Evaluation of a Testing Strategy for Ocular Hazard Classification and Labeling of Antimicrobial Cleaning Products
In 2008, the U.S. Environmental Protection Agency (EPA) submitted to NICEATM a testing strategy to assess the eye irritation potential of antimicrobial cleaning products (AMCPs) that avoided the use of live animals. The proposed testing strategy used the bovine corneal opacity and permeability, Cytosensor microphysiometer, and EpiOcular™ test methods to determine the EPA hazard category and labeling requirements for these products. ICCVAM evaluated the proposed strategy and recommended further studies to characterize its usefulness and limitations.
In 2013, the EPA Office of Pesticide Programs established the use of an alternative testing approach to assess the eye irritation potential for AMCPs in general and for other classes of pesticides and pesticide products on a case-by-case basis. This testing approach modified the 2008 proposal to consider the ICCVAM evaluation and studies submitted by product registrants. A detailed policy document is available on the EPA website.
Background on the AMCP Testing Strategy Evaluation
The EPA collaborated with seven consumer product companies to develop the 2008 proposal. The Institute for In Vitro Sciences, Inc., (IIVS) coordinated the collaboration, performed additional testing to complete parallel sets of in vivo and in vitro data, and prepared a background review document describing the final approach.
The EPA and the consumer product companies requested that NICEATM and ICCVAM to conduct a technical review of the scientific validity of the AMCP testing strategy. The goal of the review was to determine whether the AMCP testing strategy could, with a reasonable degree of certainty, be used to make appropriate hazard classification and labeling decisions for AMCPs.
NICEATM and ICCVAM used the IIVS background review document and additional data and information as the basis for a draft summary review document (SRD) and draft ICCVAM recommendations. The draft SRD and draft recommendations were reviewed in May 2009 by an independent international scientific peer review panel. ICCVAM considered the panel's comments, as well as comments from the Scientific Advisory Committee on Alternative Toxicological Methods and the public, before finalizing its recommendations for Federal agencies.
ICCVAM concluded that, at that time, there were insufficient data with which to adequately demonstrate that the proposed strategy could classify test substances to all four EPA ocular hazard categories. ICCVAM recommended future studies that could further characterize the usefulness and limitations of a testing strategy for AMCPs.
Submission Letter from Dr. Rodger Curren, IIVS, to Dr. William Stokes, NICEATM
The ICCVAM recommendations and ICCVAM-recommended protocols for the test methods are contained in the ICCVAM Test Method Evaluation Report: Current Validation Status of a Proposed In Vitro Testing Strategy for U.S. Environmental Protection Agency Ocular Hazard Classification and Labeling of Antimicrobial Cleaning Products (2010).
The ICCVAM recommendations were transmitted to Federal agencies in September 2010. Agency responses indicated acceptance or endorsement of the ICCVAM recommendations.
Background on the ICCVAM Evaluation of the Low Volume Eye Test
As part of its evaluation of the AMCP testing strategy, ICCVAM also reviewed the validation status of the low volume eye test (LVET). The LVET is similar to the traditional in vivo rabbit eye test, but uses a smaller volume of test substance and a different application procedure. Data generated using the LVET was used as reference data to partially substantiate the validity of the in vitro test methods used in the AMCP testing strategy.
ICCVAM recommended that the LVET should not be used for future regulatory testing. If animals must be used in ocular safety testing, ICCVAM recommends use of a modified rabbit eye test as recommended with topical anesthetics, systemic analgesics, and humane endpoints. The ICCVAM recommendations are included in the ICCVAM Test Method Evaluation Report: Recommendation to Discontinue Use of the Low Volume Eye Test for Ocular Safety Testing.
Recommendations and Agency Responses
The ICCVAM recommendations were communicated to Federal agencies in letters from Dr. Linda Birnbaum, Director, NIEHS. These letters and responses received from Federal agencies are available below.
- National Institutes of Environmental Health Sciences (NIEHS)
- Letter from Linda Birnbaum, Ph.D., DABT, ATS, Director, NIEHS, to the ICCVAM Committee (January 14, 2011)
- Agency for Toxic Substances and Disease Registry (ATSDR)
- Letter from Dr. Birnbaum to Thomas R. Frieden, M.D., M.P.H., Administrator, ATSDR
- Response from Dr. Frieden (received February 11, 2011)
- Consumer Product Safety Commission (CPSC)
- Letter from Dr. Birnbaum to Inez Moore Tenenbaum, Chairman, CPSC
- Response from Todd Stevenson, Office of the Secretary (received March 11, 2011)
- Environmental Protection Agency (EPA)
- Letter from Dr. Birnbaum to Lisa P. Jackson, Administrator, EPA
- Response from John Fowle, Ph.D., DABT, Office of Pesticide Programs (received February 28, 2011)
- Food and Drug Administration (FDA)
- Letter from Dr. Birnbaum to Margaret Hamburg, M.D., Commissioner
- Response from Jesse L. Goodman, M.D., M.P.H. , Chief Scientist and Deputy Commissioner for Science and Public Health (received March 2, 2011)
- National Cancer Institute (NCI)
- Letter from Dr. Birnbaum to Harold E. Varmus, M.D., Director, NCI
- Response from Dr. Varmus (received February 8, 2011)
- National Institutes of Health (NIH)
- Letter from Dr. Birnbaum to Francis S. Collins, M.D., Ph.D., Director, NIH
- Response from Dr. Collins (received November 29, 2010)
- National Institute for Occupational Safety and Health (NIOSH)
- Letter from Dr. Birnbaum to John Howard, M.D., Director, NIOSH
- Response from Dr. Howard (received December 16, 2010)
- National Library of Medicine (NLM)
- Letter from Dr. Birnbaum to Donald A.B. Lindberg, M.D., Director, NLM
- Response from Dr. Lindberg (received January 13, 2011)
- Occupational Safety and Health Administration (OSHA)
- Letter from Dr. Birnbaum to David Michaels, Ph.D., M.P.H., Assistant Secretary of Labor for Occupational Safety and Health, OSHA
- Response from Dr. Michaels (received November 29, 2010)
- U.S. Department of Agriculture
- Letter from Dr. Birnbaum to Tom Vilsack, Secretary of Agriculture
- Response from Jose Diez, Associate Deputy Administrator, Veterinary Services (received October 7, 2010)
- U.S. Department of Defense
- Letter from Dr. Birnbaum to Robert M. Gates, Ph.D., Secretary of Defense
- Response from David Honey, Director, Research Directorate (received December 15, 2010)
- U.S. Department of Energy
- Letter from Dr. Birnbaum to Steven Chu, Secretary of Energy
- Response from Dr. J. Michael Kuperberg, Office of Biological and Environmental Research (received February 28, 2011)
- U.S. Department of the Interior
- Letter from Dr. Birnbaum to Ken Salazar, Secretary of the Interior
- Response from David Russ, Regional Executive, Northeast Area, U.S. Geological Survey (received January 7, 2011)
- U.S. Department of Transportation