Indoor environment and children’s health Recent developments in chemical,

International Journal of Hygiene and Environmental Health 215 (2011) 1–18Contents lists available at ScienceDirectInternational Journal of Hygiene andEnvironmentalHealthj o u r n a l h o m e p a g e :w w w.e l s e v i e r.d e /i j h ehMini-reviewIndoor environment and children’s health:Recent developments in chemical,biological,physical and social aspectsPierre Le Cann a ,b ,∗,Nathalie Bonvallot a ,b ,c ,Philippe Glorennec a ,b ,c ,Séverine Deguen a ,b ,c ,Christophe Goeury a ,Barbara Le Bot a ,baEHESP-School of Public Health,Rennes,FrancebIRSET-Research Institute for Environmental and Occupational Health,Rennes,France cINSERM-National Institute for Health and Medical Research -U625,Rennes,Francea r t i c l ei n f oArticle history:Received 22April 2011Received in revised form 22July 2011Accepted 25July 2011Keywords:Indoor environment ChemicalBiological and physical exposure Respiratory illness ChildrenSocial health inequalitiesa b s t r a c tMuch research is being carried out into indoor exposure to harmful agents.This review focused on the impact on children’s health,taking a broad approach to the indoor environment and including chem-ical,microbial,physical and social aspects.Papers published from 2006onwards were reviewed,with regards to scientific context.Most of publications dealt with chemical exposure.Apart from the ongo-ing issue of combustion by-products,most of these papers concerned semi volatile organic compounds (such as phthalates).These may be associated with neurotoxic,reprotoxic or respiratory effects and may,therefore,be of particular interest so far as children are concerned.In a lesser extent,volatile organic compounds (such as aldehydes)that have mainly respiratory effects are still studied.Assessing exposure to metals is still of concern,with increasing interest in bioaccessibility.Most of the papers on microbial exposure focused on respiratory tract infections,especially asthma linked to allergens and bio-aerosols.Physical exposure includes noise and electromagnetic fields,and articles dealt with the auditory and non auditory effects of noise.Articles on radiofrequency electromagnetic fields mainly concerned questions about non-thermal effects and papers on extremely low-frequency magnetic fields focused on the char-acterization of exposure.The impact of the indoor environment on children’s health cannot be assessed merely by considering the effect of these different types of exposure:this review highlights new findings and also discusses the interactions between agents in indoor environments and also with social aspects.© 2011 Elsevier GmbH. All rights reserved.IntroductionPeople in modern society spend approximately 90%of their time indoors,in their homes,workplaces,schools and public spaces (EPA,2008).It is estimated that approximately 2/3of this time is spent at home.Despite improvements in the quality of indoor envi-ronments,there are still many health outcomes associated with these environments.Concerns about the recent increase in the incidence of respiratory disease and allergies worldwide have stim-ulated research into potential causes in the indoor environment (Chan-Yeung and Becker,2006).A growing body of epidemio-logic research has shown associations between dampness,common indoor materials or their emissions in homes or other specific microenvironments,and a variety of adverse respiratory and aller-∗Corresponding author at:EHESP School of Public Health,Av Prof Leon Bernard,CS 74312,35043Rennes Cedex,France.Tel.:+330299022681;fax:+330299022675.E-mail address:Pierre.Lecann@ehesp.fr (P.Le Cann).gic health effects,including the increased risk of asthma,pulmonary infections and allergies.For example,exposure to mold can cause human health effects through three different mechanisms:allergy,infection by the mold and toxic irritant effects (Bush and Peden,2006).Moreover,children could be considered sensitive to indoor pollutants since their lung structure and immune system is not fully developed and exposure to harmful agents in infancy would be “irremediable”.Because of their exploratory behavior (e.g.,fre-quent mouthing of hands and other objects),young children are often more vulnerable to environmental exposure.In Europe it is estimated that 3.6%of deaths of children under the age of 4are caused by indoor air pollutants (Valent et al.,2004).The overarching recommendation No 1published by the World Health Organization is:“Improve the well-being of girls and women and the circumstances in which their children are born,put major emphasis on early child development and education for girls and boys,improve living and working conditions and create social protection policy supportive of all,and create conditions for a flourishing older life.”(WHO,2008).Pollution in the indoor environment is a complex mixture of agents migrating indoors from the outdoor air in addition to agents1438-4639/$–see front matter © 2011 Elsevier GmbH. All rights reserved.doi:10.1016/j.ijheh.2011.07.0082P.Le Cann et al./International Journal of Hygiene and Environmental Health215 (2011) 1–18generated by indoor sources.To evaluate the impact of harmful indoor environment agents on public health,chemical,biological and physical agents must all be considered.This article reviews and summarizes recent papers published since2006on links between children’s heath and the indoor environment.It considers associations between health effects in children and indoor chemical,biological and physical agents, indoor materials and activities.It includes data on new types of contamination or exposure to pollutants suspected of having an impact on children’s health.The interactions between agents and with social aspects are then discussed.Studies specifically covering adults,risks associated with liv-ing near local or specific industrial facilities,risks from combustion such as tobacco smoke,carbon monoxide and traffic pollution that are already well documented,well-known outdoor pollutants such as ozone,particulates(as PM10or PM2.5),nitrogen dioxide and risks associated with infectious agents were excluded.Material and methodThe ISI web of knowledge and Pubmed websites were used to retrieve relevant articles(keywords child,indoor environment,...) in the literature published from2006to2010.Additional publica-tions were selected from the bibliographies in the studies retrieved.Studies meeting the following criteria were selected:-publication in peer-reviewed scientific journals;-and publications in English;-and investigation of children’s indoor environment with mea-surements of agents that may affect infants and children (respiratory effects,allergies,endocrine disruption,neurotoxic-ity;etc.);-or investigation of relationships between child pathologies and indoor exposure in micro-environments.Studies specifically covering adults,risks associated with liv-ing near local or specific industrial facilities,risks from combustion such as tobacco smoke,carbon monoxide and traffic pollution that are already well documented,well-known outdoor pollutants such as ozone,particulates(as PM10or PM2.5),nitrogen dioxide and risks associated with infectious agents were excluded.Thefindings are presented by type of agent(biological,chemi-cal and physical)and broader issues such as interactions between different agents and social aspects are then discussed.ResultsRecent advances indoor environment exposure and children’s health are presented in a synthetic form in Table1.Chemical agentsThis section covers metals,volatile organic compounds(VOCs) such as formaldehyde or benzene,semi volatile organic compounds (SVOCs)such as phthalates used as plasticizers,pesticides,polybro-modiphenylethers used asflame retardants,etc.Indoor exposure to chemicals occurs through inhalation,ingestion and dermal path-ways.In general,metals(at least in their inorganic forms)are in particulate,irrespirable form and may be ingested especially by children during their hand to mouth activity.VOCs are in gaseous form and thus mainly affect children via the respiratory pathway. SVOCs are present in gaseous,respirable particulate and settled dust particulate form leading to potential respiratory,oral and der-mal exposure.Metals,especially lead,and VOCs have been studied for many years.Interest in SVOCs is more recent and most of the papers retrieved concerned SVOCs.Exposure to SVOCs is much more complex and involves all these pathways to different degrees and by different mechanisms in the indoor environment.MetalsLead is well known as an indoor pollutant but it is still the subject of the majority of papers,especially in the USA.For other metals, a quite new development concerns bioavailability consideration. Considering the drastic decrease of lead exposures in occidental countries,recent articles dealt with the effects at current low expo-sures(Jones et al.,2009)and how to reduce them.Jacobs and Nevin (2006)validated a model,over a period of20years,for predicting high Blood Lead Levels(BLL).He concluded that replacing win-dow frames painted with lead-based paint explained a large part of the decrease in high BLL and that to eliminate BLL greater than 10␮g/dL by2010would require a window replacement policy.In their review Levin et al.(2008)referred to the importance of expo-sure to lead-based paint but stated that other sources(including diet and consumer goods such as toys)should be studied to reach the2010goal.Additional evidence of intellectual impairment at BLLs less than10␮g/dL was provided by Jusko et al.(2008)and Miranda et al.(2007).This helped to stimulate discussion about the current limit of10␮g/dL,with US Centers for Disease Control and Prevention maintaining their position but arguing for better pri-mary prevention.A major contribution to this discussion was the publication of analyzed data(1999–2004)from the National Health and Nutrition Examination Survey(NHANES)(Dixon et al.,2009; Gaitens et al.,2009).Results for2155children aged from1to5years showed that8.1%had BLL greater than5␮g/dL and that lead con-centrations infloor dust,to a greater extent than dust wipe samples from windows,was a major predictor of BLL,even where the con-centrations were below federal U.S.standards.These recent results confirm lead toxicity without any apparent threshold at even lower levels,and relevance for public health of these frequent low expo-sures.The authors concluded that lead in dust should be kept as low as possible to prevent children from lead exposure.Regarding dust lead content,Kumar and Scott(2009)stated that indoor dust lead loadings were quite high in India,but larger and representa-tive samples are required to further assess the importance of the problem,that is beginning to be more studied in Asia.Glorennec et al.(2010)used isotopic analysis in a hot spot of lead exposures in France and successfully identify sources,even-that’s the nov-elty compared to previous uses of isotopic analysis-for BLL lower than10␮g/dL.Another important aspect of assessing the exposure to lead in dust was described by Wilson et al.(2007a).He stud-ied which combinations of rooms sampled were likely to predict high BLL.This was particularly useful for designing a lead exposure survey,although the numbers studied were limited(72),and not representative(all children were from Milwaukee).A complemen-tary aspect of assessing the exposure to lead and metals in general is assessing bioaccessibility,using analytical methods that were more commonly used for soils(Demetriades et al.,2010;Le Bot et al., 2011,2010;Rashed,2008;Rieuwerts et al.,2006;Turner and Ip, 2007;Turner and Simmonds,2006;Yu et al.,2006).These authors, and notably Ibanez et al.in their review(Ibanez et al.,2010)empha-sized the variability of bioaccessibility–an interesting aspect of Yu’s paper was to compare bioaccessibility for different particle sizes–and the importance of taking it into account for assessing the risk of exposure to metals.This is particularly important in areas where there are still high levels of industrial lead emissions,leading to high BLL,for example in China(Ye et al.,2007).Volatile organic compounds(VOCs)Volatile organic compounds(VOCs)are a major group of chem-icals that evaporate easily at room temperature and are commonly found in indoor air(Barro et al.,2009).They are emitted from aP.Le Cann et al./International Journal of Hygiene and Environmental Health215 (2011) 1–185wide range of consumer products used in indoor environments and building materials,such as cleaning products,paints,floor coverings,cosmetic products,furnishing,adhesives,etc.Many fam-ilies of chemicals are considered as VOCs but recent literature (presented in details below)focuses only on aldehydes,chlo-rine derivatives and aromatic compounds.Other studies looked at activities that may emit VOCs,such as cleaning or renovation work,rather than specific agents.It is well known that VOCs con-taminate indoor environments,especially in homes(Barro et al., 2009;Mendell,2007).Sources and personal exposure of VOCs have been widely studied before2006.Some of these exposures are mainly from indoor air(Zhang and Smith,2003).VOCs’con-tamination and ensuing exposure are still of concern(Ashmore and Dimitroulopoulou,2009)and particular in specific micro-environment such as schools,day-care centers,public buildings... (Kotzias et al.,2009).The respiratory effects of VOCs have been widely studied.The most studied in the past concern upper airway symptoms such as eyes,nose and throat irritation(Pappas et al., 2000).Some hypotheses were emitted on a possible influence of VOCs exposure on the allergic status of subjects,especially consid-ering infants and asthma.Even if no strong conclusions were set up,new data tends to confirm these hypotheses(Choi et al.,2009; McGwin et al.,2009;Mendell,2007).Recent data associated with child health focused on specific micro-environments.The characterization of indoor air quality in schools included measurements of4aromatic compounds(ben-zene,toluene,ethyl-benzene and xylene collectively known as BTEX)and formaldehyde.Results suggested that outdoor contam-ination could not predict specific pollution in classrooms from toluene,ethylbenzene or xylene,and that local outdoor air con-centrations were not good indicators of the personal exposure of children(Stranger et al.,2007,2008).Moreover,the indoor/outdoor ratio for formaldehyde measured in Korean classrooms(6.3)con-firmed that indoor sources played a major role in the exposure of children at school(Sohn et al.,2009).New results are also available for chlorinated swimming-pools where disinfection by-products,such as trihalomethanes,halo-genated acetic acids and chloramines are emitted(Zwiener et al., 2007).Some of these results support the hypothesis that there is a relationship between swimming-pool attendance and respira-tory effects(asthma,chronic bronchitis and pulmonary epithelium damage identified by the measurement of serum pulmonary pro-teins)in341children from10to13years old(exhaled nitric oxide increased with swimming-pool attendance)(Bernard et al., 2006,2007;Nickmilder and Bernard,2007).Chlorine deriva-tives,in particular chloramines,are suspected of causing these symptoms.Another study confirmed previous data about the asso-ciation between chloramines and upper respiratory tract irritation (Kaydos-Daniels et al.,2008).However,no association between respiratory and allergic symptoms(irritation,asthma,atopy)and swimming pool attendance was observed in a prospective longitu-dinal study with more than5000children(Font-Ribera et al.,2011). The exposure to disinfection by-products was estimated from ques-tionnaires on swimming pool attendance without measurement of chlorine derivatives such as chloramines.Nevertheless this study is interesting regarding the design and the number of subjects fol-lowed.Recentfindings on the identification of high levels of 2-heptanone and n-butylacetate inside neonatal incubators com-pared with ambient air(Prazad et al.,2008),suggested a possible impact on developing infants.As no other studies have investigated air quality in incubators or health effects of neonatal exposure,no conclusions could be drawn.Recent epidemiological studies investigated the health effects of VOCs exposure at home.Higher concentrations of formaldehyde and several aromatic compounds(benzene,ethylbenzene,xylene,styrene,trimethylbenzene)were found in the homes of patients with atopic dermatitis or allergic asthma than in control homes (Choi et al.,2009).In addition,McGwin et al.made a systematic review on formaldehyde exposure and risk of asthma and calcu-lated pooled odds ratio,and demonstrate a significant association with childhood asthma(McGwin et al.,2009).These results con-firm the allergic potential of formaldehyde and the probable role of aromatic compounds in the development of asthma and other allergic symptoms(Mendell,2007).This hypothesis was supported by an in vitro study which showed that aromatic compounds(but not aliphatic)stimulated the release of pro-inflammatory proteins from human lung epithelial cells in culture(Fischader et al.,2008). In addition,recentfindings show that even at low concentrations, VOCs could be associated with a higher risk of asthma,especially aldehyde and aromatic compounds(Hulin et al.,2010).Another study showed that home improvement(painting,decorating,etc.) carried out before birth and during thefirst years of life could nearly double the risk of eczema or allergic symptoms in early child-hood(Herbarth et al.,2006).Decorating was associated with the emission of VOCs in indoor air,but no specific chemicals were mea-sured in this study.Renovation activities could be responsible for an increase in inflammatory markers(interleukin8and monocyte chemo-attractant protein-1)in children,especiallyfloor-covering (Herberth et al.,2009).In this context,Herbarth and Matysik(2010) showed that a waiting period up to2months was optimal before the use of rooms after a renovation.Studies on contamination in homes,housing characteristics and personal exposure assessment did not produce new conclusions but confirmed that the largest contribution of VOCs to exposure is from homes compared to outdoors and offices(Gokhale et al.,2008) and that airflow rates affected VOC contaminant levels indoors. Semi-volatile organic compounds(SVOCs)Increasing attention has been paid to indoor contamination with SVOCs over the pastfive years.Pesticides and biocides are still studied,followed now by polybrominated diphenylethers(PBDEs) and phthalate and polycyclic aromatic hydrocarbons(PAHs).Poly-chlorinated biphenyls(PCBs)and perfluorinated compounds(PFCs) have been studied to a lesser extent and other compounds(such as organophosphates,organotins,musks...)are emerging.The phys-ical chemical properties of SVOCs show that they are adsorbed in the solid phase and released into the air(gas and particulate mat-ter)during their lifetime(Salthammer and Bahadir,2009;Weschler et al.,2008).Children are exposed by inhalation,dermal contact and ingestion(Lioy,2006).Pollutants may also persist if they are bound to indoor dust due to minor influence of biotic(e.g.,micro-bial)or abiotic(e.g.,photolysis)degradation and other dissipation processes(e.g.,volatilization,dissolution)of the SVOC reservoir. This leads to a greater exposure potential indoor than outdoors (Hwang et al.,2008;Rudel and Perovich,2009).SVOCs are here-after considered family by family but issue of global exposure is developed in the discussion section.Pesticides.Children were already known to be exposed to pesti-cides in the home from various sources such as domestic use,drift from nearby agricultural areas and take-home from their parents’workplaces.In addition,children could be also exposed at school in rural area(Cheng et al.,2009).Some of pesticides(organophospho-rous,organochlorine or carbamates insecticides)are well-known neurotoxins.Epidemiological studies have already shown limited evidence supporting associations between pesticide exposure and cancer or birth outcomes,but the results are inconsistent(Wigle et al.,2008,2007).Specific groups such as farm children have been shown to be more exposed than other children and have been already subject of epidemiological studies.This subject is still of concern(Bradman6P.Le Cann et al./International Journal of Hygiene and Environmental Health215 (2011) 1–18et al.,2007;Coronado et al.,2006;Curwin et al.,2007;Hoppin et al., 2006)with exposure assessment performed by measuring urinary biomarkers and home contamination(dust/air).Coronado et al. (2006)observed a direct correlation between the concentration of organophosphate pesticides in house dust and the concentra-tion of urinary metabolites in children as did Becker et al.(2006) with permethrin.Curwin et al.(2007)confirmed that farm children generally had higher pesticide(atrazine and chlorpyrifos)dose esti-mates than non-farm children.Morgan et al.(2007,2008)and Tulve et al.(2008)confirmed that children could be exposed by oral,res-piratory and dermal routes but major determinants are not fully understood and approaches for measuring and assessing dermal exposure in a residential setting have not been sufficiently evalu-ated(Hubal et al.,2006).However,Keenan et al.(2010)clarified the magnitude of indoor pyrethroid exposure following the use of fogger.In this case,dermal contact was the primary route of human exposure.Concerning concentration levels,the novelty concerned investigation of inter-home variability of concentrations(Whyatt et al.,2007;Williams et al.,2008),in different seasons(winter and summer)and different home locations(urban,rural or farm) (Obendorf et al.,2006).Recent data included,for thefirst time,the concentrations of ten pyrethroids and two organophosphates in an urban setting and showed the presence of some pyrethroids in all houses(Julien et al.,2008).Urinary3,5,6-trichloro-2-pyridinol has been proposed as a biomarker for chlorpyrifos prenatal exposure (Whyatt et al.,2009)and associated with indoor air ing biomarkers measurements,Wilson et al.observed that children’s exposure to chlorpyrifos and diazinon were mainly due to inhala-tion(around40%)and dietary ingestion(around50%).In addition, authors observed that interhome variability in children’s exposure was greater than within home variability,and that exposure had decreased with time and age,which is consistent with regulatory restrictions and natural behavioral changes of the older children (Wilson et al.,2010).Metayer and Buffler(2008)found an association between indoor pesticide exposure and childhood leukemia.These results were confirmed by a meta-analysis which shows positive asso-ciations between the use of residential pesticides and leukemia (Turner et al.,2009).Finally,a recent study confirms trends already observed between pesticide exposure during pregnancy and adverse birth outcomes even if exposures were estimated by indirect approaches(Petit et al.,2010).Polycyclic aromatic hydrocarbons(PAHs).PAHs are by-products of incomplete combustion from burning heating oil and fossil fuels (Gevao et al.,2007;Lioy,2006;Weschler,2009).However,in con-trary of other combustion by-products,PAHs are discussed here because they may be also found in other indoor sources,such as par-quetflooring glue(Gevao et al.,2007).Exposure assessment to PAHs is of continuing interest(Choi et al.,2008;Cirillo et al.,2006;Freire et al.,2009)because benzo(a)pyrene is known to be carcinogenic. Studies on children exposure reported concentrations of PAHs in indoor air and/or dust samples collected from homes(Gevao et al., 2007;Maertens et al.,2008;Naspinski et al.,2008).There was con-siderable variation in the concentration levels of PAHs indoors in different countries(Naspinski et al.,2008)and different areas(rural and urban)(Cirillo et al.,2006).Gevao et al.showed that no sig-nificant indoor contamination sources were found compared to outdoors for each compounds measured(Gevao et al.,2007)and outdoor PAH levels were reported as an important determinant of indoor concentrations(Rudel et al.,2010);this was confirmed by Choi et al.(2008)for pregnant women especially during the hot season but not by Mielzynska et al.(2006)who used biomarkers to assess the effects of exposure in children and concluded that sources of exposure might be both outdoor and indoor.In other cases,food appears to be the main source of exposure of children to PAHs(Cirillo et al.,2006).Children may,therefore,be exposed to PAHs in many different ways,not only in indoor envi-ronments,but an exposure assessment reveals that dust ingestion accounts for about42%of the non-dietary intake for children(Gevao et al.,2007).Another study on the evaluation of lifetime cancer risk from PAHs in homes,revealed that,for preschool children,exposure levels were acceptable(based on an excess risk of1–100×10−6)in 46out of51homes,but greater than100ppm(corresponding to an excess risk of10−4)in the other5(Maertens et al.,2008). Polychlorinated biphenyls(PCBs).PCBs are recognized as develop-mental neurotoxins inducing cognitive deficits in children(Rudel and Perovich,2009;Wigle et al.,2008).They were banned in the USA in1977but are still of concern for human health and the environment as they are persistent and shown to be endocrine disrupting chemicals(EDCs)and probable human carcinogens(Ye et al.,2007).PCBs are found in heat transferfluids,stabilizers for PVC,pesticide extenders,electronic equipment and used as addi-tives likeflame-retardant(Rudel et al.,2010;Weschler,2009). Other sources such as building materials have recently been identi-fied(Hwang et al.,2008)with highest levels identified in buildings constructed during the1950s to1970s(Rudel et al.,2010).In accor-dance,Hwang et al.(2008)found correlation between dust content and the age of the house.Exposure to PCBs in indoor air and dust is considered to be more significant than exposure outdoors because of the higher concentrations found indoors(Rudel et al.,2010).Inhalation and dust ingestion are,therefore,significant exposure routes for chil-dren,although diet is the major source of exposure(Hwang et al., 2008;Rudel and Perovich,2009),that is confirmed by Roosens et al. (2010a)who precised that food intake contributed more than99% of the combined PCB intake from food and dust for Belgian students. Polybrominated diphenylethers(PBDEs).Many publications(Gevao et al.,2006;Harrad et al.,2009;Hwang et al.,2008;Tan et al., 2007)confirm the ubiquitous presence of polybrominated diphenyl ethers(PBDEs),a major class offlame retardants,in indoor envi-ronments.Degradation products have also been identified in dust (Lupton et al.,2010).These compounds are already known to be present in human bodies(Hites,2004)but the question of the pre-dominant route of exposure is still unresolved and is the main scope of numerous recent studies,while other interesting studies focus on health effects.Increased levels of higher-brominated congeners were associ-ated with the recent purchase of new upholstered furniture or mattresses in a Californian study(Rose et al.,2010).The dust inges-tion pathway is of particular concern especially for children in North America(Lorber,2008),where PBDEs are more used.This may explain that North American body burdens are higher than European ones as mentioned by Frederiksen et al.(2009).Wang et al.(2010)observed(N=27)in an urban area of South China dust loadings comparable to North American ones but it would need to be confirmed on a larger and representative sample of dwellings. Given the high variability in dust intake,this pathway could be pre-dominant for a small proportion of the population or not neglictible (20–40%)for the most exposed,even in Europe where dietary intake is predominant(Roosens et al.,2010b).Fischer et al.(2006)com-pared PBDE concentrations in blood taken from a particular family and observed higher levels in children than in adults,suggesting that house dust ingestion could be responsible for higher levels of PBDE,especially BDE-209congener.Similarfindings were found by Lunder et al.(2010)and Toms et al.(2008)),and Stapleton et al. (2008)observed similar PBDEs profiles in dust and hand wipes.An interesting study by Huwe et al.(2008)also supported the hypoth-esis of importance of the dust pathway by testing–in rats–the。