Oral reference dose (RfD) derivation for five bisphenol A alternatives integrating BMD and NOAEL/LOAEL approaches

Yan Xia ¹, Wenhua Ma ², Jing Cao ³

¹Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development of the Ministry of Education, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Center for Disease Prevention and Control of Guangdong Province, Guangzhou 510430, PR China.
²The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou 511400, PR China.
³Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development of the Ministry of Education, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, PR China.
⁴Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development of the Ministry of Education, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Center for Disease Prevention and Control of Guangdong Province, Guangzhou 510430, PR China; The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou 511400, PR China.
⁵Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Center for Disease Prevention and Control of Guangdong Province, Guangzhou 510430, PR China.

⁰Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong Basic Research Center of Excellence for Ecological Security and Green Development, Key Laboratory of City Cluster Environmental Safety and Green Development of the Ministry of Education, School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou 510006, PR China; Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Center for Disease Prevention and Control of Guangdong Province, Guangzhou 510430, PR China.

Ecotoxicology and Environmental Safety +

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August 26, 2025

View abstract on PubMed

Summary

This study establishes crucial reference doses for five bisphenol A (BPA) alternatives, including bisphenol B (BPB) and bisphenol AF (BPAF). These findings provide vital data on the health risks of BPA substitutes, supporting public health protection.

Area Of Science

Environmental Health
Toxicology
Endocrinology

Background

Bisphenols (BPs), including bisphenol A (BPA), are prevalent in industrial applications and consumer products.
BPA's endocrine-disrupting properties have led to regulatory restrictions due to adverse health effects.
Increased use of BPA alternatives necessitates characterization of their toxicity.

Purpose Of The Study

To derive reference doses (RfDs) for five BPA alternatives: bisphenol B (BPB), bisphenol P (BPP), bisphenol Z (BPZ), bisphenol AF (BPAF), and bisphenol AP (BPAP).
To address the knowledge gap regarding the toxicity thresholds of commonly used BPA substitutes.
To refine risk assessment methodologies for endocrine-disrupting chemicals.

Main Methods

Integrated epidemiological data and animal experiments for toxicity assessment.
Employed Benchmark Dose (BMD) modeling and NOAEL/LOAEL approaches to calculate RfDs.
Utilized uncertainty analysis to quantify risk metrics and ensure robust estimations.

Main Results

Derived BMD-based RfDs: BPB (1.05 μg/kg-bw/day), BPP (0.23 μg/kg-bw/day), BPZ (5.13 μg/kg-bw/day).
Derived NOAEL/LOAEL-based RfDs: BPAF (0.04 ng/kg-bw/day), BPAP (2.31 ng/kg-bw/day).
Quantified toxicity thresholds for key BPA alternatives.

Conclusions

Established scientifically-derived reference doses for five BPA alternatives, enhancing risk assessment.
Highlighted potential health risks associated with BPA substitutes, informing regulatory decisions.
Provided evidence-based data to support public health policies and safeguard against chemical exposures.

Keywords:

Benchmark dose Bisphenols Human exposure Oral exposure Reference dose