[Federal Register Volume 78, Number 219 (Wednesday, November 13, 2013)]
[Notices]
[Pages 68076-68077]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-27095]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Request for Information on Alternative Skin Sensitization Test 
Methods and Testing Strategies and for Comment on ICCVAM's Proposed 
Activities

SUMMARY: The Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) is developing a U.S. plan for the 
evaluation of alternative skin sensitization test methods and testing 
strategies. The National Toxicology Program (NTP) Interagency Center 
for the Evaluation of Alternative Toxicological Methods (NICEATM) 
requests information that ICCVAM might use to develop this plan and 
comments on proposed ICCVAM activities.

DATES: Information should be submitted by December 9, 2013.

ADDRESSES: Responses submitted by email to [email protected] are 
preferred. NICEATM, National Institute of Environmental Health 
Sciences, P.O. Box 12233, Mail Stop: K2-16, Research Triangle Park, NC 
27709. Web site: http://ntp.niehs.nih.gov/go/niceatm.

FOR FURTHER INFORMATION CONTACT: Dr. Warren S. Casey, Acting Director, 
NICEATM; email: [email protected]; telephone: (919) 316-4729.

SUPPLEMENTARY INFORMATION: 
    Background: Allergic contact dermatitis (ACD), a skin reaction 
characterized by localized redness, swelling, blistering, or itching 
after direct contact with a skin allergen, is an important public 
health challenge. ACD frequently develops in workers and consumers 
exposed to skin-sensitizing chemicals and products. Pesticides and 
other marketed chemicals, including cosmetic ingredients, are routinely 
tested for skin sensitization hazard so that products can be 
appropriately labeled for safe use and handling. Fostering the 
evaluation and promotion of alternative test methods for regulatory use 
in skin sensitization hazard assessment has been one of ICCVAM's long-
standing priorities (see http://ntp.niehs.nih.gov/go/40445).
    Skin sensitization is a complex process. For substances that 
initiate the process through covalent binding to skin proteins, the key 
biological events have been fairly well characterized. These events 
form the basis for an ``adverse outcome pathway'' (AOP) for skin 
sensitization (OECD, 2012). An AOP is a conceptual model that links 
exposure to a substance to a toxic effect by identifying the sequence 
of biochemical events required to produce the toxic effect. The AOP for 
skin sensitization provides a framework for the development of 
alternative toxicity tests that can assess chemical effects on each 
biological event in the pathway and thereby provide evidence on whether 
a substance causes skin sensitization.
    ICCVAM is committed toward continued work in this area and believes 
it has promise for the near-term development of testing strategies that 
do not require the use of animals. Specific ICCVAM or NICEATM 
activities include the following:
     ICCVAM consideration of a nomination from the National 
Institute of Occupational Safety and Health to assess the electrophilic 
allergen screening assay, a test method that identifies electrophilic 
substances that may produce skin sensitization by measuring their 
tendency to bind to skin proteins, the first key event in the AOP.
     NICEATM collaboration with academic scientists to develop 
and evaluate chemical structure--activity relationship (SAR) models to 
predict skin sensitization.
     NICEATM collaboration with industry scientists to develop 
an open-source Bayesian network as an operational framework for an 
integrated testing strategy that uses multiple physicochemical, in 
silico, in chemico, and in vitro inputs to predict skin sensitization 
properties of test substances.
     NICEATM evaluation of various high-throughput screening 
assays for skin sensitization in coordination with NIEHS Tox21 
activities.
    ICCVAM is also aware of significant international efforts to 
replace the use of animals in skin sensitization testing for hazard and 
potency assessment by government organizations including the 
Organisation for Economic Co-operation and Development (OECD) and the 
European Union Reference Laboratory for Alternatives to Animal Testing 
(EURL ECVAM), and by the industry organization Cosmetics Europe 
(formerly COLIPA). Some specific ICCVAM and NICEATM activities include:
     Providing expertise and advice to EURL ECVAM to support 
their evaluation of several in chemico or in vitro methods (the direct 
peptide reactivity assay, human cell line activation test, 
KeratinoSens\SM\, and myeloid U937 skin sensitization test), which 
cover key events in the AOP for skin sensitization (Adler et al., 
2011).
     Participation in the International Cooperation on 
Alternative Test Methods (ICATM, http://ntp.niehs.nih.gov/go/40113), 
through which ICCVAM and NICEATM help eliminate redundancy in 
validation studies sponsored by ICATM partners and promote 
harmonization in the resultant test method recommendations.
     Communication with trade associations and non-government 
organizations (e.g., Cosmetics Europe) to receive information regularly 
on efforts toward evaluation of alternative test methods for skin 
sensitization that cover key events in the AOP and data integration for 
hazard identification and potency assessment.
    ICCVAM's Proposed Plans: ICCVAM's involvement with national and 
international efforts (see Background above) is consistent with its 
goal to advance the state of the science for alternative test methods 
and testing strategies for skin sensitization. ICCVAM is developing a 
plan of action to augment and support this goal and, as such, is 
considering the following activities:
     Holding implementation workshops and webinars, and 
developing guidance documents to promote the use of validated test 
methods and testing strategies for skin sensitization.
     Participating in OECD skin sensitization activities to 
ensure that new and relevant test guidelines and guidances meet U.S. 
regulatory requirements as well as foster cross-fertilization between 
domestic and international research efforts in skin sensitization.
     Participating in validation management groups sponsored by 
ICATM partner organizations to ensure that the relevant validation 
studies for skin sensitization test methods and strategies meet U.S. 
regulatory needs as well as those of the sponsoring country.
     Providing expertise, data, and other resources when 
feasible to support NICEATM's efforts in the development of an 
integrated testing strategy for skin sensitizers.
     Evaluating alternative test method and testing strategy 
submissions for skin sensitization for reliability and relevance for 
the intended purpose.
     Consulting with organizations that are currently 
developing alternative test methods and testing strategies for skin 
sensitization to provide guidance that will increase U.S. regulatory 
acceptance.

[[Page 68077]]

     Encouraging developers of alternative test methods and 
testing strategies for skin sensitization to discuss their projects 
with ICCVAM and NICEATM to facilitate refinement of the methods to meet 
U.S. regulatory needs.
     Communicating information about the availability of 
funding or other resources to stakeholders that are developing 
alternative test methods and testing strategies for skin sensitization.
     Conducting, cosponsoring, and/or participating in 
workshops to review the state of the science and soliciting or 
providing input for future activities on development and validation of 
test methods and testing strategies for skin sensitization.
    Request for Comments: ICCVAM invites its stakeholders to consider 
the proposed activities identified above and provide comment on the 
following:
     The role that ICCVAM should play in the development and 
evaluation of alternative skin sensitization test methods and testing 
strategies.
     The potential contributions that regulated industries, 
nongovernment organizations, or other interested parties might make 
toward these efforts.
    Request for Information: As noted above, ICCVAM is developing plans 
to augment and support activities that will advance the state of the 
science for alternative skin sensitization test methods and testing 
strategies. As part of this process, ICCVAM is interested in receiving 
information on the state of the science regarding alternative test 
methods and testing strategies for skin sensitization and about 
activities of which ICCVAM may not be aware.
    Input Received: Information and comments in response to this notice 
can be submitted by email ([email protected]). Persons should 
include their name, affiliation (if applicable), mailing address, 
telephone, email, and sponsoring organization (if any) with their 
communications. The deadline for receipt of the requested information 
is December 9, 2013. Responses to this notice will be posted on the NTP 
Web site (http://ntp.niehs.nih.gov/go/40498) and persons submitting 
them will be identified by name and affiliation or sponsoring 
organization, if applicable. During development of its plan for 
advancing alternative skin sensitization test methods and testing 
strategies, ICCVAM will carefully consider the information and comments 
received in response to this notice and will also consult with ICATM 
partners and the OECD.
    Responses to this request are voluntary. No proprietary, 
classified, confidential, or sensitive information should be included 
in responses. This request for input is for planning purposes only and 
is not a solicitation for applications or an obligation on the part of 
the U.S. Government to provide support for any ideas identified in 
response to the request. Please note that the U.S. Government will not 
pay for the preparation of any information submitted or for its use of 
that information.
    Background Information on ICCVAM and NICEATM: ICCVAM is an 
interagency committee composed of representatives from 15 Federal 
regulatory and research agencies that require, use, generate, or 
disseminate toxicological and safety testing information. ICCVAM 
conducts technical evaluations of new, revised, and alternative safety 
testing methods and integrated testing strategies with regulatory 
applicability. ICCVAM also works to promote the scientific validation 
and regulatory acceptance of testing methods that more accurately 
assess the safety and hazards of chemicals and products and that 
replace, reduce, or refine (enhance animal well-being and lessen or 
avoid pain and distress) animal use. NICEATM provides scientific and 
operational support for ICCVAM and conducts independent validation 
studies and other activities to assess the usefulness and limitations 
of new, revised, and alternative test methods and strategies. ICCVAM 
and NICEATM welcome the public nomination of new, revised, and 
alternative test methods and strategies for validation studies and 
technical evaluations. Additional information about NICEATM and ICCVAM 
can be found on the NTP Web site at http://ntp.niehs.nih.gov/go/niceatm 
and http://ntp.niehs.nih.gov/go/iccvam.
    The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3) provides 
the authority for ICCVAM and NICEATM involvement in activities relevant 
to the development of alternative test methods. The ICCVAM 
Authorization Act established ICCVAM as a permanent interagency 
committee of the NIEHS under NICEATM. As stated in the ICCVAM 
Authorization Act, ICCVAM acts to ensure that new and revised test 
methods are validated to meet the needs of Federal agencies, increase 
the efficiency and effectiveness and Federal agency test method review, 
and optimize utilization of scientific expertise outside the Federal 
Government.

References

    Adler S, Basketter D, Creton S, et al. 2011. Alternative (non-
animal) methods for cosmetics testing: current status and future 
prospects-2010. Arch Toxicol 85: 367-485.
    OECD. 2012. OECD Series on Testing and Assessment No. 168. The 
Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent 
Binding to Proteins. Part 1: Scientific Assessment. Paris:OECD 
Publishing. Available: http://www.oecd.org/env/ehs/testing/seriesontestingandassessmentpublicationsbynumber.htm.

    Dated: November 6, 2013.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2013-27095 Filed 11-12-13; 8:45 am]
BILLING CODE 4140-01-P