Today's requirements in food, drug and chemical control.

Abstract

Abstract The acute toxicity tests which generate LD50's or LC 50's have been used for several decades to detect potential acute hazards to humans who are exposed to toxic substances. Several federal regulatory agencies use the results of these tests in regulating chemicals such as food additives, drugs, products found in homes such as pesticides and household cleaners, chemicals produced in industrial environments and chemicals which are transported in interstate commerce.Acute toxicity data are used by these federal agencies in many different ways depending upon their regulatory missions and the regulations that these agencies utilize to accomplish their missions. For instance, the Federal Hazardous Substances Act regulations used by the Consumer Product Safety Commission address the specific labeling of consumer products dependent upon the calculated oral or dermal LD50. In some instances, a consumer product can be banned from commerce as an imminent hazard dependent upon the peculiar toxicity of the product.However, the Food and Drug Administration with the authority contained in the Federal Food, Drug and Cosmetic Act uses acute toxicity data in determining the approvability of intentional food additives and indirect food additives contained in food packaging. In addition, such data are used to provide guidance for the design of longer term studies in man and animal needed to obtain food and drug approvals.Since many federal regulatory agencies require acute toxicity tests in some phase of their regulatory activities, it was decided to develop common guidelines for these tests. As a result, the Interagency Regulatory Liaison Group (IRLG) was established in 1977, in part to develop guidelines to resolve existing test protocols and to design tests to be used by all IRLG agencies for chemical testing.In mid 1979, a draft acute oral toxicity protocol for rodents was released for general public comment. As a result of this action, the guidelines were modified to incorporate some of the expressed public ideas. One modification provided for the use of a limit test involving 10 rats dosed at a level of 5g/kg which could preclude the use of further numbers of animals. If no compound related mortality was observed at this dose, the compound would be considered as non‐toxic. The acute toxicity guidelines were finalized and published in January, 1981.Although the IRLG recognizes that at present the acute toxicity rodent test is the most reliable method to determine potential acute hazards to man, it also recognizes that alternatives such as in vitro tests may prove useful once further research and development refine them to the point of regulatory utility.