A Review of the LD50 and Its Current Role in Hazard Communication

There is a vital safety requirement to appropriately warn users of chemical products that have acute hazards. As there is a very large amount and wide variety of chemical products, there is also a need to generalize acute hazards of chemicals so they can be reduced to a standardized, simple warning that can be found on a safety datasheet or product label. Acute lethality provides one simple, generalized indicator of the toxicity of a chemical product. The acute lethality hazard is typically determined using the LD50 which is defined as the median dose predicted to kill 50% of a given test population. The purpose of this paper is to provide a review of the LD50, including its history, the current studies used to develop it, and its integrated role in hazard communication. Continual improvement in animal welfare and reduction in animal costs has been one of the primary drivers of change for the LD50 and its regulatory integration. There are currently several well-established animal testing protocols designed to minimize the number of animals needed to produce an LD50 estimate that is sufficient for acute toxicity hazard communication. The utility of these animal testing protocols is further enhanced by ongoing regulatory adoption of The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) that integrates LD50 data into a common hazard communication language. GHS can allow for multiple regulatory agencies to enforce a single and consistent hazard communication for a chemical or mixture without requiring new animal testing. This paper reviews the current progress and limitations of LD50 integration with GHS as well as approaches that can be taken to better streamline integration.