[Federal Register Volume 64, Number 118 (Monday, June 21, 1999)]
[Notices]
[Pages 33109-33111]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-15725]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
National Institute of Environmental Health Sciences (NIEHS);
Corrositex: An In Vitro Test Method for Assessing Dermal
Corrosivity Potential of Chemicals, Report Now Available
SUMMARY: The report entitled ``Corrositex: An In Vitro Test
Method for Assessing Dermal Corrosivity Potential of Chemicals,'' NIH
Publication 99-4495, is now available and may be obtained as described
in this notice. The report describes the results of an independent peer
review evaluation of the validation status of Corrositex
that was conducted on January 21, 1999 Federal Register 63 FR 57303,
October 27, 1998). Corrositex was proposed by In Vitro
International, Inc., Irvine, CA, as an alternative toxicological test
method for assessing the dermal corrosivity potential of chemicals and
chemical mixtures. The review was coordinated by the Interagency
Coordinating Committee on the Validation of Alternative methods
(ICCVAM) and the National Toxicology Program (NTP) Interagency Center
for the Evaluation of Alternative Toxicological Methods (NICEATM). The
review was sponsored by NIEHS and the NTP.
Background
Pub. L. 103-43 directed NIEHS to develop and validate alternative
methods that can reduce or eliminate the use of animals in acute or
chronic toxicity testing, establish criteria for the validation and
regulatory acceptance of alternative testing methods, and recommend a
process through which scientifically validated alternative
[[Page 33110]]
methods can be accepted for regulatory use. Criteria and processes for
validation and regulatory acceptance were developed in conjunction with
13 other Federal agencies and programs with broad input from the
public. These are described in the document ``Validation and Regulatory
Acceptance of Toxicological Test Methods: A Report of the Ad Hoc
Interagency Coordinating Committee on the Validation of Alternative
Methods,'' NIH publication 97-3981, March 1997, which is available on
the Internet at http://ntp-server.niehs.nih.gov/htdocs/ICCVAM/
iccvam.html. ICCVAM was subsequently established in a collaborative
effort by NIEHS and 13 other Federal regulatory and research agencies
and programs. The Committee's functions include the coordination of
interagency reviews of toxicological test methods and communication
with stakeholders throughout the process of test method development and
validation. The following Federal regulatory and research agencies and
organizations participate in this effort:
Consumer Product Safety Commission
Department of Defense
Department of Energy
Department of Health and Human Services
Agency for Toxic Substances and Disease Registry
Food and Drug Administration
National Institute for Occupational Safety and Health/CDC
National Institutes of Health
National Cancer Institute
National Institute of Environmental Health Sciences
National Library of Medicine
Department of the Interior
Department of Labor
Occupational Safety and Health Administration
Department of Transportation
Research and Special Programs Administration
Environmental Protection Agency
ICCVAM determined that there was sufficient information available
to merit an independent scientific peer review evaluation of the
Corrositex test method. Peer review is an essential
prerequisite for consideration of a method for regulatory acceptance.
The peer review panel was charged with developing a scientific
consensus on the usefulness and limitations of the test method.
Description of the Method
Corrositex is an in vitro method used to determine the
dermal corrosive potential of chemicals and chemical mixtures.
Corrositex is based on the ability of a corrosive chemical
or chemical mixture to pass through, by diffusion and/or destruction/
erosion, a biobarrier and to elicit a color change in the underlying
liquid Chemical Detection System (CDS). The biobarrier is composed of a
hydrated collagen matrix in a supporting filter membrane, while the CDS
is composed of water and pH indicator dyes. Test chemicals and chemical
mixtures, including solids and liquids, are applied directly to the
biobarrier. The time it takes for a test chemical or chemical mixture
to penetrate the biobarrier and produce a color change in the CDS is
compared to a classification chart to determine corrosivity/
noncorrosivity and to identify the appropriate U.S. Department of
Transportation (U.S. DOT) packing group. Chemicals are prescreened for
compatibility with the assay by directly applying the test chemical or
chemical mixture to the CDS; if a color change is not induced, then the
test chemical or chemical mixture does not qualify for testing with
this assay. The U.S. DOT currently accepts the use of
Corrositex to assign subcategories of corrosivity (packing
groups) for specific chemical classes for labeling purposes according
to United Nations (UN) Committee of Experts on the Transport of
Dangerous Goods guidelines.
Conclusions and Recommendations
The peer review panel concluded that for specific testing
circumstances such as that required by the U.S. DOT,
Corrositex is useful as a stand-alone assay for evaluating
the corrosivity or noncorrosivity of acids, bases, and acid
derivatives. In other testing circumstances, and for other chemical and
product classes, the peer review panel concluded that
Corrositex may be used as part of a tiered assessment
strategy. In this approach, negative responses must be followed by
dermal irritation testing, and positive responses require no further
testing unless the investigator is concerned about potential false
positive responses. The panel recommended that in either testing
strategy, an investigator may conclude that confirmation testing is
necessary based on consideration of supplemental information, such as
pH, structure-activity relationships, and other chemical and/or testing
information. These conclusions are based on the assumption that the
method will be performed in accordance with the following peer review
panel recommendations:
1. The protocol should incorporate the following:
It should be explicitly stated that the biobarrier should
be allowed to harden on a level surface and to cool overnight before
use.
Guidance should be provided on how to evaluate an aberrant
value, even though replicate variability has been shown to be very low.
The IVI Corrositex Data Sheets provided with
the test kit should contain a provision for recording the performance
of the positive and negative controls. This information should be used
to determine the suitability of the test results.
Description of the test protocol would benefit from the
addition of a flow diagram illustrating the steps in the procedure.
2. In future studies, compliance with Good Laboratory Practice
(GLP) guidelines and inclusion of quality control procedures would
improve data quality and credibility.
3. Positive and negative control values should be reported
concurrently with each assay to demonstrate that the test is working
properly.
4. Laboratories unfamiliar with conducting the test should obtain
appropriate training and conduct tests with test reference chemicals
before undertaking any testing of unknown chemicals and chemical
mixtures.
5. Prior to the use of Corrositex, pH testing should be
conducted, given the ease and cost effectiveness of conducting a pH
test. Such information could be used in the future to re-evaluate the
agreement between pH and Corrositex in identifying
corrosivity.
The peer review panel also concluded that Corrositex
offers advantages with respect to animal welfare considerations.
Corrositex, when used as a stand-alone assay for some
testing applications such as transportation purposes, can replace the
use of animals for corrosivity testing of qualified chemicals in some
chemical classes. When used as part of a tiered testing strategy for
corrrosivity, there is a reduction in the number of animals required
because positive results usually eliminate the need for animal testing,
and when further testing in animals is determined to be necessary, only
one animal is required to confirm a corrosive chemical.
Corrositex also provides for refinement in that most of the
chemicals that are identified as negative by Corrositex or
nonqualifying in the detection system are unlikely to be corrosive when
tested in the in vivo test for irritation potential.
The peer review panel's report was accepted by ICCVAM and has been
forwarded to Federal agencies for their determination of the regulatory
[[Page 33111]]
acceptability and applicability of the test method according to their
statutory mandates.
Obtaining the Report
The full report contains 238 pages and includes the results of the
independent peer review evaluation and supporting documentation,
including the original test method submission and supporting data
evaluations conducted by NICEATM.
To receive a copy of the report, please contact NICEATM at PO Box
12233, MD EC-17, Research Triangle Park, NC 27709 (mail), 919-541-3398
(phone), 919-541-0947 (fax), or [email protected] (email). The
report will also be available on the ICCVAM/NICEATM website at http://
iccvam.niehs.hih.gov.
Dated: June 15, 1999.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
[FR Doc. 99-15725 Filed 6-18-99; 8:45 am]
BILLING CODE 4140-01-M