[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