[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