[Federal Register Volume 79, Number 31 (Friday, February 14, 2014)]
[Rules and Regulations]
[Pages 8825-8832]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-03260]
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Rules and Regulations
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Federal Register / Vol. 79, No. 31 / Friday, February 14, 2014 /
Rules and Regulations
[[Page 8825]]
CONSUMER PRODUCT SAFETY COMMISSION
[CPSC Docket No. CPSC-2013-0010]
16 CFR Part 1500
Hazardous Substances and Articles; Administration and Enforcement
Regulations: Final Rule; Revisions to Supplemental Definition of
``Strong Sensitizer''
AGENCY: Consumer Product Safety Commission.
ACTION: Final rule.
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SUMMARY: The U.S. Consumer Product Safety Commission (CPSC or
Commission) amends it regulations to revise the supplemental definition
of ``strong sensitizer'' under the Federal Hazardous Substances Act
(FHSA). The revised definition of ``strong sensitizer'' eliminates
redundancy, removes certain subjective factors, incorporates new and
anticipated technology, places the criteria for classification of
strong sensitizers in the order of importance, defines criteria for
``severity of reaction,'' and provides for the use of a weight-of-
evidence approach to determine whether a substance is a strong
sensitizer.
DATES: The rule will become effective on March 17, 2014.
FOR FURTHER INFORMATION CONTACT: Carol Afflerbach, Compliance Officer,
Office of Compliance and Field Operations, U.S. Consumer Product Safety
Commission, 4330 East-West Highway, Bethesda, MD 20814; email:
[email protected].
SUPPLEMENTARY INFORMATION:
A. Background
The 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 by the FHSA are products containing substances that are
toxic, corrosive, an irritant, flammable or combustible, generate
pressure through decomposition, heat or other means, or are strong
sensitizers.
Included within the FHSA's definition of ``hazardous substance'' is
``any substance or mixture of substances'' that ``is a strong
sensitizer,'' 15 U.S.C. 1261(f)1(iv). Section 2(k) of the FHSA, 15
U.S.C. 1261(k), defines ``strong sensitizer'' as a substance which will
cause on normal living tissue through an allergic or photodynamic
process a hypersensitivity which becomes evident on reapplication of
the same substance and which is designated as such by the Commission.
Before designating any substance a strong sensitizer, the Commission,
upon consideration of the frequency of occurrence and severity of the
reaction, shall find that the substance has a significant potential for
causing hypersensitivity.
On August 12, 1961, the U.S. Food and Drug Administration (FDA)
(which at that time administered the FHSA), issued regulations under
the FHSA that supplemented the statutory definition of ``strong
sensitizer'' by explaining that a `` `strong allergic sensitizer' is a
substance that produces an allergenic sensitization in a substantial
number of persons that come into contact with it'' and specifying that
``[a]n allergic sensitization develops by means of an `antibody
mechanism' in contradistinction to a primary irritant reaction which
does not arise because of the participation of an `antibody mechanism.'
'' 26 FR 7333, 7334. The regulation (the 1961 supplemental definition)
listed five substances that the FDA had determined met the statutory
definition for ``strong sensitizer'': (1) Paraphenylenediamine and
products containing it; (2) powdered orris root and products containing
it; (3) epoxy resins systems containing in any concentration
ethylenediamine, diethylenetriamine, and diglycidyl ethers of molecular
weight less than 200; (4) formaldehyde and products containing 1
percent or more of formaldehyde; and (5) oil of bergamot and products
containing 2 percent or more of oil of bergamot. Id. at 7335. Neither
the FDA nor the CPSC has added any strong sensitizers to this list in
the 1961 supplemental definition.
In 1973, Congress transferred the responsibility for the
administration of the FHSA to the Commission. On May 30, 1984, the
Commission revoked the 1961supplemental definition because the 1961
supplemental definition did not account for more recent scientific
theories and was narrower than the statutory definition. 49 FR 22464.
On August 14, 1986, the Commission issued a rule supplementing the
statutory definition of ``strong sensitizer'' (1986 supplemental
definition). 51 FR 29094. The 1986 supplemental definition clarified
how the statutory definition should be interpreted and explained the
factors the Commission would consider in determining whether a
substance is a strong sensitizer. The 1986 supplemental definition
stated that an ``allergic'' response is one that is directed by the
immune system, such that a sensitization reaction could not be caused
by an irritant or other nonallergenic qualities of the substance. The
1986 supplemental definition also clarified that active sensitizers--
substances that produce a sensitivity reaction solely as the result of
a person's first exposure to the substance as opposed to a reaction
after reapplication of the same substance--are included in the class of
substances that can be determined to be strong sensitizers. The 1986
supplemental definition did not address strong sensitizers that cause
hypersensitivity by a photodynamic process, principally because
Commission staff was unaware of any household product subject to the
FHSA that would cause significant exposure of consumers to a
photodynamic chemical.
In 2005, recognizing that the science on sensitization had changed
since promulgation of the 1986 supplemental definition, the CPSC
convened a panel of scientific experts from academia, industry, and the
federal government to examine the available scientific and medical
information concerning sensitizers, and if appropriate, propose
revisions to the supplemental definition of ``strong sensitizer.''
Based on the panel's input, CPSC staff developed a draft technical
report on proposed revisions to the supplemental definition. In 2007,
the draft technical report underwent federal agency and external
scientific peer review. In 2008,
[[Page 8826]]
CPSC staff revised the draft technical report based on the input
received from federal agency and external scientific peer reviewers.
Subsequently, CPSC staff drafted a revision of the ``strong
sensitizer'' supplemental definition, based on the peer reviewed
technical report.
The Commission approved publication of a notice of proposed
rulemaking (NPR) to revise the supplemental definition of ``strong
sensitizer'' (proposed definition or proposed rule). 78 FR 15660 (March
12, 2013). The proposed definition of ``strong sensitizer'' eliminates
redundancy, removes certain subjective factors, incorporates new and
anticipated technology, ranks the criteria for classification of strong
sensitizers in the order of importance, defines criteria for ``severity
of reaction,'' and provides for the use of a weight-of-evidence
approach to determine whether a substance is a strong sensitizer.
In addition, the Commission approved publication of a notice of
availability for a document prepared by CPSC staff titled, ``Strong
Sensitizer Guidance.'' 78 FR 15710 (March 12, 2013). This guidance
document was intended to clarify each component of the revised ``strong
sensitizer'' definition and assist manufacturers in understanding how
CPSC staff would assess whether a substance or product containing that
substance should be considered a strong sensitizer and how the
Commission would make such a determination.
B. Response to Comments on the Proposed Rule
We received five comments on the NPR. The following individuals or
entities submitted comments: a consulting toxicologist; the
International Fragrance Association of North America; the People for
the Ethical Treatment of Animals (PETA); the International Science
Consortium and the Physicians Committee for Responsible Medicine; the
American Chemistry Council; and the Diisocyanates Panel of the American
Chemistry Council.
Several commenters expressed general support for the proposed rule
and made statements supporting specific aspects of the rule. For
example, several commenters supported deleting the reference to
sensitizers that occasionally induce an allergic response on first
exposure so that substances that merely cause irritation upon initial
exposure will not be considered strong sensitizers. Similarly, a
commenter agreed with the proposal's emphasis that sensitization is an
immunologically mediated, multi-stage process that occurs over a period
of time. Several commenters raised issues that resulted in minor
organizational and terminology changes to the proposed rule. All of the
comments can be viewed at: www.regulations.gov, by searching under the
docket number of the rulemaking, CPSC-2013-0010. Following is a summary
of, and responses to, the comments.
Harmonization with International Criteria
Comment: Two commenters recommended that the CPSC take action to
align the agency's chemical classification regulations and practices
with internationally harmonized criteria, encouraging the Commission to
implement the Globally Harmonized System of Classification and Labeling
of Chemicals (GHS). One of the commenters argued that harmonization of
chemical classification and labeling will promote regulatory efficiency
and facilitate trade without lowering the level of health and
environmental protection afforded by current U.S. laws and regulations.
One of the commenters recommended that the Commission use the GHS cut-
off value criteria for determining whether a substance is a sensitizer,
unless there has been sensitization testing on the substance or product
containing the substance.
Response: The GHS is a system for standardizing and harmonizing the
classification and labeling of chemicals, but the GHS is not a
regulation or a standard. The intent of the GHS is to provide an
internationally comprehensible system for communicating chemical
hazards to all sectors (e.g., consumers, workers, emergency responders,
and the public) along the entire life cycle of the chemical. The GHS
establishes agreed-upon hazard classification and communication
criteria with explanatory information on how to apply the system.
Implementation of the GHS by the Commission would be broad-reaching,
with potential impact beyond the FHSA, possibly involving the revision
of existing CPSC statutes and regulations. The request that the
Commission implement the GHS, therefore, goes well beyond the limited
scope of this rulemaking proceeding.
Description of Strong Sensitizer Determination Process
Comment: Two commenters requested a description of the
administrative process that would be used to make a determination that
a substance or product containing a substance is a strong sensitizer so
that stakeholders will be aware of opportunities for participation in
the process.
Response: Under the FHSA, the Commission must first designate a
substance a ``strong sensitizer'' for the substance to be considered a
``strong sensitizer.'' (15 U.S.C 1261(k)). Such a designation would
occur in a separate proceeding that is outside the scope of this
action. The current action relates only to the regulatory definition of
a ``strong sensitizer,'' not to the designation of a particular
substance as a strong sensitizer.
Labeling Requirement for Strong Sensitizers
Comment: One commenter requested that the Commission set forth the
circumstances under which a substance or product containing a substance
that has been designated a strong sensitizer would not require labeling
under Section 2(p) of the FHSA (15 U.S.C. 1261(p).
Response: A substance that is a strong sensitizer or a product
containing a strong sensitizer would not require labeling, unless the
substance met the FHSA definition of ``hazardous substance.'' A
``hazardous substance'' is one that is a strong sensitizer (or has
another of the specified ``hazardous substance'' characteristics) and
``may cause substantial personal injury or substantial illness during
or as a proximate result of any customary or reasonably foreseeable
handling or use, including reasonably foreseeable ingestion by
children.'' 15 U.S.C. 1261(f). Thus, manufacturers of products
containing a strong sensitizer would have to determine whether the
concentrations and availability of the substance in their products
could cause substantial injury or illness as a result of reasonably
foreseeable handling or use. Labeling under section 2(p) of the FHSA
would only be required if the product containing a strong sensitizer
would cause substantial injury or illness as a result of reasonably
foreseeable handling or use.
The Commission would also have the option of issuing a rule under
Section 3(a) of the FHSA to designate a strong sensitizer as a
hazardous substance to reduce uncertainty about which products would be
considered a hazardous substance. Id. 15 U.S.C. 1262(a)(1). A hazardous
substance that is not labeled properly with appropriate cautionary
statements in accordance with section 2(p) of the FHSA is considered a
``misbranded hazardous substance.'' Id. 15 U.S.C. 1261(p). Introducing,
delivering for introduction, or receiving in interstate commerce a
[[Page 8827]]
misbranded hazardous substance is a prohibited act. Id. 15 U.S.C.
1263(a) and (c).
Effect of Rule on Regulation of Products and Risk Management Actions
Comment: One commenter asserted that replacing the 1986
supplemental definition with the proposed definition could have far-
reaching effects on the regulation of products at a broader level and
stated that classifying substances as strong sensitizers may prompt
risk management actions by the CPSC or other regulatory bodies. The
commenter encouraged the CPSC to see that classification determinations
fully reflect a science- and risk-based approach that considers the
degree of hazard and extent of exposure potential.
Response: The Commission does not believe that replacing the 1986
supplemental definition with the final rule definition will have ``far-
reaching effects.'' The rule does not designate any particular
substance as a strong sensitizer, but the rule revises the regulatory
definition of ``strong sensitizer.'' A separate proceeding involving a
specific substance would be required before the agency could declare a
substance to be a strong sensitizer. This rule simply provides guidance
about the information and data that CPSC would consider and the
relative importance of the information in making a strong sensitizer
determination.
Moreover, the determination that a substance is a strong sensitizer
does not, by itself, require any action by a manufacturer. Under the
FHSA, labeling or other regulatory action implicating risk management
factors is required only when a substance meets the definition of
``hazardous substance.'' (15 U.S.C. 1261(f)). A substance that the
Commission designates as a strong sensitizer could be a ``hazardous
substance'' under the FHSA, ``if such substance or mixture of
substances may cause substantial personal injury or substantial illness
during or as a proximate result of any customary or reasonably
foreseeable handling or use, including reasonably foreseeable ingestion
by children.'' Therefore, by definition, the FHSA considers exposure
and requires a case-by-case hazard assessment. The final rule
definition reflects both a science- and risk-based approach so that the
decision for classification is not based solely on a product's
ingredients.
Separate Treatment of Type I and Type IV Allergies in Sensitizer
Definition
Comment: One commenter recommended that Type I and Type IV
allergies be addressed separately in the final rule definition because
these types of allergies have different potential for causing illness,
discomfort, and chronic morbidity; and consideration of different types
of data would be necessary to evaluate the potential of substances that
trigger these two different types of reactions to cause substantial
illness.
Response: A Type I allergy or immediate hypersensitivity is an
allergic reaction provoked by reexposure to a specific type of allergen
due to the production of specific antibodies. A Type IV allergy or
delayed hypersensitivity is an allergic reaction that typically arises
1 to 3 days after exposure to an allergen and is not an antibody-
mediated response. We agree that evaluating whether a substance is a
strong sensitizer will depend on the substance and the allergic
response the substance induces. However, we believe that the final rule
definition would be significantly and unnecessarily more complex if
these two types of allergies were separated into different categories.
The criteria contained in the supplemental definition allow for
flexibility in assessing all types of allergic reactions to
sensitizers. In addition, the final rule definition includes the
various potential routes of exposure for sensitizers, as well as
anatomic sites of an allergic response. The outcome of exposure,
whether a dermal or respiratory response, likely will require the
analysis of different data for evaluation. Evaluating whether a
substance is a strong sensitizer requires a case-by-case inquiry, based
on high-quality relevant data. The Strong Sensitizer Guidance document
explains the approach CPSC staff would take in evaluating the potential
causal link between exposure to strong sensitizers and these two types
of hypersensitivity. We believe that the final rule definition provides
the flexibility for assessing these two types of allergic reactions to
sensitizers without the need for specifically differentiating them.
Acceptance of Data From Certain QSAR Models
Comment: One commenter requested that the Commission revise the
proposed definition to provide for the acceptance of data from
Quantitative Structure-Activity Relationship (QSAR) models
(mathematical models that relate a quantitative measure of chemical
structure to biological activity) that the Organisation for Economic
Co-operation and Development (OECD) has evaluated and approved for
specific applicability domains.
Response: The final rule definition specifically states that in
determining whether a substance has a significant potential for causing
hypersensitivity, chemical or functional properties of the substance of
interest, in addition to QSAR data, can be considered. The panel of
experts and external peer reviewers determined that QSAR data are not
sufficient as stand-alone analyses for determining potency of a
sensitizer but that QSAR analysis could be used in a weight-of-evidence
approach.
The OECD Council Act relating to the Mutual Acceptance of Data
(MAD), which was agreed to by all OECD member countries, established
that safety data developed in one member country will be accepted for
use by the relevant registration authorities in assessing the chemical
or product in another OECD country (i.e., the data do not have to be
generated a second time for the purposes of safety assessment), under
the assurance that the data were developed in compliance with the
Principles of Good Laboratory Practice. Therefore, if a manufacturer
submitted QSAR data to the Commission when the Commission was
determining whether a substance is a strong sensitizer, the Commission
would take the QSAR data into consideration. However, this QSAR data
would not take precedence over high-quality human and animal data. The
Commission believes that modifying the proposed definition in response
to this comment is not warranted.
Ordering of Factors To Be Considered in Determining Whether a Substance
Is a Strong Sensitizer
Comment: One commenter suggested revising the order of the factors
that would be taken into consideration to determine whether a substance
is a ``strong'' sensitizer and including a reference in that paragraph
to unranked data that appears elsewhere in the proposed definition. The
commenter requests: (1) Shifting the order of factors as they appear in
the paragraph listing the factors to be considered in determining
whether a sensitizer is ``strong''--for example moving ``well-conducted
animal studies'' to the end of the list; (2) moving two of the unranked
factors listed in the proposed supplemental definition (quantitative
structure-activity relationship information and bioavailability data)
into the list of ranked factors as the third and fourth priority
position; and (3) separating existing versus new in vitro and in vivo
studies into different factor categories.
[[Page 8828]]
Response: CPSC based the order of ranked data criteria in the
proposed definition on extensive input from the international panel of
scientific experts from academia, industry, and the federal government.
We concurred with the panelists' suggestion to rank and list the
qualifying factors in order of importance in the final rule definition,
instead of ``any or all,'' which is how the factors appear in the 1986
supplemental definition.
The Commission believes that the ranked list of criteria for
determining whether a substance or product containing a substance is a
``strong'' sensitizer should remain as stated in the proposed
definition but that the reference to unranked factors, such as
quantitative structure-activity relationship information, in silico
data and bioavailability data, should be moved to the end of the list
of ranked factors so that the order is more logical. The list of
criteria reflects Commission policy that human data take precedence
over animal data and takes into consideration the value and relevance
that the particular data would provide in making a determination of
sensitizing strength, and therefore, the potential to cause
hypersensitivity. The criteria list is consistent with the CPSC Animal
Testing Policy, the FHSA Chronic Hazard Guidelines, and Commission
policy that strongly encourage the use of scientifically validated
alternatives to animal testing and the use of existing information,
including expert opinion, prior human experience, and prior animal
testing results.
Consistency of Order of Factors Listed Throughout the Rule
Comment: One commenter pointed out that the factors to be
considered in determining whether a substance has a ``significant
potential for causing hypersensitivity'' were not listed in the same
order when listed as factors to be considered in determining whether a
substance is a ``strong'' sensitizer. The commenter requested that the
Commission be consistent when listing the types of data in these two
paragraphs.
Response: We agree that the order of factors should be consistent
in these paragraphs. Therefore, we have modified the proposed
definition by: (1) moving ``chemical or functional properties of the
substance'' to the end of the last sentence in the first paragraph of
section (ii); and (2) in the same sentence reversing the positions of
in vitro and in vivo.
Use of Existing Animal Testing Data
Comment: One commenter recommended that we specify that existing
animal testing data be submitted to the CPSC for consideration in
making a strong sensitizer determination before additional animal
testing data is generated.
Response: As stated in the CPSC Animal Testing Policy, codified at
16 CFR 1500.232, neither the FHSA, nor the regulations issued under the
FHSA, require animal testing to determine whether a hazard exists. 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.
However, the Commission's policy encourages manufacturers subject to
the FHSA to use existing alternatives to animal testing wherever
possible; supports limiting animal testing 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's animal testing policy encourages manufacturers of products
subject to the FHSA to use existing alternatives to animal testing,
whenever possible, such as: prior human experience (e.g., published
case studies); in vitro or in silico test methods that have been
approved by the Commission; literature resources containing the results
of prior animal testing or limited human tests; and expert opinion. We
believe that the animal testing policy codified at 16 CFR 1500.232,
sufficiently communicates the preference for alternatives to animal
testing, whenever possible, including the submission of relevant
existing data resulting from prior animal testing.
Consideration of in Vitro Studies in Making Strong Sensitizer
Determinations
Comment: One commenter asked why in vitro studies were added to the
list of factors to consider in determining whether a substance is a
strong sensitizer when such studies are not validated to determine
potency. Another commenter requested that data from well-conducted in
vitro assays be considered by the Commission in making this
determination.
Response: The 1986 supplemental definition and the final rule
definition both list in vitro data as a factor to be considered in
determining whether a substance is a strong sensitizer. We agree that
currently, there are no validated in vitro assays for sensitizer
potency determination. However, a large number of in vitro assays are
in development, undergoing validation, or have completed validation for
the determination of sensitization. The European Union Reference
Laboratory for Alternatives to Animal Testing (EURL-ECVAM) completed
validation of an in vitro assay and an in chemico assay this year.
EURL-ECVAM recommended that neither assay could be used as a stand-
alone test; although EURL-ECVAM determined that the assays could be
included in a weight-of-evidence approach or integrated testing
strategy. Although the assays have some limitations, EURL-ECVAM
concluded that with further work, these assays might be able to
contribute to the assessment of sensitizer potency. As stated in the
strong sensitizer guidance document, the CPSC would follow a weight-of-
evidence approach, using all available validated tools (including both
positive and negative data), in determining whether a substance is a
strong sensitizer.
Consideration of Reports of Consumer Incidents
Comment: One commenter recommended including in the list of factors
to be considered in determining whether a substance is a strong
sensitizer, the CPSC's and manufacturers' records of incidents of
consumer hypersensitivity to a substance or product containing a
substance.
Response: We agree that incident reports are an important
consideration in determining a substance's ability to cause
hypersensitivity. The final rule definition lists ``case histories'' as
information that the Commission may consider in determining whether a
substance has a significant potential for causing hypersensitivity. The
term ``case histories'' includes reports of incidents of consumer
hypersensitivity to a substance or product containing the substance
that are received by manufacturers or the CPSC. Commission staff will
consider revising the Strong Sensitizer Guidance document to provide
additional clarification regarding the types and sources of incident
reports that CPSC should consider when determining whether a substance
is a strong sensitizer.
Description of ``Clinically Important Reaction''
Comment: The proposed definition provides that in determining
whether a substance is a strong sensitizer, the Commission must
consider the severity of the reaction to the substance and only
designate substances as strong
[[Page 8829]]
sensitizers that cause a ``clinically important reaction.'' The
proposed definition includes a list of four potential reactions to
strong sensitizer exposure that would be characterized as ``clinically
important'' or manifestations of ``substantial illness.'' One of the
clinically important reactions listed in the proposed definition is
``substantial physical discomfort or distress.'' One commenter noted
that ``discomfort and distress are actually perceptual (mental),
although they may be caused by various agents (e.g., physical, chemical
agent, biological).'' The commenter suggested replacing the phrase
``substantial physical discomfort and distress'' with the phrase
``physiological stress resulting in discomfort or distress.''
Response: We agree that the phrase ``substantial physical
discomfort or distress'' may not be clear, but we believe that
``physiological stress resulting in discomfort or distress,'' as
suggested by the commenter, may also be too vague. We have replaced
``substantial physical discomfort or distress'' with ``substantial
physiological effects, such as discomfort and distress,'' as a factor
to be considered in determining whether a strong sensitizer produces
``substantial illness.'' We believe that this phrase reflects better a
scenario such as a systemic allergic contact dermatitis rash.
Meaning of ``Chronic Morbidity''
Comment: One commenter asked whether the reference to ``chronic
morbidity'' as a factor in determining whether a strong sensitizer
produces ``substantial illness'' was associated with a specific length
of time, such as 90 days.
Response: The proposed definition includes a list of four potential
reactions to strong sensitizer exposure that would be characterized as
``clinically important'' or manifestations of ``substantial illness.''
One of the clinically important reactions listed in the proposed
definition is ``chronic morbidity.'' The Commission does not view the
use of the term ``chronic'' as referring to a specific length of time.
Under the FHSA Chronic Hazard Guidelines (16 CFR 1500.135), which are
broad guidelines containing a number of assumptions, methodologies, and
procedures for determining chronic hazard and risk, the Commission does
not set a length of time for ``chronic,'' but instead, the Commission
leaves the determination open to expert judgment. We have replaced the
phrase ``chronic morbidity'' with ``persistent morbidity'' in the final
rule definition to clarify that a ``clinically important reaction'' is
a substantial illness that occurs over an extended period of time.
Addition of ``Mortality'' to ``Substantial Illness'' Factors
Comment: One commenter suggested that ``mortality'' be added to the
list of factors to be considered in determining whether a strong
sensitizer produces substantial illness.
Response: Mortality (i.e., death) is not an illness but is a
distinct endpoint that in rare cases could result from substantial
uncontrolled anaphylaxis. We have revised the definition to include:
``or in rare cases, mortality'' at the end of the section that lists
the types of reactions to substances that may be considered
``substantial illness.''
Removal of Oil of Bergamot From List of Strong Sensitizer Substances
Comment: One commenter requested that oil of bergamot (and products
containing 2 percent or more of oil of bergamot) be removed from the
list of ``strong sensitizer'' substances.
Response: Oil of bergamot is a phototoxin that FDA listed as a
``strong sensitizer'' (the list appears in 16 CFR 1500.13). The current
rulemaking proceeding only addresses revisions to the supplemental
definition of ``strong sensitizer.'' To make any changes to the
existing list of substances currently considered to be strong
sensitizers, the Commission would need to conduct a separate
proceeding.
C. Revisions to the Strong Sensitizer Supplemental Definition
As discussed in Section B, above, the comments received in response
to the NPR generally supported the Commission's replacement of the 1986
supplemental definition of ``strong sensitizer'' with the proposed
definition. However, several commenters recommended additional changes
that we have determined should be incorporated into the supplemental
definition of strong sensitizer. Below, we discuss the differences
between the 1986 supplemental definition and the proposed definition,
along with the changes we have made to the proposed definition, based
on comments and that have been incorporated into the final rule.
1. Definition of ``Sensitizer'' (Sec. 1500.3(c)(5)(i))
The 1986 supplemental definition specified that a ``sensitizer''
will ``induce an immunologically-mediated (allergic) response,
including allergic photosensitivity,'' that will become evident upon
reexposure to the same substance, or occasionally, on first exposure,
by virtue of active sensitization.
The final rule reflects the traditional definition for
``sensitization''; sensitization is a multi-stage immune-mediated
process that occurs over a period of time. Replacing the phrase
``immunologically-mediated (allergic) response'' with
``immunologically-mediated hypersensitivity,'' captures those
substances that sensitize through atypical mechanisms, rather than by
inducing an obvious ``immunologically-mediated response.'' The final
rule also eliminates the last sentence of the current definition based
on concerns that the sentence could be misinterpreted to include
substances that cause an irritant response only \1\ (the response that
is noted after the first exposure to a substance is more frequently an
irritant response and not an allergic response). Typically, allergic
responses are the result of a two-step process: (1) induction
(sensitization), which requires sufficient or cumulative exposure to
induce an immune response with few or no symptoms; and (2) elicitation
when an individual who has been sensitized demonstrates symptoms upon
subsequent exposures. The final rule includes the phrase ``variable
period of exposure'' to reflect the latency period that is a
characteristic in the development of sensitization. This section of the
final rule is the same as proposed.
---------------------------------------------------------------------------
\1\ An ``irritant response'' is a nonimmune mediated response
and one that results from direct injury to the tissue. An irritant
is any agent that is capable of producing cell damage in any
individual if applied for sufficient time and concentration.
---------------------------------------------------------------------------
2. Determination of Significant Potential for Causing Hypersensitivity
(Sec. 500.3(c)(5)((ii))
The statutory definition of ``strong sensitizer'' requires that,
before designating a substance as a strong sensitizer, the Commission
``upon consideration of the frequency of occurrence and severity of
reaction, shall find that the substance has a significant potential for
causing hypersensitivity.'' 15 U.S.C. 1261(k).
As discussed in the NPR, the proposed definition added qualifiers
for susceptibility profiles--genetics, age, gender, and atopic status--
to the information and data listed in the 1986 supplemental definition
that may be considered in determining whether a substance has a
significant potential for causing hypersensitivity. These
characteristics are well-known modifiers in the development and
exacerbation of allergic responses to chemical sensitizers. In response
to a
[[Page 8830]]
comment, for the final rule, we have reordered the list as it appeared
in the proposed definition so that the final definition presents the
factors to be considered in determining whether a substance has a
significant potential for causing hypersensitivity. This represents the
same order as the factors to be considered in determining whether a
substance is a ``strong'' sensitizer. This reordering results in
``chemical or functional properties of the substance'' becoming the
last category on the list, and the references to in vitro and in vivo
experimental studies are reversed.
As discussed in the NPR, the proposed definition also replaced the
term ``normal'' with ``non-sensitized,'' which describes more
accurately the general control population. This remains the same in the
final rule.
As discussed in the NPR, the proposed definition incorporated the
factors to be considered in determining whether a substance is a
``strong'' sensitizer into the subsection explaining ``significant
potential for causing hypersensitivity.'' The 1986 supplemental
definition of ``strong sensitizer'' contains a separate subsection that
sets forth factors that should be considered in determining the
strength of a sensitizer. (16 CFR 1500.3(c)(5)(ii)). This section of
the 1986 supplemental definition includes several factors that are
subjective rather than quantitative (i.e., physical discomfort,
distress, hardship) and allows for risk assessment considerations in
connection with an analysis that should only be a hazard
characterization step.
As discussed in the NPR, the proposed definition eliminated the
``quantitative or qualitative risk assessment factor. '' We believe
this terminology is confusing because the language places a risk
assessment step within the hazard identification step of the process of
determining whether a product containing a strong sensitizer is a
hazardous substance that requires labeling. The NPR proposed definition
remains the same in the final rule, except for the reordering of
certain factors in response to a comment.
As discussed in the NPR, the proposed definition makes clear that a
weight-of-the-evidence approach is to be used in determining the
strength of a sensitizer because of the imprecise nature of some of the
current factors and the potential lack of information or data available
to permit useful consideration of certain factors. Rather than allow an
``any or all'' approach to the factors that would be considered by the
Commission in determining whether a sensitizer is strong, the revision
ranks data sources in order of importance following the FHSA preference
for human data over animal data and takes into consideration the value
and relevance that certain data would provide in evaluating the
potential of a substance to cause hypersensitivity. For example, the
proposed definition expressed a preference for general population
epidemiological studies over occupational studies because the degree of
sensitization in the workplace is likely to be greater than that of the
general population, due to greater exposure (both in time and
concentration) to the sensitizing agent. The ranking of data sources
remains the same in the final rule.
As discussed in the NPR, the proposed definition listed additional
factors that the Commission can consider in determining a substance's
sensitizing potential, for which validated methods currently do not
exist but are in development, such as: Quantitative Structure-Activity
Relationships (QSARs), and in silico \2\ data, along with the caveat
that using these techniques would be in addition to consideration of
human and animal data. We have revised the definition in the final rule
to reposition these factors from the end of Section 1500.3(c)(5)(ii) to
follow immediately the listing of ranked factors that are to be
considered in determining whether a substance is a ``strong''
sensitizer.
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\2\ QSARs are mathematical models that relate a quantitative
measure of chemical structure to biological activity. In silico data
is a computational approach using sophisticated computer models for
the determination of a sensitizing potential. Both of these
approaches are evolving methodologies that have not yet been
validated, but are being pursued as testing options that would
reduce the numbers of expensive laboratory and animal experiments
being carried out.
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As discussed in the NPR, the proposed definition provided that for
a substance to be considered a ``strong'' sensitizer, the substance
must be found to produce a ``clinically important reaction,'' which is
defined as a reaction with a significant impact on the quality of life.
The Commission has revised the proposed definition in response to a
comment to replace ``substantial physical effects'' with ``substantial
physiological effects'' as a factor to be considered in determining
whether a strong sensitizer produces ``substantial illness''; to
replace ``chronic morbidity'' with ``persistent morbidity''; and to add
``or in rare cases, mortality'' to the end of section 1500.3(c)(5)(ii).
The change from ``physical'' to ``physiological'' is intended to
describe more accurately and broadly the body's response to exposure to
a substance that could rise to the level of a clinically important
reaction. The change from ``chronic'' to ``persistent,'' also made in
response to a comment, is intended to convey more clearly that a
substantial illness may be one that endures for an extended period of
time.
As discussed in the NPR, the proposed definition also directed the
Commission to consider the location of the hypersensitivity response,
such as the face, hands, and feet, and the persistence of clinical
manifestations in determining whether the substance produces a
``clinically important reaction.'' This aspect of the NPR remains the
same in the final rule.
3. Definition of Normal Living Tissue (Sec. 1500.3(c)(5)(iii))
The statutory definition of ``strong sensitizer'' specifies that a
strong sensitizer is a substance that will cause hypersensitivity on
``normal living tissue.'' The 1986 supplemental definition identifies
skin and other organ systems, such as the respiratory or
gastrointestinal tract, as types of ``normal living tissue'' in which
the allergic hypersensitivity reaction can occur. The proposed
definition adds a specific reference to mucous membranes, such as
ocular and oral systems, as additional types of normal living tissue
upon which a substance can cause a hypersensitivity that warrants a
determination that a substance is a ``strong sensitizer.'' This remains
the same in the final rule.
D. Staff Guidance and Notice of Availability
Commission staff developed a guidance document that is intended to
clarify the ``strong sensitizer'' definition and assist manufacturers
in understanding how CPSC staff would assess whether a substance and/or
product containing that substance should be considered a ``strong
sensitizer.'' A Notice of Availability was published in the Federal
Register on March 12, 2013 (78 FR 15710), which provided a link to the
location on the Commission's Web site where the staff guidance document
can be found. Several commenters included questions and observations
regarding the guidance document in their submissions addressing the
proposed revision to the definition of ``strong sensitizer.''
Commission staff will review these comments, and where appropriate,
will revise the guidance document.
E. Impact on Small Businesses
The Commission certifies that this rule will not a have a
significant impact on a substantial number of small entities
[[Page 8831]]
under section 605(b) of the Regulatory Flexibility Act (RFA), 5 U.S.C.
605(b). For the NPR, the Commission's Directorate for Economic Analysis
prepared an assessment of the impact of the proposed definition of
``strong sensitizer.'' That assessment found that there would be little
or no effect on small businesses and other entities because the
amendment, which simply modifies the existing supplemental definition
of ``strong sensitizer,'' will not result in compliance actions.
Products will not need to be modified to comply with the revised
supplemental definition, nor will the revised supplemental definition
impose any additional testing or recordkeeping burdens. The obligation
to label a product as a strong sensitizer and any costs associated with
that obligation will not arise until the Commission has designated a
particular substance contained in the product as a strong sensitizer,
which would occur only in connection with a separate process.
Thereafter, we would assess the potential small business impact of
designating the particular substance as a strong sensitizer. Whether
the final rule would impose any indirect burden on small businesses or
other entities is unknown because the impact of the changes to the
supplemental definition of strong sensitizer on future strong
sensitizer designation proceedings is not known. The Commission did not
receive any comments concerning the impact the rule would have on small
businesses and is not aware of any information that would alter the
assessment stated in the NPR.
F. 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.
G. Executive Orders
According to Executive Order 12988 (February 5, 1996), agencies
must state in clear language the preemptive effect, if any, of new
regulations. Section 18 of the FHSA addresses the preemptive effect of
certain rules issued under the FHSA. 15 U.S.C. 1261n. Because this
rulemaking would revise a regulatory definition, rather than issue a
labeling or banning requirement, section 18 of the FHSA does not
provide for the rule to have preemptive effect.
H. 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.
I. 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 March 17, 2014.
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 read as follows:
Authority: 15 U.S.C. 1261-1278.
0
2. Revise paragraph (c)(5) of Sec. 1500.3 to read as follows:
Sec. 1500.3 Definitions
* * * * *
(c) * * *
(5) The definition of strong sensitizer in section 2(k) of the
Federal Hazardous Substances Act (restated in paragraph (b)(9) of this
section) is supplemented by the following definitions:
(i) Sensitizer. A sensitizer is a substance that is capable of
inducing a state of immunologically mediated hypersensitivity
(including allergic photosensitivity) following a variable period of
exposure to that substance. Hypersensitivity to a substance will become
evident by an allergic reaction elicited upon reexposure to the same
substance.
(ii) Significant potential for causing hypersensitivity. (A) Before
designating any substance a ``strong sensitizer,'' the Commission shall
find that the substance has significant potential for causing
hypersensitivity. Significant potential for causing hypersensitivity is
a relative determination that must be made separately for each
substance. The determination may be based on documented medical
evidence of hypersensitivity reactions upon subsequent exposure to the
same substance obtained from epidemiological surveys or case histories;
controlled in vivo or in vitro experimental studies; susceptibility
profiles (e.g., genetics, age, gender, atopic status) in non-sensitized
or allergic subjects; and chemical or functional properties of the
substance.
(B) In determining whether a substance is a ``strong'' sensitizer,
the Commission shall consider the available data for a number of
factors, following a weight-of-evidence approach. The following factors
(if available), ranked in descending order of importance, should be
considered: well-conducted clinical and diagnostic studies,
epidemiological studies, with a preference for general population
studies over occupational studies, well-conducted animal studies, well-
conducted in vitro test studies, cross-reactivity data, and case
histories.
(C) Additional consideration may be given to Quantitative
Structure-Activity Relationships (QSARs), in silico data, specific
human sensitization threshold values, other data on potency and
sensitizer bioavailability, if data are available and the methods
validated. Bioavailability is the dose of the allergen available to
interact with a tissue. Bioavailability is a reflection of how well the
skin or another organ can absorb the allergen and the actual
penetrating ability of the allergen, including factors such as size and
composition of the chemical.
(D) Criteria for a ``well-conducted'' study would include:
validated outcomes, relevant dosing, route of administration, and use
of appropriate controls. Studies should be carried out according to
national and/or international test guidelines and according to good
laboratory practice (GLP), compliance with good clinical practice
(GCP), and good epidemiological practice (GEP).
(E) Before the Commission designates any substance as a ``strong''
sensitizer, frequency of occurrence and range of severity of reactions
in exposed subpopulations having average or high susceptibility will be
considered. The minimal severity of a reaction for the purpose of
designating a material as a ``strong sensitizer'' is a clinically
important reaction. A clinically important reaction would be considered
one with a significant impact on quality of life. Consideration should
be given to the location of the hypersensitivity response, such as the
face, hands, and feet as well as persistence of clinical
manifestations. For example, strong sensitizers may produce substantial
illness, including any or all of the following: substantial
physiological effects, such as discomfort and distress, substantial
hardship, functional or structural impairment, persistent morbidity, or
in rare cases, mortality.
[[Page 8832]]
(iii) Normal living tissue. The allergic hypersensitivity reaction
occurs in normal living tissues, including the skin, mucous membranes
(e.g., ocular, oral), and other organ systems, such as the respiratory
tract and gastrointestinal tract, either singularly or in combination,
following sensitization by contact, ingestion, or inhalation.
* * * * *
Dated: February 11, 2014.
Todd A. Stevenson,
Secretary, U.S. Consumer Product Safety Commission.
[FR Doc. 2014-03260 Filed 2-13-14; 8:45 am]
BILLING CODE 6355-01-P