Re-Visiting Alternative Chemical Selection as ECHA Considers Evaluating Bisphenols as a Group: A Case-Study of Bisphenol A vs Bisphenol S

Posted on Behalf of  Dami Adebambo

2,2-bis(4-hydroxyphenyl)propane (CAS# 80-05-7), commonly known as bisphenol A (BPA), is a chemical that was previously widely used in a variety of consumer products (Calafat et al. 2008). While the most recent FDA assessment in 2014 concluded that “BPA is safe at the current levels occurring in food” (FDA 2014), some state regulatory agencies and jurisdictions across the US and even the FDA have placed restrictions on the use of BPA in certain consumer products, particularly baby bottles and thermal receipts (NCSL 2020). Outside of the US, regulatory agencies across some European countries and the European Chemicals Agency (ECHA) have placed even much wider-reaching restrictions (ECHA 2020a.). Hence, there has been a gradual shift towards using bisphenol analogs such as bisphenol S (BPS) in products often labeled as “BPA-free” (ECHA 2020b.).

Ideally, substitutes used to replace a chemical should be effective, yet different enough to possess a less controversial toxicological profile than the original chemical. However, BPS (2,2-bis(4-hydroxyphenol)sulfone) is structurally similar to BPA, and emerging evidence shows that it is also capable of interacting with certain estrogen and aryl hydrocarbon receptors, similar to BPA (Kitamura et al. 2005, Stossi et al. 2014). Consequently, in 2019, a proposal was made by Belgian authorities “to harmonize the classification and labeling of [BPS] as toxic to reproduction” (ECHA 2020c.). ECHA’s Committee for Risk Assessment is expected to give its opinion on this proposal in spring 2021 and are currently considering grouping “bisphenols as a group rather than as individual substances” for a more comprehensive regulatory strategy (ECHA 2020c.). Hence, it is imperative to begin the process of safety evaluation of alternative chemicals early on to ensure consumer safety and ward off eventual restrictive regulatory actions.

Avoiding regrettable substitutions: A 3-step guide

This guide aims to assist in optimizing the selection of chemical alternatives by highlighting major steps to consider based on an analysis performed by the Environmental Protection Agency for “Bisphenol A Alternatives in Thermal Paper” (USEPA 2015) (as outlined in Figure 1 below).

Step 1: Analysis of functionality and necessity

This first step requires analyzing the purpose and function of the chemical to determine if product redesign can be feasibly accomplished to eliminate its use. If elimination is not possible, this step should be further utilized for identifying viable alternatives or substitute chemicals.

Step 2: Comprehensive exposure and hazard assessment of alternatives and comparison to chemical to be replaced

In this step, comprehensive exposure, toxicological, and ecotoxicological hazard assessments are performed. Tools such as those designed by the EPA – DfE Alternatives Assessment Criteria for Hazard Evaluation – can be utilized in this process. Data on human health effect endpoints such as acute and repeated dose toxicity, carcinogenicity, genotoxicity, reproductive and developmental toxicity, sensitization, and irritation, etc. should be reviewed from available literature or estimated through in-silico modeling. Environmental fate should be estimated by assessing chemical bioaccumulation, biodegradation, and environmental persistence. Further, aquatic and terrestrial toxicity should also be assessed, where information is available. While these processes are extensive and may require soliciting the services of toxicological experts, it is vital for screening out alternatives that are of equivalent or greater hazard in order to identify viable, functional substitutes. This screen will also ensure that investments are not made in alternatives that would potentially end up being subject to government regulation or consumer push-back.

Step 3: Evaluation of technological, economic, and life-cycle factors

After screening, a smaller list of viable and safer alternatives can then be assessed for technical and economic feasibility. Further, a life-cycle analysis should be performed to ensure that the different stages involved in manufacturing and getting the chemical to market do not have potential adverse effects on human health or the environment.


Cardno ChemRisk has a diverse team with expertise in the safety assessment, potential toxicity evaluation, and regulatory landscape of Bisphenol-A and its analogs. Our scientists conduct in-depth exposure and toxicological assessments to identify the health risks associated with various chemicals and potential alternatives. If you would like to learn more about our capabilities or have any further questions regarding this topic, please contact Dr. Dami Adebambo or Dr. Marisa Kreider.