Hazardous Substances and Articles; Administration and Enforcement Regulations: Revisions to Animal Testing Regulations, 73289-73294 [2012-29258]

Agencies

• Consumer Product Safety Commission

[Federal Register Volume 77, Number 237 (Monday, December 10, 2012)]
[Rules and Regulations]
[Pages 73289-73294]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-29258]


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CONSUMER PRODUCT SAFETY COMMISSION

[CPSC Docket No. CPSC-2012-0036]

16 CFR Part 1500


Hazardous Substances and Articles; Administration and Enforcement 
Regulations: Revisions to Animal Testing Regulations

AGENCY: Consumer Product Safety Commission.

ACTION: Final rule.

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SUMMARY: The U.S. Consumer Product Safety Commission (CPSC or 
Commission) amends regulations on the CPSC's animal testing methods 
under the Federal Hazardous Substances Act (FHSA).

DATES: This rule is effective on 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

    The Federal Hazardous Substances Act (FHSA), 15 U.S.C. 1261-1278, 
requires appropriate cautionary labeling on certain hazardous household 
products to alert consumers to the potential hazards that a product may 
present. Among the hazards addressed

[[Page 73290]]

by the FHSA are products that are toxic, corrosive, irritants, 
flammable, combustible, or strong sensitizers. The FHSA and the 
Commission regulations at 16 CFR part 1500 provide certain definitions 
and test methods related to testing on animals to determine the 
existence of the hazards addressed by the FHSA.
    On June 29, 2012, the Commission issued a notice of proposed 
rulemaking to amend and to update regulations on the CPSC's animal 
testing methods under the FHSA. 77 FR 38754. The Commission proposed 
amendments to the regulations that interpret, supplement, or provide 
alternatives to definitions of animal test methods used to aid in the 
classification of hazardous substances under the FHSA.
    In addition, on June 29, 2012, the Commission 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 and test methods 
of the Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM; https://iccvam.niehs.nih.gov/home.htm) 
approved by the Commission. 77 FR 38751. The proposed codification at 
16 CFR 1500.232 would make the ICCVAM recommendations and the 
Commission's animal testing policy more accessible and transparent to 
interested parties. The Commission has also established a Web page on 
the CPSC's Web site at https://www.cpsc.gov/library/animaltesting.html 
regarding the ICCVAM recommendations and new developments in test 
methods that avoid or further reduce or refine animal testing. The 
final statement on the CPSC's animal testing policy is published 
elsewhere in this Federal Register.

B. Response to Comments on the Proposed Rule

    In the Federal Register of June 29, 2012, we published a proposed 
rule on revisions to the animal testing regulations (77 FR 38754). We 
received three comments on the proposed rule. Two of the comments were 
from individuals and the third 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.

1. Non-animal Testing Alternatives

    Comment: All three commenters urge the Commission to more strongly 
consider non-animal testing alternatives. One commenter suggests that 
the NPR underemphasizes in vitro and in silico alternatives to animal 
testing throughout relevant sections of 16 CFR part 1500. The commenter 
gives examples of in vitro tests to support this assertion.
    Response: The Commission agrees that in vitro and in silico tests 
should be mentioned in the regulation as general options in a testing 
strategy and the rule has been revised accordingly.

2. Alternatives

    Comment: One commenter notes that the Commission's stated 
preference for human data/experience over animal testing results is not 
referenced in the relevant sections of 16 CFR part 1500. The commenter 
also provides a number of examples where in vivo test methods were 
detailed while the preference for alternatives was mentioned only 
briefly.
    Response: The FHSA direct that reliable human experience data take 
precedence over differing results from animal tests. 15 U.S.C. 
1261(h)(2). Therefore, the Commission would always consider human 
experience with products and substances first, when it exists, followed 
by a thorough examination of the existing animal database. The 
Commission likewise recommends this approach to manufacturers who are 
labeling substances to indicate a hazard. Accordingly, the proposed 
rule has been revised to make the preference for human data clearer in 
the regulatory text.

3. In Vivo Testing

    Comment: One commenter suggests that the regulations uncouple 
definitions of toxic effects from specific animal test results and that 
these animal tests are ``enumerated with such detail as part of the 
definition [as to be] problematic.'' The commenter urges the Commission 
to remove nearly all references to the in vivo tests that comprise the 
existing text of 16 CFR 1500.3(c)(1-4), 1500.40, 1500.41, and 1500.42.
    Response: The Commission disagrees that the hazard definitions 
using animal test methods are problematic. The test methods currently 
described in the FHSA and relevant sections of 16 CFR part 1500 are 
intended to show how the Commission would make a hazard determination 
in the absence of human experiential data, existing animal data, or 
another acceptable alternative, and are not mandatory or even 
necessarily recommended test methods for manufacturers. These methods 
set a baseline standard for hazard testing against which alternative 
tests can be compared for validity and reliability. They serve as the 
baseline because they have been used traditionally in hazard testing, 
not because they are considered superior to other methods. Therefore, 
while we understand the need to be clear on the discretionary nature of 
in vivo testing, these methods cannot be removed from the regulations 
altogether. However, the proposed rule has been revised to emphasize 
the use of in vitro and other alternative test methods and prior human 
experience throughout the relevant sections of 16 CFR part 1500.
Other Comments
    Comment: One commenter states that CPSC's animal testing guidelines 
Web site should not be limited to listing ICCVAM test methods, but 
should include new methods than can replace animal-based tests. In 
addition, this commenter requests that the Web site contain a process 
that would allow the public to propose changes to the test methods on 
the Web site.
    Response: We address these comments in further detail in response 
to the comments on the Final Statement on Animal Testing Policy 
published elsewhere in this Federal Register. In that policy statement 
we indicate that alternative test methods beyond those reviewed and 
recommended by ICCVAM may be acceptable. 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 FHSA), the 
CPSC staff will review such data on a case-by-case basis before it will 
post any changes on the animal testing policy Web site. Although the 
Commission welcomes input from the public regarding new test methods, 
proposed changes to the test methods will be posted on the animal 
testing guidelines Web page only after review of the data regarding the 
proposed test method by CPSC staff.

C. Revisions to Animal Testing Regulations

    1. Definition of highly toxic. Currently, the test methods in Sec.  
1500.3(c)(1)(ii)(A) through (C), used in the definitions of oral, 
inhalation, and dermal toxicity, respectively, each describe a method 
for defining a substance as highly toxic.
    Because there are other Commission-approved test methods that may 
be used

[[Page 73291]]

by CPSC staff or the public for toxicity testing and defining a 
substance as highly toxic, as reflected in the ICCVAM recommendations 
and outlined in the CPSC's statement of policy on animal testing 
published elsewhere in this Federal Register, the proposed rule added 
language (in underline) under new Sec.  1500.3(c)(1)(iii) as follows: A 
substance that produces a result of `highly toxic' in any of the 
approved test methods described in the CPSC's animal testing policy set 
forth in 16 CFR 1500.232.
    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule provides additional 
language (in underline) to Sec.  1500.3(c)(1) as follows:

    To provide flexibility as to the number of animals tested, and 
to emphasize in vitro testing methods, the following is an 
alternative to the definition of ``highly toxic'' in section 2(h) of 
the act (and paragraph (b)(6) of this section).

In addition, the final rule provides additional language (in underline) 
to Sec.  1500.3(c)(1)(iii) as follows:

    A substance that produces a result of `highly toxic' in any of 
the approved test methods described in the CPSC's animal testing 
policy set forth in 16 CFR 1500.232, including data from in vitro or 
in silico test methods that the Commission has approved; or a 
validated weight-of-evidence analysis comprising all of the 
following that are available: existing human and animal data, 
structure activity relationships, physicochemical properties, and 
chemical reactivity data.

    2. Definition of toxic. Currently, the test methods in Sec.  
1500.3(c)(2)(i)(A) through (C) used in the definitions of oral, 
inhalation, and dermal toxicity, respectively, each describe a method 
for defining a substance as toxic.
    Because there are other Commission-approved test methods that may 
be used by CPSC staff or the public for toxicity testing and defining a 
substance as toxic, as reflected in the ICCVAM recommendations, and 
outlined in the CPSC's statement of policy on animal testing, the 
proposed rule added language (in underline) under new Sec.  
1500.3(c)(2)(iii) as follows:

    Toxic also applies to any substance that can be labeled as such, 
based on the outcome of any of the approved test methods described 
in the CPSC's animal testing policy set forth in 16 CFR 1500.232.

    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule provides additional 
language (in underline) to Sec.  1500.3(c)(2) as follows:

    To give specificity to the definition of ``toxic'' in section 
2(g) of the act (and restated in paragraph (b)(5) of this section), 
the following supplements that definition. ``Toxic'' applies to any 
substance that is ``toxic'' (but not ``highly toxic'') on the basis 
of human experience. The following categories are not intended to be 
inclusive.

    In addition, in the final rule, the Commission is moving the text 
from proposed section (iii) to section (i) to more accurately reflect 
that the text applies to the section on acute toxicity, rather than to 
create a separate section. Accordingly, the last sentence in Sec.  
1500.3(c)(2)(i) has been revised (in underline) as follows:

    Toxic also applies to any substance that can be labeled as such, 
based on the outcome of any of the approved test methods described 
in the CPSC's animal testing policy set forth in 16 CFR 1500.232, 
including data from in vitro or in silico test methods that the 
Commission has approved; or a validated weight-of-evidence analysis 
comprising all of the following that are available: existing human 
and animal data, structure activity relationships, physicochemical 
properties, and chemical reactivity data.

    3. Definition of corrosive. 16 CFR 1500.3(c)(3) currently states 
that: Corrosive means ``a substance that causes visible destruction or 
irreversible alterations in the tissue at the site of contact. A test 
for a corrosive substance is whether, by human experience, such tissue 
destruction occurs at the site of application. A substance would be 
considered corrosive to the skin if, when tested on the intact skin of 
the albino rabbit by the technique described in Sec.  1500.41, the 
structure of the tissue at the site of contact is destroyed or changed 
irreversibly in 24 hours or less. Other appropriate tests should be 
applied when contact of the substance with other than skin tissue is 
being considered.''
    The proposed rule added the following text (in underline) to 16 CFR 
1500.3(c)(3):

    Corrosive means a substance that causes visible destruction or 
irreversible alterations in the tissue at the site of contact. A 
test for a corrosive substance is whether, by human experience, such 
tissue destruction occurs at the site of application. A substance 
would be considered corrosive to the skin if a weight-of-evidence 
analysis suggests that it is corrosive or if, when tested by the in 
vivo technique described in Sec.  1500.41, the structure of the 
tissue at the site of contact is destroyed or changed irreversibly 
in 24 hours or less. Other appropriate tests should be applied when 
contact of the substance with other than skin tissue is being 
considered. A substance could also be labeled corrosive based on the 
outcome of any of the approved test methods described in the CPSC's 
animal testing policy set forth in 16 CFR 1500.232.

    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule provides additional 
language (in underline) to Sec.  1500.3(c)(3) as follows:

    Corrosive means a substance that causes visible destruction or 
irreversible alterations in the tissue at the site of contact. A 
test for a corrosive substance is whether, by human experience, such 
tissue destruction occurs at the site of application. A substance 
would be considered corrosive to the skin if a weight-of-evidence 
analysis suggests that it is corrosive, or validated in vitro test 
method suggests that it is corrosive, or if, when tested by the in 
vivo technique described in Sec.  1500.41, the structure of the 
tissue at the site of contact is destroyed or changed irreversibly 
in 24 hours or less. Other appropriate tests should be applied when 
contact of the substance with other than skin tissue is being 
considered. A substance could also be labeled corrosive based on the 
outcome of any of the approved test methods described in the CPSC's 
animal testing policy set forth in 16 CFR 1500.232, including data 
from in vitro or in silico test methods that the Commission has 
approved; or a validated weight-of-evidence analysis comprising all 
of the following that are available: existing human and animal data, 
structure activity relationships, physicochemical properties, and 
chemical reactivity data.

    4. Definition of irritant, primary irritant, and eye irritant. 
Currently, 16 CFR 1500.3(c)(4) provides that the test methods for 
irritant, primary irritant, and eye irritant reference 16 CFR 1500.41 
and 1500.42, which each describe a specific animal test method and 
outcome. For example, 16 CFR 1500.41 states that primary irritation to 
the skin is measured by a patch-test technique on the abraded and 
intact skin of the albino rabbit, clipped free of hair. A minimum of 
six subjects are used in the skin tests. To test for eye irritants, 16 
CFR 1500.42 requires the use of six albino rabbits. Such tests require 
the test material be placed in one eye of each animal, while the other 
eye remains untreated, to serve as a control to assess the grade of 
ocular reaction.
    The proposed rule added the following language (in underline) to 
Sec.  1500.3(c)(4):

    The definition of irritant in section 2(j) of the act (restated 
in paragraph (b)(8) of this section) is supplemented by the 
following: Irritant includes primary irritant to the skin, as well 
as substances irritant to the eye or to mucous membranes. Primary 
irritant means a substance that is not corrosive and that human 
experience data indicate is a primary irritant; and/or means a 
substance that results

[[Page 73292]]

in an empirical score of five or more when tested by the method 
described in 1500.41; and/or a substance that can be considered a 
primary irritant based on the outcome of any of the approved test 
methods described in the CPSC's animal testing policy set forth in 
16 CFR 1500.232. Eye irritant means a substance that human 
experience data indicate is an irritant to the eye; and/or means a 
substance for which a positive test is obtained when tested by the 
method described in 1500.42; and/or means a substance that can be 
considered an eye irritant based on the outcome of any of the 
approved test methods described in the CPSC's animal testing policy 
set forth in 16 CFR 1500.232.

    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule provides additional 
language (in underline) to Sec.  1500.3(c)(4) as follows:

    The definition of irritant in section 2(j) of the act (restated 
in paragraph (b)(8) of this section) is supplemented by the 
following: Irritant includes primary irritant to the skin, as well 
as substances irritant to the eye or to mucous membranes. Primary 
irritant means a substance that is not corrosive and that human 
experience data indicate is a primary irritant; and/or means a 
substance that results in an empirical score of five or more when 
tested by the method described in Sec.  1500.41; and/or a substance 
that can be considered a primary irritant based on the outcome of 
any of the approved test methods described in the CPSC's animal 
testing policy set forth in 16 CFR 1500.232, including data from in 
vitro or in silico test methods that the Commission has approved; or 
a validated weight-of-evidence analysis comprising all of the 
following that are available: existing human and animal data, 
structure activity relationships, physicochemical properties, and 
chemical reactivity data. Eye irritant means a substance that human 
experience data indicate is an irritant to the eye; and/or means a 
substance for which a positive test is obtained when tested by the 
method described in 1500.42; and/or means a substance that can be 
considered an eye irritant based on the outcome of any of the 
approved test methods described in the CPSC's animal testing policy 
set forth in 16 CFR 1500.232, including data from in vitro or in 
silico test methods that the Commission has approved; or a validated 
weight-of-evidence analysis comprising all of the following that are 
available: existing human and animal data, structure activity 
relationships, physicochemical properties, and chemical reactivity 
data.

    5. Method of Testing Toxic Substances
    The method of testing toxic substances is set forth under 16 CFR 
1500.40. This method details an acute dermal toxicity assay using 
rabbits. The method is referenced in Sec.  1500.3(c)(1)(ii)(C) and 
(c)(2)(C). The proposed rule added the following text (in underline) to 
Sec.  1500.40 immediately after the heading titled, ``Method of testing 
toxic substances'':

    Guidelines for testing the toxicity of substances, including 
testing that does not require animals, are presented in the CPSC's 
animal testing policy set forth in 16 CFR 1500.232. A weight-of-
evidence analysis is recommended to evaluate existing information 
before in vivo tests are considered. This analysis, when deemed 
necessary to carry out, should include any of the following: 
existing human and animal data, in vitro data, structure activity 
relationships, physicochemical properties, and chemical reactivity. 
When in vivo testing is necessary, a sequential testing strategy is 
recommended to reduce the number of test animals.

    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule modifies the language (in 
underline) to Sec.  1500.40 as follows:

    Guidelines for testing the toxicity of substances, including 
testing that does not require animals, are presented in the CPSC's 
animal testing policy set forth in 16 CFR 1500.232. A weight-of-
evidence analysis, including any of the following: existing human 
and animal data, structure activity relationships, physicochemical 
properties; and chemical reactivity, or validated in vitro or in 
silico testing are recommended to evaluate existing information 
before in vivo tests are considered. If in vivo testing is 
conducted, a sequential testing strategy is recommended to reduce 
the number of test animals.

    6. Method of Testing Primary Irritant Substances
    The method of testing primary irritant substances is set forth 
under 16 CFR 1500.41. This method details an acute dermal toxicity 
assay using rabbits. The method is referenced in Sec.  1500.3(c)(3) and 
(4). The proposed rule added the following text (in underline) to Sec.  
1500.41 immediately after the heading titled, ``Method of testing 
primary irritant substances'':

    Guidelines for testing the dermal irritation and corrosivity 
properties of substances, including testing that does not require 
animals, are presented in the CPSC's animal testing policy set forth 
in 16 CFR 1500.232. A weight-of-evidence analysis is recommended to 
evaluate existing information before in vivo tests are considered. 
This analysis should include all of the following that are 
available: human and animal data, structure activity relationships, 
physicochemical properties, and dermal toxicity. When in vivo 
testing is necessary, a sequential testing strategy is recommended 
to reduce the number of test animals. The method of testing the 
dermal corrosivity and primary irritation of substances referred to 
in Sec.  1500.3(c)(3) and (4), respectively, is a patch-test 
technique on the abraded and intact skin of the albino rabbit, 
clipped free of hair* * *

    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule modifies the language (in 
underline) to Sec.  1500.41 as follows:

    Guidelines for testing the dermal irritation and corrosivity 
properties of substances, including testing that does not require 
animals, are presented in the CPSC's animal testing policy set forth 
in 16 CFR 1500.232. A weight-of-evidence analysis or a validated in 
vitro test method is recommended to evaluate existing information 
before in vivo tests are considered. This analysis should include 
all of the following that are available: human and animal data, 
structure activity relationships, physicochemical properties, and 
dermal toxicity. If in vivo testing is conducted, a sequential 
testing strategy is recommended to reduce the number of test 
animals. The method of testing the dermal corrosivity and primary 
irritation of substances referred to in Sec.  1500.3(c)(3) and (4), 
respectively, is a patch-test technique on the abraded and intact 
skin of the albino rabbit, clipped free of hair * * *.

    7. Test for Eye Irritants
    Section 1500.42 of 16 CFR provides a detailed animal test for eye 
irritation. The method is referenced in Sec.  1500.3(c)(4), which 
defines irritation. The proposed rule added the following text (in 
underline) to Sec.  1500.42 immediately after the heading titled, 
``Test for eye irritants'':

    Guidelines for in vivo and in vitro testing of ocular irritation 
of substances, including testing that does not require animals, are 
presented in the CPSC's animal testing policy set forth in 16 CFR 
1500.232. A weight-of-evidence analysis is recommended to evaluate 
existing information before in vivo tests are considered. This 
analysis should include any of the following: existing human and 
animal data on ocular or dermal irritation, structure activity 
relationships, physicochemical properties, and chemical reactivity. 
When in vivo testing is necessary, a sequential testing strategy is 
recommended to reduce the number of test animals. Additionally, the 
routine use of topical anesthetics, systemic analgesics, and humane 
endpoints to avoid or minimize pain and distress in ocular safety 
testing is recommended. (a)(1) In the method of testing the ocular 
irritation of a substance referred to in Sec.  1500.3(c)(4), six 
albino rabbits are used for each test substance* * *
    In response to comments that request that the rule contain more 
references to human experience or in vitro or in silico tests as non-
animal testing alternatives, the final rule modifies the language (in 
underline) to Sec.  1500.42 as follows:

    Guidelines for in vivo and in vitro testing of ocular irritation 
of substances, including testing that does not require animals, are 
presented in the CPSC's animal testing policy set forth in 16 CFR 
1500.232. A weight-of-evidence analysis or a validated in vitro test 
method is recommended to evaluate existing

[[Page 73293]]

information before in vivo tests are considered. This analysis 
should include any of the following: existing human and animal data 
on ocular or dermal irritation, structure activity relationships, 
physicochemical properties, and chemical reactivity. If in vivo 
testing is conducted, a sequential testing strategy is recommended 
to reduce the number of test animals. Additionally, the routine use 
of topical anesthetics, systemic analgesics, and humane endpoints to 
avoid or minimize pain and distress in ocular safety testing is 
recommended. (a)(1) In the method of testing the ocular irritation 
of a substance referred to in Sec.  1500.3(c)(4), six albino rabbits 
are used for each test substance* * *

    8. Editorial changes
    The proposed rule eliminates the reference in Sec.  1500.42(c) to 
the ``Illustrated Guide for Grading Eye Irritation by Hazardous 
Substances,'' and the accompanying note. The referenced guide is out of 
print, and photocopies are rare. Accordingly, the proposed rule amended 
Sec.  1500.42(c) to reference guidelines from the U.S. Environmental 
Protection Agency (EPA) and the Organisation for Economic Co-operation 
and Development (OECD) as follows:

    To assist testing laboratories and others interested in 
interpreting ocular irritation test results, the CPSC animal testing 
policy Web page at https://www.cpsc.gov/library/animaltesting.html 
will contain the scoring system defined in the U.S. EPA's Test 
Guideline, OPPTS 870.2400: Acute Eye Irritation \1\ or the OECD Test 
Guideline 405: Acute Eye Irritation/Corrosion.\2\

    \1\ EPA. 1998. Health Effects Test Guidelines, OPPTS 870.2400 
Acute Eye Irritation. EPA 712-C-98-195. Washington, DC: U.S. 
Environmental Protection Agency. (Available: https://iccvam.niehs.nih.gov/SuppDocs/FedDocs/EPA/EPA_870_2400.pdf)
    \2\ OECD. 2002. OECD Guideline for the Testing of Chemicals 405: 
Acute Eye Irritation/Corrosion. Paris: Organisation for Economic Co-
operation and Development. (Available: https://iccvam.niehs.nih.gov/SuppDocs/FedDocs/OECD/OECDtg405.pdf)

    The only change made to this section was to update the Web page 
link for the CPSC animal testing guidelines.

C. Impact on Small Businesses

    The Commission certifies that this rule will not a have a 
significant impact on a substantial number of small entities under 
section 605(b) of the Regulatory Flexibility Act (RFA), 5 U.S.C. 
605(b). The Commission's Directorate for Economic Analysis prepared an 
assessment of the impact of amending the regulations on animal testing. 
That assessment found that there would be little or no effect on small 
businesses and other entities because the amendments will not result in 
product modifications in order to comply, and they will not result in 
additional testing or recordkeeping burdens.

D. Environmental Considerations

    Generally, CPSC rules are considered to ``have little or no 
potential for affecting the human environment,'' and environmental 
assessments and environmental impact statements are not usually 
prepared for these rules (see 16 CFR 1021.5(c)(1)). The Commission does 
not expect the rule to have any adverse impact on the environment under 
this categorical exclusion.

E. Executive Orders

    According to Executive Order 12988 (February 5, 1996), agencies 
must state in clear language the preemptive effect, if any, of new 
regulations. The preemptive effect of regulations such as this proposed 
rule is stated in section 18 of the FHSA. 15 U.S.C. 1261n.

F. Paperwork Reduction Act

    This rule would not impose any information collection requirements. 
Accordingly, this rule is not subject to the Paperwork Reduction Act, 
44 U.S.C. 3501-3520.

G. Effective Date

    The Administrative Procedure Act generally requires that a 
substantive rule be published not less than 30 days before its 
effective date, unless the agency finds, for good cause shown, that a 
lesser time period is required. 5 U.S.C. 553(d)(3). The final rule will 
take effect 30 days after publication in the Federal Register.

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.

    Accordingly, 16 CFR part 1500 is amended as follows:

PART 1500--[AMENDED]

0
 1. The authority citation for part 1500 continues to reads as follows:

    Authority:  15 U.S.C. 1261-1278.

0
2. Section1500.3 is amended by:
0
a. Revising paragraph (c)(1) introductory text;
0
b. Adding paragraph (c)(1)(iii);
0
c. Revising paragraph (c)(2) introductory text;
0
d. Revising paragraph (c)(2)(i) and
0
e. Revising paragraphs (c)(3) and (4).
    The revisions and addition read as follows:


Sec.  1500.3  Definitions

* * * * *
    (c) * * *
    (1) To provide flexibility as to the number of animals tested, and 
to emphasize in vitro testing methods, the following is an alternative 
to the definition of ``highly toxic'' in section 2(h) of the act (and 
paragraph (b)(6) of this section); Highly toxic means:
* * * * *
    (iii) A substance that produces a result of `highly toxic' in any 
of the approved test methods described in the CPSC's animal testing 
policy set forth in 16 CFR 1500.232, including data from in vitro or in 
silico test methods that the Commission has approved; or a validated 
weight-of-evidence analysis comprising all of the following that are 
available: existing human and animal data, structure activity 
relationships, physicochemical properties, and chemical reactivity 
data.
    (2) To give specificity to the definition of ``toxic'' in section 
2(g) of the act (and restated in paragraph (b)(5) of this section), the 
following supplements that definition. ``Toxic'' applies to any 
substance that is ``toxic'' (but not ``highly toxic'') on the basis of 
human experience. The following categories are not intended to be 
inclusive. * * *
    (i) The number of animals tested shall be sufficient to give a 
statistically significant result and shall be in conformity with good 
pharmacological practices. Toxic also applies to any substance that can 
be labeled as such, based on the outcome of any of the approved test 
methods described in the CPSC's animal testing policy set forth in 16 
CFR 1500.232, including data from, including data from in vitro or in 
silico test methods that the Commission has approved; or a validated 
weight-of-evidence analysis comprising all of the following that are 
available: existing human and animal data, structure activity 
relationships, physicochemical properties, and chemical reactivity 
data.
* * * * *
    (3) Corrosive means a substance that causes visible destruction or 
irreversible alterations in the tissue at the site of contact. A test 
for a corrosive substance is whether, by human experience, such tissue 
destruction occurs at the site of application. A substance would be 
considered corrosive to the skin if a weight-of-evidence analysis 
suggests that it is corrosive, or validated in vitro test method 
suggests that it is corrosive, or if, when tested by the in vivo 
technique described in Sec.  1500.41, the structure of the tissue at 
the site of contact is destroyed or changed irreversibly in 24 hours or 
less. Other appropriate tests should be applied when contact of the 
substance with

[[Page 73294]]

other than skin tissue is being considered. A substance could also be 
labeled corrosive based on the outcome of any of the approved test 
methods described in the CPSC's animal testing policy set forth in 16 
CFR 1500.232, including data from in vitro or in silico test methods 
that the Commission has approved; or a validated weight-of-evidence 
analysis comprising all of the following that are available: Existing 
human and animal data, structure activity relationships, 
physicochemical properties, and chemical reactivity data.
    (4) The definition of irritant in section 2(j) of the act (restated 
in paragraph (b)(8) of this section) is supplemented by the following: 
Irritant includes primary irritant to the skin, as well as substances 
irritant to the eye or to mucous membranes. Primary irritant means a 
substance that is not corrosive and that human experience data indicate 
is a primary irritant; and/or means a substance that results in an 
empirical score of five or more when tested by the method described in 
1500.41; and/or a substance that can be considered a primary irritant 
based on the outcome of any of the approved test methods described in 
the CPSC's animal testing policy set forth in 16 CFR 1500.232, 
including data from in vitro or in silico test methods that the 
Commission has approved; or a validated weight-of-evidence analysis 
comprising all of the following that are available: existing human and 
animal data, structure activity relationships, physicochemical 
properties, and chemical reactivity data. Eye irritant means a 
substance that human experience data indicate is an irritant to the 
eye; and/or means a substance for which a positive test is obtained 
when tested by the method described in 1500.42; and/or means a 
substance that can be considered an eye irritant based on the outcome 
of any of the approved test methods described in the CPSC's animal 
testing policy set forth in 16 CFR 1500.232, including data from in 
vitro or in silico test methods that the Commission has approved; or a 
validated weight-of-evidence analysis comprising all of the following 
that are available: existing human and animal data, structure activity 
relationships, physicochemical properties, and chemical reactivity 
data.
* * * * *

0
3. Amend Sec.  1500.40 by revising the introductory text to read as 
follows:


Sec.  1500.40  Method of testing toxic substances.

    Guidelines for testing the toxicity of substances, including 
testing that does not require animals, are presented in the CPSC's 
animal testing policy set forth in 16 CFR 1500.232. A weight-of-
evidence analysis, including any of the following: existing human and 
animal data, structure activity relationships, physicochemical 
properties; and chemical reactivity, or validated in vitro or in silico 
testing are recommended to evaluate existing information before in vivo 
tests are considered. If in vivo testing is conducted, a sequential 
testing strategy is recommended to reduce the number of test animals. 
The method of testing the toxic substances referred to in Sec.  
1500.3(c)(1)(ii)(C) and (c)(2)(iii) is as follows:
* * * * *

0
4. In Sec.  1500.41, add five sentences at the start of the 
introductory text to read as follows:


Sec.  1500.41  Method of testing primary irritant substances.

    Guidelines for testing the dermal irritation and corrosivity 
properties of substances, including testing that does not require 
animals, are presented in the CPSC's animal testing policy set forth in 
16 CFR 1500.232. A weight-of-evidence analysis or a validated in vitro 
test method is recommended to evaluate existing information before in 
vivo tests are considered. This analysis should include all of the 
following that are available: human and animal data, structure activity 
relationships, physicochemical properties, and dermal toxicity. If in 
vivo testing is conducted, a sequential testing strategy is recommended 
to reduce the number of test animals. The method of testing the dermal 
corrosivity and primary irritation of substances referred to in Sec.  
1500.3(c)(3) and (4), respectively, is a patch-test technique on the 
abraded and intact skin of the albino rabbit, clipped free of hair. * * 
*
* * * * *

0
5. Amend Sec.  1500.42 by adding introductory text, revising the first 
sentence of paragraph (a)(1), and revising paragraph (c) to read as 
follows:


Sec.  1500.42  Test for eye irritants.

    Guidelines for in vivo and in vitro testing of ocular irritation of 
substances, including testing that does not require animals, are 
presented in the CPSC's animal testing policy set forth in 16 CFR 
1500.232. A weight-of-evidence analysis or a validated in vitro test 
method is recommended to evaluate existing information before in vivo 
tests are considered. This analysis should include any of the 
following: Existing human and animal data on ocular or dermal 
irritation, structure activity relationships, physicochemical 
properties, and chemical reactivity. If in vivo testing is conducted, a 
sequential testing strategy is recommended to reduce the number of test 
animals. Additionally, the routine use of topical anesthetics, systemic 
analgesics, and humane endpoints to avoid or minimize pain and distress 
in ocular safety testing is recommended.
    (a)(1) In the method of testing the ocular irritation of a 
substance referred to in Sec.  1500.3(c)(4), six albino rabbits are 
used for each test substance * * *
* * * * *
    (c) To assist testing laboratories and others interested in 
interpreting ocular irritation test results, the CPSC animal testing 
policy Web page at https://www.cpsc.gov/library/animaltesting.html will 
contain the scoring system defined in the U.S. EPA's Test Guideline, 
OPPTS 870.2400: Acute Eye Irritation \1\ or the OECD Test Guideline 
405: Acute Eye Irritation/Corrosion.\2\
---------------------------------------------------------------------------

    \1\ EPA. 1998. Health Effects Test Guidelines, OPPTS 870.2400 
Acute Eye Irritation. EPA 712-C-98-195. Washington, DC: U.S. 
Environmental Protection Agency. (Available: https://iccvam.niehs.nih.gov/SuppDocs/FedDocs/EPA/EPA_870_2400.pdf)
    \2\ OECD. 2002. OECD Guideline for the Testing of Chemicals 405: 
Acute Eye Irritation/Corrosion. Paris: Organisation for Economic Co-
operation and Development. (Available: https://iccvam.niehs.nih.gov/SuppDocs/FedDocs/OECD/OECDtg405.pdf)

    Dated: November 29, 2012.
Todd A. Stevenson,
Secretary, U.S. Consumer Product Safety Commission.
[FR Doc. 2012-29258 Filed 12-7-12; 8:45 am]
BILLING CODE 6355-01-P