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8-OHdG mediates the association of co-exposure to fifty-five typical endocrine-disrupting chemicals with renal function: a cross-section investigation in Southern Chinese adults

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Abstract

Individual typical endocrine-disrupting chemicals (EDCs), including organophosphate triesters (OPEs), parabens, triclosan (TCS), bisphenols, benzophenones (BPs), phthalates (PAEs), and synthetic phenolic antioxidants (SPAs), are associated with renal dysfunction. However, the combined effects and underlying mechanisms of mixed EDC exposure on renal function remain unclear. Two hundred ninety-nine adult participants were enrolled in the cross-sectional survey conducted in Guangzhou, China. Urinary levels of 7 OPEs, 6 parabens, TCS, 14 bisphenols, 8 BPs, 15 PAEs, 4 SPAs, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were determined, and estimated glomerular filtration rate (eGFR) was served as the outcome index. We found elevated levels of diphenyl phosphate (DPP), bisphenol A (BPA), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-butyl phthalate (MBP) showed dose-responsive associations with eGFR decline, However, nonlinear associations were observed for bis(2-butoxyethyl) hydrogen phosphate (BBOEP), TCS, 4-hydroxybenzophenone (HBP), mono-n-pentyl phthalate (MnPP), and mono-benzyl phthalate (MBzP). The quantile-based g-computation model demonstrated that a quartile increase in the EDC mixture corresponded to a 0.383-SD decrease (95% CI − 0.658 ~  − 0.108, P = 0.007) in eGFR. Notably, BPA was identified as the primary contributor to this effect. Moreover, 8-OHdG mediated the eGFR decline associated with EDC mixtures with a mediation proportion of 25.49%. A sex-modified effect was also observed (P = 0.004), indicating that exposure to the mixture of EDC was linked to more pronounced renal dysfunction in females. Our novel findings suggest that exposure to a typical mixture of EDCs is associated with renal dysfunction in the general adult population of Southern China. Furthermore, 8-OHdG may play a role in the pathogenesis of EDC mixture-related renal dysfunction.

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Availability of data and materials

The raw data of the study are available upon request from the corresponding author.

Abbreviations

OPEs:

Organophosphate triesters

TCS:

Triclosan

BPs:

Benzophenones

PAEs:

Phthalates

SPAs:

Synthetic phenolic antioxidants

DPP:

Diphenyl phosphate

BPA:

Bisphenol A

MEHHP:

Mono-(2-ethyl-5-hydroxyhexyl) phthalate

MBP:

Mono-butyl phthalate

BBOEP:

Bis(2-butoxyethyl) hydrogen phosphate

HBP:

4-Hydroxybenzophenone

MnPP:

Mono-n-pentyl phthalate

MBzP:

Mono-benzyl phthalate

DEHP:

Di-(2-ethylhexyl) phthalate

EDCs:

Endocrine-disrupting chemicals

eGFR:

Estimated glomerular filtration rate

8-OHdG:

8-Hydroxy-2′-deoxyguanosine

CKD:

Chronic kidney disease

DF:

Detection frequency

LOD:

Limits of detection

GLMs:

Generalized linear models

RCS:

Restricted cubic spline

qgcomp:

Quantile-based g-computation

WQS:

Weighted quantile sum regression

FDR:

False discovery rate

SD:

Standard deviation

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Acknowledgements

This work was supported by the doctors, nurses, and other staff employed in the Community Health Centers of Guangzhou. And the analysis of urinary chemical concentrations was helped by Professor Da Chen and his team at Jinan University in Guangzhou.

Funding

This work was financially supported by the National Key Research and Development Program of China (No. 2018YFE0106900) and the National Natural Science Foundation of China (Nos. 82173471 and 82003409).

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, 510080, Guangdong, China

    Qingfei Chen, Qilong Liao, Yan Liu, Zhaorui Zhang, Dehua Wu, Yanrong Lv, Jingyao Qin, Qing Liu, Shuangqi Li, Zihao Long, Xiumei Xing, Qing Wang, Xiaowen Zeng, Guanghui Dong & Yongmei Xiao

  2. Joint International Research Laboratory of Environment and Health, Ministry of Education, School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China

    Qingfei Chen, Xiumei Xing, Xiaowen Zeng, Guanghui Dong, Mengjun Hou & Yongmei Xiao

  3. School of Public Health, Guangzhou Medical University, Xinzao Town, Panyu District, Guangzhou, 511436, Guangdong, China

    Qifei Deng & Zhaorui Zhang

  4. State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou, 510530, People’s Republic of China

    Qilong Liao

  5. Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, School of Public Health, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou, 510080, Guangdong, China

    Qing Wang & Mengjun Hou

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Contributions

Qingfei Chen, Qifei Deng, Qilong Liao: conceptualization, data curation, methodology, software, visualization, writing—original draft preparation. Yan Liu, Zhaorui Zhang, Dehua Wu, Yanrong Lv, Jingyao Qin, Qing Liu: data curation, methodology, conceptualization, formal analysis. Qingfei Chen, Shuangqi Li, Guanghui Dong: data curation, visualization, formal analysis. Xiumei Xing, Xiaowen Zeng, Zihao Long, and Yongmei Xiao: project administration, supervision. Qing Wang, Xiaowen Zeng, Qifei Deng, Xiumei Xing, and Mengjun Hou: provided administrative, technical, or material support. Yongmei Xiao and Guanghui Dong: obtained funding. Yongmei Xiao: conceptualization, methodology, supervision, writing—review and editing. All authors were responsible for the acquisition, analysis, or interpretation of data. All authors assisted in the critical revision of the manuscript for important intellectual content.

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Correspondence to Yongmei Xiao.

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The study protocol (No. 2018027) was approved by the Ethics Committee of Medical Research, School of Public Health, Sun Yat-sen University. We received consent from the participants before this investigation.

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Qingfei Chen, Qifei Deng, and Qilong Liao contributed equally to this work and shared the first authorship.

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Chen, Q., Deng, Q., Liao, Q. et al. 8-OHdG mediates the association of co-exposure to fifty-five typical endocrine-disrupting chemicals with renal function: a cross-section investigation in Southern Chinese adults. Environ Sci Pollut Res 31, 30779–30792 (2024). https://doi.org/10.1007/s11356-024-33266-1

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  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-024-33266-1

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