As we move from the first 10 risk evaluations to the next 20 high-priority risk evaluations, it is imperative that the 2016 TSCA amendments be followed for current and future risk evaluations. These amendments require the use of best available science and the weight of the scientific evidence when evaluating new and existing chemicals. They also require establishing a transparent systematic review process.
Best available science is information that has been evaluated based on its strengths, limitations, and relevance. Factors that help determine the best available science include: peer review, statistical significance, objectivity, consideration of exposure, and reproducibility. Weight of the scientific evidence is a systematic review method that uses pre-established protocols to comprehensively, objectively, transparently, and consistently identify, evaluate, and integrate the evidence.
1,3-Butadiene is one of the 20 high-priority chemicals undergoing the TSCA risk evaluation process. It is important to note that the designation of 1,3-butadiene as a high-priority chemical “does not constitute a finding of risk” and should not be cause for concern. A high-priority designation simply means EPA has nominated 1,3-butadiene for further risk evaluation. 1,3-Butadiene is not sold to or used directly by consumers, but rather primarily is used as a chemical intermediate in the manufacture of polymers such as synthetic rubbers or elastomers. Polymers made from 1,3-butadiene are used to make products used by consumers such as tires, carpet backing, plastic gloves, wetsuits, rubber hoses, and gaskets; however, little to no 1,3-butadiene is present in the final products.
Best Available Science Must Be Used in the Risk Assessment
The safety of the general public, of workers, and the environment is a top priority for the American Chemistry Council (ACC). We believe that focusing on the tenets laid out in the 2016 amendments, such as using best available science and considering the weight of evidence when determining risk, is critical, especially as EPA evaluates chemical substances such as 1,3-butadiene.
When determining the potential risk of a chemical, the best available science is research of the highest quality that has been peer reviewed, can be replicated, and is relevant to the evaluation. This scientific evidence includes information on hazards and exposure potential of the chemical; persistence and bioaccumulation; potentially exposed or susceptible subpopulations; conditions of use or significant changes in the use; and the volume or significant changes in volume that is manufactured or processed. Use of the best available science and appropriate systematic review principles can result in a thorough, high quality risk assessment and prevent poor-quality studies from forming the basis of a risk assessment.
One of the main responsibilities of the ACC Butadiene TSCA Risk Evaluation Consortium is to provide EPA with the best available science and advocate that EPA consider high-quality epidemiology studies. Therefore, the Consortium is actively engaging and informing EPA about the best available science through a series of webinars covering several important topics relevant to the hazard and exposure assessments for 1,3-butadiene.
From 2002 to Today
1,3-Butadiene was last evaluated by EPA in 2002, by EPA’s Integrated Risk Information System (IRIS) program, which conducts hazard assessment of chemicals. The IRIS assessment of 1,3-butadiene is out of date, and more recent and robust data are now available. Since the 2002 IRIS assessment, we have learned a great deal of new information about 1,3-butadiene, especially as it relates to pathways of exposure, species differences in metabolism, and cancer potency. We have been working diligently to inform policy makers, manufacturers, and downstream users on new studies and potential hazards and exposures.
For example, the Texas Commission on Environmental Quality (TCEQ) assessment used more up-to-date epidemiology data, compared to EPA’s 2002 IRIS assessment. Specifically, the exposure estimates and the University of Alabama at Birmingham (UAB) epidemiology study of leukemia mortality in synthetic rubber polymer workers were updated (See page 30 of the TCEQ assessment). The TCEQ assessment also underwent peer-review by an independent, third-party peer-review panel. Both the Peer-Review Report and the Final Development Support Document are available for review.
We believe that the TSCA program provides an excellent opportunity to apply the latest data on exposure and hazard to the human health and environmental risk assessment of 1,3-butadiene. The TSCA risk assessment will include consideration of both cancer and non-cancer endpoints. On the cancer side, the epidemiology data has undergone several updates since 2002, and now includes a validation and uncertainty analysis of worker exposure estimates (Sathiakumar et al., 2007; Graff et al., 2005), as well as cancer mortality observations in both male and female workers (Sathiakumar et al., 2015, 2019). On the non-cancer side, there is a study that evaluated reproductive and developmental toxicity end points (Nemec et al., 2003). This study provided valuable information to understand the mode-of-action and the lack of human relevance for these end points. In addition, advances in analytical methods to measure specific hemoglobin adducts in laboratory animals and occupationally exposed workers (Albertini et al., 2003; Boysen et al., 2007, 2012) provide key data to support improved methods to account for large species differences (Motwani and Tornquist 2014) in how rodents and humans metabolize 1,3-butadiene.
Because of these notable differences, it’s imperative that EPA relies on the more relevant human studies when determining risk. In the case of 1,3-butadiene, EPA previously ignored findings from high-quality epidemiology studies conducted by UAB investigators and instead relied on rodent studies, despite a wealth of information regarding stark differences in metabolism between species for both cancer and non-cancer end points.
The Importance of Transparent Systematic Review and Lessons from the First Ten Risk Evaluations
The 2016 TSCA amendments call for the establishment of a transparent systematic review process. A systematic review process shows the criteria for how research was measured and how that research was used when evaluating risk. A very transparent, objective, and clear systematic review process helps ensure that the best available science is consistently used when determining risk. EPA’s TSCA systematic review process is currently being reviewed by the National Academy of Sciences (NAS).
It is essential for EPA to follow the framework in the 2016 TSCA amendments to establish a modern chemical management system that enhances public, industry, and government confidence in the federal chemical regulatory system. We believe that the principles in the 2016 TSCA amendments, primarily those of best available science, weight of the scientific evidence, and a transparent systematic review process, ensure relevant and accurate risk evaluations for chemicals like 1,3-butadiene. It is important that newer, more relevant studies, like the study showing stark differences between how rodents and humans metabolize 1,3-butadiene, inform TSCA evaluations instead of outdated studies and risk assessments. It is imperative that relevant, high quality studies like the ones mentioned above be heavily weighed when determining the risk of 1,3-butadiene to humans.