REGULATION & COMPLIANCE issued for public comment in the autumn of 2025, the agency declined to proffer a definition of unreasonable risk. Nonetheless, it requested public comments on whether and how a definition for unreasonable could be constructed.
Since the 1996 TSCA amendments, without a definition of unreasonable risk, the EPA has repeatedly stated that it weighs relevant risk factors in determining unreasonable risk. These factors include, for example, the type and severity of health effects attributed to the chemical under review, the population exposed to the chemical, its environmental effects and the inevitable uncertainties associated with the EPA’ s efforts to assess the chemical’ s risks.
In proposing changes to the Framework Rule, the EPA once again reaffirmed the utility of these risk factors. But in practice these factors have proven unhelpful in constraining its discretion in determining what is unreasonable risk. The result is that the agency has effectively eliminated the word‘ unreasonable’ from unreasonable risk.
Assessing the margin
To assess risk from non-cancer effects, the EPA relies on the margin of exposure( MoE) approach, which in turn relies on identifying a point of departure( POD). The POD is the lowest point on a doseresponse curve for the chemical under evaluation. This can, for example, can be the no-observed adverse effect level( NOAEL) for the most sensitive health endpoint relevant to humans based on animal studies.
To determine the MoE, the EPA divides the PoD by the exposure concentration associated with a condition of use( CoU). EPA compares this MoE to the socalled benchmark MoE, which accounts for the total uncertainty in a PoD. These uncertainties include, among others, the variation in sensitivity to the chemical within the human population and interspecies variability – the uncertainty associated with extrapolating animal data to humans.
Thus, if the calculated MoE is at or above the benchmark MoE, there are few if any concerns for non-cancer human health effects. On the other hand, the EPA assumes that there is risk present if the calculated MoE is below the benchmark MoE.
To assess risk from cancer, the EPA invariably assumes that any exposure to the chemical will present some cancer risk. Thus, its benchmarks for cancer are expressed as the incremental probability that an individual exposed to the chemical over a lifetime will develop cancer. For workers, this probability is one out of 10,000; for consumers, the probability spans one out of 10,000 to one out of 1,000,000.
But what about unreasonable risk?
Despite the EPA’ s repeated assurances that no bright line exists to demarcate unreasonable risk from no unreasonable risk and that it relies on the risk factors discussed above, its risk evaluations tell a different story. Peruse any risk evaluation issued to date, including the most recent draft risk evaluation for 1,2-dichloroethane, and you will invariably see that the agency determines that a condition of use presents unreasonable risk if the calculated MoE is less than the benchmark MoE.
Even though the overall probability of developing cancer in the US is about four out of ten, unreasonable risk for workers is equated to a cancer risk exceeding one out of 10,000; and for consumers the EPA may determine unreasonable risk even if the incremental cancer risk from exposure to the chemical is far more remote. Thus, the agency has effectively defined unreasonable risk as the presence of any risk, however negligible.
Environmental risk
The story is the same for assessing unreasonable risk to the environment. The EPA relies on the risk quotient( RQ) approach in which the predicted environmental concentration of the chemical is divided by the concentration that results in potential concern to aquatic and terrestrial species.
If the RQ is < 1, then risk is not indicated according to the EPA. In other words, there is no risk of injury to the environment. If the RQ is the boundary between risk and no risk, then how does the EPA determine unreasonable risk? We turn once again to the draft risk evaluation for 1,2-dichloroethane in which the agency determines that manufacturing and disposal are the only two CoUs that present unreasonable risk. Why? Because the RQs are > 1.
The consequences of the EPA’ s unreasonable approach to unreasonable risk are vast. Its risk evaluations become a quest for identifying any risk, which it invariably finds because exposure estimates are often unrealistic. Similarly, the agency’ s overly conservative interpretation of the available hazard information further obfuscates its evaluation of real-life, actual risks associated with the CoUs, let alone identifying‘ unreasonable risk.’
What is desperately needed is a definition of what is and is not unreasonable risk. The revisions to the Framework Rule present the agency with a golden opportunity to put‘ unreasonable’ back into‘ unreasonable risk.’ ●
David B. Fischer, MPH
COUNSEL
KELLER AND HECKMAN k + 1 202 434 4224 J fischer @ khlaw. com j www. khlaw. com
JAN / FEB 2026 SPECCHEMONLINE. COM
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