Moving beyond the LC50: possible constraints and opportunities from a regulatory perspective

The U.S. Environmental Protection Agency (EPA) is responsible for regulating pesticides.  Its process for evaluating the potential risks of pesticides to non-target organisms, including beneficial insects such as bees, has been vetted through its external peer review process, i.e., the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP).  The process that was developed is also consistent with what is used by other regulatory authorities globally.  Historically, EPA has relied on the median lethal dose or concentration to 50% of the organisms tested, i.e., the LD₅₀ or LC₅₀, as a means of assessing the likelihood and magnitude of an adverse effect following an acute exposure; however, in addition to lethal endpoints, the Agency has also relied on other lines of evidence such as sublethal effects to assess risk to non-target organisms.  While the LD₅₀ and LC₅₀ have served as effective measurement endpoints for assessing acute risk, there is concern whether lethality-based endpoints are sufficiently protective measures of acute toxicity.  For the Agency, the utility of sublethal effects data in risk assessment depends on the quality of the data available to establish a dose-response relationship, whether these data support the development of an effect dose or effect concentration for 50% of the organisms tested, i.e., ED₅₀ or EC₅₀, and the extent to which there are clear linkages between these measurement endpoints to the Agency’s assessment endpoints of impaired growth, survival and reproduction.  In addition, the ability of current guideline test designs to reliably measure sublethal endpoints may be limited as well.  Although there are challenges associated with the quantitative use of additional data such as sublethal effects in assessing risk, such data can be used qualitatively as an additional line of evidence to support risk assessment conclusions.