[Federal Register Volume 77, Number 237 (Monday, December 10, 2012)]
[Rules and Regulations]
[Pages 73286-73289]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-29260]
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CONSUMER PRODUCT SAFETY COMMISSION
[Docket No. CPSC-2012-0037]
16 CFR Part 1500
Codification of Animal Testing Policy
AGENCY: Consumer Product Safety Commission.
ACTION: Final rule.
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SUMMARY: The Consumer Product Safety Commission (CPSC or Commission)
codifies its statement of policy on animal testing that provides
guidance for manufacturers of products subject to the Federal Hazardous
Substances Act (FHSA) regarding replacement, reduction, and refinement
of animal testing methods.
DATES: Effective January 9, 2013.
FOR FURTHER INFORMATION CONTACT: Leslie E. Patton, Ph.D., Project
Manager, Office of Hazard Identification and Reduction, U.S. Consumer
Product Safety Commission, 4330 East West Highway, Bethesda, MD 20814;
telephone (301) 504-7848; lpatton@cpsc.gov.
SUPPLEMENTARY INFORMATION:
A. Background
On June 29, 2012, the Commission issued a notice of proposed
rulemaking to amend regulations on the CPSC's animal testing methods
under 16 CPR part 1500 to clarify alternative test methods that
replace, reduce, or refine animal testing. 77 FR 38754. The final rule
on the Commission's regulations on animal testing under 16 CFR part
1500 is published elsewhere in this Federal Register. The final rule on
revisions to the animal testing regulations is effective 30 days after
publication of the rule in the Federal Register.
In addition, on June 29, 2012, the Commission also proposed to
codify its statement of policy on animal testing to reflect new methods
accepted by the scientific community as replacements, reductions, or
refinements to animal tests including recommendations of and test
methods of the Interagency Coordinating Committee on the Validation of
Alternative Methods (ICCVAM; http://iccvam.niehs.nih.gov/home.htm). 77
FR 38751. Codification at 16 CFR 1500.232 would make the ICCVAM
recommendations and Commission's animal testing policy more accessible
and transparent to interested parties. Although the Commission proposed
to make the animal testing policy effective on the date of publication
in the Federal Register, because the animal testing policy references
sections of the animal testing regulations in 16 CFR part 1500, we will
make the statement of policy effective on the same date, 30 days after
publication of the policy in the Federal Register. The Commission has
also established a Web page on the CPSC's Web site at http://www.cpsc.gov/library/animaltesting.html regarding the ICCVAM
recommendations and new developments in test methods that replace,
reduce, or refine animal testing. After consideration of the comments,
the Commission codifies its final statement of policy on animal
testing.
[[Page 73287]]
B. Response to Comments on the Proposed Policy
In the Federal Register of June 29, 2012, we published a proposed
statement of policy on animal testing (77 FR 38751). We received two
comments on the proposed statement. One commenter was an individual and
the other comment was submitted jointly by the Alternatives Research
and Development Foundation, American Anti-Vivisection Society, Humane
Society of the United States, People for the Ethical Treatment of
Animals, and the Physicians Committee for Responsible Medicine. Both
commenters support the use of alternative test methods to eliminate or
reduce the use of animals.
1. Alternative Test Methods
Comment: One commenter states that alternative test methods
approved for testing potentially hazardous substances were too limited
as laid out in the Commission's proposal, and requests that the CPSC
broaden its recommendations to in vitro and in silico tests beyond
those already approved by the Commission through ICCVAM. Specifically,
the commenter recommends adding methods that were already approved by
other regulatory bodies, such as the Organisation for Economic
Cooperation and Development (OECD) or the European Centre for the
Validation of Alternative Methods (ECVAM EURL). The commenter further
suggests that Sec. 1500.232(b) should include any ``scientifically
acceptable'' non-animal alternative that is ``fit for the purpose,''
not limited to those expressly approved by the Commission, nor to those
that had undergone an official regulatory validation process.
Response: The Commission agrees that alternatives outside of those
which ICCVAM has approved may be acceptable for hazard testing. For
hazard testing for the purpose of labeling under FHSA, alternative test
methods beyond those reviewed and recommended by ICCVAM may be
acceptable because ICCVAM's purview is not exhaustive. In addition,
data derived from scientifically valid testing methods can be used to
make hazard determinations for substances regulated under FHSA,
assuming tests are reliable, reproducible, and accurate. The Commission
encourages hazard testing that supports the replacement, reduction, and
refinement of animal test methods while simultaneously maintaining a
high degree of scientific integrity. Therefore, if a manufacturer or
other entity performs a hazard test for FHSA labeling purposes that has
not been previously approved by the Commission (i.e., an ICCVAM-
recommended test method or one of the tests described in the current
version of the FHSA), CPSC staff will consider the data on a case-by-
case basis and, upon review, determine whether to post the test method
on the animal testing Web site.
In the final statement of policy, we refer to in vitro and in
silico methods, in general, as alternative test methods that a
manufacturer may wish to consider in lieu of animal testing. We also
refer generally to methods that have been deemed acceptable by other
national or international organizations, but do not refer to them
specifically in the regulations on animal testing under 15 CFR 1500.3,
1500.40-42. The CPSC animal testing Web page at http://www.cpsc.gov/library/animaltesting.html is the platform on which the CPSC will list
alternative methods.
Comment: One commenter states that the guidance should explicitly
state that ``when faced with a decision between a non-animal or animal-
based approach, the non-animal approach must be taken.''
Response: Although the Commission is issuing this guidance in part
to encourage non-animal alternatives to testing, it cannot require
manufacturers to adhere to its guidelines. As stated in the CPSC
Chronic Hazard Guidelines (57 FR 46626, October, 9, 1992), the
Commission does not enforce guidelines as mandatory requirements for
manufacturers. A manufacturer may follow a different but scientifically
supportable analysis to determine the potential hazard of a substance
as reflected in the alternative test methods posted on the CPSC animal
testing Web page at http://www.cpsc.gov/library/animaltesting.html.
2. In Vivo Tests
Comment: One commenter requests that all details on in vivo testing
procedures be deleted from Sec. 1500.232, including the LD50/LC50
assays at 1500.232(b)(1)(i), the method of testing dermally toxic
substances at 1500.232(b)(1)(ii), and the ocular irritation assay at
1500.232(b)(1)(iii).
Response: The FHSA currently defines acute hazards based on animal
test results and identifies irritation and toxicity tests that use
animals. Although they are not superior, these in vivo test methods
remain the baseline to which alternative methods are compared and
therefore should remain in the text. Furthermore, the in vivo testing
described in sections of CFR part 1500 does remain an option to
manufacturers performing hazard testing of substances. However, the
Commission will emphasize that the use of in vitro and other
alternative test methods, including a weight-of-evidence approach, and
prior human experience are recommended over in vivo tests whenever
possible throughout the statement of policy. Furthermore, the
Commission reiterates its preference for reliable human experience over
animal test data. These changes are reflected throughout the summary
and statement of policy.
3. Dermal Sensitization Test
Comment: One commenter requests the addition of section
1500.232(b)(1)(iv) on alternative test methods for dermal sensitization
testing.
Response: The Commission agrees and will add the following section
to the statement of animal testing policy:
Dermal sensitization--An acceptable in vitro test method
(examples of valid in vitro tests are identified on the Commission's
animal testing Web site at: http://www.cpsc.gov/library/animaltesting.html), or weight-of-evidence analysis is recommended
before in vivo animal sensitization testing is considered to
determine appropriate cautionary labeling. The weight-of-evidence
analysis should incorporate any existing data on humans and animals,
validated in vitro or in silico test results and any other relevant
physicochemical properties that indicate the substance might be a
dermal sensitizer. If there is any indication from this analysis
that the substance is sensitizing to the skin, the substance should
be labeled appropriately.
4. Other Comments
Comment: One commenter requests that we reorder the paragraphs in
Sec. 1500.232(a) to ensure that manufacturers first consider the most
human-relevant data and methods in determining appropriate labeling
Response: The Commission has already stated a preference for human
over animal data throughout the statement of policy, and will maintain
the current order of the paragraphs in the animal testing policy.
List of Subjects in 16 CFR Part 1500
Consumer protection, Hazardous substances, Imports, Infants and
children, Labeling, Law enforcement, Reporting and recordkeeping
requirements, and Toys.
For the reasons given above, the Commission amends 16 CFR part 1500
as follows:
PART 1500--[AMENDED]
0
1. The authority for part 1500 continues to read as follows:
[[Page 73288]]
Authority: 15 U.S.C. 1261-1278, 122 Stat. 3016.
0
2. Add Sec. 1500.232 to read as follows:
Sec. 1500.232 Statement on animal testing policy.
(a) Summary. (1) The U.S. Consumer Product Safety Commission issues
this statement of policy on animal testing and alternatives to animal
testing of hazardous substances regulated under the Federal Hazardous
Substances Act (FHSA). The FHSA requires appropriate cautionary
labeling on certain hazardous household products to alert consumers to
the potential hazard(s) that the products may present. Among the
hazards addressed by the FHSA are toxicity, corrosivity, sensitization,
and irritation.
(2) In order to determine the appropriate cautionary labeling, it
is necessary to have objective criteria by which the existence of each
hazard can be determined. Hazards such as toxicity, tissue
corrosiveness, eye irritancy, and skin irritancy result from the
biological response of living tissue and organs to the presence of the
hazardous substance. One means of characterizing these hazards is to
use animal testing as a proxy for the human reaction. In fact, the FHSA
defines the hazard category of ``highly toxic'' in terms of animal
toxicity when groups of 10 or more rats are exposed to specified
amounts of the substance. The Commission's regulations under the FHSA
concerning toxicity and irritancy allow the use of animal tests to
determine the presence of the hazard when human data or existing animal
data are not available.
(3) Neither the FHSA nor the Commission's regulations requires
animal testing. The FHSA and its implementing regulations only require
that a product be labeled to reflect the hazards associated with that
product. If animal testing is conducted, Commission policy supports
limiting such tests to a minimum number of animals and advocates
measures that eliminate or reduce the pain or discomfort to animals
that can be associated with such tests. The Commission has prepared
this statement of policy with respect to animal testing to encourage
the manufacturers subject to the FHSA to follow a similar policy.
(4) In making the appropriate hazard determinations, manufacturers
of products subject to the FHSA should use existing alternatives to
animal testing whenever possible. These include: prior human experience
(e.g., published case studies), in vitro or in silico test methods that
have been approved by the Commission, literature sources containing the
results of prior animal testing or limited human tests (e.g., clinical
trials, dermal patch testing), and expert opinion (e.g., hazard
assessment, structure-activity analysis). If a manufacturer or other
entity performs a hazard test for FHSA labeling purposes that has not
been previously approved by the Commission, CPSC staff will consider
the data on a case-by-case basis and, upon review, determine whether to
post the test method on the animal testing Web site. The Commission
recommends resorting to animal testing only when the other information
sources have been exhausted. At this time, the Commission recommends
use of the most humane procedures with the fewest animals possible to
achieve reliable results. Recommended procedures are summarized in the
following statement and can be accessed on the Commission's Web page
at: http://www.cpsc.gov/library/animaltesting.html. If a manufacturer
or other entity performs a hazard test for FHSA labeling purposes that
has not been previously approved by the Commission (e.g., an ICCVAM-
recommended test method or one of the tests described in the current
version of the FHSA), CPSC staff will consider the data on a case-by-
case basis and, upon review, determine whether to post the test method
on the animal testing Web site.
(b) Statement of policy on animal testing. (1) Neither the FHSA nor
the Commission's regulations requires animal testing. Reliable human
experience always takes precedence over results from animal data. In
the cases where animal tests are conducted, the Commission prefers test
methods that reduce stress and suffering in test animals and that use
fewer animals while maintaining scientific integrity. To this end, the
Commission reviews recommendations on alternative test methods
developed by the scientific and regulatory communities. Current
descriptions of test method recommendations approved by or known to the
Commission can be accessed via the Internet at: http://www.cpsc.gov/library/animaltesting.html. The Commission strongly supports the use of
scientifically sound alternatives to animal testing. The following
parts of this section outline some of these alternatives. Testing
laboratories and other interested persons requiring assistance
interpreting the results obtained when a substance is tested in
accordance with the methods described here, or in following the testing
strategies outlined in the section, should refer to the Commission's
animal testing Web page at: http://www.cpsc.gov/library/animaltesting.html.
(i) Acute toxicity. The traditional FHSA animal test for acute
toxicity determines the median lethal dose (LD50) or lethal
concentration (LC50), the dose or concentration that is expected to
kill half the test animals. Procedures for determining the median LD50/
LC50 are described in section 2(h)(1) of the Act and supplemented in
Sec. 1500.3(c)(1) and (2) and the test method outlined in Sec.
1500.40. The Commission recommends in vitro alternatives over in vivo
LD50/LC50 tests, or using modifications of the traditional LD50/LC50
test during toxicity testing that reduce the number of animals tested
whenever possible. Data from in vitro or in silico test methods that
have not been approved by the Commission may be submitted to the
Commission for consideration of their acceptability. Commission-
approved testing alternatives are identified on the Web site at: http://www.cpsc.gov/library/animaltesting.html and include:
(A) In vitro and in vivo test methods that have been scientifically
validated and approved for use in toxicity testing by the Commission;
(B) Valid in vitro methods to estimate a starting dose for an acute
in vivo test;
(C) A sequential version of the traditional LD50/LC50 tests
described in Sec. 1500.3(c)(1) and (2) and the test method described
in Sec. 1500.40, in which dose groups are run successively rather than
simultaneously;
(D) A limit-dose test where the LD50/LC50 is determined as a point
estimate, which can still be used to categorize a hazard, although it
gives no information on hazard dose-response. In the limit test,
animals (10 rats) each receive a single dose of product at 5g per
kilogram of body weight. If not more than one animal dies in 14 days,
the product is considered to have an LD50 of greater than 5g/kg, and
thus, deemed to be nontoxic. Only if two or more animals die is a
second group of 10 rats tested (at a lower dose). This procedure
reduces the number of animals tested from the 80 to 100 animals
involved in a full LD50 test to, typically, 10 to 20 rats per product.
This reduction in the number of animals tested is justified because an
exact LD50 is not required by either the FHSA or the regulations. The
FHSA requires only a categorical determination that the toxicity is
greater than 5g/kg, between 50 mg/kg and 5g/kg, or less than 50 mg/kg.
(ii) Dermal irritation/corrosivity. An acceptable in vitro test
method or weight-of-evidence analysis is
[[Page 73289]]
recommended before in vivo dermal irritation testing is considered to
determine appropriate cautionary labeling. The weight-of-evidence
analysis should incorporate any existing data on humans and animals,
validated in vitro or in silico test results (valid tests are
identified on the Commission's animal testing Web site at: http://www.cpsc.gov/library/animaltesting.html), the substance's dermal
toxicity, evidence of corrosivity/irritation of one or more
structurally related substances or mixtures of such substances, data
demonstrating low or high pH (<=2 or >=11.5) of the substance, and any
other relevant physicochemical properties that indicate the substance
might be a dermal corrosive or irritant. If there is any indication
from this analysis that the substance is either corrosive or irritating
to the skin, the substance should be labeled appropriately. If the
substance is not corrosive in vitro, but no data exist regarding its
irritation potential, human patch testing should be considered. If in
vitro data are unavailable, human patch testing is not an option, and
there are insufficient data to determine the weight-of-evidence, a
tiered in vivo animal test is recommended.
(A) In a tiered in vivo dermal study, a single rabbit is tested
initially. If the outcome is positive for corrosivity, testing is
stopped, and the substance is labeled appropriately. If the substance
is not corrosive, two more rabbits should be patch-tested to complete
the assessment of skin irritation potential.
(B) If a tiered test is not feasible, the Commission recommends the
test method described in Sec. 1500.41. Note that in any in vivo dermal
irritation test method, the Commission recommends using a semiocclusive
patch to cover the animal's test site and eliminating the use of stocks
for restraint during the exposure period, thereby allowing the animal
free mobility and access to food and water.
(iii) Ocular irritation. A weight-of-evidence analysis is
recommended to evaluate existing information before any in vivo ocular
irritation testing is considered. This analysis should incorporate any
existing data on humans and animals, validated in vitro or in silico
test data (identified on the Commission's animal testing Web site at:
http://www.cpsc.gov/library/animaltesting.html), the substance's dermal
corrosivity/irritation (primary skin irritants and corrosives are also
usually eye irritants and therefore do not need to be tested in the
eye), evidence of ocular irritation of one or more structurally related
substances or mixtures of such substances, data demonstrating high
acidity or alkalinity of the substance, and any other relevant
physicochemical properties that indicate the substance might be a
dermal corrosive or irritant or ocular irritant.
(A) When the weight-of-evidence is insufficient to determine a
substance's ocular irritation, a Commission-approved in vitro or in
silico assay for ocular irritancy should be run to assess eye
irritation potential and determine labeling. Examples of Commission-
validated in vitro assays are identified on the Commission's animal
testing Web site at: http://www.cpsc.gov/library/animaltesting.html).
If no valid in vitro test exists, the test strategy for determining
dermal corrosion/irritation outlined in paragraph (b)(1)(ii)(B) of this
section can be followed to determine ocular irritation.
(B) If the dermal test strategy outlined in section paragraph
(b)(1)(ii)(B) of this section leads to a conclusion of not corrosive, a
tiered in vivo ocular irritation test should be performed, in which a
single rabbit is exposed to the substance initially. If the outcome of
this initial test is positive, testing is stopped, and the substance is
labeled an eye irritant. If the outcome of this initial test is
negative, one to two more rabbits are tested for ocular irritation, and
the outcome of this test will determine the label. If a tiered test is
not feasible, the Commission recommends the test method described in
Sec. 1500.42.
(C) When any ocular irritancy testing on animals is conducted,
including the method described in Sec. 1500.42, the Commission
recommends a threefold plan to reduce animal suffering: The use of
preemptive pain management, including topical anesthetics and systemic
analgesics that eliminate or reduce suffering that may occur as a
result of the application process or from the test substance itself (an
example of a typical preemptive pain treatment is two applications of
tetracaine ophthalmic anesthetic, 10-15 minutes apart, prior to
instilling the test material to the eye); post-treatment with systemic
analgesics for pain relief; and implementation of humane endpoints,
including scheduled observations, monitoring, and recording of clinical
signs of distress and pain, and recording the nature, severity, and
progression of eye injuries. The specific techniques that have been
approved by the Commission can be found at: http://www.cpsc.gov/library/animaltesting.html.
(iv) Dermal sensitization. An acceptable in vitro test method
(examples of valid in vitro tests are identified on the Commission's
animal testing Web site at: http://www.cpsc.gov/library/animaltesting.html), or weight-of-evidence analysis is recommended
before in vivo animal sensitization testing is considered to determine
appropriate cautionary labeling. The weight-of-evidence analysis should
incorporate any existing data on humans and animals, validated in vitro
or in silico test results, and any relevant physicochemical properties
that indicate the substance might be a dermal sensitizer. If there is
any indication from this analysis that the substance is sensitizing to
the skin, the substance should be labeled appropriately.
(2) [Reserved].
Dated: November 29, 2012.
Todd A. Stevenson,
Secretary, Consumer Product Safety Commission.
[FR Doc. 2012-29260 Filed 12-7-12; 8:45 am]
BILLING CODE 6355-01-P