Benchmark dose in the presence of coexposure to melamine and diethylhexyl phthalate and urinary renal injury markers in pregnant women.

Chu-Chih Chen, Yin-Han Wang, Chia-Fang Wu, Chia-Jung Hsieh, Shu-Li Wang, Mei-Lien Chen, Hui-Ju Tsai, Sih-Syuan Li, Chia-Chu Liu, Yi-Chun Tsai, Tusty-Jiuan Hsieh, Ming-Tsang Wu

Journal: Environmental research 2022;215(Pt 1):114187

PMID: 36037918

Full Text on Elsevier Science View on PubMed

Abstract

Environmental exposures to mixtures of toxic chemicals have potential interaction effects that may lead to hazard index values exceeding one. However, current regulation levels, such as tolerable daily intake (TDI), are mostly based on experimental studies conducted with a single chemical compound. In this study, we assessed the relationships between melamine and di-(2-ethylhexyl) phthalate (DEHP) exposure and their coexposure with the early renal injury markers N-acetyl -D-glucosaminidase (NAG), albumin/creatinine ratio (ACR), and microalbuminuria in 1236 pregnant women. Various generalized linear models with interaction terms and Bayesian kernel machine regression models were used for the (co-)exposure response associations. We derived the benchmark dose (BMD) and the corresponding one-sided 95% confidence bound BMDL based on the estimated (covariate-adjusted) average daily intake of melamine and DEHP metabolites measured in spot urine of the women collected during the third trimester. Given a benchmark response of 0.1, the BMDL level of melamine (DEHP) exposure on NAG (ACR, microalbuminuria) was 2.67 (11.20, 4.45) μg/kg_bw/day, and it decreased to as low as 1.46 (3.83, 2.73) μg/kg_bw/day when considering coexposure to DEHP (melamine) up to the 90th percentile. Both the exposure threshold levels of melamine and DEHP for early renal injuries in pregnant women were several-fold to one order lower than the current recommended TDIs by the WHO and the US FDA and EPA and were even lower considering coexposure. Because of concurrent exposures in real-world environments, more stringent regulation levels are recommended in susceptible populations, such as pregnant women, due to potential synergistic mixture effects.

Address: Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Taiwan; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan. Electronic address: [email protected].; Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan; International Master Program of Translational Medicine, National United University, Taiwan.; Department of Public Health, Tzu Chi University, Hualien, Taiwan.; National Environmental Health Research Center, National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.; Institute of Environmental and Occupational Health Sciences, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan; Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan; Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Department of Marine Biotechnology and Resources, College of Marine Sciences, National Sun Yat-Sen University, Kaohsiung, 804201, Taiwan.; Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Public Health, Kaohsiung Medical University, Taiwan; Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Taiwan. Electronic address: [email protected].

DOI: 10.1016/j.envres.2022.114187

Link outs

Free resources

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-TIMP1-2

Subscription / membership required

Full Text Sources:

MeSH Terms: Albumins, Albuminuria, Bayes Theorem, Benchmarking, Biomarkers, Creatinine, Diethylhexyl Phthalate, Environmental Exposure, Environmental Pollutants, Female, Hexosaminidases, Humans, Kidney, Phthalic Acids, Pregnancy, Pregnant People, Triazines