The Interrelation of Environmental di-2-Ethylhexyl Phthalate (DEHP) and Melamine Exposure, Biomarkers of Oxidative Stress and Early Kidney Injury in Children and Adolescents Over Time-The 2011 Taiwan Food Scandal

Background: Exposure to di-(2-ethylhexyl) phthalate (DEHP)-tainted food from 2011 Taiwan food scandal increased children’s risk of microalbuminuria, possibly modified by melamine, was reported. This prospective cohort study is to investigate the temporal and interrelationship of exposure to DEHP-tainted foods, environmental DEHP exposure, and melamine, with markers of oxidative stress and renal injury over time. Methods: Children and adolescents possibly exposed to phthalate-tainted foodstuffs received surveys between August 2012 and October 2016 at first wave, second and third follow-up waves. Oxidative stress markers including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-OHdG), and renal injury markers including urine albumin/creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase (NAG), were measured. Past DEHP exposure levels were categorized based on US EPA and European Food Safety Authority’s recommended tolerable daily intake levels, 20 and 50 μg/kg/day, respectively. Findings: Two hundred, 170, and 159 subjects were at the first, second, and third waves. General estimated equation modeling revealed significant main effects of past DEHP exposure and time on urinary ACR. When examining the temporal interaction of past DEHP exposure and time effect on urinary ACR, we found most of interaction variables were negative, but only the interaction of high past DEHP and second wave reached significant (P for interaction = 0.018). Current melamine exposure was significantly associated with urinary ACR, 8-OHdG, and MDA levels over time. Interpretation: DEHP-tainted food intake had its highest impact on increased urinary ACR at the beginning. This increase partially diminished over time. Environmental melamine exposure may increase urinary ACR and markers of oxidative stress over time. Funding: This work was financially supported by grants from Kaohsiung Medical University Hospital, (KMUH109-9R80); from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE), Kaohsiung Medical University Research Center Grant (KMU- TC109A01); from Ministry of Science and Technology (MOST109-2314-B-037- 066; 109-2314-B-037-072-; 107-2314-B-037-109-); from National Health Research Institutes ( NHRI-EX110-10703PI), all in Taiwan. None of these institutions played any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interest: All authors have declared that no competing interests exist. Ethical Approval: This study was dubbed the RAPIT cohort and was approved by the Institutional Review Boards (IRBs) of NHRI, MHWHs, and KMUH.