Chapter 2
Current Toxicology Requirements for Registration Downloaded by HONG KONG UNIV SCIENCE TECHLGY on May 4, 2018 | https://pubs.acs.org Publication Date: March 12, 1987 | doi: 10.1021/bk-1987-0336.ch002
Raymond A. Cardona Uniroyal Chemical Company, Inc., Crop Protection Research & Development, Bethany, CT 06525
The Environmental Protection Agency (EPA) is responsible for pesticide regulation and for insuring the safety of pesticide products. To this end, the EPA has promulgated testing guidelines designed to fulfill pesticide registration requirements. Laboratory animal studies form the primary basis for predicting the potential hazards of pesticides to public health. EPA toxicology data requirements include acute testing, subchronic and chronic feeding/oncogenicity studies, a two generation reproduction and teratogenicity study, mutagenicity testing and a rodent metabolism study. These requirements and problems encountered in interpretation of data obtained from toxicity testing are discussed. Future directions of research to fulfill toxicology data requirements are described. The Environmental Protection Agency (EPA), under the authority of the Federal Insecticide, Fungicide and Rodenticide Act (FIFFA), is responsible for pesticide regulation. Data requirements for pesticide registration, and guidelines for evaluating the toxicity of pesticides to nonhuman organisms and for relating the results of these studies to human safety evaluations, have been developed by EPA(1,2). Toxicity studies required by EPA for pesticide registration are listed in Table 1. The major toxicity categories include acute, subchronic, chronic and mutagenicity testing. Evaluation of teratogenicity and adverse reproductive effects are included under chronic testing. Animal metabolism and dermal penetration studies are found in a special testing category. Acute Toxicity The initial step in the safety evaluation of a pesticide product is the determination of its acute toxicity (Table I). Laboratory animals, usually rats and rabbits, are exposed to a single dose of the test substance. Toxic effects resulting from ingestion, 0097-6156/87/0336-0014$06.00/0 © 1987 American Chemical Society
Ragsdale and Kuhr; Pesticides ACS Symposium Series; American Chemical Society: Washington, DC, 1987.
Downloaded by HONG KONG UNIV SCIENCE TECHLGY on May 4, 2018 | https://pubs.acs.org Publication Date: March 12, 1987 | doi: 10.1021/bk-1987-0336.ch002
2. CARDONA
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Current Toxicology Requirements for Registration
inhalation, skin and eye contact are determined over a two to three week post-exposure observation period. I f repeated dermal exposure i s expected to occur, a dermal s e n s i t i z a t i o n study i n guinea pigs i s required. An acute delayed neurotoxicity study i s required only i f the t e s t substance i s f o r food use and i s an organophosphate, which causes acetyl cholinesterase depression, or i f i t i s structura l l y related to a substance that causes delayed neurotoxicity. The purpose of acute t o x i c i t y testing i s to establish r e l a t i v e t o x i c i t y to other chemicals by defining the median l e t h a l dose (LD50 and LC50), to provide i n i t i a l information on the mode of toxic action, to i d e n t i f y possible synergistic interactions and to evaluate design for subchronic t e s t s . Data from these tests are used to determine the signal word and the hazard warning statements which appear on the pesticide product label? for example, i f the pesticide i s acutely toxic (oral LD50 i n r a t
