children's environmental health research—highlights from the columbia center for...

Children’s Environmental HealthResearch—Highlights from theColumbia Center for Children’sEnvironmental Health

FREDERICA PERERA,a,b SHEILA VISWANATHAN,a,b

ROBIN WHYATT,a,b DELIANG TANG,a,b RACHEL L. MILLER,b,c

AND VIRGINIA RAUHb,d

aDepartment of Environmental Health Sciences, Mailman School ofPublic Health of Columbia University, New York, New York 10032, USAbColumbia Center for Children’s Environmental Health, Columbia University,New York, New York 10032, USAcDivision of Pulmonary, Allergy, Critical Care Medicine, College ofPhysicians and Surgeons, Department of Medicine, Columbia University,New York, New York 10032, USAdHeilbrum Center for Population and Family Health, Columbia University,New York, New York 10032, USA

ABSTRACT: A growing body of evidence has been generated indicatingthat the fetus, infant, and young child are especially susceptible to en-vironmental toxicants as diverse as polycyclic aromatic hydrocarbons(PAHs), pesticides, lead, mercury, polychlorinated biphenyls (PCBs), andenvironmental tobacco smoke (ETS). Exposures to these toxicants maybe related to the increases in recent decades in childhood asthma, can-cer, and developmental disability. The Columbia Center for Children’sEnvironmental Health (CCCEH), located in New York City, has devel-oped four cohorts around the world to elucidate the relationships betweenthese exposures and childhood illness. This article summarizes the recentfindings from the Center’s projects in the context of current research inchildren’s environmental health.

KEYWORDS: children; environmental health; research; review; PAH;pesticides; ETS; asthma; cancer; developmental disability

Address for correspondence: Frederica P. Perera, DrPH, Department of Environmental Health Sci-ences, Mailman School of Public Health of Columbia University, and Columbia Center for Children’sEnvironmental Health, 100 Haven Avenue, Tower III, 25F, New York, NY 10032. Voice: 212-304-7280;fax: 212-544-1943.

e-mail: [email protected]

Ann. N.Y. Acad. Sci. 1076: 15–28 (2006). C© 2006 New York Academy of Sciences.doi: 10.1196/annals.1371.018

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16 ANNALS NEW YORK ACADEMY OF SCIENCES

INTRODUCTION

Today’s children are growing up in an environment quite different fromthat of their parents or grandparents. Exponential growth in technology,consumption, manufacturing, and population has defined the past decade. Fu-eling this growth is the development of new products and chemicals. Overthe past five decades, over 80,000 synthetic chemical compounds have beencreated; 2000–3000 new chemicals are submitted for review by the Environ-mental Protection Agency (EPA) on a yearly basis.1 Of high-volume chemicalscurrently in circulation, only 43% have been tested for potential human tox-icity, and only 7% have been studied for possible effects on development.2–4

In addition to the concerns about exposure to an increasingly diverse array ofchemicals, there is mounting evidence that the fetus and infant are significantlymore sensitive to a variety of environmental toxicants than adults because ofdifferential exposure, physiologic immaturity, and a longer lifetime over whichdisease initiated in early life can develop.5

The incidences of several childhood diseases and disorders have been in-creasing in recent decades. For example, there has been more than a 50%increase in asthma-associated school absences between 1980 and 1996 as wellas an increase in the estimated annual number of physician office visits andhospital outpatient visits among children aged 5–14 years.6 The incidence ofcancer in children younger than 15 years of age increased from 124.3 permillion in 1975–1979 to 139.9 per million in 1990–1995.7 Developmental dis-abilities, the name given to a broad group of conditions caused by learningor physical impairments, affect an estimated 17% of U.S. children under theage of 18 years.8 The high rates of these childhood disorders have significantsocial impacts and medical costs for individual families and the country asa whole. Therefore, there is a need to understand the role of environmentalfactors in childhood disease and neurodevelopmental disorders and to identifythe primary environmental toxins affecting children’s health so that preven-tive measures can be taken. Here we define environmental factors as toxicexposures due to lifestyle (smoking and diet) and pollutants in the workplace,ambient air, and water and food supply.

Differential Exposure and Susceptibility

It is important to distinguish children from adults when assessing environ-mental health impacts because of their unique behaviors and biological charac-teristics that can increase vulnerability to certain toxicants. For example, exper-imental and human data indicate that the fetus and young child are especiallyvulnerable to the toxic effects of environmental tobacco smoke (ETS), poly-cyclic aromatic hydrocarbons (PAHs), particulate matter (PM), nitrosamines,pesticides, polychlorinated biphenyls (PCBs), metals, and radiation.5 The dif-

PERERA et al.: CHILDREN’S ENVIRONMENTAL HEALTH RESEARCH 17

ferential susceptibility of the fetus and newborn in part is due to increasedexposure and altered biological susceptibility; nutritional deficits, genetic pre-dispositions, and social stressors also contribute.

Increased Exposure

Behaviors common in childhood, which are not observed in adults, can have amajor effect on the biological availability of toxicants in children. For example,young children breathe air closer to the ground, exposing them to particles andvapors present in carpets and soil. While playing and crawling around on thefloor, children can inhale or dermally absorb toxicants, which are subsequentlyabsorbed more efficiently in children than in adults.9 Compounding the effectsof this behavior is the fact that infants have twice the breathing rate of theaverage adult. Also, most young children display hand-to-mouth behavior andthumb-sucking habits that can increase exposure.

Dietary habits of children may also cause increased exposure to some toxi-cants. Children under 5 years of age eat three to four times more food per unitof body weight than the average adult American; and the average one-year olddrinks 10–20 times more juice than the average adult.10 Dermal exposures mayalso be higher, as a typical newborn has more than double the surface area ofskin per unit of body weight than an adult.11

Biological Susceptibility

Human infants and children differ from adults not only in their size andpotential for exposure but also in their ability to metabolize environmentaltoxins. The in utero and childhood periods are characterized by rapid physicaland mental growth and gradual maturation of major organ systems. In fact,typical newborns double their weight within 6 months of birth and integral partsof the nervous and immune systems are formed during the first 6 years of life.12

Additionally, sex organ development, myelination, and alveoli formation beginlate in pregnancy and continue until adolescence.9 As cells are proliferatingrapidly and organ systems are immature, they are sensitive to the potentiallyharmful effects of environmental toxins.

Absorption, metabolism, and excretion pathways in infants and childrendiffer from those in adults. These pathways dictate the amount of a toxi-cant, in its various forms, that is present in the body. Epidemiological stud-ies with biomarkers have demonstrated placental transfer of toxicants, andin some cases slower fetal clearance of chemicals such as PAHs, PCBs, andmercury.13–15 An infant’s kidney filtration rate is lower than an adult’s, thusincreasing potential susceptibility.9

Finally, infants and children have more years of future life than most adults.Thus, there is more time for early exposures to trigger diseases that have long


latency periods. For example, early exposure to carcinogens will be more likelyto lead to cancer than the same exposure experienced later in life.

Modifying Factors

Increased susceptibility to certain environmental exposures in childhood isnot only due to biological and behavioral traits associated with early growthand development. Nutritional factors, genetics, and psychosocial stressors canalso modify the effect of these exposures.

Nutrition

Most of the research on micronutrients has focused on their main effects, butthere is some evidence of interactions with environmental exposures. Certainmicronutrient deficiencies have been associated with childhood asthma, ad-verse birth outcomes, child development, and childhood cancer. For example,essential fatty acids are associated with low birth weight reduced head circum-ference, and cognitive and motor function.16–18 Nutritional status modulatesinflammatory response to air pollution and its effects on childhood asthma.Evidence for this includes the presence of antioxidants in the airway surfaceliquid of the lung, which reduces oxidative stress and prevents airway inflam-mation, thereby limiting asthma-like symptoms.19–21 By removing free radi-cals and oxidant intermediates, antioxidants protect DNA from the genotoxic,procarcinogenic effects of chemicals that bind to the DNA.22,23 Nutritionaldeficiencies, in some cases, may be closely related to lower socioeconomicstatus, although variations exist within each socioeconomic bracket.

Genetics

Genetic susceptibility can take the form of common polymorphisms or hap-lotypes that modulate the individual response to a toxic exposure. For example,two genes have been identified that can increase an individual’s vulnerabilityto organophosphates (OPs), such as chlorpyrifos, by reducing the reservoirof functioning protective enzymes.24 The first gene has a prevalence of 4%and results in a poorly functioning form of the enzyme acetylcholinesterase;the second gene results in a relatively inactive form of the enzyme paraox-onase (prevalence of 30–38%), an enzyme that detoxifies chlorpyrifos beforethe toxin can inhibit acetylcholinesterase.25 Evidence of an interaction betweenthe paraoxonase 1 (PON1) genotype and OP pesticides includes the findingthat the effect of chlorpyrifos on head circumference at birth was signifi-cant only among women with low PON1 activity.26 Other examples of gene–environment interactions involve the gene coding for the d Alanine (d-ALA)


enzyme that affects lead metabolism and storage,25 and genetic polymorphismin the dopamine transporter that is associated with increased behavioral prob-lems in children prenatally exposed to tobacco smoke.27 Other research hasfound that the P450 and glutathione-S-transferase gene families play a role inthe activation and detoxification of various xenobiotics. For example, the P450and glutathione-S-transferase genes are involved in the metabolism of PAHsand can influence the level of PAH–DNA damage. PAH–DNA adduct levelsin human placenta were significantly higher in infants with the cytochrome-P450 1A1 (CYP1A1) MspI restriction site, a genetic marker associated withlung cancer risk, than in infants without the restriction site.28 GlutathioneS-transferase T1 (GSTT1) null was also shown to be a marker for lower birthweight and preterm birth among babies of pregnant women who actively usedtobacco.23 Children carrying the glutathione S-transferase M1 (GSTM1) nullgene who were exposed in utero to tobacco smoke had increased risk forpersistent asthma and wheezing.29 GSTM1null in asthmatic children also isassociated with increased susceptibility to the harmful effects of ozone, suchas reduced forced expiratory flow.30

Individual- and Community-Level Psychosocial Stressors

The notion that individual- and community-level conditions can produceprofound effects on host susceptibility to disease is derived from the long-standing existence of strong social class gradients in health.31 Recent studieshave shown that women who live in violent, crime-ridden, physically decayedneighborhoods are more likely to experience pregnancy complications andadverse birth outcomes, after adjusting for a range of individual-level sociode-mographic attributes and health behaviors.32,33 Other studies have suggestedthat the stresses of racism and community segregation are associated with lowerbirth weight.34 Several have shown that the effects of individual poverty on birthoutcomes are exacerbated by residence in a disadvantaged neighborhood.35 Inone of the few studies that has measured interactions between physical toxi-cants and individual psychosocial stressors, an analysis of Northern Manhattanmothers and toddlers done at the Columbia Center for Children’s Environmen-tal Health (CCCEH cohort) found that the risk of developmental delay amongchildren exposed prenatally to maternal ETS was significantly greater amongthose whose mothers experienced material hardship during pregnancy.36

Children’s Disorders Related to Environmental Factors

Cancer Risk/Genetic Damage

Environmental exposures are quickly gaining recognition as potential riskfactors for childhood cancer.37 Several studies suggest that the fetus clears


carcinogens less efficiently than the adult and thus may be more vulnerable togenetic damage and the resultant risk of cancer. For example, carcinogen-DNAadducts are a marker of increased cancer risk.38 Experimental evidence showsthat the amount of PAHs crossing the placenta and reaching the fetus is less thanone-tenth of the dose to the mother,39,40 yet the levels of PAH–DNA adductsmeasured in rodent fetal tissue are higher than expected.41 Similarly, researchin mothers and newborns has consistently shown that PAH–DNA adduct levelsin the white blood cells (WBC) of newborns were similar to or exceeded thosein paired maternal samples, despite the estimated 10-fold lower dose of theparent compound to the fetus.42–44 In addition, fetal plasma cotinine levels werehigher than in paired maternal samples, suggesting reduced ability of the fetusto clear carcinogenic cigarette smoke constituents.42,43 This research indicatesthat the differential effect of exposure to PAHs in the fetus is not limited to aparticular ethnic or geographic group.43 Increased adducts in the fetus relativeto the adult could result from lower levels of phase II (detoxification) enzymesand decreased DNA repair efficiency in the fetus.42,45–47

Chromosomal aberrations have been associated with increased risk of cancerin multiple studies48,49 and are another biomarker used to detect the preclinicaleffects of cancer-causing environmental toxicants. In New York City newborns,maternal exposure to airborne PAHs during pregnancy has been associated withincreased frequency of chromosomal aberrations in WBC, suggesting that riskof cancer can be increased by exposure in the womb.50 Studies have also linkedmaternal tobacco smoking to increased chromosomal aberrations in WBC ofnewborns.51 Other research has shown an approximately 10-fold higher risk ofinfant acute myeloid leukemia with increasing maternal consumption of DNAtopo 2 inhibitor-containing foods, raising concerns about benzene, a topo 2inhibitor.52

Respiratory Disease/Asthma

An estimated 9 million (12.5%) children aged <18 years in the United Stateshave had asthma diagnosed at some time in their lives.53 A recent study foundthat over 25% of elementary school children in Harlem had asthma.54 Envi-ronmental factors are known or suspected to contribute to these high rates ofdisease. There are critical windows in both prenatal and postnatal developmentduring which exposure to irritants and other toxicants can modify the forma-tion and maturation of the lung. The complete development of the human lungoccurs through the sixth to eighth years of life.55 But there is recent evidencefrom the CCCEH cohort study that important adaptive immune responses maybegin in utero. These include findings that cord blood T cell proliferation inresponse to specific allergens can occur independently of maternal sensitiza-tion.56 Moreover, prenatal exposure to PAHs with ETS was associated with anincreased risk of respiratory symptoms at the age of 2 years.57


The association of diminished air quality with the increased prevalence ofrespiratory symptoms has been documented internationally, including studiesin Holland and Indonesia, indicating that the prevalence of respiratory symp-toms increases as air quality decreases.58,59 Pesticide exposure has also beenassociated with respiratory disease and multiple chronic respiratory symptomsin children.60 Finally, it recently has been demonstrated that multiple toxicants(in this case, prenatal PAHs and postnatal ETS) can act synergistically to in-crease risk of respiratory symptoms in children at 12 months and probableasthma at 24 months.57

Neurobehavioral Disorders

The exquisitely sensitive process of the development of the human centralnervous system involves the production of 100 billion nerve cells and 1 trillionglial cells, which then must follow a precise stepwise choreography involvingmigration, synaptogenesis, selective cell loss, and myelination.61 A mistakeat any one step can have permanent consequences. Experimental studies ofprenatal and neonatal exposure to the OP chlorpyrifos have demonstrated neu-rochemical and behavioral effects as well as selected brain cell loss.62,63 Thebehavioral and morphologic effects of developmental toxicants are highly de-pendent on the timing as well as on the dose and duration of exposure. This isillustrated by both rodent and human studies showing that the effect of irradi-ation on brain malformation is heightened during the window of susceptibilityof fetal development.61 Adverse neurological development, including loweredintelligence, diminished school performance, and increased rates of behavioralproblems have been associated with exposure to low levels of a number of en-vironmental toxicants and pollutants. Cohort studies have demonstrated thatlow-level exposure to lead (even below 10 �g/dL in blood) during early child-hood is inversely associated with neuropsychological development through thefirst 10 years of life.64–67 There is evidence that even blood lead levels below10 �g/dL may be associated with reduced cognitive functioning.68 Prenatalexposure to PCBs and methylmercury, predominantly from maternal seafoodconsumption, has been associated with neurocognitive deficits.69

Selected Research Findings from the CCCEH

PAHs

PAHs are commonly found in ambient air70 and are listed among the 189hazardous air pollutants covered under the Clean Air Act. Incomplete com-bustion of organic material (gasoline and diesel fuels, coal, oil, and tobaccoproducts) is the major source of PAHs.71,72 Common sources of PAHs in the


urban environment include traffic, particularly diesel trucks and buses, heatingfuels, and cigarette smoke. A number of PAHs are known human carcinogens,and laboratory studies indicate that the PAH fraction of respirable PM maycause developmental deficits in infants.22,73 Studies also suggest that some ofthe PAH fraction of diesel exhaust particulates (DEP) may potentiate allergicresponses.74

A CCCEH cohort study evaluated the effects of prenatal exposure to airbornePAHs (monitored during pregnancy by personal air sampling of the mother) onbirth outcomes, after controlling for the effects of known determinants of fetalgrowth.75 Researchers found mean birth weight and head circumference to belower among newborns born to African American mothers with higher PAHexposures.75 There was also a significant interaction between PAH adductsand ETS such that the combined exposure to high ETS and high adducts had asignificant multiplicative effect on birth weight and head circumference amongboth African American and Dominican newborns.76 The observed associationsbetween prenatal PAHs and reduced fetal growth are of concern because severalstudies have reported that reduced birth weight or head circumference at birthor during the first year of life correlates with poorer cognitive functioning andschool performance in childhood.77 The finding was consistent with the priorobservation that the levels of PAH–DNA adducts in cord blood of Caucasiannewborns in Poland were significantly associated with lower birth weight,reduced length, and head circumference.22 More recently, follow-up of childrenin the CCCEH had shown that elevated prenatal exposure to airborne PAHs(measured by personal monitoring during pregnancy) was associated with asignificant increase in risk of developmental delay at age 3 (odds ratio 2.9).78

Pesticides

Insecticides are a class of chemicals that are generally designed to disruptneurological pathways in animals and are thus effective for their original pur-pose of eliminating bothersome insects and other pests. Although insects aremore susceptible to the effects of certain pesticides, including pyrethroids, be-cause of lower levels of detoxifying enzymes, human exposure to pesticidesmay be of concern because of the widespread application of the toxicants. Ap-proximately 80–90% of American households use pesticides.79 Children areexposed to pesticides from multiple sources as the substances are sprayed onfood, grass, and in homes and schools.

Organochlorines like dichlorodiphenyltrichloroethane (DDT) have beenphased out and replaced with less persistent pesticides like OPs, carba-mates, and pyrethroids. Chlorpyrifos, diazinon (OPs), cis-permethrin, trans-permethrin (pyrethroids), propoxur, and bediocarb (carbamates) have been thepesticides most commonly detected in house dust and indoor air.80–82 Despitetheir lower persistence, OPs and carbamates can inhibit acetylcholinesterase in


humans. The mechanisms of action of pyrethroids, pyrethrins, and organochlo-rines is to interfere with nerve cell function.25 The neurotoxic effects of thesepesticides may place burdens on early neurodevelopment of the fetus andmay possibly have long-term effects on children, although experimental andepidemiological studies are quite limited. Animal studies have shown that ex-posure to relatively small doses of chlorpyrifos at key developmental momentscan cause permanent changes in brain function.62,83

A CCCEH cohort study found that, prior to the EPA phase-out of the pesticidechlorpyrifos in 2001, 71% of newborns had detectable levels of the pesticide incord blood.84 The mean cord blood chlorpyrifos level was 6.9 pg/g, comparedto 1.3 pg/g after the ban.85 The researchers found that among babies born priorto the EPA phase-out, prenatal chlorpyrifos and diazinon exposures measuredby cord blood concentrations were significantly associated with impaired fetalgrowth.86 Lower air and cord blood levels of the pesticides as well as lack ofassociation with birth weight and birth length were observed after the 2001phase-out,86 indicating the efficacy of the regulatory action.

Future Steps in Children’s Environmental Health

In conclusion, much has been learned about certain types of risk factorsfor environmental health-related diseases in children. Rising rates of asthma,certain cancers, and developmental disability and the growing evidence thatrisk of certain adult disease is associated with in utero and childhood exposuresindicate that maintaining an “early focus” can have a significant impact on theoverall burden of disease. When preventive measures have been enacted basedon this knowledge, children’s health has benefited. Incorporating strategicprinciples to translate existing and future data into public health policy willensure future benefits in children’s environmental health.

REFERENCES

1. U. S. EPA. 1996. Proposed Guidelines for Carcinogen Risk Assessment. Office ofResearch and Development.Washington, DC.

2. NATIONAL ACADEMY OF SCIENCES. 1984. Toxicity Testing: Needs and Priorities.National Academy Press. Washington, DC.

3. GOLDMAN, L.R. & S.H. KODURU. 2000. Chemicals in the environment and devel-opmental toxicity to children: a public health and policy perspective. Environ.Health Perspect. 108(Suppl. 3):443–448.

4. LANDRIGAN, P.J., B. SONAWANE D. MATTISON, et al. 2002. Chemical contaminantsin breast milk and their impacts on children’s health: an overview. Environ. HealthPerspect. 110: A313–A315.

5. PERERA, F.P., S.M. ILLMAN, P.L. KINNEY, et al. 2002. The challenge of preventingenvironmentally related disease in young children: community-based researchin New York City. Environ. Health Perspect. 110: 197–204.


6. MANNINO, D.M., D.M. HOMA, L.J. AKINBAMI, et al. 2002. Surveillance forasthma—United States, 1980–1999. MMWR Surveill. Summ. 51: 1–13.

7. RIES, L.A.G., M.P. EISNER, C.L. KOSARY, et al. 2002. SEER Cancer StatisticsReview, 1973–1999. http://seer.cancer.gov/csr/1973 1999/. National Cancer In-stitute. Bethesda, MD. Accessed August 12, 2003.

8. BOYLE, C.A., P. DECOUFLE & M. YEARGIN-ALLSOPP. 1994. Prevalence and healthimpact of developmental disabilities in US children. Pediatrics 93: 399–403.

9. BEARER, C.F. 1995. Environmental health hazards: how children are different fromadults. Future Child. 5: 11–26.

10. WILES, R. & C. CAMPBELL. 1993. Pesticides in Children’s Food. Washington, DC:Environmental Working Group, 1993.

11. INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY. 1986. Principles for EvaluatingHealth Risks From Chemicals During Infancy and Early Childhood: The Needfor a Special Approach. Environmental Health Criteria, 59 ed. World HealthOrganization. Geneva, Switzerland.

12. SONAWANE, B. & R. BELILES. 1997. The susceptibility of children to immuno-toxic and neurotoxic agents. Children’s Environmental Health Network. lst Na-tional Research Conference on Children’s Environmental Health. Washington,DC.

13. PERERA, F.P. 1996. Molecular epidemiology: insights into cancer susceptibility,risk assessment, and prevention. J. Natl. Cancer Inst. 88: 496–509.

14. NATIONAL RESEARCH COUNCIL. 2000. Toxicological Effects of Methylmercury.National Academy Press. Washington, DC.

15. RAMIREZ, G.B., M.C. CRUZ, O. PAGULAYAN, et al. 2000. The Tagum study I:analysis and clinical correlates of mercury in maternal and cord blood, breastmilk, meconium, and infants’ hair. Pediatrics 106: 774–781.

16. CRAWFORD, M.A., W. DOYLE, P. DRURY, et al. 1989. n-6 and n-3 fatty acids duringearly human development. J. Intern. Med. 225(Suppl. 1): 159–169.

17. VOIGT, R.G., C.L. JENSEN, J.K. FRALEY, et al. 2002. Relationship between omega3long-chain polyunsaturated fatty acid status during early infancy and neurode-velopmental status at 1 year of age. J. Hum. Nutr. Diet. 15: 111–120.

18. MAKRIDES, M., M. NEUMANN, K. SIMMER, et al. 1995. Are long-chain polyunsat-urated fatty acids essential nutrients in infancy? Lancet 345: 1463–1468.

19. HATCH, G.E. 1995. Asthma, inhaled oxidants, and dietary antioxidants. Am. J.Clin. Nutr. 61(Suppl.): 625S–630S.

20. GREENE, L.S. 1995. Asthma and oxidant stress: nutritional, environmental, andgenetic risk factors. J. Am. Coll. Nutr. 14: 317–324.

21. PEAT, J.K., W.J. BRITON, C.M. SALOME, et al. 1987. Bronchial hyperresponsives-ness in two populations of Australian school children. III. Effect of exposure toenvironmental allergens. Clin. Allergy 17: 297–300.

22. PERERA, F.P., R.M. WHYATT, W. JEDRYCHOWSKI, et al. 1998. Recent developmentsin molecular epidemiology: a study of the effects of environmental polycylicaromatic hydrocarbons on birth outcomes in Poland. Am. J. Epidemiol. 147:309–314.

23. WANG, X., B. ZUCKERMAN, C. PEARSON, et al. 2002. Maternal cigarette smoking,metabolic gene polymorphism, and infant birth weight. JAMA 2002. 287: 195–202.

24. MUTCH, E., P.G. BLAIN & F.M. WILLIAMS. 1992. Interindividual variations in en-zymes controlling organophosphate toxicity in man. Hum. Exp. Toxicol. 11:109–116.


25. GREATER BOSTON PHYSICIANS FOR SOCIAL RESPONSIBILITY. 2000. In Harm’s Way:Toxic Threats to Child Development. Greater Boston Physicians for Social Re-sponsibility. Cambridge, MA.

26. BERKOWITZ, G.S., J.B. WETMUR, E. BIRMAN-DEYCH, et al. 2004. In utero pesti-cide exposure, maternal paraoxonase activity, and head circumference. Environ.Health Perspect. 112: 388–391.

27. KAHN, R.S., J. KHOURY, W.C. NICHOLS & B.P. LANPHEAR. 2003. Role of dopaminetransporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J. Pediatr. 143: 104–110.

28. WHYATT, R.M., D.A. BELL, R.M. SANTELLA, et al. 1998. Polycyclic aromatichydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 in-duction and genotype. Carcinogenesis 19: 1389–1392.

29. GILLILAND, F.D., Y.F. LI, L. DUBEAU, et al. 2002. Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobaccosmoke on asthma and wheezing in children. Am. J. Respir. Crit. Care Med. 166:457–463.

30. ROMIEU, I., J.J. SIENRA-MONGE, M. RAMIREZ-AGUILAR, et al. 2004. Genetic poly-morphism of GSTM1 and antioxidant supplementation influence lung functionin relation to ozone exposure in asthmatic children in Mexico City. Thorax 59:8–10.

31. CASSEL, J. 1976. The contribution of the social environment to host resistance: thefourth Wade Hampton Frost Lecture. Am. J. Epidemiol. 104: 107–123.

32. ZAPATA, B.C., A. REBOLLEDO, E. ATALAH, et al. 1992. The influence of social andpolitical violence on the risk of pregnancy complications. Am. J. Public Health82: 685–690.

33. KLIEGMAN, R. 1992. Perpetual poverty: child health and the underclass. Pediatrics89: 710–713.

34. DAVID, R.J. & J.W. COLLINS. 1997. Differing birth weight among infants of US-born blacks, African-born blacks, and US-born whites. N. Engl. J. Med. 337:1209–1214.

35. WISE, P.H. 1993. Confronting racial disparatities in infant mortality: reconcilingscience and politics. Am. J. Prev. Med. 31: 7–16.

36. RAUH, V.A., R.M. WHYATT, R. GARFINKEL, et al. 2004. Developmental effects ofexposure to environmental tobacco smoke and material hardship among inner-city children. J. Neurotoxicol. Teratol. 26: 373–385.

37. VAN LAREBEKE, N.A., L.S. BIRNBAUM, M.A. BOOGAERTS, et al. 2005. Unrecognizedor potential risk factors for childhood cancer. Int. J. Occup. Environ. Health. 11:199–201.

38. PERERA, F.P. 2000. Molecular epidemiology: on the path to prevention? J. Natl.Cancer Inst. 92: 602–612.

39. SRIVASTAVA, V.K., S.S. CHAUHAN, P.K. SRIVASTAVA, et al. 1986. Fetal transloca-tion and metabolism of PAH obtained from coal fly ash given intratracheally topregnant rats. J. Toxicol. Environ. Health 18: 459–469.

40. NEUBERT, D. & S. TAPKEN. 1988. Transfer of benzo(a)pyrene into mouse embryosand fetuses. Arch. Toxicol. 62: 236–239.

41. LU, L.J., R.M. DISHER, M.V. REDDY, & K. RANDERATH. 1986. 32P-postlabelingassay in mice of transplacental DNA damage induced by the environmental car-cinogens safrole, 4-aminobiphenyl and benzo(a)pyrene. Cancer Res. 46: 3046–3054.


42. WHYATT, R.M., W. JEDRYCHOWSKI, K. HEMMINKI, et al. 2001. Biomarkers of poly-cyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures inpaired maternal and newborn blood samples as a measure of differential suscep-tibility. Cancer Epidemiol. Biomarker Prev. 10: 581–588.

43. PERERA, F.P., D. TANG, W. JEDRYCHOWSKI, et al. 2004. Biomarkers in maternal andnewborn blood indicate heightened fetal susceptibility to procarcinogenic DNAdamage. Environ. Health Perspect. 112: 1133–1136.

44. PERERA, F.P., D. TANG, R.M. WHYATT, et al. 2004. Comparison of PAH-DNA adducts in four populations of mothers and newborns in the U.S.,Poland and China. 94th Annual Meeting. American Association for CancerResearch. Washington, DC.

45. CALABRESE, E.J. 1986. Age and Susceptibility to Toxic Substances. John Wileyand Sons. New York, NY.

46. NATIONAL ACADEMY OF SCIENCES. 1993. Pesticides in the Diets of Infants andChildren. National Academy Press. Washington, DC.

47. LAIB, R.J., K.P. KLEIN & H.M. BOLT. 1985. The rat liver foci bioassay: age depen-dence of induction by vinyl chloride of ATP-deficient foci. Carcinogenesis 6:65–68.

48. HAGMAR, L., A. BROGGER, I.L. HANSTEEN, et al. 1994. Cancer risk in humanspredicted by increased levels of chromosomal aberrations in lymphocytes: Nordicstudy group on the health risk of chromosome damage. Cancer Res. 54: 2919–2922.

49. BONASSI, S., L. HAGMAR, U. STROMBERG, et al. 2000. Chromosomal aberrationsin lymphocytes predict human cancer independently of exposure to carcinogens.European study group on cytogenetic biomarkers and health. Cancer Res. 60:1619–1625.

50. BOCSKAY, K.A., D. TANG, M.A. ORJUELA, et al. 2005. Chromosomal aberrationsin cord blood are associated with prenatal exposure to carcinogenic polycyclyicaromatic hydrocarbons. Cancer Epidemiol. Biomarker Prev. 14: 506–511.

51. PLUTH, J.M., M.J. RAMSEY & J.D. TUCKER. 2000. Role of maternal exposures andnewborn genotypes on newborn chromosome aberration frequencies. Mutat. Res.465: 101–111.

52. ROSS, J.A. 1998. Maternal diet and infant leukemia: a role for DNA topoisomeraseII inhibitors? Int. J. Cancer Suppl. 11: 26–28.

53. DEY, A.N. & B. BLOOM. 2005. Summary health statistics for U.S. children: NationalHealth Interview Survey, 2003. Vital Health Stat. 10: 223.

54. NICHOLAS, S.W., B. JEAN-LOUIS, B. ORTIZ, et al. 2005. Addressing the childhoodasthma crisis in Harlem: the Harlem children’s zone asthma initiative. Am. J.Public. Health 95: 245–249.

55. PLOPPER, C.G. & M.V. FANUCCI. 2000. Do urban environmental pollutants exacer-bate childhood lung disease? Environ. Health Perspect. 108: A252–A253.

56. MILLER, R.L., G. CHEW, C.A. BELL, et al. 2001. Prenatal exposure, maternal sen-sitization, and sensitization in utero to indoor allergens in an inner-city cohort.Am. J. Respir. Crit. Care. Med. 164: 995–1001.

57. MILLER, R.L., R. GARFINKEL, M. HORTON, et al. 2004. Polycyclic aromatic hydro-carbons, environmental tobacco smoke, and respiratory symptoms in an inner-city birth cohort. Chest 126: 1071–1078.

58. HONG, C.Y., S.E. CHIA, D. WIDJAJA, et al. 2004. Prevalence of respiratory symptomsin children and air quality by village in rural Indonesia. J. Occup. Environ. Med.46: 1174–1179.


59. JANSSEN, N.A., B. BRUNEKREEF, P. VAN VLIET, et al. 2003. The relationship be-tween air pollution from heavy traffic and allergic sensitization, bronchial hy-perresponsiveness, and respiratory symptoms in Dutch schoolchildren. Environ.Health Perspect. 111: 1512–1518.

60. SALAMEH, P.R., I. BALDI, P. BROCHARD, et al. 2003. Respiratory symptoms inchildren and exposure to pesticides. Eur. Respir. J. 22: 507–512.

61. FAUSTMAN, E.M. 2000. Mechanisms Underlying Children’s Susceptibility toEnvironmental Toxicants. Environ. Health Perspect. 108: (Suppl. 1): 13–21.

62. CHANDA, S.M. & C.N. POPE. 1996. Neurochemical and neurobehavioral effects ofrepeated gestational exposure to chlorpyrifos in maternal and developing rats.Pharmacol. Biochem. Behav. 53: 771–776.

63. CAMPBELL, C.G., F.J. SEIDLER, & T.A. SLOTKIN. 1997. Chlorpyrifos inter-feres with cell development in rat brain regions. Brain Res. Bull. 43: 179–189.

64. BAGHURST, P.A., A.J. MCMICHAEL, N.R. WIGG, et al. 1992. Environmental expo-sure to lead and children’s intelligence at the age of seven years. The Port Piriecohort study. N. Engl. J. Med. 327: 1279–1284.

65. BELLINGER, D.C., K.M. STILES, & H.L. NEEDLEMAN. 1992. Low level lead exposure,intelligence and academic achievement: a long-term follow-up study. Pediatrics90: 855–861.

66. NEEDLEMAN, H. & C. GATSONIS. 1990. Low-level lead exposure and the IQ ofchildren: A meta-analysis of modern studies. JAMA 263: 673–678.

67. CANFIELD, R.L., C.R. HENDERSON, D.A. CORY-SLECHTA, et al. 2003. Intellectualimpairment in children with blood lead concentrations below 10 �g per deciliter.N. Engl. J. Med. 348: 1517–1521.

68. LANPHEAR, B.P., K. DIETRICH, P. AUINGER & C. COX. 2000. Cognitive deficitsassociated with blood lead concentrations <10 microg/dL in US children andadolescents. Public Health Rep. 115: 521–529.

69. GRANDJEAN, P., P. WEIHE, V.W. BURSE, et al. 2001. Neurobehavioral deficits asso-ciated with PCB in 7-year-old children prenatally exposed to seafood neurotox-icants. Neurotoxicol. Teratol. 23: 305–317.

70. INTERNATIONAL AGENCY FOR RESEARCH ON CANCER. 1983. Polynuclear AromaticCompounds. Part l. Chemical, Environmental, and Experimental Data. IARCMonographs on the Evaluation of the Carcinogenic Risk of Chemicals to Hu-mans. International Agency for Research on Cancer, Lyon, France.

71. CHUANG, J.C., G.A. MACK, M.R. KUHLMAN & N.K. WILSON. 1991. Polycyclicaromatic hydrocarbons and their derivatives in indoor and outdoor air in aneight-home study. Atmos Environ. 25B: 369–380.

72. LEWTAS, J. 1994. Human exposure to complex mixtures of air pollutants. Toxicol.Lett. 72: 163–169.

73. COHEN, A.J. & C.A. POPE III. 1995. Lung cancer and air pollution. Environ. HealthPerspect. 103(Suppl. 8): 219–224.

74. TAKENAKA, H., K. ZHANG, D. DIAZ-SANCHEZ, et al. 1995. Enhanced human IgEproduction results from exposure to the aromatic hydrocarbons from diesel ex-haust: direct effects on B-cell IgE production. J. Allergy Clin. Immunol. 95: 103–115.

75. PERERA, F., V. RAUH, W.Y. TSAI, et al. 2003. Effects of transplacental exposure toenvironmental pollutants on birth outcomes in a multi-ethnic population. EnvironHealth Perspect. 111: 201–205.


76. PERERA, F.P., V. RAUH, R.M. WHYATT, et al. 2004. Molecular evidence of an inter-action between prenatal environmental exposures on birth outcomes in a multi-ethnic population. Environ. Health Perspect. 112: 662–630.

77. HACK, M., N. BRESLAU, B. WEISSMAN, et al. 1991. Effect of very low birth weightand subnormal head size on cognitive ability at school age. N. Engl. J. Med. 325:231–237.

78. PARERA, F.P., V. RAUH, R.W. WHYATT, et al. Effect of prenatal exposure to airbornepolycyclic aromatic hydrocarbons on neurodevelopment in the first three years oflife among inner-city children. Environ. Health Perspect. doi:10.1289/ehp.9084.[Online 24 April 2006].

79. LANDRIGAN, P.J., L. CLAUDIO, S.B. MARKOWITZ, et al. 1999. Pesticides andinner-city children: exposures, risks, and prevention. Environ. Health Perspect.107(Suppl. 3): 431–437.

80. WHITMORE, R., F.W. IMMERMAN, D.E. CAMANN, et al. 1994. Non-occupationalexposures to pesticides for residents of two U.S. cities. Arch. Environ. Contam.Toxicol. 26: 47–59.

81. LEWIS, R.G., R.C. FORTMANN & D.E. CAMANN. 1994. Evaluation of methods formonitoring potential exposure of small children to pesticides in the residentialenvironment. Arch. Environ. Contam. Toxicol. 26: 37–46.

82. CAMANN, D.E., J.S. COLT, S.I. TEITELBAUM, et al. 2000. Pesticide and PAH distri-butions in house dust from seven areas of USA. SETAC Conference, Abstract570. Society of Environmental Toxicology and Chemistry.

83. SONG, X., F.J. SEIDLER, J.L. SALEH, et al. 1997. Cellular mechanisms for develop-mental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade.Toxicol. Appl. Pharmacol. 145: 158–174.

84. WHYATT, R.M., D.B. BARR, D.E. CAMANN, et al. 2003. Contemporary-use pesti-cides in personal air samples during pregnancy and blood samples at deliveryamong urban minority mothers and newborns. Environ. Health Perspect. 111:749–756.

85. WHYATT, R.M., D. CAMANN, F.P. PERERA, et al. 2005. Biomarkers in assessingresidential insecticide exposures during pregnancy and effects on fetal growth.Toxicol. Applied Pharmacol. 206: 246–254.

86. WHYATT, R.M., D.E. CAMANN, Y. COSME, et al. 2004. Persistence of chlorpyrifosand diazinon in the indoor environment following U.S. regulatory action to banresidential use. International Society for Exposure Analysis, Abstract.

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