What Is LD50?

A 2018 peer-reviewed review of US agency testing requirements explains that the LD50 is the dose of a test substance expected to kill 50 percent of the animals tested by the oral or dermal route, that the LC50 is the equivalent for inhalation, and that these values from acute toxicity tests in rodents are used to assign substances to toxicity categories that determine the hazard warnings on product labels. It notes that the 1981 LD50 test used 30 or more animals per chemical, while current oral test designs use five to nine.

The EPA's pesticide labeling rule sets four acute toxicity categories, with Category I the highest, and bases most human hazard and precautionary label statements on them. An oral LD50 up to and including 50 mg/kg is Category I, over 50 through 500 mg/kg is Category II, over 500 through 5,000 mg/kg is Category III, and over 5,000 mg/kg is Category IV, with separate cutoffs for dermal LD50 and inhalation LC50.

The category sets the signal word. The EPA requires Category I products to carry DANGER on the front panel, plus the word Poison in red and a skull and crossbones when the category is based on oral, inhalation or dermal toxicity, while Category II products carry WARNING and Category III products carry CAUTION. OSHA's workplace hazard classification also sorts chemicals into four acute toxicity categories using approximate LD50 or LC50 values, and notes that newer methods using fewer animals consider other indicators such as significant clinical signs of toxicity.

Animal numbers have limits. A 2018 review in Interdisciplinary Toxicology says acute toxicity results may vary greatly from species to species and from laboratory to laboratory, and that because LD50 is not tested on humans, its relation to humans is only a guess, since the human lethal dose may not be predicted exactly from animal studies.