High-throughput transcriptomics toxicity assessment of eleven data-poor bisphenol A alternatives

Area of Science:

• Environmental Health
• Toxicology
• Genomics

Background:

• Bisphenol A (BPA) is an endocrine-disrupting chemical with widespread use.
• Regulatory actions against BPA have led to the adoption of alternative chemicals.
• Concerns exist regarding the safety and toxicity of these BPA alternatives as regrettable substitutes.

Purpose of the Study:

• To assess the toxicity of eleven data-poor legacy chemicals structurally similar to BPA.
• To evaluate the potential of in vitro high-throughput transcriptomics (HTTr) for identifying hazardous BPA alternatives.
• To compare the potency of BPA alternatives to BPA itself using transcriptomic endpoints.

Main Methods:

• Utilized in vitro high-throughput transcriptomics (HTTr) on human breast cancer MCF-7 cells.
• Exposed cells to BPA and eleven alternative chemicals at concentrations ranging from 0.1 to 25 μM.
• Analyzed global transcriptomic changes and a specific estrogen receptor alpha (ERα) biomarker signature.

Main Results:

• Nine out of eleven tested chemicals significantly altered gene expression compared to controls.
• One alternative, 2,4'-Bisphenol A, activated the ERα biomarker at the same concentration as 4,4'-BPA.
• This alternative demonstrated higher potency by inducing transcriptomic changes at lower concentrations than BPA.

Conclusions:

• In vitro HTTr effectively identifies potential hazards in BPA alternatives.
• Results address data gaps for screening assessments of BPA substitutes.
• Identified potential candidates for safer alternatives to Bisphenol A.