 levels in the schoolchildren were positively correlated with their mothers' levels, except for MEHP, 11 whereas fathers were less correlated with their children. The DEHP intake in this study was higher 12 than that of most other studies. Moreover, 10% of the children and 3% of the adults exceeded the 13 Reference Dose (RfD) value (20 g/kg/day) of the U.S. Environmental Protection Agency, which 14 indicates that it is important to focus on children's DEHP exposure because the children exceeded 15 the RfD more than adults among the same families who shared similar exposure sources. Our 16 results will contribute to considerations of the regulations for some phthalates and the actual 17 phthalate exposure levels in the Japanese population. 18 3

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