Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme

Yirün, Anıl; ERKEKOGLU, PİNAR; Erdemli Kose, Selinay Basak; Mercan, Nigar

doi:10.5336/pharmsci.2020-79267

Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme

Nigar MERCAN, (Hacettepe Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, Ankara, Türkiye)

Selinay KÖSE, (Hacettepe Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, Ankara, Türkiye)

Anıl YİRÜN, (Hacettepe Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, Ankara, Türkiye)

Pınar ERKEKOĞLU (Hacettepe Üniversitesi, Eczacılık Fakültesi, Farmasötik Toksikoloji Anabilim Dalı, Ankara, Türkiye)

Literatür Eczacılık Bilimleri Dergisi

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Yıl: 2021 Cilt: 10 Sayı: 3 Sayfa Aralığı: 308 - 321 Metin Dili: Türkçe DOI: 10.5336/pharmsci.2020-79267 İndeks Tarihi: 17-02-2022

Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme

Öz:

Otizm spektrum bozukluğu (OSB), tekrar eden davranışlar ve sınırlı dikkatin yanı sıra sosyal fonksiyon eksiklikleri ve iletişim alanlarında bozulmayla karakterize kompleks nörogelişimsel bir bozukluk olarak tanımlanmaktadır. OSB’nin ortaya çıkmasında, çok sayıda mekanizma rol oynamaktadır. Bunlar arasında en önemlileri; oksidatif stres, mitokondriyal disfonksiyon, serotonerjik sistemde anomaliler, beyaz cevher yapısında anormal değişiklikler, anormal sitokin düzeyleri, immün sistem disregülasyonu, beyin dokusuna karşı oluşan fetalmaternal antikorlar ve mikroglial aktivasyondur. Bu bozukluğa sebep olan başlıca etmenler; genetik faktörler, çevresel etkenler ve prenatal faktörlerdir. Erken dönemde çevresel maruziyetler, genetik yatkınlıklarla birlikte otizmin ortaya çıkmasında etkili olabilir. Bireylerin genetik yatkınlığı ve toplumun geneline göre daha duyarlı olmaları da bu çevresel etkenlerin, otizm ve benzeri nörogelişimsel bozuklukları oluşturma riskini artırabilir. Prenatal maruziyet, otizmin ortaya çıkmasının en önemli olası nedeni olarak kabul edilebilir. Ayrıca farklı çevresel maruziyetler ve kalıtsal özellikler arasındaki etkileşimin, otizm fenotipinde gözlemlenen heterojenliği de açıklayabileceği varsayılmaktadır. Endokrin bozucu kimyasal maddeler (EDC) endokrin sistemin işleyişini değiştirerek, organizmada ve doğacak nesillerde olumsuz sağlık etkilerine neden olan ekzojen madde veya madde karışımları olarak tanımlanır. EDC’lere maruziyet sonucu, otizm ve diğer nörogelişimsel hastalıkların riskinin arttığı düşünülmektedir. Bu derleme kapsamında; OSB, belirtileri, ortaya çıkmasında etkili olan faktörler ve çevresel faktörlerden EDC’lerin (ftalatlar, poliklorlu bifeniller, perflorokimyasallar, organoklorlu pestisitler, bisfenol A, ağır metaller) OSB ile olası ilişkisi hakkında bilgi verilmesi amaçlanmıştır.

Anahtar Kelime:

Possible Roles of Endocrine Disrupting Chemicals in Autism Spectrum Disorders: Systematic Review

Öz:

Autism spectrum disorder (ASD) is defined as a complex neurodevelopmental disorder, characterized by recurrent behaviors and limited attention, as well as social function deficiencies and disruption in communication. Many mechanisms play a role in the emergence of ASD. The most important mechanisms are oxidative stress, mitochondrial dysfunction, serotonergic system abnormalities, abnormal changes in white matter structure, abnormal cytokine levels, immune system dysregulation, fetal maternal antibodies against brain tissue and microglial activation. Main factors causing ASD are genetic factors, environmental factors and prenatal factors. Environmental exposures in early stages of life, together with genetic predisposition, might be effective in the emergence of autism. Individuals' genetic predisposition and higher sensitivity compared to general population may also increase the risk of these environmental factors to cause autism and similar neurodevelopmental disorders. Prenatal exposure can be considered as the most important possible cause of autism. It is also assumed that interaction between different environmental exposures and hereditary characteristics may explain the heterogeneity observed in autistic phenotype. Endocrine disrupting chemicals (EDCs) are defined as exogenous substances or mixtures that change the functioning of endocrine system and cause negative health effects in an organism and the future generations. Risk of autism and other neurodevelopmental diseases is thought to increase as a result of exposure to endocrine disruptors. In this study, we aimed to give information about ASD, symptoms, factors that affect its occurrence and the possible association between EDCs (phthalates, polychlorinated biphenyls, perfluorochemicals, organochlorine pesticides, bisphenol A, heavy metals) and ASD.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Özeren gS. Otizm spektrum bozukluğu (OSB) ve hastalığa kanıt penceresinden bakış. Acıbadem Univ Sağlık Bilim Derg. 2013;4(2): 57-63.
2. Sacco R, Lintas C, Persico AM. Autism genetics: methodological issues and experimental design. Sci China Life Sci. 2015;58(10): 946-57.
3. Bailey A, Le Couteur A, gottesman I, Bolton P, Simonoff E, Yuzda E, et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med. 1995;25(1): 63-77.
4. gupta AR, State MW. Autismo: genética [Autism: genetics]. Braz J Psychiatry. 2006 May;28 Suppl 1:S29-38.
6. Tohum Türkiye Otizm Erken Tanı ve Eğitim Vakfı [İnternet]. © 2020 Tohum Otizm Vakfı. [Erişim tarihi: 20.01.2020]. Erişim linki:
7. Landrigan PJ. What causes autism? Exploring the environmental contribution. Curr Opin Pediatr. 2010;22(2):219-25.
8. Wilson CE, gillan N, Spain D, Robertson D, Roberts g, Murphy CM, et al. Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an adult autism spectrum disorder diagnostic clinic. J Autism Dev Disord. 2013;43(11):2515-25.
9. Erdemli-Köse SB, Balcı A, Yirun A, Erkekoğlu P. Tiyomersal maruziyeti ve otizm spektrum bozuklukları arasındaki olası ilişkinin değerlendirilmesi. [Evaluation of the possible association between thiomersal exposure and autism spectrum disorders]. J Lit Pharm Sci. 2020;9(3):304-18.
10. Bodur ş, Soysal Aş. [Early Diagnosis and Importance of Autism]. Sted. 2004;13(10):394-8.
11. Caglayan AO. genetic causes of syndromic and non-syndromic autism. Dev Med Child Neurol. 2010;52(2):130-8.
12. Tordjman S, Somogyi E, Coulon N, Kermarrec S, Cohen D, Bronsard g, et al. gene × Environment interactions in autism spectrum disorders: role of epigenetic mechanisms. Front Psychiatry. 2014;5:53.
13. Dietert RR, Dietert JM, Dewitt JC. Environmental risk factors for autism. Emerg Health Threats J. 2011;4:7111.
14. Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005;161(10):916-25; discussion 926-8.
15. Erden S, Nalbant K. Autism spectrum disorder and prenatal risk factors. Selçuk Med J. 2019;35(4):282-90.
16. Özbaran B. Otizm spektrum bozukluklarında çevresel faktörler etkili midir? [Do environmental factors have ınfluence on autism spectrum disorder?]. Pediatr Res. 2014;1(4):170-3.
17. Diamanti-Kandarakis E, Bourguignon JP, giudice LC, Hauser R, Prins gS, Soto AM, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293-342.
18. Lauretta R, Sansone A, Sansone M, Romanelli F, Appetecchia M. Endocrine disrupting chemicals: effects on endocrine glands. Front Endocrinol (Lausanne). 2019;10:178.
19. Yeşilkaya E. Endokrin bozucular. [Endocrine disruptors]. J Pediatr. 2008;6(3):76-82.
20. Liang DW, Zhang T, Fang HH, He J. Phthalates biodegradation in the environment. Appl Microbiol Biotechnol. 2008;80(2):183-98.
21. Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: toxicology and exposure. Int J Hyg Environ Health. 2007;210(5):623-34.
22. Frederiksen H, Skakkebaek NE, Andersson AM. Metabolism of phthalates in humans. Mol Nutr Food Res. 2007;51(7):899-911.
23. Jeddi MZ, Janani L, Memari AH, Akhondzadeh S, Yunesian M. The role of phthalate esters in autism development: a systematic review. Environ Res. 2016;151:493-504.
24. Carbone S, Ponzo OJ, gobetto N, Samaniego YA, Reynoso R, Scacchi P, et al. Antiandrogenic effect of perinatal exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate increases anxiety-like behavior in male rats during sexual maturation. Horm Behav. 2013;63(5):692-9.
25. Lichtensteiger W, Bassetti-gaille C, Faass O, Axelstad M, Boberg J, Christiansen S, et al. Differential gene expression patterns in developing sexually dimorphic rat brain regions exposed to antiandrogenic, estrogenic, or complex endocrine disruptor mixtures: glutamatergic synapses as target. Endocrinology. 2015;156(4):1477-93.
26. Miodovnik A, Engel SM, Zhu C, Ye X, Soorya LV, Silva MJ, et al. Endocrine disruptors and childhood social impairment. Neurotoxicology. 2011;32(2):261-7.
27. Testa C, Nuti F, Hayek J, De Felice C, Chelli M, Rovero P, et al. Di-(2-ethylhexyl) phthalate and autism spectrum disorders. ASN Neuro. 2012;4(4):223-9.
28. Kardas F, Bayram AK, Demirci E, Akin L, Ozmen S, Kendirci M, et al. Increased serum phthalates (MEHP, DEHP) and bisphenol a concentrations in children with autism spectrum disorder: the role of endocrine disruptors in autism etiopathogenesis. J Child Neurol. 2016;31(5):629-35.
29. Durmaz E, Koçer giray B. Çevresel bir endokrin bozucu: bisfenol A ve toksik etkilerinin değerlendirilmesi. [An environmental endocrine disrupter: bisphenol A and evaluation of its toxic effects]. Çocuk Sağlığı ve Hastalıkları Dergisi. 2013;56(4):192-9.
30. Masuno H, Iwanami J, Kidani T, Sakayama K, Honda K. Bisphenol a accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol Sci. 2005;84(2):319-27.
31. Braun JM, Kalkbrenner AE, Calafat AM, Yolton K, Ye X, Dietrich KN, et al. Impact of early-life bisphenol A exposure on behavior and executive function in children. Pediatrics. 2011; 128(5):873-82.
32. Wolstenholme JT, Taylor JA, Shetty SR, Edwards M, Connelly JJ, Rissman EF. gestational exposure to low dose bisphenol A alters social behavior in juvenile mice. PLoS One. 2011;6(9):e25448.
33. Stein TP, Schluter MD, Steer RA, guo L, Ming X. Bisphenol A exposure in children with autism spectrum disorders. Autism Res. 2015;8(3):272-83.
34. Braun JM, Yolton K, Dietrich KN, Hornung R, Ye X, Calafat AM, et al. Prenatal bisphenol A exposure and early childhood behavior. Environ Health Perspect. 2009;117(12):1945-52.
35. Foresta C, Tescari S, Di Nisio A. Impact of perfluorochemicals on human health and reproduction: a male's perspective. J Endocrinol Invest. 2018;41(6):639-45.
36. Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei C, et al. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case-control study in the Danish National Birth Cohort. Environ Health Perspect. 2015;123(4):367-73.
37. Hu Q, Franklin JN, Bryan I, Morris E, Wood A, DeWitt JC. Does developmental exposure to perfluorooctanoic acid (PFOA) induce immunopathologies commonly observed in neurodevelopmental disorders. Neurotoxicology. 2012;33(6):1491-8.
38. Sobolewski M, Conrad K, Allen JL, Weston H, Martin K, Lawrence BP, et al. Sex-specific enhanced behavioral toxicity induced by maternal exposure to a mixture of low dose endocrine-disrupting chemicals. Neurotoxicology. 2014;45:121-30.
39. Lau C, Thibodeaux JR, Hanson Rg, Rogers JM, grey BE, Stanton ME, et al. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation. Toxicol Sci. 2003;74(2):382-92.
40. Johansson N, Fredriksson A, Eriksson P. Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology. 2008;29(1):160- 9.
41. Liew Z, Ritz B, Bach CC, Asarnow RF, Bech BH, Nohr EA, et al. Prenatal exposure to perfluoroalkyl substances and IQ scores at age 5; a study in the danish national birth cohort. Environ Health Perspect. 2018;126(6): 067004.
42. Eriksson P, Fredriksson A. Neurotoxic effects in adult mice neonatally exposed to 3,3'4,4'5- pentachlorobiphenyl or 2,3,3'4,4'-pentachlorobiphenyl. Changes in brain nicotinic receptors and behaviour. Environ Toxicol Pharmacol. 1998;5(1):17-27.
43. ghosh S, Mitra PS, Loffredo CA, Trnovec T, Murinova L, Sovcikova E, et al. Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: indicator of disease and disorder development in humans. Environ Res. 2015;138:202-16.
44. Mitchell MM, Woods R, Chi LH, Schmidt RJ, Pessah IN, Kostyniak PJ, et al. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environ Mol Mutagen. 2012;53(8):589-98.
45. Kimura-Kuroda J, Nagata I, Kuroda Y. Disrupting effects of hydroxy-polychlorinated biphenyl (PCB) congeners on neuronal development of cerebellar Purkinje cells: a possible causal factor for developmental brain disorders? Chemosphere. 2007;67(9):S412-20.
46. Jolous-Jamshidi B, Cromwell HC, McFarland AM, Meserve LA. Perinatal exposure to polychlorinated biphenyls alters social behaviors in rats. Toxicol Lett. 2010;199(2):136-43.
47. Wayman gA, Bose DD, Yang D, Lesiak A, Bruun D, Impey S, et al. PCB-95 modulates the calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environ Health Perspect. 2012;120(7): 1003-9.
48. Eriksson P, Fredriksson A. Developmental neurotoxicity of four ortho-substituted polychlorinated biphenyls in the neonatal mouse. Environ Toxicol Pharmacol. 1996;1(3):155-65.
49. Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, et al. Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: association with autism spectrum disorder and intellectual disability. Environ Health Perspect. 2017;125(3):474-80.
50. Lemaire g, Terouanne B, Mauvais P, Michel S, Rahmani R. Effect of organochlorine pesticides on human androgen receptor activation in vitro. Toxicol Appl Pharmacol. 2004;196(2): 235-46.
51. Androutsopoulos VP, Hernandez AF, Liesivuori J, Tsatsakis AM. A mechanistic overview of health associated effects of low levels of organochlorine and organophosphorous pesticides. Toxicology. 2013;307:89-94.
52. Saeedi Saravi SS, Dehpour AR. Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: a review. Life Sci. 2016;145:255-64.
53. Lee I, Eriksson P, Fredriksson A, Buratovic S, Viberg H. Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin. Toxicology. 2015;335:1-10.
54. Roberts EM, English PB, grether JK, Windham gC, Somberg L, Wolff C. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Environ Health Perspect. 2007;115(10):1482-9.
55. Ribas-Fitó N, Torrent M, Carrizo D, Mu-ozOrtiz L, Júlvez J, grimalt JO, et al. In utero exposure to background concentrations of DDT and cognitive functioning among preschoolers. Am J Epidemiol. 2006;164(10):955-62.
56. Dallaire R, Muckle g, Rouget F, Kadhel P, Bataille H, guldner L, et al. Cognitive, visual, and motor development of 7-month-old guadeloupean infants exposed to chlordecone. Environ Res. 2012;118:79-85.
57. Martin S, griswold W. Human health effects of heavy metals. Environmental Science and Technology Briefs for Citizens. 2009;15(1):1-6.
58. Mohod CV, Dhote J. Review of heavy metals in drinking water and their effect on human health. IJIRSET. 2013;2(7):2992-6.
59. Hill DS, Cabrera R, Wallis Schultz D, Zhu H, Lu W, Finnell RH, et al. Autism-like behavior and epigenetic changes associated with autism as consequences of ın utero exposure to environmental pollutants in a mouse model. Behav Neurol. 2015;2015:426263.
60. Blaurock-Busch E, Amin OR, Rabah T. Heavy metals and trace elements in hair and urine of a sample of arab children with autistic spectrum disorder. Maedica (Bucur). 2011;6(4): 247-57.
61. Blaurock-Busch E, Amin OR, Dessoki HH, Rabah T. Toxic metals and essential elements in hair and severity of symptoms among children with autism. Maedica (Bucur). 2012;7(1): 38-48.
62. Yassa HA. Autism: a form of lead and mercury toxicity. Environ Toxicol Pharmacol. 2014;38(3):1016-24.
63. Mohamed Fel B, Zaky EA, El-Sayed AB, Elhossieny RM, Zahra SS, Salah Eldin W, et al. Assessment of hair aluminum, lead, and mercury in a sample of autistic Egyptian children: environmental risk factors of heavy metals in autism. Behav Neurol. 2015;2015:545674.
64. Fiore M, Barone R, Copat C, grasso A, Cristaldi A, Rizzo R, et al. Metal and essential element levels in hair and association with autism severity. J Trace Elem Med Biol. 2020;57:126409.
65. Hessabi M, Rahbar MH, Dobrescu I, Bach MA, Kobylinska L, Bressler J, et al. Concentrations of lead, mercury, arsenic, cadmium, manganese, and aluminum in blood of romanian children suspected of having autism spectrum disorder. Int J Environ Res Public Health. 2019;16(13):2303.
66. Rahbar MH, Samms-Vaughan M, Ardjomand-Hessabi M, Loveland KA, Dickerson AS, Chen Z, et al. The role of drinking water sources, consumption of vegetables and seafood in relation to blood arsenic concentrations of Jamaican children with and without Autism Spectrum Disorders. Sci Total Environ. 2012;433:362-70.

APA	Mercan N, Erdemli Kose S, Yirün A, ERKEKOGLU P (2021). Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. , 308 - 321. 10.5336/pharmsci.2020-79267
Chicago	Mercan Nigar,Erdemli Kose Selinay Basak,Yirün Anıl,ERKEKOGLU PİNAR Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. (2021): 308 - 321. 10.5336/pharmsci.2020-79267
MLA	Mercan Nigar,Erdemli Kose Selinay Basak,Yirün Anıl,ERKEKOGLU PİNAR Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. , 2021, ss.308 - 321. 10.5336/pharmsci.2020-79267
AMA	Mercan N,Erdemli Kose S,Yirün A,ERKEKOGLU P Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. . 2021; 308 - 321. 10.5336/pharmsci.2020-79267
Vancouver	Mercan N,Erdemli Kose S,Yirün A,ERKEKOGLU P Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. . 2021; 308 - 321. 10.5336/pharmsci.2020-79267
IEEE	Mercan N,Erdemli Kose S,Yirün A,ERKEKOGLU P "Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme." , ss.308 - 321, 2021. 10.5336/pharmsci.2020-79267
ISNAD	Mercan, Nigar vd. "Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme". (2021), 308-321. https://doi.org/10.5336/pharmsci.2020-79267

APA	Mercan N, Erdemli Kose S, Yirün A, ERKEKOGLU P (2021). Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. Literatür Eczacılık Bilimleri Dergisi, 10(3), 308 - 321. 10.5336/pharmsci.2020-79267
Chicago	Mercan Nigar,Erdemli Kose Selinay Basak,Yirün Anıl,ERKEKOGLU PİNAR Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. Literatür Eczacılık Bilimleri Dergisi 10, no.3 (2021): 308 - 321. 10.5336/pharmsci.2020-79267
MLA	Mercan Nigar,Erdemli Kose Selinay Basak,Yirün Anıl,ERKEKOGLU PİNAR Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. Literatür Eczacılık Bilimleri Dergisi, vol.10, no.3, 2021, ss.308 - 321. 10.5336/pharmsci.2020-79267
AMA	Mercan N,Erdemli Kose S,Yirün A,ERKEKOGLU P Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. Literatür Eczacılık Bilimleri Dergisi. 2021; 10(3): 308 - 321. 10.5336/pharmsci.2020-79267
Vancouver	Mercan N,Erdemli Kose S,Yirün A,ERKEKOGLU P Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme. Literatür Eczacılık Bilimleri Dergisi. 2021; 10(3): 308 - 321. 10.5336/pharmsci.2020-79267
IEEE	Mercan N,Erdemli Kose S,Yirün A,ERKEKOGLU P "Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme." Literatür Eczacılık Bilimleri Dergisi, 10, ss.308 - 321, 2021. 10.5336/pharmsci.2020-79267
ISNAD	Mercan, Nigar vd. "Otizm Spektrum Bozukluklarında Endokrin Bozucu Kimyasal Maddelerin Olası Rolleri: Sistematik Derleme". Literatür Eczacılık Bilimleri Dergisi 10/3 (2021), 308-321. https://doi.org/10.5336/pharmsci.2020-79267