[Federal Register Volume 77, Number 141 (Monday, July 23, 2012)]
[Pages 43087-43089]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-17788]



Nomination of an In Vitro Test Method for the Identification of 
Contact Allergens: Request for Comments and Data

AGENCY: Division of the National Toxicology Program (DNTP), National 
Institute of Environmental Health Sciences (NIEHS), National Institutes 
of Health (NIH).

ACTION: Request for Comments and Data.


SUMMARY: On behalf of the Interagency Coordinating Committee on the 
Validation of Alternative Methods

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(ICCVAM), the NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM) requests public comment on an ICCVAM 
test method nomination for validation studies. The validation studies 
are proposed to determine the usefulness and limitations of an in vitro 
test method to identify electrophilic substances that have the 
potential to produce allergic contact dermatitis (ACD). NICEATM also 
requests data generated using in vivo and in vitro test methods for 
assessing ACD hazard potential, including but not limited to guinea pig 
methods, the murine local lymph node assay, the direct protein 
reactivity assay, the human cell line activation test, and the 
KeratinoSens\TM\ assay. Data will be used to develop integrated testing 
and decision strategies that will also consider incorporation of the 
nominated test method following adequate validation studies.

DATES: Comments and test method data for assessing ACD hazard potential 
should be submitted by September 6, 2012. Comments and data submitted 
after this date will be considered in the evaluation where feasible.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director, 
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle 
Park, NC 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (email) 
niceatm@niehs.nih.gov. Courier address: NICEATM, NIEHS, Room 2034, 530 
Davis Drive, Morrisville, NC 27560.



    The development of alternatives to animal testing for ACD is an 
ICCVAM priority (ICCVAM, 2008). See http://iccvam.niehs.nih.gov/methods/immunotox/immunotox.htm for more information on ICCVAM 
evaluations of ACD test methods.

Test Method Nomination for Validation Studies

    An essential first step in the adverse outcome pathway for skin 
sensitization is the binding of a potential sensitizer to a dermal 
protein (Karlberg et al., 2008). Chipinda and co-workers described a 
rapid screening assay for substances that might react with proteins 
using the substance nitrobenzenethiol, which contains a reactive thiol 
group found in proteins, as a probe (Chipinda et al., 2010). 
Subsequently, a second probe, pyridoxalamine, was added to enable 
accurate detection of potential sensitizers that react with amine 
groups found in proteins. Covalent binding of the test substance to the 
probe is monitored by loss of absorbance or fluorescence. The modified 
assay identifies electrophilic skin sensitizers, but not prohaptens, 
which must be metabolized for skin sensitizing activity. The advantages 
of this assay include (1) The ability to obtain results using low test 
chemical concentrations, which reduces solubility problems; (2) the 
ability to run the assay without specialized equipment such as a high 
performance liquid chromatograph, a flow cytometer, or a mass 
spectrometer; the assays require only a simple spectrophotometer and 
fluorometer; (3) low cost; and (4) rapid results (assay time is less 
than half a day).
    Once validation criteria have been appropriately addressed through 
validation studies, this method may have the potential to meet 
regulatory requirements for identifying skin sensitizers in a range of 
applications as a screening test and as a component of an integrated 
testing and decision strategy. The test developer from the National 
Institute of Occupational Safety and Health submitted a nomination 
requesting that NICEATM and ICCVAM evaluate this method as a screening 
assay for identification of contact allergens, and proposes 
collaborations with NICEATM to conduct validation studies and determine 
the most appropriate decision criteria to maximize the sensitivity and 
specificity of the in chemico assay. The cover letter for the 
nomination can be viewed on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/SuppDocs/submission.htm#nomination).

Draft ICCVAM Priority and Draft Recommended Activities

    Based on the information provided by the test method developer and 
consideration of the ICCVAM prioritization criteria, ICCVAM considers 
that the nomination is of sufficient interest and applicability to 
warrant validation studies to characterize its usefulness and 
limitations for predicting ACD potential of chemicals and products. 
ICCVAM's draft position is that the nomination should have a high 
priority for the proposed studies. The ICCVAM preliminary evaluation of 
the method can be viewed on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/methods/immunotox/EASA.htm). ICCVAM proposed 
contributions to such studies would include review and comments on: (1) 
The optimization and standardization of the test method protocol, (2) 
the validation study design, and (3) reference chemical selection for 
the validation study. Federal agency programs will consider the 
nomination priority and recommended activities in determining potential 
support for validation activities.
    As part of the nomination review process, NICEATM invites public 
comments on the relative draft priority assigned by ICCVAM and the 
appropriateness of the proposed activities. ICCVAM will finalize its 
recommendations on the priority and activities for this nomination 
after considering comments received from the public and the Scientific 
Advisory Committee on Alternative Toxicological Methods (SACATM), which 
will comment on the ICCVAM draft recommendations at its meeting on 
September 5-6, 2012. Information about the SACATM meeting is available 
on the NTP Web site (http://ntp.niehs.nih.gov/go/32822).

Background Information on ICCVAM, NICEATM, and SACATM

    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 and promotes the scientific validation and 
regulatory acceptance of test methods that more accurately assess the 
safety and hazards of chemicals and products and that reduce, refine 
(enhance animal well-being and lessen or avoid pain and distress), or 
replace animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 
285l-3) established ICCVAM as a permanent interagency committee of the 
NIEHS under NICEATM. NICEATM administers ICCVAM, provides scientific 
and operational support for ICCVAM-related activities, and conducts 
independent validation studies to assess the usefulness and limitations 
of new, revised, and alternative test methods and strategies. NICEATM 
and ICCVAM welcome the public nomination of new, revised, and 
alternative test methods and strategies for validation studies and 
technical evaluations. Additional information about ICCVAM and NICEATM 
can be found on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).
    SACATM was established in response to the ICCVAM Authorization Act 
[Section 285l-3(d)] and is composed of scientists from the public and 
private sectors. SACATM advises ICCVAM, NICEATM, and the Director of 
the NIEHS and NTP regarding statutorily

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mandated duties of ICCVAM and activities of NICEATM. SACATM provides 
advice on priorities and activities related to the development, 
validation, scientific review, regulatory acceptance, implementation, 
and national and international harmonization of new, revised, and 
alternative toxicological test methods. Additional information about 
SACATM, including the charter, roster, and records of past meetings, 
can be found at http://ntp.niehs.nih.gov/go/167.


Chipinda I, Ajibola RO, Morokinyo MK, Ruwona TB, Simoyi RH, Siegel 
PD. 2010. Rapid and simple kinetics screening assay for 
electrophilic dermal sensitizers using nitrobenzenethiol. Chem Res 
Toxicol 23: 918-925.
ICCVAM. 2008. The NICEATM-ICCVAM Five-Year Plan (2008-2012): A Plan 
to Advance Alternative Test Methods of High Scientific Quality to 
Protect and Advance the Health of People, Animals, and the 
Environment. NIH Publication No. 08-6410. Research Triangle Park, 
NC: NIEHS. Available: http://iccvam.niehs.nih.gov/docs/5yearplan.htm.
Karlberg A-T, Bergstr[ouml]m MA, B[ouml]rje A, Luthman, K, Nilsson 
JLG. 2008. Allergic Contact Dermatitis--Formation, Structural 
Requirements, and Reactivity of Skin Sensitizers. Chem Res Toxicol 
21: 53-69.

    Dated: July 11, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-17788 Filed 7-20-12; 8:45 am]