Chapter 11
Recent Revision to the U.S. Environmental Protection Agency Residue Chemistry Guidance Christine L. Olinger
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Office of Pesticide Programs, U.S. Environmental Protection Agency, Health Effects Division (7509C), 401 M Street S.W.; Washington, DC 20460
The U.S. EPA guidance on performance of pesticide residue chemistry studies has undergone extensive revision over the past few years. In response to registrant concerns over conflicting information on residue chemistry studies, clarifying guidance was prepared for almost every type of study. These documents have been consolidated in the OPPTS 860 Residue Chemistry Guidelines. Additional draft guidance on anticipated residues and tolerances on imported commodities has been distributed since the 860 guidelines were finalized in August 1996. Highlights of all of the residue chemistry guidelines will be reviewed.
The U.S. Environmental Protection Agency (EPA) 860 Residue Chemistry Guidelines were finalized and published in August 1996. This document is a comprehensive overview of the pesticide residue chemistry studies submitted to the Agency in support of pesticide tolerances and registrations and was developed from the Subdivision Ο Pesticide Assessment Guidelines (Residue Chemistry) and clarifying guidance prepared in response to the reregistration rejection rate project. Highlights of the 860 guidance will be discussed in this paper. The revised Anticipated Residue and Import Tolerance guidance presented in June 1997 to the FIFRA Scientific Advisory Panel (SAP), a peer review panel external to the Agency, will be discussed as well. The types of residue chemistry studies to be discussed are designed to answer the questions what are the potential pesticide residues in human foods and animal foods, and how much residue is present? Nature of the residue studies provide residue chemists with qualitative information on how the pesticide is altered when applied to plants or animals or ingested by livestock. Residue analytical methods are the tools used to determine how much residue is present. Storage stability studies provide information on residue stability when treated samples are stored. Magnitude of residue studies answer the question how much residue is present on the raw or processed commodity.
U . S . government w o r k . Published 1999 A m e r i c a n C h e m i c a l Society
Garner et al.; International Pesticide Product Registration Requirements ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
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84 Rotational crop studies are used to determine appropriate intervals for planting rotated crops or whether tolerances are needed on rotated crops. 860 Residue Chemistry Guidelines When the FIFRA amendments were first passed in 1988 requiring EPA to reregister all pesticide active ingredients initially registered prior to 1984, the Agency recognized the need to ensure that studies submitted to the Agency must be of sufficient quality to avoid endless resubmissions. The Agency examined the rejection rates of studies by discipline and identified the major factors for which they were rejected. After working with industry, residue chemists identified several areas where Agency guidance on study conduct and reporting was deficient or contradictory. Therefore, starting in 1992, the Agency developed a series of guidance documents on metabolism studies, storage stability, crop field trials, and so on. At the same time, the Health Effects Division (HED) had an on-going project re-evaluating what used to be known as Table 2, the livestock feeds table. In 1995 the Agency initiated a project to harmonize guidelines across the Agency to avoid duplication to the extent possible. HED used this opportunity to combine all residue chemistry guidance into a single cohesive document. No longer would reviewers and registrants need to consult Subdivision Ο Residue Chemistry Guidelines, the Data Reporting Guidelines, the Standard Evaluation Procedures and receive conflicting information. The draft 860 Residue Chemistry guidelines were first published in 1995. Comments received from industry, grower groups, trade associations, IR-4, etc., were addressed and incorporated into the final guidance when published in August 1996 (/). Since some of the guidance eventually incorporated into 860 was first developed almost five years ago and so is not new, this paper highlights the salient features of each type of study. Nature of the Residue Studies. These studies are designed to characterize and identify the metabolites of the parent pesticide in plants and animals. Radiolabeled material is used to facilitate the identification of the total toxic residue (TTR). Dermal animal metabolism studies are required if the pesticide is to be used as a direct animal treatment, and oral studies are required if livestock feeds are treated. Assuming the dosing is correct, probably the most significant factor which led to rejection of metabolism studies was inadequate characterization and identification. Registrants and petitioners requested guidance on to what extent the breakdown products need to be characterized and identified. In response, the Agency has developed flow charts to assist investigators in determining the extent to which characterization and identification should be attempted. The strategy for characterization and identification of extractable residues is presented in the flow chart presented in Figure 1; a second flow chart presented in Figure 2 describes procedures for characterizing non-extractable residues. Residue Analytical Methods. Residue methods are used for enforcement of pesticide tolerances and for collection of residue data used for assessing dietary exposure and
Garner et al.; International Pesticide Product Registration Requirements ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
85 Figure 1. Characterization and Identification of Extractable Residues 14C-Treated Raw Agricultural Commodity
Total 14C Residue (TRR - Determine by Combustion)
< 10 ppb No Metabolism Work
> 10 ppb Extraction Aqueous and Organic
Total 14C-Extractables
Non-Extractable
10-50 ppb Partition Analysis of Organosolubles
< 10 ppb No Further Work
> 50 ppb Characterize and Identify Organic and Aqueous Phases
Figure 2. Characterization and Identification of Non-Extractable/Bound Residues Non-Extractable Residues
