The aim of this study was to investigate the relationship between autism spectrum disorders development and exposure to mono-(2-ethylhexyl)-phthalate (MEHP), di-(2-ethylhexyl)-phthalate (DEHP), and bisphenol A (BPA), 1 of the endocrine disruptors, among phthalates. The study included 48 children with autism spectrum disorder (27 boys, 21 girls) and 41 healthy subjects (24 boys, 17 girls) as controls. Serum MEHP, DEHP, and BPA levels were measured by using high-performance liquid chromatography. Children with autism spectrum disorder had significantly increased serum MEHP, DEHP, and BPA concentrations (0.47 ± 0.14 µg/ml, 2.70 ± 0.90 µg/ml, 1.25 ± 0.30 ng/ml) compared to healthy control subjects (0.29 ± 0.05 µg/ml, 1.62 ± 0.56 µg/ml, 0.88 ± 0.18 ng/ml) respectively (P = .000). The fact that higher serum MEHP, DEHP, and BPA were found levels in the autism spectrum disorder group compared to healthy controls suggests that endocrine disruptors may have a role in the pathogenesis of autism spectrum disorders.
KimYSLeventhalBLKohYJ. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry. 2011;168(9):904–912. Erratum in 2013;170(6):689.
3.
RodierPM. Environmental exposures that increase the risk of autism spectrum disorders. In: AmaralDGDawsonGGeschwindDH, eds. Autism Spectrum Disorders. New York, NY: Oxford University Press; 2011:863–874.
4.
BrownASSouranderAHinkka-Yli-SalomäkiS. Elevated maternal C-reactive protein and autism in a national birth cohort. Mol Psychiatry. 2014;19(2):259–264.
5.
VolkHELurmannFPenfoldB. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013;70(1):71–77.
6.
O’RoakBJStateMW. Autism genetics: strategies, challenges, and opportunities. Autism Res. 2008;1(1):4–17.
7.
LoshMChildressDLamKPivenJ. Defining key features of the broad autism phenotype: a comparison across parents of multiple- and single-incidence autism families. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(4):424–433.
8.
RossignolDAGenuisSJFryeRE. Environmental toxicants and autism spectrum disorders: a systematic review. Transl Psychiatry. 2014;4:e360.
9.
BaileyALe CouteurAGottesmanI. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995;25(1):63–77.
10.
HerbertMRRussoJPYangS. Autism and environmental genomics. Neurotoxicology. 2006;27(5):671–684.
11.
NebesioTDPescovitsOH. Environmental effects on puberty. The role of endocrine disruptors in pubertal development. In: WalvoordECPescovitsOH, eds. When Puberty Is Precocious: Scientific and Clinical Aspects. Totowa, NJ: Humana Press; 2007:425–442.
12.
FrederiksenHSkakkebaekNEAnderssonAM. Metabolism of phthalates in humans. Mol Nutr Food Res. 2007;51(7):899–891.
13.
Agency for Toxic Substances and Disease Registry. Toxicological Profile for Diethylphthalate. Atlanta, GA: Department of Health and Human Services, Public Health Service; 1995.
14.
LiLZhangTQinXS. Exposure to diethylhexyl phthalate (DEHP) results in a heritable modification of imprint genes DNA methylation in mouse oocytes. Mol Biol Rep. 2014;41(3):1227–1235.
15.
TestaCNutiFHayekJ. Di-(2-ethylhexyl) phthalate and autism spectrum disorders. ASN Neuro. 2012;4(4):223–229.
16.
SteinTPSchluterMDSteerRAMingX. Autism and phthalate metabolite glucuronidation. J Autism Dev Disord. 2013;43(11):2677–2685.
17.
RochesterJR. Bisphenol A and human health: a review of the literature. Reprod Toxicol. 2013;42:132–155.
18.
WolstenholmeJTTaylorJAShettySR. Gestational exposure to low dose bisphenol A alters social behavior in juvenile mice. PLOS ONE. 2011;6(9):e25448.
19.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
20.
SchoplerEReichlerRJDeVellisRFDalyK. Toward objective classification of childhood autism: Childhood Autism Rating Scale (CARS). J Autism Dev Disord. 1980;10(1):91–103.
ParisIRuggieriFMazzeoPCarlucciG. Simultaneous determination of di-(2-ethylhexyl)-phthalate and mono-(2-ethylhexyl)-phthalate in human plasma by HPLC. Anal Lett. 2003;36:2645–2654.
23.
XiaoQLiYOuyangH. High-performance liquid chromatographic analysis of bisphenol A and 4-nonylphenol in serum, liver and testis tissues after oral administration to rats and its application to toxicokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;830:322–329.
24.
AkınLKendirciMNarinF. The endocrine disruptor bisphenol A may play a role in the aetiopathogenesis of polycystic ovary syndrome in adolescent girls. Acta Paediatr. 2015;104(4):e171–e177.
25.
MuhleRTrentacosteSVRapinI. The genetics of autism. Pediatrics. 2004;113(5):e472–e486.
TrasandeLSpanierAJSathyanarayanaS. Urinary phthalates and increased insulin resistance in adolescents. Pediatrics. 2013;132(3):e646–e655.
28.
EngelSMMiodovnikACanfieldRL. Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ Health Perspect. 2010;118(4):565–571.
29.
RoelfsemaMTHoekstraRAAllisonC. Are autism spectrum conditions more prevalent in an information-technology region? A school-based study of three regions in the Netherlands. J Autism Dev Disord. 2012;42(5):734–739.
30.
KhalilNEbertJRWangL. Bisphenol A and cardiometabolic risk factors in obese children. Sci Total Environ. 2014;470-471:726–732.
31.
European Food Safety Authority. Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food from the Commission Related to 2-BIS(4-HYDROXYPHENYL)-PROPANE (Bisphenol A). 2006Available at:http://www.efsa.europa.eu/it/scdocs/doc/428.pdf.
32.
vom SaalFSCookePSBuchananDL. A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior. Toxicol Ind Health. 1998;14(1-2):239–260.
33.
vom SaalFSAkingbemiBTBelcherSM. Flawed experimental design reveals the need for guidelines requiring appropriate positive controls in endocrine disruption research. Toxicol Sci. 2010;115(2):612–613.
34.
KimSMHanDHLyooHS. Exposure to environmental toxins in mothers of children with autism spectrum disorder. Psychiatry Investig. 2010;7(2):122–127.
35.
EskenaziBMarksARBradmanA. Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect. 2007;115(5):792–798.
36.
YeşilkayaE.[Endocrine disruptors]. J Current Pediatr. 2008;6:76–82.
37.
JiangYXiaWYangJ. BPA-induced DNA hypermethylation of the master mitochondrial gene PGC-1α contributes to cardiomyopathy in male rats. Toxicology. 2015;329:21–31.
38.
KaurKChauhanVGuFChauhanA. Bisphenol A induces oxidative stress and mitochondrial dysfunction in lymphoblasts from children with autism and unaffected siblings. Free Radic Biol Med. 2014;76:25–33.
39.
JiangYXiaWZhuY. Mitochondrial dysfunction in early life resulted from perinatal bisphenol A exposure contributes to hepatic steatosis in rat offspring. Toxicol Lett. 2014;228(2):85–92.
40.
SavchukISöderOSvechnikovK. Mono-2-ethylhexyl phthalate stimulates androgen production but suppresses mitochondrial function in mouse leydig cells with different steroidogenic potential. Toxicol Sci. 2015;145(1):149–156.
41.
LiXFangEFScheibye-KnudsenM. Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis. Sci Rep. 2014;4:6434.
42.
MD. RossignolDAFryeRE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012;17(3):290–314.
