Environmental Factor, August 2009, National Institute of Environmental Health Sciences
Public Comments Invited on Ocular Safety Testing Recommendations
By Debbie McCarley
The National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), (http://ntp.niehs.nih.gov/pubhealth/evalatm/index.html) in conjunction with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), (http://ntp.niehs.nih.gov/pubhealth/evalatm/iccvam/index.html) announced the availability of an independent scientific peer review panel report on alternative ocular safety testing methods and approaches and invited public comments in the July 13 issue of the Federal Register. The report endorses proposed recommendations by ICCVAM that are expected to improve the well-being and reduce the numbers of animals used to determine if consumer products and other chemicals can cause eye injuries. NICEATM asks that comments be submitted in response to the request (https://tools.niehs.nih.gov/webforms/index.cfm/main/formViewer/form_id/521/to/niceatm) electronically or in writing by August 28, 2009 (see text box). (http://www.niehs.nih.gov/news/newsletter/2009/august/science-public.cfm#bluebox)
The meeting (https://ntp.niehs.nih.gov/pubhealth/evalatm/publications-and-presentations/presentations-at-scientific-meetings/sot-2009/index.html) of the panel of 22 expert scientists from six countries was held May --21 at the Consumer Product Safety Commission (CPSC) headquarters in Bethesda, Md., chaired by A. Wallace Hayes, Ph.D., of the Harvard University School of Public Health. The members reviewed new test methods and strategies proposed for determining if chemicals and substances may cause eye injuries. The panel was convened by NICEATM and ICCVAM to consider methods and strategies to further reduce animal use for eye safety testing and to avoid or minimize pain and distress in cases when animal use is necessary.
The panel recommended that pain-relieving drugs should always be used before any in vivo ocular irritancy testing. In addition, the group recommended an enhanced protocol of specific pain-relieving drugs and schedule of administration to effectively avoid or minimize discomfort. ICCVAM proposed several clinical conditions that could be used as humane endpoints to terminate ocular safety studies earlier than the typical 21-day observation period because they were considered sufficiently predictive of certain outcomes. The panel endorsed most of the proposed humane endpoints and agreed that they should be routinely used. The Panel also recommended that more detailed observations of the eye should be routinely conducted using a slit lamp biomicroscope to assess the severity of lesions, such as the depth of corneal injuries.
"The routine use of topical anesthetics and analgesics for ocular safety studies will ensure the most humane use of animals, and avoid pain and discomfort that might occur without the use of such agents," said William Stokes, D.V.M., the executive director of ICCVAM and director of NICEATM, and an assistant surgeon general in the U.S. Public Health Service. "Importantly, since ocular testing is one of the four most common safety tests conducted, it will have a significant impact on the improvement of animal welfare."
ICCVAM's recommendations support the recently released NAS report, "Recognition and Alleviation of Pain and Distress in Laboratory Animals," that calls for identification of humane endpoints and increased efforts to alleviate pain and distress.
The Panel also agreed with ICCVAM that two non-animal test methods, the Bovine Corneal Opacity and Permeability and the Cytosensor Microphysiometer® test methods, could be used in certain circumstances as screening tests to identify substances that do not cause sufficient eye irritation to trigger hazard labeling. These recommendations, if adopted by Federal agencies, are expected to further reduce animal use for ocular safety testing, and may potentially eliminate animal pain and distress in situations where animal testing is still required.
The panel evaluated the validation status of each of the proposed alternative test methods and applications according to established federal and international. The reviewers also commented on draft ICCVAM recommendations regarding the usefulness and limitations of each proposed test method and application.
The Panel's report is available online or by request (see text box). (http://www.niehs.nih.gov/news/newsletter/2009/august/science-public.cfm#bluebox)
(Debbie McCarley is the Special Assistant to Rear Admiral William Stokes, D.V.M., D.A.C.L.A.M., director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods.)
The ICCVAM/NICEATM Mandate
Federal regulations require that new, revised and alternative test methods be determined to be valid for their proposed use before agencies can adopt them for regulatory purposes. ICCVAM, which has members from 15 Federal agencies, coordinates the technical evaluations of new, revised and alternative methods for regulatory safety testing of chemicals and products. ICCVAM will consider the Panel's report, (http://iccvam.niehs.nih.gov/methods/ocutox/PeerPanel09.htm) along with comments from the public and its scientific advisory committee, in preparing final test method recommendations that will be forwarded to Federal agencies later this year. Acceptance of these recommendations by Federal agencies could result in fewer animals being required for identification of ocular hazards, as well as eliminating or minimizing pain and distress in cases where animal testing is still required.
In 2007, ICCVAM recommended two non-animal methods for use to identify substances that could cause permanent eye damage. These methods were accepted by Federal agencies and may now be used instead of conventional animal tests for certain regulatory testing purposes. The use of these two alternative test methods will likely reduce the use of live animals for eye safety testing by 10 percent or more and eliminate eye safety testing in animals of most substances likely to cause the most severe pain and discomfort. In June of this year, these two nonanimal methods, the Bovine Corneal Opacity and Permeability (BCOP) and isolated chicken eye (ICE), were adopted by the Organization for Economic Co-operation and Development (OECD). They can now be used in the 30-member countries to identify substances that may cause irreversible or severe eye damage without the use of live animals.
The goal of NICEATM and ICCVAM is to achieve the regulatory acceptance of alternative test methods that will benefit animal welfare by reducing, refining and replacing animal use - the 3Rs of alternative testing - and benefit public health by ensuring continued or improved protection of human and animal health and the environment.
Comments may be submitted electronically by email (email@example.com) and the NICEATM/ICCVAM Web site. (http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm) Written comments should be addressed to the attention of NICEATM Director William Stokes, D.V.M., by fax (919-541-0947) or at the following addresses: NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle Park, N.C.27709 (mail) or NIEHS, 530 Davis Drive, Room 2035, Durham, NC 27713 (courier).