Federal Register, Volume 77 Issue 237 (Monday, December 10, 2012)

[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; http://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 http://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 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):

[[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.

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* * *

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:

[[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 http://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: http://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: http://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 http://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\
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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