IN THIS EPA UPDATE
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UPDATE
Date:
Fri, 13 Dec 2002 17:39:08 -0500
From:
Stephen Tvedten <steve@getipm.com>
Organization: Get Set Inc. (www.getipm.com)
To: Paul Helliker <phelliker@cdpr.ca.gov>
Director, State of California, Department of Pesticide
Regulation
cc: Christine Whitman whitman.christine@epa.gov
IN THIS EPA UPDATE:
1) EPA Announces Revision of Two Toxicity Test Guidelines to Include Alternative Test Methods
2) EPA Set to Announce Revision of Toxicity Test Guidelines to Include Alternative Test Methods
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1) EPA Announces Revision of Two Toxicity Test Guidelines to Include Alternative Test Methods
EPA's Office of Prevention, Pesticides and Toxic Substances (OPPTS) is announcing the revision of two OPPTS Test Guidelines for toxicity testing. The revised guidelines, for Acute Oral Toxicity and Skin Sensitization testing, incorporate alternative test methods which enhance animal welfare while providing essential data needed to ensure protection of human health. Such guidelines had previously been developed internationally through the Organization for Economic Cooperation and Development (OECD). Harmonized OPPTS versions of these two methods were subsequently reviewed by external scientists serving on EPA's Science Advisory Panel.
The new guidelines incorporate alternative test methods which provide for enhanced animal welfare by reducing the number of animals required and calling for use of humane practices for treatment of experimental animals during laboratory testing, as recommended by OECD. The revised Up-and-Down Procedure replaces the traditional acute test method in the Acute Oral Toxicity guideline and provides for determination of the LD50 and confidence intervals. The revised Skin Sensitization guideline provides for using an alternative test method, the Local Lymph Node Assay, where appropriate. OPPTS is continuing to explore ways to broaden the applicability of this and other alternative methods for such testing.
The new Acute Oral Toxicity guideline, calling for use of the revised Up-and-Down Procedure, should be used for acute oral toxicity studies initiated after December 17, 2002. In addition, the Agency also encourages persons performing skin sensitization studies to use the Local Lymph Node Assay where it is suitable. Interested parties are encouraged to contact the Agency prior to initiating any such studies.
These actions will be published in separate Federal Register Notices of Availability and will be accessible through EPA's website at www.epa.gov/fedrgstr. The Notice of Availability for the Acute Oral Toxicity guideline will be published during the week of December 16, 2002. The Notice of Availability for the Skin Sensitization guideline will be published in January 2003.
While the Up-and-Down Procedure has been recommended across programs in the Office of Pollution Prevention and Toxics (OPPT) for some time now as indicated by the Agency's High Production Volume Program website, the revised procedure described in the new Acute Oral Toxicity Guideline should be used for acute oral toxicity studies initiated after December 17, 2002, for both industrial and pesticidal chemicals.
The full text of the announcement is attached. For further information on this action, contact Deborah McCall in the Office of Pesticide Programs at 703-305-7109 for both guidelines, Dr. Elizabeth Margosches (OPPT) at 202-564-7636 for the Acute Oral Toxicity guideline, or Ronald Ward (OPPT).at 202-564-8926 for the Skin Sensitization guideline.
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2) EPA Set to Announce Revision of Toxicity Test Guidelines to Include Alternative Test Methods
EPA's Office of Prevention, Pesticides, and Toxic Substances (OPPTS) plans to publish Notices of Availability in the Federal Register to announce the revision of two test guidelines in the OPPTS Harmonizd Test Guidelines. The guidelines, 870.1100 Acute Oral Toxicity and 870.2600 Skin Sensitization, are being revised to incorporate alternative test methods that have been recently reviewed by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP). Because the alternative methods are new approaches to testing for these endpoints, interested parties are encouraged to be on the alert for the Federal Register notices and to contact the Agency prior to initiating any such studies. A brief description of the changes is presented in the following paragraphs.
870.1100 Acute Oral Toxicity. An improved Up-and-Down Procedure protocol for acute oral toxicity testing was developed by a team of regulatory and industry scientists to provide the types of testing data needed for U.S. agencies to make regulatory decisions. The Agency strongly recommends the use of the revised Up-and-Down Procedue, as detailed in the revised guideline, to meet the testing requirements for for industrial chemicals and registration of pesticide products registered by the Agency. The revised guideline was reviewed by EPA's Scientific Advisory Panel in a public meeting on December 12, 2001, and recommendations of the Panel have been incorporated into the test protocol.
Acute oral toxicity studies initiated after December 17, 2002 should be conducted in accordance with the Up-and-Down Procedure described in the guideline. This Up-and-Down Procedure was adopted by the Organization for Economic Cooperation and Development (OECD) as Test Guideline 425 in December 2001. A software program to assist laboratory users in the conduct of the test was also developed, and the Agency strongly encourages use of this software program. The test guideline, software package, users' manual and related documentation are available on the Internet at http://www.epa.gov/oppfead1/harmonization.
The Up-and-Down test procedure in this guideline is of value in reducing the number of animals required to determine the acute oral toxicity of a chemical. The revised protocol includes a Primary Test and a Limit Test, and provides for determination of the confidence intervals for the LD50 and observation of toxic signs. Moreover, use of guidance for humane endpoints should reduce the overall suffering of animals in this type of test. This test procedure is optimized when starting doses are set as close as possible to the actual LD50 and when dose spacing is based on the best estimate of the dose-response curve. Therefore, all available information on the test substance should be considered by the testing laboratory prior to conducting the study in order to determine if a preliminary estimate of the LD50 and the slope of the dose-response curve can be made. Initial information may include the identity and chemical structure of the substance; its physical chemical properties; the results of any other in vitro or in vivo toxicity tests on the substance or mixtures; toxicological data on structurally related substances or similar mixtures; and the anticipated use(s) of the substance. Practical guidance for laboratories conducting the test is included in the paper, "Alternative Methods for Acute Oral Toxicity Testing: Practical Guidance for Implementation," in the July/August 2002 issue of the journal Lab Animal.
870.2600 Skin Sensitization. The Local Lymph Node Assay (LLNA) is a test method for assessing the allergic contact dermatitis (skin sensitization) potential of chemicals and compounds. In 1998, upon review by the FIFRA SAP, LLNA was incorporated as a screening test in OPPTS Test Guideline 870.2600 Skin Sensitization. Following additional studies to validate the method, the LLNA was endorsed by the SAP in December 2001 as a full stand-alone assay. The LLNA can be used to predict sensitization potential for a broad range of pesticides and industrial chemicals consisting of single organic substances, but not including aqueous mixtures. The test method provides quantitative data and reduces animal suffering. OPPTS guideline 870.1100 Skin Sensitization has been revised to include LLNA as a stand-alone assay for appropriate applications. The OPPTS guideline has also been harmonized with OECD's Guideline 429 for LLNA, which was adopted in April 2002.
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