Vitamin E Alleviates Diethylhexyl Phthalate-Induced Haemato-logical Changes and Splenic Oxidative Injury in Male Sprague-Dawley Rats
DOI:
https://doi.org/10.30683/1929-2279.2019.08.06Keywords:
Diethylhexyl phthalate, rat, spleen, oxidative stress, antioxidant, vitamin E.Abstract
Di-2-ethylhexyl phthalate (DEHP) is a ubiquitous environmental toxicant with high exposure potential to man mainly through leaching from water and foods plastics packages. Exposure to DEHP is associated with cancers, cardiovascular diseases, and splenic toxicity. In the present study, the effect of alpha tocopherol (α- tocopherol) on the DEHP- induced alteration in hematology and oxidative injury in the spleen of male Sprague Dawley rats was investigated. Animals were exposed daily for six weeks to 5 mg/kg bd.wt DEHP and 10 mg/kg bd.wt Vitamin E either alone or in combination. Control rats were given olive oil throughout the duration of the experiment. Organ weight indices and hematology parameters including packed cell volume (PCV), white blood cells (WBC), lymphocytes and neutrophils were determined in test and control rats. In addition, malondialdehyde, superoxide dismustase (SOD), catalase and glutathione-S-transferase (GST) activities were determined in the spleen. Histology of the spleen was also evaluated. Hematoxicity of DHEP was characterized by decreased PCV, WBC counts and neutrophil, while eosinophil was markedly elevated. DHEP administration resulted in oxidative stress that was manifested by elevated MDA and GST coupled with decreases in SOD and catalase activities. The spleen sections from DEHP-treated rats showed congestion and hyperplasia. However, Vitamin E modulated the hematological parameters and alleviated oxidative changes caused by DEHP exposure. Vitamin E also prevented DHEP associated lesions in the spleen. Therefore, Vitamin E could be useful in controlling hematotoxicty and splenic oxidative injury caused by DEHP intoxication
References
Shelby M. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di (2-ethylhexyl) Phthalate (DEHP). NTP-CERHR monograph 2006; 18.
AgPU. Arbeitsgemeinschaft PVC and Umwelt e. V.—Plasticizers market data. http://www.pvcpartner. com/fileadmin/user_upload/downloads/Weichmacher/Marktdaten_Weichmacher_230106.lin_ en.pdf. 2006;12
Rahman M, Brazel CS. The Plasticizer Market: An Assessment of Traditional Plasticizers and Research Trends to Meet New Challenges. Progress in Polymer Science 2004; 29(12): 1223-1248. https://doi.org/10.1016/j.progpolymsci.2004.10.001 DOI: https://doi.org/10.1016/j.progpolymsci.2004.10.001
Dobrzyńska MM. Phthalates—Widespread Occurrence and the Effect on Male Gametes. Part I. General Characteristics, Sources and Human Exposure. Rocz Panstw Zakl Hig 2016; 67(2): 97-103.
Yu L, Li HX, Guo JY, Huang YQ, Wang H, Talukder M, Jin-Long L. Di (2-ethyl Hexyl) Phthalate (DEHP)-induced Spleen Toxicity in Quail (Coturnix japonica) via Disturbing Nrf2-mediated Defense Response. Environmental Pollution 2019; 251: 984-989. https://doi.org/10.1016/j.envpol.2019.05.061 DOI: https://doi.org/10.1016/j.envpol.2019.05.061
Koniecki D, Rong W, Richard PM, Jiping Z. Phthalates in Cosmetic and Personal Care Products: Concentrations and Possible Dermal Exposure. Environ Res 2011; 111(3): 329-336. https://doi.org/10.1016/j.envres.2011.01.013 DOI: https://doi.org/10.1016/j.envres.2011.01.013
Chen YH, Fu SC, Huang JK, Cheng HF, Kang JJ. A Review on the Response and Management of the Plasticizer-tainted Food Incident in Taiwan. Journal of Food Drug Analysis 2013; 21: 242-246. https://doi.org/10.1016/j.jfda.2012.11.001 DOI: https://doi.org/10.1016/j.jfda.2012.11.001
Yen TH, Lin-Tan DT, Lin JL. Food Safety Involving Ingestion of Foods and Beverages Prepared with Phthalate-plasticizer Containing Clouding Agents. Journal of the Formosan Medical Association 2014; 110 (11): 671-684. https://doi.org/10.1016/j.jfma.2011.09.002 DOI: https://doi.org/10.1016/j.jfma.2011.09.002
Cao XL. Phthalate Esters in Foods: Sources, Occurrence, and Analytical Methods. Comprehensive. Review of Food Science. Food Safe 2010; 9: 21-43. https://doi.org/10.1111/j.1541-4337.2009.00093.x DOI: https://doi.org/10.1111/j.1541-4337.2009.00093.x
UBA. Umweltbundesamt. Schriftenreihe Umwelt & Gesundheit: Phthalat-Belastung der Bevölkerung in Deutschland: Expositions relevante Quellen, Aufnahmepfade und Toxikokinetik am Beispiel von DEHP und DINP - Kurzfassung & Summary. Berlin 2012
Erythropel HC, Milan M, Jim AN, Richard LL, Viviane Y. Leaching of the Plasticizer Di(2-ethylhexyl) phthalate (DEHP) from Plastic Containers and the Question of Human Exposure. Appl Microbiol Biotech 2014; 98: 9967-9981. https://doi.org/10.1007/s00253-014-6183-8 DOI: https://doi.org/10.1007/s00253-014-6183-8
Sioen I, Fierens T, Van Holderbeke M, Geerts L, Bellemans M, De Maeyer M, Servaes K, Vanermen G, Boon PE, De Henauw S. Phthalates Dietary Exposure and Food Sources for Belgian Preschool Children and Adults. Environ Int 2012; 48: 102-108. https://doi.org/10.1016/j.envint.2012.07.004 DOI: https://doi.org/10.1016/j.envint.2012.07.004
Ying G, Zhang Z, Liu L, Li Y, Ren N, Kannan K. Occurrence and Profiles of Phthalates in Foodstuffs from China and Their Implications for Human Exposure. J Agric Food Chem 2012; 60(27): 6913-6919. https://doi.org/10.1021/jf3021128 DOI: https://doi.org/10.1021/jf3021128
Mao W, Liu S, Liu Z, Zhang L, Song Y, Zhou P, Yong L, Sui H. Concentration Analysis of Phthalic Acid Esters in Animal-origin Foods. J Chin Inst Food Sci Technol 2016; 16: 161-166.
D’Alessandro A, Travis N, Kirk CH. Rapid Detection of DEHP in Packed Red Blood Cells Stored under European and US Standard Conditions. Blood Transfus 2016; 14(2): 140-144.
Becker K, Margarete S, Jürgen A, Wolfgang H, Holger MK, Regine N, Elke R, Christoph S, Bernd S, Detlef U. DEHP Metabolites in Urine of Children and DEHP in House Dust. International Journal of Hygiene and Environmental Health 2004; 207: 409-41. https://doi.org/10.1078/1438-4639-00309 DOI: https://doi.org/10.1078/1438-4639-00309
Jan LL. Phthalates. In reproductive and developmental toxicology. Ramesh C. Gupta Eds. 2011; 48: pp. 637-655. https://doi.org/10.1016/B978-0-12-382032-7.10048-7 DOI: https://doi.org/10.1016/B978-0-12-382032-7.10048-7
Kamrin MA. Phthalate Risks, Phthalate Regulation and Public Health: A Review. J Toxicol Environ 2009; 12: 157-174. https://doi.org/10.1080/10937400902729226 DOI: https://doi.org/10.1080/10937400902729226
Liu H, Yuanyuan W, Bo Y, Yanfang Z, Bo F, He L. Improving Volatile Fatty Acid Yield from Sludge Anaerobic Fermentation Through Self-forming Dynamic Membrane Separation. Bioresource Technology 2016; 218: 92-100. https://doi.org/10.1016/j.biortech.2016.06.077 DOI: https://doi.org/10.1016/j.biortech.2016.06.077
Gobas FA, Victoria SO, Laura FT-R, Meara AC, Kathryn EC, Michael GI. Chemical Activity‐based Environmental Risk Analysis of the Plasticizer Di‐ethylhexyl Phthalate and its Main Metabolite Mono‐ethylhexyl Phthalate. Environ Toxicol Chem 2016; 36: 1483-1492. https://doi.org/10.1002/etc.3689 DOI: https://doi.org/10.1002/etc.3689
Du ZH, Xia J, Sun XC, Li XN, Zhang C, Zhao HS, Zhu SY, Li JL. A Novel Nuclear Xenobiotic Receptor (AhR/PXR/CAR)-Mediated Mechanism of DEHP-induced Cerebellar Toxicity in Quails (Coturnix Japonica) via Disrupting CYP Enzyme System Homeostasis. Environ Pollut 2017; 226: 435-443. https://doi.org/10.1016/j.envpol.2017.04.015 DOI: https://doi.org/10.1016/j.envpol.2017.04.015
Zhang W, Shen XY, Zhang WW, Chen H, Xu WP, Wei W. The Effects of Di 2-ethyl Hexyl Phthalate (DEHP) on Cellular Lipid Accumulation in HepG2 Cells and its Potential Mechanisms in the Molecular Level. Toxicol Mech Methods 2017; 27: 245-52. https://doi.org/10.1080/15376516.2016.1273427 DOI: https://doi.org/10.1080/15376516.2016.1273427
Trasande L, Teresa MA, Sathyanarayana S. Race/Ethnicity-Specific Associations of Urinary Phthalates with Childhood Body Mass in a Mationally Representative Sample. Environ Health Perspect 2013; 121: 501-6. https://doi.org/10.1289/ehp.1205526 DOI: https://doi.org/10.1289/ehp.1205526
Pant N, Shukla M, Kumar PD, Shukla Y, Mathur N, Kumar GY, Krishna SD. Correlation of Phthalate Exposures with Semen Quality. Toxicol Appl Pharmacol 2008; 231(1): 112-6. https://doi.org/10.1016/j.taap.2008.04.001 DOI: https://doi.org/10.1016/j.taap.2008.04.001
Kim S, Cho S, Ihm H. Possible role of phthalate in the pathogenesis of endometriosis: in vitro, animal, and human data. J Clin Endocrinol Metab 2015; 100(12): 1502-1511. DOI: https://doi.org/10.1210/jc.2015-2478
Ventrice P, Ventrice D, Russo E, De Sarro G. Phthalates: European Regulation, Chemistry, Pharmacokinetic and Related Toxicity. Environ Toxicol Pharmacol 2013; 36(1): 88-96. https://doi.org/10.1016/j.etap.2013.03.014 DOI: https://doi.org/10.1016/j.etap.2013.03.014
Sathyanarayana S., Grady R, Emily SB, Redmon B, Ruby HN, Julia SB, Nicole RB, Shanna HS. First Trimester Phthalate Exposure and Male Newborn Genital Anomalies. Environ Res 2016; 151: 777-782. https://doi.org/10.1016/j.envres.2016.07.043 DOI: https://doi.org/10.1016/j.envres.2016.07.043
Latini G, De Felice C, Giuseppe P, Del Vecchio A, Irma P, Fabrizio R, Pietro M. In Utero Exposure to Di-(2-ethylhexyl) Phthalate and Duration of Human Pregnancy. Environ Health Perspect 2003; 111: 1783-1785. https://doi.org/10.1289/ehp.6202 DOI: https://doi.org/10.1289/ehp.6202
Kim M, Yun SJ, Chung GS. Determination of Phthalates in Raw Bovine Milk by Gas Chromatography/Time-of-Flight Mass Spectrometry (GC/TOF-MS) and Dietary Intakes. Food Addit Contam (Part A) 2009; 26: 134-138. https://doi.org/10.1080/02652030802342471 DOI: https://doi.org/10.1080/02652030802342471
Rowdhwa S, Jiaxiang C. Toxic Effects of Di-2-ethylhexyl Phthalate: An Overview. BioMed Res Int 2018; 1750368. https://doi.org/10.1155/2018/1750368 DOI: https://doi.org/10.1155/2018/1750368
Rusyn I, Corton JC. Mechanistic Considerations for Human Relevance of Cancer Hazard of Di(2-ethylhexyl) Phthalate. Mutat Res 2012; 750(2): 141-158. https://doi.org/10.1016/j.mrrev.2011.12.004 DOI: https://doi.org/10.1016/j.mrrev.2011.12.004
Erkekoglu P, Naciye DZ, Belma KG, Walid R, Murat K, Isabelle H-F, Alain F, Esin A, Filiz H. The Effects of Di (2- ethylhexyl) Phthalate on Rat Liver in Relation to Selenium Status. Int J Exp Pathol 2014; 95: 64-77. https://doi.org/10.1111/iep.12059 DOI: https://doi.org/10.1111/iep.12059
Lee GY, Han SN. The Role of Vitamin E in Immunity. Nutrients 2018; 10: 1614. https://doi.org/10.3390/nu10111614 DOI: https://doi.org/10.3390/nu10111614
Zingg JM. Vitamin E: A Role in Signal Transduction. Annu Rev Nutr 2015; 35: 135-173. https://doi.org/10.1146/annurev-nutr-071714-034347 DOI: https://doi.org/10.1146/annurev-nutr-071714-034347
Górnicka M, Anna C, Jadwiga H, Małgorzata ED, Joanna F, Krzysztof G, Agata W. α-Tocopherol Protects the Heart, Muscles, And Testes from Lipid Peroxidation in Growing Male Rats Subjected to Physical Efforts. Oxidative Medicine and Cellular Longevity 2019; 8431057. https://doi.org/10.1155/2019/8431057 DOI: https://doi.org/10.1155/2019/8431057
Ranard KM, John WE Jr. Effects of Dietary RRR α-Tocopherol Vs All-Racemic α-Tocopherol on Health Outcomes. Nutrition Reviews 2018; 76(3): 141-153. https://doi.org/10.1093/nutrit/nux067 DOI: https://doi.org/10.1093/nutrit/nux067
Mohd M, Siti S, Ab-Rahim S, Mohd H, Rajikin M. Vitamin E as an Antioxidant in Female Reproductive Health. Antioxidants 2018; 7(2): 22. https://doi.org/10.3390/antiox7020022 DOI: https://doi.org/10.3390/antiox7020022
Rizvi S, Syed TR, Ahmed F, Ahmad A, Abbas S, Mahdi F. The Role of Vitamin E in Human Health and Some Diseases. Sultan Qaboos University Medical Journal 2014; 14(2): 157-165.
Traber MG. Vitamin E Inadequacy in Humans: Causes and Consequences. Adv Nutr 2014; 5: 503-514. https://doi.org/10.3945/an.114.006254 DOI: https://doi.org/10.3945/an.114.006254
Shati AA. Ameliorative Effect of Vitamin E on Potassium Dichromate-Induced Hepatotoxicity in Rats. Journal of King Saud University – Science 2014; 26: 181-189. https://doi.org/10.1016/j.jksus.2013.12.001 DOI: https://doi.org/10.1016/j.jksus.2013.12.001
Khodamoradi N, Alireza K, Iraj S, Siamak S, Abdolrahman S. Effect of Vitamin E on Lead Exposure-Induced Learning and Memory Impairment in Rats. Physiol Behav 2015; 144: 90-4. https://doi.org/10.1016/j.physbeh.2015.03.015 DOI: https://doi.org/10.1016/j.physbeh.2015.03.015
Villani V, Zucchella C, Cristalli G, Galiè E, Bianco F, Giannarelli D, Carpano S, Spriano G, Pace A. Vitamin E Neuroprotection Against Cisplatin Ototoxicity. Head and Neck 2016; 38(S1): 2118-2121. https://doi.org/10.1002/hed.24396 DOI: https://doi.org/10.1002/hed.24396
Amraoui W, Nesrine A, Fatiha B, Mahieddine B, Faiza T, Amel B, Cherif A, Mahfoud M. Modulatory Role of Selenium and Vitamin E, Natural Antioxidants, Against Bisphenol A-Induced Oxidative Stress in Wistar Albino Rats. Toxicol Res 2018; (3): 231-239. https://doi.org/10.5487/TR.2018.34.3.231 DOI: https://doi.org/10.5487/TR.2018.34.3.231
Huang X, Yang F, Wei F, Jing D, Yajiao D, Guanqing X, Kaiyu W, Yongqiang D, Yi G, Ping O, Defang C, Shiyong Y. Potential Ability for Metallothionein and Vitamin E Protection Against Cadmium Immunotoxicity in Head Kidney and Spleen of Grass Carp (Ctenopharyngodon Idellus). Ecotoxicology and Environmental Safety 2019; 170: 246-252. https://doi.org/10.1016/j.ecoenv.2018.11.134 DOI: https://doi.org/10.1016/j.ecoenv.2018.11.134
National Research Council of the National Academies. Guide for the care and use of laboratory animals. Institute of Laboratory Animal Research, Division of Earth and Life Studies, National Academy Press, Washington, D.C., USA 2011.
Loff S, Kabs F, Witt K, Sartoris J, Mandl B, Niessen K, Waag K. Polyvinylchloride Infusion Lines Expose Infants to Large Amounts of Toxic Plasticizers. J Pediat Surg 2000; 35(12): 1775-1781. https://doi.org/10.1053/jpsu.2000.19249 DOI: https://doi.org/10.1053/jpsu.2000.19249
Kavlock R, Kim B, Robert C, Michael C, Elaine F, Paul F, Mari G, Rogene H, Irwin H, Ruth L, Jennifer S, Katherine S, Sonia T, Rochelle T, Paige W, Timothy Z. NTP Center for The Evaluation of Risks to Human Reproduction: Phthalates Expert Panel Report On the Reproductive and Developmental Toxicity of Di-N-Butyl Phthalate. Reprod Toxicol 2002; 16(5): 489-527. https://doi.org/10.1016/S0890-6238(02)00033-3 DOI: https://doi.org/10.1016/S0890-6238(02)00033-3
Arcadi FA, Costa C, Imperatore C, Marchese A, Rapidisarda A, Salemi M, Trimarchi GR, Costa G. Oral Toxicity of Bis(2-Ethylhexyl) Phthalate During Pregnancy and Suckling in Long-Evans Rat. Food Chem Toxicol 1998; 36: 963-970. https://doi.org/10.1016/S0278-6915(98)00065-9 DOI: https://doi.org/10.1016/S0278-6915(98)00065-9
Lewis SM, Bain JB, Bates I. Dacie and Lewis Practical Haematology. Churchill Livingstone Elsevier Ltd. 2006.
Bjorner M, Zhu L. A Minimally Invasive, Low-stress Method for Serial Blood Collection in Aging Mice. Pathobiology of Aging and Age-related Diseases 2019; 9: 1647400. https://doi.org/10.1080/20010001.2019.1647400 DOI: https://doi.org/10.1080/20010001.2019.1647400
Esterauer H, Cheeseman KH. Determination of Aldehydic Lipid Peroxidation Products: Malonaldehyde and 4-hydroxynonenal. Meth Enzymol 1990; 186: 407-21. https://doi.org/10.1016/0076-6879(90)86134-H DOI: https://doi.org/10.1016/0076-6879(90)86134-H
Wills E. Lipid Peroxide Formation in Microsomes. Relationship of Hydroxylation to Lipid Peroxide Formation. Biochem J 1969; 113: 333-341. https://doi.org/10.1042/bj1130333 DOI: https://doi.org/10.1042/bj1130333
Aebi HE. Catalase. in Methods of Enzymatic Analysis. Bergmeyer HU, Ed., Verlag Chemie, Weinhem 1983; pp. 273-286.
Marklund S, Marklund G. Involvement of the Superoxide Anion Radical in the Autoxidation of Pyrogallol and a Convenient Assay for Superoxide Dismutase. Eur J Biochem 1974; 47: 469-74. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x DOI: https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
Habig WH, Michael JP, William BJ. Glutathione S- Transferase, the First Enzymatic Step in Mercapturic Acid Formation. J Bio Chem 1974; 249: 7130-9. https://doi.org/10.1080/15287390903212923 DOI: https://doi.org/10.1016/S0021-9258(19)42083-8
Kwack JS, Kim BK, Kim SH, Lee MB. Comparative Toxicological Evaluation of Phthalate Diesters and Metabolites in Sprague-Dawley Male Rats for Risk Assessment. J Toxicol Environ Health A 2009; 72(21-22): 1446-54. DOI: https://doi.org/10.1080/15287390903212923
Jilani T, Bushra M, Mohammad PI. Vitamin E Supplementation Enhances Hemoglobin and Erythropoietin Levels in Mildly Anemic Adults. Acta Haematol 2008; 119: 45-47. https://doi.org/10.1159/000115784 DOI: https://doi.org/10.1159/000115784
Cruz D, De Cal M, Garzotto F, Brendolan A, Nalesso D, Corradi V, Ronco C. Effect of Vitamin E-coated Dialysis Membranes on Anemia in Patients with Chronic Kidney Disease: An Italian Multicenter Study. Int J Artif Organs 2008; 31: 545-55. https://doi.org/10.1177/039139880803100610 DOI: https://doi.org/10.1177/039139880803100610
Sultana N, Begum N, Begum S, Ferdousi S, Ali T. Oral Supplementation of Vitamin E Reduces Osmotic Fragility of RBC in Hemolytic Anemic Patients with G6PD Deficiency. Pak J Physiol 2009; 5(1): 25-28. https://doi.org/10.3329/bsmmuj.v1i1.3688 DOI: https://doi.org/10.3329/bsmmuj.v1i1.3688
Jilani T, Iqba MP. Does Vitamin E Have a Role in Treatment and Prevention of Anemia? Pakistan Journal of Pharmaceutical Sciences 2011; 24(2): 237-42.
Ahmadivand S, Hamid F, Alireza M, Soheil E, Ashkan Z. Effects of (Anti) Androgenic Endocrine Disruptors (DEHP and Butachlor) on Immunoglobulin M (IgM) and Leukocytes Counts of Male Rainbow Trout (Oncorhynchus Mykiss). Bull Environ Contam Toxicol 2015; 94(6): 695-700. https://doi.org/10.1007/s00128-015-1503-y DOI: https://doi.org/10.1007/s00128-015-1503-y
Wang SC, Zhang Q, Zheng S, Chen M, Zhao F, Xu S. Atrazine Exposure Triggers Common Carp Neutrophil Apoptosis via the CYP450s/ROS Pathway. Fish and Shellfish Immunol 2019; 84: 551-557. https://doi.org/10.1016/j.fsi.2018.10.029 DOI: https://doi.org/10.1016/j.fsi.2018.10.029
Philipp K, Mona S, Alexander NW, Nikolaus R, Markus R, Horst VB, Charaf B, Dirk R, Julia S, Dominik H. Neutrophils: Between Host Defence, Immune Modulation and Tissue Injury. PLoS Pathog 2015; 11(3): 1004651. https://doi.org/10.1371/journal.ppat.1004651 DOI: https://doi.org/10.1371/journal.ppat.1004651
Rosales C, Lowell AC, Schnoor M, Uribe-Querol E. Neutrophils: Their Role in Innate and Adaptive Immunity. J Immunol Res 2017; 9748345. https://doi.org/10.1155/2017/9748345 DOI: https://doi.org/10.1155/2017/9748345
Melis D, Casa RD, Parini R, Rigoldi M, Cacciapuoti C, Marcolongo P, Benedetti A, Gaudieri V, Andria G, Parenti G. Vitamin E Supplementation Improves Neutropenia and Reduces the Frequency of Infections in Patients with Glycogen Storage Disease Type Ib. Eur J Pediatr 2009; 168: 1069-1074. https://doi.org/10.1007/s00431-008-0889-5 DOI: https://doi.org/10.1007/s00431-008-0889-5
You H, Chen S, Mao L, Li B, Yuan Y, Li R, Yang X. The Adjuvant Effect Induced by Di-(2-ethylhexyl) Phthalate (DEHP) is Mediated Through Oxidative Stress in a Mouse Model of Asthma. Food Chem Toxicol 2014; 71: 272-81. https://doi.org/10.1016/j.fct.2014.06.012 DOI: https://doi.org/10.1016/j.fct.2014.06.012
Svoboda M. Stress in Fishes (a review). Bull. VURH Vodnany 2001; 4: 169-191.74.
Gui-sheng Z. Effect of Diethyl Phthalate on the Biochemical Markers of Brain, Testis and Testicular Tissue Structure in Cyprinus carpio Linnaeus. J Saf Environ 2014; 5: 075.
Abubakar MG, Taylor A, Gordon AF. Regional Accumulation of Aluminum in the Rat Brain is Affected by Dietary Vitamin E. J Trace Elem Med Biol 2004; 18: 53-9. https://doi.org/10.1016/j.jtemb.2004.02.001 DOI: https://doi.org/10.1016/j.jtemb.2004.02.001
Wang IJ, Wilfried JK. Oxidative Stress-Related Genetic Variants May Modify Associations of Phthalate Exposures with Asthma. IJERPH 2017; 14: 162. https://doi.org/10.3390/ijerph14020162 DOI: https://doi.org/10.3390/ijerph14020162