Do Industrial Pollutants Contribute to Autism?

Polychlorinated Biphenyl

Polychlorinated biphenyls (PCBs) are a class of synthetic chemicals widely manufactured in the 1960s for use as coolants and lubricants in industrial settings. Because of mounting evidence of adverse health effects, the manufacture of PCBs was banned in 1976 in most industrialized countries; however, the damage had already been done. PCBs are extremely persistent in the soil, water, and air and remain a public health concern1. Unfortunately, PCBs are well-established developmental neurotoxicants that adversely affect both cognitive and motor development in exposed children4, 5, 6, 7. Less is known about the effects of PCB exposure on the social and emotional development of children. A recent animal research study found that perinatal PCB exposure impaired social approach and investigation, behaviors also impaired in individuals with Autism Spectrum Disorders8. Clearly, more clinical and epidemiological research is needed to fully characterize the impact of PCB exposure on autism and Autism Spectrum Disorders.

 

Chlorination Byproducts

In 1998, concerned parents, educators, and clinicians in Brick Township, New Jersey, noticed a worrying increase in the number of autism diagnoses. The Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry (ATSDR) reported the prevalence of Autism Spectrum Disorders in Brick Township as 6.7 cases per 1000 children, far higher than the national average at the time2.The ATSDR also determined that the municipal drinking water was heavily contaminated with water chlorination byproducts, specifically perchloroethylene (PCE) and the trihalomethanes (THMs) chloroform and bromoform, from 1987 to1995. In 2000, the ATSDR concluded that there was no direct link between THM and PCE contamination of drinking water and the increased prevalence of Autism Spectrum Disorders in Brick Township2.However, a recent animal research study suggests that this conclusion may have been premature. In this study, male (but not female) mice provided with THM- and PCE-contaminated drinking water developed autistic-like behaviors after gestational and postnatal exposure3.These results suggest that males may be uniquely sensitive (at specific developmental time points) to the synergistic effects of PCE and trihalomethanes.

 

Traffic-Related Air Pollutants

Traffic-related air pollution (TRAP) is defined by the EPA as all emissions generated by mobile sources. These emissions are a complex mixture of greenhouse gases, particulate matter, volatile organic compounds, polycyclic aromatic hydrocarbons, and metals. Many components of TRAP are also deemed Hazardous Air Pollutants (HAPs), compounds associated with adverse human health effects. Children are especially sensitive to the deleterious effects of TRAP. In 2006, a comprehensive geo-spatial study of the San Francisco Bay area reported positive associations between autism rates and estimated heavy metal and chlorinated solvent concentrations in the ambient air around the birth residence9.This study also suggested a potential increase in autism risk with exposure to diesel exhaust particles; however, this association was moderate. Given that TRAP is a complex mixture, the authors further note that the concentration of these chemicals was highly inter-correlated, therefore the specific contribution a compound or group of compounds was difficult to ascertain. Interestingly, one animal research study found that pregnant mice exposed to diesel exhaust particles bore offspring with severe abnormalities in fetal brain development and pathological findings similar to those reported in autism.10

Prenatal exposure to another hazardous component of air pollution, polycyclic aromatic hydrocarbons, is strongly associated with impaired cognitive development in case studies of 3- and 5-year-old children.11,1 2 In a rare gene-environment autism study, genetically susceptible mice exposed to the polycyclic aromatic hydrocarbon benzo(a)pyrene while pregnant developed offspring with behavioral deficits and with decreased expression of the MET gene, a suspected autism risk gene.13 This study demonstrated that autism susceptibility genes are sensitive to specific environmental exposures. Finally, a 2011 report released by the Childhood Autism Risks from Genetics and the Environment (CHARGE) study described a clear positive association between residential proximity to freeways and Autism Spectrum Disorder diagnoses, emphasizing the need for further examination of the association between autism and individual hazardous air pollutants.14

Therefore future examination of the association between autism and air pollution is needed.

 

Phthalates

Phthalates are ubiquitous synthetic compounds commonly used as plasticizers. High molecular weight (HMW) phthalates are found in PVC plastics (including vinyl flooring), building material, medical devices and food packaging. Low molecular weight (LMW) phthalates are common components of medications and personal care products. Phthalates are known to causes allergies and disrupt the endocrine system.17The first study to report a positive association between phthalates and autism was a multi-phase cross-sectional study analyzing the relationship between indoor environmental variables and asthma/allergies in young Swedish children16. The authors note that this study was not designed to focus on autism; therefore further study of a larger autistic population is warranted. There are currently no published studies that evaluate the association between prenatal phthalate exposures in a study population with clinically diagnosed ASD.

 

Polybrominated diphenyl ether (PDBE)

Polybrominated diphenyl ether (PBDE) flame-retardants are a large class of brominated congeners widely used in foam furniture, carpeting, car seats, electronics, appliances, building materials and textiles. PBDEs are ubiquitous and lipophilic, readily crossing the placenta and mobilizing into breast milk. This bioavailability has resulted in mounting concerns about the developmental effects of PBDE exposures.  In animal research studies, prenatal or perinatal exposures to PBDEs caused permanent deficits in spontaneous behavior, learning, and memory and aversion to unfamiliar stimuli, all common features of Autism Spectrum Disorders 18. A recent gene x environment (GxE) examined the effects of perinatal PBDE exposure in the Mecp2 truncation mutant mouse, a genetically and epigenetically susceptible model.  This study found that prenatal exposure to the PBDE congener BDE-47 resulted in female-specifc, genotype-independent effects including reduced sociability and a genotype-dependent compensatory upregulation of the methyltransferase Dnmt3a resulting in a reversal of social novelty learning impairments. Other consequences of the Mecp2 mutation and PBDE-exposure "double hit" model included deficits in learning and long-term memory in female offsprings19. However, the Childhood Autism Risks from Genetics and the Environment (CHARGE) study has failed to identify any difference in blood PBDE levels between children with autism and neurotypical childrens20. That study was limited by post-diagnosis sampling, which does not reflect early-life or prenatal exposure, and future studies of prenatal or infant exposures are warranted. Clearly, the role of the indoor environment is a growing and intriguing area of autism research.







References:
  1. Winneke G (2011) Developmental aspects of environmental neurotoxicology: Lessons from lead and polychlorinated biphenyls. J Neurol Sci 308:9-15. PMID: 21679971.
  2. Bertrand J, Mars A, Boyle C, Bove F, Yeargin-Allsopp M, Decoufle P (2001) Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation. Pediatrics 108:1155-1161. PMID: 11694696.
  3. Guariglia SR, Jenkins EC, Jr., Chadman KK, Wen GY (2011) Chlorination byproducts induce gender specific autistic-like behaviors in CD-1 mice. Neurotoxicology. PMID: 21740927.
  4. Schantz SL, Widholm JJ, Rice DC (2003) Effects of PCB exposure on neuropsychological function in children. Environ Health Perspect 111:357-576. PMID: 12611666.
  5. Jacobson JL, Jacobson SW (1996) Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med 335:783-789. PMID: 8703183.
  6. Stewart PW, Lonky E, Reihman J, Pagano J, Gump BB, Darvill T (2008) The relationship between prenatal PCB exposure and intelligence (IQ) in 9-year-old children. Environ Health Perspect 116:1416-1422. PMID: 18941588.
  7. Vreugdenhil HJ, Lanting CI, Mulder PG, Boersma ER, Weisglas-Kuperus N (2002) Effects of prenatal PCB and dioxin background exposure on cognitive and motor abilities in Dutch children at school age. J Pediatr 140:48-56. PMID: 11815763.
  8. Jolous-Jamshidi B, Cromwell HC, McFarland AM, Meserve LA (2010) Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats. Toxicol Lett 199:136-143. PMID: 20813172.
  9. Windham GC, Zhang L, Gunier R, Croen LA, Grether JK (2006) Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco bay area. Environ Health Perspect 114:1438-1444. PMID: 16966102.
  10. Sugamata M, Ihara T, Sugamata M, Takeda K (2006) Maternal exposure to diesel exhaust leads to pathological similarity to autism in newborns. J Health Sci 52:486-488.
  11. Perera FP, Rauh V, Whyatt RM, Tsai WY, Tang D, Diaz D, Hoepner L, Barr D, Tu YH, Camann D, Kinney P (2006) Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children. Environ Health Perspect 114:1287-1292. PMID: 16882541.
  12. Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, Ho SM (2009) Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 4:e4488. PMID: 19221603.
  13. Sheng L, Ding X, Ferguson M, McCallister M, Rhoades R, Maguire M, Ramesh A, Aschner M, Campbell D, Levitt P, Hood DB (2010) Prenatal polycyclic aromatic hydrocarbon exposure leads to behavioral deficits and downregulation of receptor tyrosine kinase, MET. Toxicol Sci 118:625-634. PMID: 20889680.
  14. Volk HE, Hertz-Picciotto I, Delwiche L, Lurmann F, McConnell R (2011) Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect 119:873-877. PMID: 21156395.
  15. Zhang J, Smith KR (2003) Indoor air pollution: a global health concern. Br Med Bull 68:209-225. PMID: 14757719.
  16. Larsson M, Weiss B, Janson S, Sundell J, Bornehag CG (2009) Associations between indoor environmental factors and parental-reported autistic spectrum disorders in children 6-8 years of age. Neurotoxicology 30:822-831. PMID: 19822263.
  17. Pak VM, McCauley LA, Pinto-Martin J (2011) Phthalate exposures and human health concerns: A review and implications for practice. AAOHN J 59:228-233; quiz 234-225. PMID: 21534504.
  18. Costa LG, Giordano G (2007) Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants. Neurotoxicology 28:1047-1067. PMID: 17904639.
  19. Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH, Chi LH, Kostyniak PJ, Pessah IN, Berman RF, Lasalle JM (2012) Long- lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Hum Mol Genet. 2012 Mar 19. PMID: 22343140.
  20. Hertz-Picciotto I, Bergman A, Fangstrom B, Rose M, Krakowiak P, Pessah I, Hansen R, Bennett DH (2011) Polybrominated diphenyl ethers in relation to autism and developmental delay: a case-control study. Environ Health 10:1. PMID:21205326.



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