Environmental assessment of avermectins by the US Food and Drug Administration

The Center of Veterinary Medicine (CVM) of the Food and Drug Administration (FDA) is required under the National Environmental Policy Act (NEPA) to include in its decision making, an objective consideration of the potential environmental impacts associated with each contemplated action. As part of the application process for new animal drugs, detailed data must be submitted in order to develop a prediction of the environmental fate and effects of the drug and/or its active metabolites. Ivermectin (22,23-dihydroavermectin B1) is a highly active antiparasitic animal drug utilized in a variety of injectable, oral and topical formulations. Residues of this drug may reach the environment through manufacturing and animal wastes and may potentially have effects on terrestrial and aquatic organisms. A comprehensive data base has been submitted to the FDA in support of the environmental assessments for ivermectin drug products. Detailed information has been submitted on the physical and chemical properties, introduction, fate and effects of the ivermectins in the environment. These data indicate that ivermectin binds tightly to soil and is subject to photodegradation and biotransformation to less active compounds. In contrast, ivermectin is highly toxic to certain aquatic organisms but would not be expected to partition into the aquatic environment. Much lower toxicity has been demonstrated toward bacteria, fungi, earthworms, plants and birds. CVM evaluated ivermectin products based on the use pattern of the product, the metabolism pattern in target animals, calculations of potential ivermectin residue concentrations in the environment and data on persistence, soil sorption and acute toxicity in aquatic and terrestrial environments.