[Federal Register Volume 77, Number 141 (Monday, July 23, 2012)]
[Notices]
[Pages 43087-43089]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-17788]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
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.
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SUMMARY: On behalf of the Interagency Coordinating Committee on the
Validation of Alternative Methods
[[Page 43088]]
(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.
SUPPLEMENTARY INFORMATION:
Background
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.
References
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]
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