In the Spotlight
EPA Announces New Guidance and Policies that will reduce the use of animals in pesticide assessment
Published: June 30, 2013
Data Selection, Collection, and Evaluation
“Guiding Principles for Data Requirements” is designed to help OPP staff focus on collecting the most relevant information for an evaluation, while avoiding unnecessary data mining or study replication. In addition, the guidelines are “viewed as guidance for data waiver requests by registrants whose responsibility is to show that their pesticidal substance(s) meets the FIFRA and FFDCA protection standards.” These principles apply to both the registration of new chemicals, and the re-evaluation of existing ones, and cover such aspects as:
- understanding the nature and source of uncertainties in the data, and how they might impact risk assessments, and
- the circumstances under which additional data should be requested of registrants, and
- the use of weight-of-evidence procedures to make these determinations. The “Guiding Principles” document also provides links to relevant case studies that demonstrate these procedures.
The new guidance on data requirements for neurotoxicity, subchronic inhalation, subchronic dermal, and immunotoxicity studies provides a framework for assessing the adequacy of existing data and determining the need for new/additional studies for each of these specific study types. Again, the document is intended to guide OPP staff, but also to help registrants anticipate data needs and understand the decision process – especially the priority of factors in weight-of-evidence evaluations.
The “Guidance for Identifying, Selecting and Evaluating Open Literature Studies” provides (1) criteria for screening and documenting relevant published journal articles, (2) criteria for categorizing selected studies (as appropriate for quantitative use, appropriate for qualitative use, or unacceptable for use), and for selecting and documenting published studies that will be used in a risk assessment, and (3) guidance on how to use published quantitative and qualitative data in risk assessments.
New Testing Policies
In addition to the new guidance documents on data quality and use of existing data, the OPP formalized policies that permit reduction or replacement of animal tests in two areas: genotoxicity and eye irritation.
The EPA announcement acknowledged that the agency now accepts results from two new OECD Test Guidelines (TG), the in vitro micronucleus assay (OECD TG 487), and OECD TG488 for the transgenic rodent gene mutation assay. Although TG 488uses transgenic animals, it specifies using fewer animals and for a shorter study length than the non-transgenic animal protocol. In addition, the EPA is recommending the integration of the cytogenetic tests into repeated dose toxicity studies to satisfy the pesticide registration requirement for in vivo genotoxicity testing. Combining these in vivo tests would reduce the number of animals required for registration.
A second policy, “Use of an Alternate Testing Framework for Classification of Eye Irritation Potential of EPA Pesticide Products,” establishes a “decision tree” framework for using non-animal tests to assess Antimicrobial Products with Cleaning Claims (AMCPs). This new policy culminates a pilot program begun in 2009, during which AMCP pesticide applicants were invited to include eye irritation data gathered from one or more of three alternative toxicology tests in their submissions: the ex vivo Bovine Corneal Opacity and Permeability test (BCOP), and the in vitro EpiOcular (EO) and Cytosensor Microphysiometer (CM) assays. A pre-validation study carried out by industry provided the background for this project, and these results combined with the pilot study determined that these tests were able to predict irritancy across the EPA’s categories: I= irreversible eye damage; II=substantial but temporary eye injury; III=moderate eye irritation; IV=no warning necessary.
The new eye irritation policy permits the use of these alternative tests specifically for AMCPs with the following chemistries: alkaline and acidic, surfactant and solvent-based, and/or oxidizing (e.g., hypochlorite, peroxide, percarbonate, oxygen, bleaches). In particular, the BCOP test is specified for materials that have oxidizing properties or are otherwise expected to be moderate-to-severe eye irritants; the EO and CM tests are indicated for non-oxidizing materials, or materials expected to be only moderate irritants, at most. The EO test is further specified for non-water-soluble materials. Other pesticides within the appropriate chemical groups will be considered on a case-by-case basis. The procedure for determining the appropriate test and assigning a toxicity category is outlined in the OPP’s “decision tree” diagram (Figure 1). The BCOP test is determined by the in vitro irritancy score determined following measures of corneal opacity and permeability, the EO assay as ET50 (cell viability as measured by reduction of the tetrazolium dye MTT), and for the CM assay the MRD50 (the dose of test material that induces a 50% decrease in metabolic rate relative to a negative control).
Figure 1: EPA “decision tree” outlining the selection and evaluation of assays for hazard labeling (used with permission).
Continued Momentum Toward 21st Century Toxicology
Toxicity testing to register a single pesticide requires up to 10,000 animals. These new guidance and policy statements issued by the EPA will reduce animal testing while continuing to improve pesticide safety.