[Federal Register: April 6, 2010 (Volume 75, Number 65)]
[Proposed Rules]
[Page 17333-17349]
[DOCID:fr06ap10-20]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 372

[EPA-HQ-TRI-2010-0006; FRL-9134-1]
RIN 2025-AA28

Addition of National Toxicology Program Carcinogens; Community
Right-to-Know Toxic Chemical Release Reporting

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule.

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SUMMARY: EPA is proposing to add sixteen chemicals to the list of toxic
chemicals subject to reporting under section 313 of the Emergency
Planning and Community Right-to-Know Act (EPCRA) of 1986 and section
6607 of the Pollution Prevention Act of 1990 (PPA). These sixteen
chemicals have been classified by the National Toxicology Program (NTP)
in their Report on Carcinogens (RoC) as ``reasonably anticipated to be
a human carcinogen.'' EPA believes that these sixteen chemicals meet
the EPCRA section 313(d)(2)(B) criteria because they can reasonably be
anticipated to cause cancer in humans. As in past chemical reviews, EPA
adopted a production volume screen for the development of this proposed
rule to screen out those chemicals for which no reports are expected to
be submitted. Based on a review of the available production and use
information, these sixteen chemicals are expected to be manufactured,
processed, or otherwise used in quantities that would exceed the EPCRA
section 313 reporting thresholds.

DATES: Comments must be received on or before June 7, 2010.

ADDRESSES: Submit your comments, identified by Docket ID No. EPA-HQ-
TRI-2010-0006, by one of the following methods:
     www.regulations.gov: Follow the on-line instructions for
submitting comments.
     E-mail<EMAIL_ADDRESS>     Mail: Office of Environmental Information (OEI) Docket,
Environmental Protection Agency, Mail Code: 28221T, 1200 Pennsylvania
Ave., NW., Washington, DC 20460
     Hand Delivery: EPA Docket Center (EPA/DC), EPA West, Room
3334, 1301 Constitution Ave., NW., Washington, DC 20460. Such
deliveries are only accepted during the Docket's normal hours of
operation, and special arrangements should be made for deliveries of
boxed information.
    Instructions: Direct your comments to Docket ID No. EPA-HQ-TRI-
2010-0006. EPA's policy is that all comments received will be included
in the public docket without change and may be made available online at
http://www.regulations.gov, including any personal information
provided, unless the comment includes information claimed to be
Confidential Business Information (CBI) or other information whose
disclosure is restricted by statute. Do not submit information that you
consider to be CBI or otherwise protected through www.regulations.gov
or e-mail. The www.regulations.gov Web site is an ``anonymous access''
system, which means EPA will not know your identity or contact
information unless you provide it in the body of your comment. If you
send an e-mail comment directly to EPA without going through
www.regulations.gov, your e-mail address will be automatically captured
and included as part of the comment that is placed in the public docket
and made available on the Internet. If you submit an electronic
comment, EPA recommends that you include your name and other contact
information in the body of your comment and with any disk or CD-ROM you
submit. If EPA cannot read your comment due to technical difficulties
and cannot contact you for clarification, EPA may not be able to
consider your comment. Electronic files should avoid the use of special
characters, avoid any form of encryption, and be free of any defects or
viruses.
    Docket: All documents in the docket are listed in the
www.regulations.gov index. Although listed in the index, some
information is not publicly available, e.g., CBI or other information
whose disclosure is restricted by statute. Certain other material, such
as copyrighted material, will be publicly available only in hard copy.
Publicly available docket materials are available either electronically
in www.regulations.gov or in hard copy at the OEI Docket, EPA/DC, EPA
West, Room 3334, 1301 Constitution Ave., NW., Washington, DC. This
Docket Facility is open from 8:30 a.m. to 4:30 p.m., Monday through
Friday, excluding legal holidays. The telephone number for the Public
Reading Room is<PHONE_NUMBER>, and the telephone number for the OEI
Docket is<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: Daniel R. Bushman, Environmental
Analysis Division, Office of Information Analysis and Access (2842T),
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460; telephone number:<PHONE_NUMBER>; fax number: 202-
566-0677; e-mail<EMAIL_ADDRESS>for specific information on
this notice. For general information on EPCRA section 313, contact the
Emergency Planning and Community Right-to-Know Hotline, toll free at
(800) 424-9346 or<PHONE_NUMBER> in Virginia and Alaska or toll free,
TDD<PHONE_NUMBER>, http://www.epa.gov/epaoswer/hotline/.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Notice Apply to Me?

    You may be potentially affected by this action if you manufacture,
process, or otherwise use any of the chemicals

included in this proposed rule. Potentially affected categories and
entities may include, but are not limited to:

------------------------------------------------------------------------
                                        Examples of potentially affected
               Category                             entities
------------------------------------------------------------------------
Industry.............................  Facilities included in the
                                        following NAICS manufacturing
                                        codes (corresponding to SIC
                                        codes 20 through 39): 311\*\,
                                        31\2*\, 313\*\, 314\*\, 315\*\,
                                        316, 321, 322, 323\*\, 324,
                                        325\*\, 326\*\, 327, 331, 332,
                                        333, 334\*\, 335\*\, 336,
                                        337\*\, 339\*\, 111998\*\,
                                        211112\*\, 212324\*\, 212325\*\,
                                        212393\*\, 212399\*\, 488390\*\,
                                        511110, 511120, 511130,
                                        511140\*\, 511191, 511199,
                                        512220, 512230\*\, 519130\*\,
                                        541712\*\, or 811490\*\.

                                       * Exceptions and/or limitations
                                        exist for these NAICS codes.

                                       Facilities included in the
                                        following NAICS codes
                                        (corresponding to SIC codes
                                        other than SIC codes 20 through
                                        39): 212111, 212112, 212113
                                        (correspond to SIC 12, Coal
                                        Mining (except 1241)); or
                                        212221, 212222, 212231, 212234,
                                        212299 (correspond to SIC 10,
                                        Metal Mining (except 1011, 1081,
                                        and 1094)); or 221111, 221112,
                                        221113, 221119, 221121, 221122,
                                        221330 (Limited to facilities
                                        that combust coal and/or oil for
                                        the purpose of generating power
                                        for distribution in commerce)
                                        (correspond to SIC 4911, 4931,
                                        and 4939, Electric Utilities);
                                        or 424690, 425110, 425120
                                        (Limited to facilities
                                        previously classified in SIC
                                        5169, Chemicals and Allied
                                        Products, Not Elsewhere
                                        Classified); or 424710
                                        (corresponds to SIC 5171,
                                        Petroleum Bulk Terminals and
                                        Plants); or 562112 (Limited to
                                        facilities primarily engaged in
                                        solvent recovery services on a
                                        contract or fee basis
                                        (previously classified under SIC
                                        7389, Business Services, NEC));
                                        or 562211, 562212, 562213,
                                        562219, 562920 (Limited to
                                        facilities regulated under the
                                        Resource Conservation and
                                        Recovery Act, subtitle C, 42
                                        U.S.C. 6921 et seq.) (correspond
                                        to SIC 4953, Refuse Systems).
Federal Government                     Federal facilities.
------------------------------------------------------------------------

    This table is not intended to be exhaustive, but rather provides a
guide for readers regarding entities likely to be affected by this
action. Some of the entities listed in the table have exemptions and/or
limitations regarding coverage, and other types of entities not listed
in the table could also be affected. To determine whether your facility
would be affected by this action, you should carefully examine the
applicability criteria in part 372 subpart B of Title 40 of the Code of
Federal Regulations. If you have questions regarding the applicability
of this action to a particular entity, consult the person listed in the
preceding ``FOR FURTHER INFORMATION CONTACT'' section.

B. How Should I Submit CBI to the Agency?

    Do not submit CBI information to EPA through www.regulations.gov or
e-mail. Clearly mark the part or all of the information that you claim
to be CBI. For CBI information in a disk or CD-ROM that you mail to
EPA, mark the outside of the disk or CD-ROM as CBI and then identify
electronically within the disk or CD-ROM the specific information that
is claimed as CBI. In addition to one complete version of the comment
that includes information claimed as CBI, a copy of the comment that
does not contain the information claimed as CBI must be submitted for
inclusion in the public docket. Information so marked will not be
disclosed except in accordance with procedures set forth in 40 CFR part
2.

II. Introduction

    Section 313 of EPCRA, 42 U.S.C. 11023, requires certain facilities
that manufacture, process, or otherwise use listed toxic chemicals in
amounts above reporting threshold levels to report their environmental
releases and other waste management quantities of such chemicals
annually. These facilities must also report pollution prevention and
recycling data for such chemicals, pursuant to section 6607 of the PPA,
42 U.S.C. 13106. Congress established an initial list of toxic
chemicals that comprised more than 300 chemicals and 20 chemical
categories.
    EPCRA section 313(d) authorizes EPA to add or delete chemicals from
the list and sets criteria for these actions. EPCRA section 313(d)(2)
states that EPA may add a chemical to the list if any of the listing
criteria in Section 313(d)(2) are met. Therefore, to add a chemical,
EPA must demonstrate that at least one criterion is met, but need not
determine whether any other criterion is met. Conversely, to remove a
chemical from the list, EPCRA section 313(d)(3) dictates that EPA must
demonstrate that none of the listing criteria in Section 313(d)(2) are
met. The EPCRA section 313(d)(2) criteria are:
    (A) The chemical is known to cause or can reasonably be anticipated
to cause significant adverse acute human health effects at
concentration levels that are reasonably likely to exist beyond
facility site boundaries as a result of continuous, or frequently
recurring, releases.
    (B) The chemical is known to cause or can reasonably be anticipated
to cause in humans--

    (i) Cancer or teratogenic effects, or
    (ii) Serious or irreversible--
    (I) Reproductive dysfunctions,
    (II) Neurological disorders,
    (III) Heritable genetic mutations, or
    (IV) Other chronic health effects.

    (C) The chemical is known to cause or can be reasonably anticipated
to cause, because of
    (i) Its toxicity,
    (ii) Its toxicity and persistence in the environment, or
    (iii) Its toxicity and tendency to bioaccumulate in the
environment, a significant adverse effect on the environment of
sufficient seriousness, in the judgment of the Administrator, to
warrant reporting under this section.

    EPA often refers to the section 313(d)(2)(A) criterion as the
``acute human health effects criterion;'' the section 313(d)(2)(B)
criterion as the ``chronic human health effects criterion;'' and the
section 313(d)(2)(C) criterion as the ``environmental effects
criterion.''
    EPA has published in the Federal Register of November 30, 1994 (59
FR 61432) a statement clarifying its interpretation of the section
313(d)(2) and (d)(3) criteria for modifying the section 313 list of
toxic chemicals.

III. Background Information

A. What is the NTP and the Report on Carcinogens?

    The National Toxicology Program (NTP) is an interagency program
within the Department of Health and Human Services (DHHS) headquartered
at the National Institute of Environmental Health Sciences (NIEHS) of
the National Institutes of Health (NIH). The mission of the NTP is to
evaluate chemicals of public health concern by developing and applying
tools of modern toxicology and molecular biology. The NTP

program maintains an objective, science-based approach in dealing with
critical issues in toxicology and is committed to using the best
science available to prioritize, design, conduct, and interpret its
studies. The mission of the NTP includes the evaluation of chemicals
for their potential to cause cancer in humans.
    As part of their cancer evaluation work, the NTP periodically
publishes a Report on Carcinogens (RoC) document. The RoC was mandated
by the U.S. Congress, as part of the Public Health Service Act (Section
301(b)(4), as amended). The NTP describes the RoC as an informational
scientific and public health document that identifies and discusses
agents, substances, mixtures, or exposure circumstances that may pose a
hazard to human health by virtue of their carcinogenicity. The NTP RoC
serves as a meaningful and useful compilation of data on (1) the
carcinogenicity (ability to cause cancer), genotoxicity (ability to
damage genes), and biologic mechanisms (modes of action in the body) of
the RoC-listed substances in humans and/or in animals, (2) the
potential for human exposure to these substances, and (3) the
regulations and guidelines promulgated by Federal agencies to limit
exposures to RoC-listed substances. The NTP RoC is published
periodically, with the most recently published 11th RoC having been
released on January 31, 2005. The 11th RoC contains the NTP cancer
classifications from the most recent chemical evaluations as well as
the classifications from previous versions of the RoC.

B. What are the NTP cancer classifications and criteria?

    The NTP RoC classifies chemicals as either ``known to be a human
carcinogen'' or ``reasonably anticipated to be a human carcinogen.''
The criteria that the NTP uses to list an agent, substance, mixture, or
exposure circumstance under each classification in the RoC (Ref. 1) are
as follows:

``Known To Be Human Carcinogen:
There is sufficient evidence of carcinogenicity from studies in
humans*, which indicates a causal relationship between exposure to the
agent, substance, or mixture, and human cancer.
Reasonably Anticipated To Be Human Carcinogen:
There is limited evidence of carcinogenicity from studies in humans*,
which indicates that causal interpretation is credible, but that
alternative explanations, such as chance, bias, or confounding factors,
could not adequately be excluded,
or
there is sufficient evidence of carcinogenicity from studies in
experimental animals, which indicates there is an increased incidence
of malignant and/or a combination of malignant and benign tumors (1) in
multiple species or at multiple tissue sites, or (2) by multiple routes
of exposure, or (3) to an unusual degree with regard to incidence,
site, or type of tumor, or age at onset,
or
there is less than sufficient evidence of carcinogenicity in humans or
laboratory animals; however, the agent, substance, or mixture belongs
to a well-defined, structurally related class of substances whose
members are listed in a previous Report on Carcinogens as either known
to be a human carcinogen or reasonably anticipated to be a human
carcinogen, or there is convincing relevant information that the agent
acts through mechanisms indicating it would likely cause cancer in
humans. Conclusions regarding carcinogenicity in humans or experimental
animals are based on scientific judgment, with consideration given to
all relevant information. Relevant information includes, but is not
limited to, dose response, route of exposure, chemical structure,
metabolism, pharmacokinetics, sensitive sub-populations, genetic
effects, or other data relating to mechanism of action or factors that
may be unique to a given substance. For example, there may be
substances for which there is evidence of carcinogenicity in laboratory
animals, but there are compelling data indicating that the agent acts
through mechanisms which do not operate in humans and would therefore
not reasonably be anticipated to cause cancer in humans.
* This evidence can include traditional cancer epidemiology studies,
data from clinical studies, and/or data derived from the study of
tissues or cells from humans exposed to the substance in question that
can be useful for evaluating whether a relevant cancer mechanism is
operating in people.''

    The NTP classifications for the potential for a chemical to cause
cancer are very similar to the EPCRA section 313(d)(2)(B) statutory
criteria for listing a chemical on the list of toxic chemicals subject
to reporting under EPCRA section 313: ``(B) The chemical is known to
cause or can reasonably be anticipated to cause in humans-- (i) cancer
* * * '' The specific data used by the NTP to classify a chemical as
``Known To Be Human Carcinogen'' or ``Reasonably Anticipated To Be
Human Carcinogen'' are consistent with data used by EPA to evaluate
chemicals for their potential to cause cancer and classify chemicals as
either ``Carcinogenic to Humans'' or ``Likely to Be Carcinogenic to
Humans'' (Ref. 2).

C. What is the review process for the RoC?

    Specific details of the nomination and review process for the
development of the 11th RoC are described in the introduction to the
11th RoC (Ref. 1). In general, the RoC review process includes
evaluations by scientists from the NTP, other Federal health research
and regulatory agencies (including EPA), and nongovernmental
institutions. The RoC review process includes external peer review and
several opportunities for public comment. For the 11th RoC, two Federal
scientific review groups, the NIEHS/NTP Review Committee for the Report
on Carcinogens RG1 and the NTP Executive Committee Interagency Working
Group for the Report on Carcinogens RG2, evaluated the classification
recommendations. An EPA representative was a member of the RG2
committee. These reviews were followed by a third independent external
scientific peer review by a standing subcommittee of the NTP Board of
Scientific Counselors (the RoC Subcommittee). During the entire process
there were three opportunities for public comment. The Director of the
NTP received for review all of the recommendations of the review
groups, the opinion of the NTP Executive Committee, and all public
comments. After evaluating this information and any other relevant
information the NTP Director developed recommendations to the
Secretary, DHHS regarding whether and/or how to classify nominations in
the RoC. The final draft of the RoC was prepared by the NTP based on
the NTP Director's recommendations and was submitted it to the
Secretary, DHHS, for review and approval. Once approved, the Secretary
submitted RoC to the U. S. Congress as a final document. Submittal of
the RoC to Congress constituted publication of the report, at which
time it became available to the public.

IV. EPA's Review of the 11th RoC

A. How did EPA select the NTP RoC chemicals being proposed for
addition?

    The most recent version of the NTP RoC that EPA previously reviewed
for

possible additions to the EPCRA section 313 list was the 6th RoC
(January 12, 1994, 59 FR 1788). Each new version of the RoC adds newly
classified chemicals to the existing list. EPA's present review of the
11th RoC identified 81 chemicals that are not on the EPCRA section
list, 54 of which were previously reviewed for listing when EPA
reviewed the 6th RoC. Those previous reviews concluded that the 54
chemicals that were not proposed for addition would not be
manufactured, processed, or otherwise used at levels that exceed the
EPCRA section 313 reporting thresholds. For this review EPA only
considered the 27 chemicals that had been added to the RoC since the
6th RoC was published and thus had not been previously reviewed for
listing. Of the 27 chemicals, EPA determined that 12 are manufactured,
processed, or otherwise used in quantities sufficient to exceed
reporting thresholds for at least one facility (Ref. 3). In addition, 4
chemicals are included for addition to the polycyclic aromatic
compounds category.
    Section 313(d)(2) of EPCRA provides EPA the discretion to add
chemicals to the TRI list when there is sufficient evidence to
establish any of the listing criteria. EPA can add a chemical that
meets one criterion regardless of its production volume. But as in past
chemical reviews (e.g., January 12, 1994, 59 FR 1788), EPA adopted a
production volume screen for the development of this proposed rule to
screen out those chemicals for which no reports are expected to be
submitted. If chemicals that did not meet the production volume screen
were listed, there would be an economic burden for firms that would
have to determine that they did not exceed the reporting threshold. Yet
as no reports would be filed, there would be no information to the
public on these chemicals. EPA feels it is appropriate at this time to
focus on chemicals for which reports are likely to be filed.
    EPA reviewed the NTP 11th RoC chemical profiles and supporting
materials for each chemical being proposed for listing in this rule
(Ref. 4). Given the extensive scientific reviews conducted by the NTP
for their RoC documents, EPA's review focused on ensuring that there
were no inconsistencies with how the Agency would consider the
available data. EPA found no inconsistencies and agrees with the hazard
conclusions of the NTP 11th RoC for each of the chemicals included in
this proposed rule.

B. What technical data supports the NTP RoC classifications and EPA's
proposed additions to the EPCRA section 313 list?

    This section presents the data that supported the NTP 11th RoC
classifications of each chemical now being proposed for inclusion on
the EPCRA section 313 list and why EPA believes the data support the
addition of these chemicals to the EPCRA section 313 list. The NTP
chemical profiles, the NTP chemical background documents, and the
references cited within each of the portions of the NTP 11th RoC
chemical profiles quoted here, are all included in the docket for this
rulemaking. While they are contained in the docket and are part of the
rulemaking record, the references within the quotations cited from the
NTP 11th RoC profile documents in this section are not included in the
list of references in Unit VI. of this Federal Register notice. The
full citations for the references contained in the quotations can be
found in the NTP 11th RoC profile documents cited for each chemical.
    1. 1-Amino-2,4-Dibromoanthraquinone (CAS No. 81-49-2) (Refs. NTP
Profile/Background document (Refs. 5 and 6)). The NTP has classified 1-
amino-2,4-dibromoanthraquinone as ``reasonably anticipated to be a
human carcinogen.'' The classification is based on sufficient evidence
of carcinogenicity in experimental animals. The NTP substance profile
for 1-amino-2,4-dibromoanthraquinone (Ref. 5) included the following
summary information of the evidence of carcinogenicity:
``Carcinogenicity
    1-Amino-2,4-dibromoanthraquinone (ADBAQ) is reasonably anticipated
to be a human carcinogen based on sufficient evidence from studies in
experimental animals. Orally administered ADBAQ significantly increased
the incidences of benign and/or malignant tumors at multiple tissue
sites in two species of animals. ADBAQ caused benign and malignant
liver tumors in rats and mice of both sexes; tumors of the large
intestine, kidney, and urinary bladder in male and female rats; and
tumors of the forestomach and lung in male and female mice (NTP 1996).
    Two cohort studies evaluated the risk of cancer among workers in
plants manufacturing anthraquinone dyes; however, it is not known
whether workers were exposed specifically to ADBAQ (Gardiner et al.
1982, Delzell et al. 1989). Some evidence suggests that anthraquinone
dye workers may have an increased risk of cancer. Significant excesses
of esophageal and prostate cancer occurred among workers in some areas
of a Scottish anthraquinone dyestuffs plant, and excesses of lung and
central nervous system cancer occurred among workers at a New Jersey
anthraquinone dye and epichlorohydrin plant (Barbone et al. 1992, 1994,
Sathiakumar and Delzell 2000). Nevertheless, estimates of risk in all
studies were based on small numbers of cancer deaths, and workers may
have been exposed to other carcinogens.
Additional Information Relevant to Carcinogenicity
    Evaluation of ADBAQ's genetic effects has been hindered by ADBAQ's
limited solubility. ADBAQ caused mutations in some strains of bacteria
but not in rodent cells, which were tested at lower concentrations
(Haworth et al. 1983, NTP 1996). In mammalian cells, ADBAQ induced
chromosomal aberrations (changes in chromosome structure or number) and
sister chromatid exchange; however, the results varied between
laboratories and between trials at the same laboratory (Loveday et al.
1990, NTP 1996). Point mutations in the ras proto-oncogene (a gene
potentially associated with cancer) occurred at a higher frequency in
forestomach and lung tumors from the two-year carcinogenicity study of
ADBAQ-exposed mice than in spontaneous tumors from control mice not
exposed to ADBAQ. The predominant types of mutations were A to T
transversions and A to G transitions, suggesting that ADBAQ or its
metabolites target adenine bases in the ras proto-oncogene (Hayashi et
al. 2001).
    ADBAQ is rapidly absorbed from the gastrointestinal tract and
distributed to most soft tissues. The majority of ADBAQ is metabolized,
and both ADBAQ and its metabolites are excreted in the feces and urine.
However, the metabolites of ADBAQ have not been identified (NTP 1996).
The mechanism by which ADBAQ causes cancer is not known; however, there
is no evidence to suggest that mechanisms of tumor induction observed
in experimental animals would not occur in humans. Four other
anthraquinones (2-aminoanthraquinone, 1-amino-2- methylanthraquinone,
danthron [1,8-dihydroxyanthraquinone], and disperse blue 1) are listed
in the Report on Carcinogens as reasonably anticipated to be human
carcinogens.''
    EPA has reviewed the NTP assessment for 1-amino-2,4-
dibromoanthraquinone and agrees that

1-amino-2,4-dibromoanthraquinone can reasonably be anticipated to cause
cancer in humans. EPA believes that the evidence is sufficient for
listing 1-amino-2,4-dibromoanthraquinone on EPCRA section 313 pursuant
to EPCRA section 313(d)(2)(B) based on the available carcinogenicity
data for this chemical.
    2. 2,2-bis(Bromomethyl)-1,3-propanediol (CAS No. 3296-90-0) (Refs.
NTP Profile/Background document (Refs. 7 and 8)). The NTP has
classified 2,2-bis(bromomethyl)-1,3-propanediol as ``reasonably
anticipated to be a human carcinogen.'' The classification is based on
sufficient evidence of carcinogenicity in experimental animals. The NTP
substance profile for 2,2-bis(bromomethyl)-1,3-propanediol (Ref. 7)
included the following summary information of the evidence of
carcinogenicity:
Carcinogenicity
    The flame retardant 2,2-bis(bromomethyl)-1,3-propanediol, technical
grade (BBMP), is reasonably anticipated to be a human carcinogen based
on sufficient evidence of carcinogenicity from studies in experimental
animals which indicates there is increased incidence of malignant tumor
formation at multiple tissue sites in rats and mice. Two year dietary
studies of BBMP in F344 rats showed significantly increased incidences
of neoplasms of the skin, subcutaneous tissue, mammary gland, Zymbal
gland, oral cavity, esophagus, forestomach, small and large intestines,
mesothelium, urinary bladder, lung, thyroid gland, and seminal vesicle
and in the incidence of mononuclear cell leukemia in males, and an
increase in the incidence of neoplasms of the oral cavity, esophagus,
mammary gland, and thyroid gland in females. Similar studies in B6C3F1
mice found increased incidences of neoplasms of the harderian gland,
lung, and kidney in males and neoplasms of the harderian gland, lung,
and subcutaneous tissue in females (NTP 1996, Dunnick et al. 1997).
    A study in which BBMP was administered in the feed to male F344
rats for three months, followed by maintenance on a control diet for up
to two years, found neoplasms at the same sites as in the two-year
study of male F344 rats described above. However, this study found
higher incidences of neoplasms of the oral cavity, forestomach, small
intestine, large intestine, lung, Zymbal gland, thyroid gland, and
mesothelium than did the two-year study; these neoplasms were
considered to be related to BBMP exposure (NTP 1996, Dunnick et al.
1997).
    No published case reports or epidemiological studies of human
cancer and exposure to BBMP were found (IARC 2000).
Additional Information Relevant to Carcinogenicity
    BBMP has been shown to be mutagenic in bacterial and mammalian test
systems, under special conditions. BBMP is mutagenic in Salmonella
typhimurium strains TA100 and TA1535 only when tested in the presence
of metabolic activation (30% S9 liver homogenate from induced hamsters)
(Zeiger et al. 1992). In cultured Chinese hamster ovary cells, BBMP
induces chromosomal aberrations only in the presence of metabolic
activation, and it does not induce sister chromatid exchange with or
without activation. Male and female mice exposed to BBMP under various
conditions showed significant increases in the frequency of
micronucleated erythrocytes (NTP 1996).
    No available data suggest that mechanisms thought to account for
BBMP's induction of tumors in experimental animals would not also
operate in humans.''
    EPA has reviewed the NTP assessment for 2,2-bis(bromomethyl)-1,3-
propanediol and agrees that 2,2-bis(bromomethyl)-1,3-propanediol can
reasonably be anticipated to cause cancer in humans. EPA believes that
the evidence is sufficient for listing 2,2-bis(bromomethyl)-1,3-
propanediol on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B)
based on the available carcinogenicity data for this chemical.
    3. Furan (CAS No. 110-00-9) (Refs. NTP Profile/Background document
(Refs. 9 and 10)). The NTP has classified furan as ``reasonably
anticipated to be a human carcinogen.'' The classification is based on
sufficient evidence of carcinogenicity in experimental animals. The NTP
substance profile for furan (Ref. 9) included the following summary
information of the evidence of carcinogenicity:
``Carcinogenicity
    Furan is reasonably anticipated to be a human carcinogen based on
sufficient evidence of malignant tumor formation at multiple tissue
sites in multiple species of experimental animals (IARC 1995).
    When administered by gavage, furan induced an increase in the
incidence of hepatic cholangiocarcinoma, hepatocellular adenoma,
hepatocellular carcinoma, and mononuclear cell leukemia in male and
female F344/N rats treated for up to 2 years (NTP 1993). Gavage
administration of furan to male F344 rats for 9, 12, or 13 months
resulted in high incidences of cholangiocarcinoma by 16 months after
cessation of treatment (Maronpot et al. 1991, Elmore and Sirica 1993).
When administered by gavage, furan induced a dose-dependent increase in
the incidence of hepatocellular adenoma and carcinoma and benign
pheochromocytoma in male and female B6C3F1 mice treated up
to 2 years (NTP 1993).
    No adequate human studies of the relationship between exposure to
furan and human cancer have been reported.
Additional Information Relevant to Carcinogenicity
    In bacteria, furan induced gene mutations in Salmonella typhimurium
strain TA100 (Lee et al. 1994) and in E. coli containing bacteriophage
T7 (Ronto et al. 1992), but not in S. typhimurium strains TA98 (Lee et
al. 1994), TA1535, or TA1537 (Mortelmans et al. 1986). In Drosophila
melanogaster, it did not induce gene mutations (Foureman et al. 1994).
In mammalian in vitro systems, it induced gene mutations in mouse
lymphoma cells (McGregor et al. 1988), DNA damage in Chinese hamster
ovary (CHO) cells (NTP 1993), and chromosomal damage in CHO cells with
an exogenous metabolic activation system (NTP 1993, IARC 1995), but it
did not induce DNA damage in mouse or rat hepatocytes (Wilson et al.
1992, NTP 1993). In mammalian in vivo systems, furan induced
chromosomal aberrations in bone marrow of B6C3F1 mice (NTP
1993), but did not induce DNA damage in bone marrow or hepatocytes of
B6C3F1 mice (Wilson et al. 1992, NTP 1993) or hepatocytes of
F344/CrIBr rats (Wilson et al. 1992).
    A current hypothesis for the mechanism of furan-induced
carcinogenesis is metabolic activation of furan by cytochrome P450 to a
reactive and cytotoxic intermediate that stimulates cell replication,
increasing the likelihood of tumor induction (Chen et al. 1995,
Kedderis et al. 1993). The postulated reactive metabolite is cis-2-
butene-1,4-dial, which was recently characterized as a furan metabolite
by Chen et al. (1995). This reactive metabolite probably explains
furan's binding reactivity with proteins both in vitro (uninduced and
induced F344 male rat liver microsomes) and in vivo (F344 male rat
liver protein) in biological systems (Burka et al. 1991, Parmar and
Burka 1993). Furan metabolites may react with DNA, but Burka et al.
(1991) did not detect any

radiotracer in DNA from livers of rats treated with [\14\ C]furan.
    No data were available that would suggest that the mechanisms
thought to account for tumor induction by furan in experimental animals
would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for furan and agrees
that furan can reasonably be anticipated to cause cancer in humans. EPA
believes that the evidence is sufficient for listing furan on EPCRA
section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
    4. Glycidol (CAS No. 556-52-5) (Ref. NTP Profile/NTP study (Refs.
11 and 12)). The NTP has classified glycidol as ``reasonably
anticipated to be a human carcinogen.'' The classification is based on
sufficient evidence of carcinogenicity in experimental animals. The NTP
substance profile for glycidol (Ref. 11) included the following summary
information of the evidence of carcinogenicity:
``Carcinogenicity
    Glycidol is reasonably anticipated to be a human carcinogen based
on sufficient evidence of carcinogenicity in experimental animals (NTP
1990, IARC 2000). Two-year studies were conducted with mice and rats
that were administered glycidol by gavage. Male rats showed increased
incidences of mesotheliomas of the tunica vaginalis, fibroadenomas of
the mammary gland, gliomas of the brain, and neoplasms of the
forestomach, intestine, skin, Zymbal gland, and thyroid gland. Female
rats had increased incidences of fibroadenomas and adenocarcinomas of
the mammary gland, gliomas of the brain, neoplasms of the oral mucosa,
forestomach, clitoral gland, and thyroid gland, and leukemia. Male
B6C3F1 mice had increased incidences of neoplasms of the
harderian gland, forestomach, skin, liver, and lung. Female
B6C3F1 mice had increased incidences of neoplasms of the
harderian gland, mammary gland, uterus, subcutaneous tissue, and skin.
Other neoplasms that may be related to the administration of glycidol
were fibrosarcomas of the glandular stomach in female rats and
carcinomas of the urinary bladder and sarcomas of the epididymis in
male mice (NTP 1990).
    No adequate human studies of the relationship between exposure to
glycidol and human cancer have been reported (IARC 2000).''
    EPA has reviewed the NTP cancer assessment for glycidol and agrees
that glycidol can reasonably be anticipated to cause cancer in humans.
EPA believes that the evidence is sufficient for listing glycidol on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
    5. Isoprene (CAS No. 78-79-5) (Refs. NTP Profile/Background
document (Refs. 13 and 14)). The NTP has classified isoprene as
``reasonably anticipated to be a human carcinogen.'' The classification
is based on sufficient evidence of carcinogenicity in experimental
animals. The NTP substance profile for isoprene (Ref. 13) included the
following summary information of the evidence of carcinogenicity:
Carcinogenicity
    Isoprene is reasonably anticipated to be a human carcinogen based
on sufficient evidence of tumor formation at multiple organ sites in
multiple species of experimental animals (Melnick et al. 1994, NTP
1995, 199[9], Placke et al. 1996). Inhalation exposure of mice to
isoprene vapors induced increased incidences of neoplasms of the lung,
liver, harderian gland, forestomach, hematopoietic system, and
circulatory system. Inhalation exposure of rats to isoprene vapors
induced increased incidences of neoplasms of the mammary gland, kidney,
and testis (IARC 1999).
    No adequate human studies of the relationship between exposure to
isoprene and human cancer have been reported.
Additional Information Relevant to Carcinogenicity
    Isoprene is the 2-methyl analog of 1,3-butadiene, an industrial
chemical that has been identified as an animal and human carcinogen.
Isoprene and butadiene are metabolized to monoepoxide and diepoxide
intermediates by liver microsomal cytochrome P450-dependent
monooxygenases from several species, including humans. Detoxification
of these intermediates may occur by hydrolysis catalyzed by epoxide
hydrolase or conjugation with glutathione catalyzed by glutathione-S-
transferase. The diepoxide intermediates of isoprene and butadiene are
mutagenic in Salmonella typhimurium, whereas the parent compounds are
inactive (Gervasi et al. 1985). In mice, isoprene and 1,3-butadiene
induced sister chromatid exchanges in bone marrow cells and increased
the frequency of micronucleated erythrocytes in peripheral blood (Tice
et al. 1987, Tice et al. 1988). Common sites of neoplasm induction by
isoprene and butadiene include the mammary gland and testis in rats,
and the liver, lung, harderian gland, forestomach, and circulatory
system in mice (NTP 199[9]). Lung and harderian gland neoplasms induced
by isoprene in mice had a high frequency of unique K-ras mutations (A
to T transversions at codon 61) (Hong et al. 1997).
    No data were available that would suggest that mechanisms thought
to account for tumor induction by isoprene in experimental animals
would not also operate in humans.
    EPA has reviewed the NTP cancer assessment for isoprene and agrees
that isoprene can reasonably be anticipated to cause cancer in humans.
EPA believes that the evidence is sufficient for listing isoprene on
EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the
available carcinogenicity data for this chemical.
    6. Methyleugenol (CAS No. 93-15-2) (Refs. NTP Profile/Background
document (Refs. 15 and 16)). The NTP has classified methyleugenol as
``reasonably anticipated to be a human carcinogen.'' The classification
is based on sufficient evidence of carcinogenicity in experimental
animals. The NTP substance profile for methyleugenol (Ref. 15) included
the following summary information of the evidence of carcinogenicity:
Carcinogenicity
    Methyleugenol is reasonably anticipated to be a human carcinogen
based on sufficient evidence of carcinogenicity from studies in
experimental animals, which indicates there is an increased incidence
of malignant and/or combination of malignant and benign tumors at
multiple tissue sites in multiple species of experimental animals. In
animal studies, methyleugenol given orally to rats induced liver and
stomach tumors in both sexes and kidney, mammary gland, and skin tumors
in males. Methyleugenol given orally to mice induced benign and
malignant tumors of the liver. Tumors of the stomach in male mice also
were considered related to exposure to methyleugenol (NTP [2000]).
Earlier studies found that methyleugenol and two similar compounds, the
structurally related allylbenzenes, safrole and estragole, induced
liver tumors in mice after intraperitoneal injection (IARC 1976, Miller
et al. 1983). Safrole is listed in the Report on Carcinogens as
reasonably anticipated to be a human carcinogen and by IARC as possibly
carcinogenic to humans (Group 2B).
    No adequate human studies of the relationship between exposure to

methyleugenol and human cancer were found.
Additional Information Relevant to Carcinogenicity
    Mechanistic data indicate that liver tumors induced by
methyleugenol and structurally related allylbenzenes result from
metabolism of these compounds to DNA-reactive intermediates.
Methyleugenol may be bioactivated by three different pathways: (1)
Hydroxylation at the 1' position of the allylic side chain to yield 1'-
hydroxymethyleugenol, followed by sulfation of this intermediate to
form 1'- hydroxymethyleugenol sulfate, (2) oxidation of the 2',3'-
double bond of the allylic side chain to form methyleugenol-2,3-oxide,
and (3) O-demethylation followed by spontaneous rearrangement to form
eugenol quinone methide. Formation of protein adducts and DNA adducts
in the livers of animals (and in cultured human hepatocytes) exposed to
allylbenzenes and induction of liver tumors by these compounds in
animals have been attributed to activation via the hydroxylation
pathway, because similar effects were produced by the 1'-hydroxy
metabolites and because these effects were inhibited by pretreatment
with sulfotransferase inhibitors (Miller et al. 1983, Boberg et al.
1983, Randerath et al. 1984, Gardner et al. 1996, NTP [2000]).
    Methyleugenol, safrole, and estragole induce unscheduled DNA
synthesis in rat hepatocytes, and their corresponding 1'-hydroxy
metabolites are more potent genotoxic agents than are the parent
compounds (Howes et al. 1990, Chan and Caldwell 1992). Methyleugenol
induces morphological transformations in Syrian hamster embryo cells
(Kerckaert et al. 1996), sister chromatid exchange in Chinese hamster
ovary (CHO) cells (NTP [2000]), intrachromosomal recombination in yeast
(Schiestl et al. 1989), and DNA repair in Bacillus subtilis (Sekizawa
and Shibamoto 1982). Methyleugenol does not induce mutations in
Salmonella typhimurium (NTP [2000]) or Escherichia coli (Sekizawa and
Shibamoto 1982), chromosomal aberrations in CHO cells (NTP [2000]), or
micronucleated erythrocytes in peripheral blood of mice (NTP [2000]). A
higher frequency of [beta]-catenin mutations was observed in liver
tumors from mice treated with methyleugenol than in spontaneous liver
tumors from control mice (Devereux et al. 1999). Methyleugenol's lack
of mutagenicity in bacteria may be due to the need for sulfation in the
metabolic activation of methyleugenol to its ultimate mutagenic or
carcinogenic form.
    EPA has reviewed the NTP cancer assessment for methyleugenol and
agrees that methyleugenol can reasonably be anticipated to cause cancer
in humans. EPA believes that the evidence is sufficient for listing
methyleugenol on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
    7. Nitroarenes (selected) (Refs. NTP Profile. (Ref. 17)). The NTP
has classified five nitroarenes as ``reasonably anticipated to be a
human carcinogen.'' The five nitroarenes are: 1,6-Dinitropyrene, 1,8-
Dinitropyrene, 6-Nitrochrysene, 1-Nitropyrene, and 4-Nitropyrene. 1-
Nitropyrene is already on the EPCRA section 313 list under the
polycyclic aromatic compounds (PACs) category (November 30, 1994, 59 FR
61485). All of the members of the PACs category are listed based on
concerns for their carcinogenicity and were listed as a category
because they are structurally similar and induce a similar toxic effect
(cancer) (November 30, 1994, 59 FR 61463). Since the four other
nitroarenes are PACs and are being proposed for listing based on a
concern for carcinogenicity they are being proposed for addition to the
PACs category, and not for individual listing.
    The PACs category is one of several categories of chemicals of
special concern for which reporting is triggered at lowered thresholds.
40 CFR 372.28(a)(2). The special concern for the PACs category members
is that they are persistent, bioaccumulative, and toxic (PBT)
chemicals. More specifically, it is the persistence and bioaccumulative
properties of these chemicals that led EPA to lower reporting
thresholds (October 29, 1999, 64 FR 58666). The persistence and
bioaccumulation data for the four nitroarenes addressed in this
proposal follows the individual summaries of the cancer data for each
chemical. In addition to the data for the nitroarenes, there is a
discussion of the PBT criteria and how it was applied to the PACs
category.
    a. 1,6-Dinitropyrene (CAS No. 42397-64-8) (Refs. NTP Profile/
Background document (Refs. 17 and 18)). The NTP has classified 1,6-
dinitropyrene as ``reasonably anticipated to be a human carcinogen.''
The classification is based on sufficient evidence of carcinogenicity
in experimental animals. The NTP substance profile for 1,6-
dinitropyrene (Ref. 17) included the following summary information of
the evidence of carcinogenicity:
``Carcinogenicity
    1,6-Dinitropyrene is reasonably anticipated to be a human
carcinogen based on sufficient evidence of malignant tumor formation in
multiple species of experimental animals, at multiple sites and by
multiple routes of exposure (IARC 1989).
    When administered by subcutaneous injections, 1,6-dinitropyrene
induced injection-site sarcomas in male mice and male and female rats,
and leukemia in female rats (Tokiwa et al. 1984, Ohgaki et al. 1985,
Imaida et al. 1995). Intraperitoneal injections of 1,6-dinitropyrene
caused an increased incidence of liver-cell tumors in male mice
(Wislocki et al. 1986) and induced sarcomas of the peritoneal cavity in
female rats (Imaida et al. 1991). In two studies, squamous cell
carcinomas of the lung were induced in male rats receiving 1,6-
dinitropyrene by intrapulmonary injection (Maeda et al. 1986, Iwagawa
et al. 1989). The incidences of myeloid leukemia and lung
adenocarcinomas were significantly increased in male and female
hamsters receiving 1,6- dinitropyrene by intratracheal instillation
(Takayama et al. 1985). 1,6- Dinitropyrene induced carcinoma of the
pituitary gland in an oral study of short-term duration in rats (Imaida
et al. 1991).
    No adequate data were available to evaluate the carcinogenicity of
1,6-dinitropyrene in humans.
Additional Information Relevant to Carcinogenicity
    Intratracheal administration of 1,6-dinitropyrene to rats
previously inoculated to de-epithelialized trachea with an immortalized
bronchial cell line, caused tumors when the tracheas were then
implanted subcutaneously into nude mice (Iizasa et al. 1993). 1,6-
Dinitropyrene is genotoxic in a wide variety of assays in bacteria and
mammalian cells including human cells. 1,6-Dinitropyrene also
demonstrates evidence of cell transformation activity in vitro in rat
tracheal epithelial cells. Metabolic pathways leading to mutagenic and
clastogenic metabolites and DNA adducts of 1,6-dinitropyrene have been
described (IARC 1989).
    No data were available that would suggest that the mechanisms
thought to account for tumor induction by 1,6-dinitropyrene in
experimental animals would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for 1,6-dinitropyrene
and agrees that 1,6-dinitropyrene can reasonably be anticipated to
cause

cancer in humans. EPA believes that the evidence is sufficient for
listing 1,6-dinitropyrene in the PACs category on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for this chemical.
    b. 1,8-Dinitropyrene (CAS No. 42397-65-9) (Refs. NTP Profile/
Background document (Refs. 17 and 18)). The National Toxicology Program
has classified 1,8-dinitropyrene as ``reasonably anticipated to be a
human carcinogen.'' The classification is based on sufficient evidence
of carcinogenicity in experimental animals. The NTP substance profile
for 1,8-dinitropyrene (Ref. 17) included the following summary
information of the evidence of carcinogenicity:
``Carcinogenicity
    1,8-Dinitropyrene is reasonably anticipated to be a human
carcinogen based on sufficient evidence of malignant tumor formation in
multiple species of experimental animals, at multiple sites, and by
multiple routes of exposure (IARC 1989). When administered by
subcutaneous injections, 1,8-dinitropyrene induced injection-site
sarcomas in male mice and male and female rats, and leukemia in female
rats (Imaida et al. 1995, Ohgaki et al. 1984, 1985, Otofuji et al.
1987). Intraperitoneal injections of 1,8-dinitropyrene induced sarcomas
of the peritoneal cavity, leukemia, and mammary adenocarcinoma in
female rats (Imaida et al. 1991, 1995). The incidences of mammary
tumors, including adenocarcinomas, were increased in female rats
receiving 1,8- dinitropyrene by gavage (Imaida et al. 1991, IARC 1989).
    No adequate data were available to evaluate the carcinogenicity of
1,8-dinitropyrene in humans.
Additional Information Relevant to Carcinogenicity
    1,8-Dinitropyrene is genotoxic in a wide variety of assays in
bacteria and mammalian cells demonstrating evidence of cell
transformation activity in vitro, and metabolic pathways leading to
mutagenic and clastogenic metabolites and DNA adducts have been
described (IARC 1989).
    No data were available that would suggest that the mechanisms
thought to account for tumor induction of 1,8-dinitropyrene in
experimental animals would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for 1,8-dinitropyrene
and agrees that 1,8-dinitropyrene can reasonably be anticipated to
cause cancer in humans. EPA believes that the evidence is sufficient
for listing 1,8-dinitropyrene in the PACs category on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for this chemical.
    c. 6-Nitrochrysene (CAS No. 7496-02-8) (Refs. NTP Profile/
Background document (Refs. 17 and 19)). The National Toxicology Program
has classified 6-nitrochrysene as ``reasonably anticipated to be a
human carcinogen.'' The classification is based on sufficient evidence
of carcinogenicity in experimental animals. The NTP substance profile
for 6-nitrochrysene (Ref. 17) included the following summary
information of the evidence of carcinogenicity:
``Carcinogenicity
    6-Nitrochrysene is reasonably anticipated to be a human carcinogen
based on sufficient evidence of carcinogenicity at multiple sites in
multiple species of experimental animals (IARC 1989). In seven studies,
when administered by intraperitoneal injection, 6-nitrochrysene caused
lung tumors in male and female mice and also induced liver tumors in
female and/or male mice in three of these studies and malignant
lymphoma in one study (Busby et al. 1985, 1989, El-Bayoumy et al. 1992,
Li et al. 1994, Fu et al. 1994, Imaida et al. 1992, Wislocki et al.
1986). Dysplastic and/or adenomatous lesions of the colon were
increased in male and female rats, and colon adenocarcinomas were
increased in male rats receiving 6-nitrochrysene by intraperitoneal
injection (Imaida et al. 1992). Mammary fibroadenoma, adenocarcinoma,
and spindle cell sarcomas were increased in female rats receiving 6-
nitrochrysene by injection into the mammary gland (El-Bayoumy et al.
1993).
    No data were available to evaluate the carcinogenicity of 6-
nitrochrysene in humans.
Additional Information Relevant to Carcinogenicity
    6-Nitrochrysene induced skin tumors, mainly papillomas, in a dermal
initiation-promotion study in which 6-nitrochrysene was used as the
initiator, followed by promotion with a phorbol ester (El-Bayoumy et
al. 1982). It also caused lung and forestomach tumors when given by
intraperitoneal injection to transgenic mice carrying a human hybrid c-
Ha-ras gene (Ogawa et al. 1996). 6-Nitrochrysene is genotoxic in
several assays in bacteria and mammalian cells and induces cell
transformation in finite lifespan cells in vitro. Metabolic pathways
leading to mutagenic and clastogenic metabolites and DNA adducts have
been described (IARC 1989). The presence of 6-nitrochrysene- DNA
adducts in tumor target tissue supports the possibility that tumors
induced by this chemical are at least in part a result of chemical-
induced DNA damage. No data were available that would suggest that the
mechanisms thought to account for tumor induction by 6-nitrochrysene in
experimental animals would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for 6-nitrochrysene and
agrees that 6-nitrochrysene can reasonably be anticipated to cause
cancer in humans. EPA believes that the evidence is sufficient for
listing 6-nitrochrysene in the PACs category on EPCRA section 313
pursuant to EPCRA section 313(d)(2)(B) based on the available
carcinogenicity data for this chemical.
    d. 4-Nitropyrene (CAS No. 57835-92-4) (Refs. NTP Profile/Background
document (Refs. 17 and 20)). The National Toxicology Program has
classified 4-nitropyrene as ``reasonably anticipated to be a human
carcinogen.'' The classification is based on sufficient evidence of
carcinogenicity in experimental animals. The NTP substance profile for
4-nitropyrene (Ref. 17) included the following summary information of
the evidence of carcinogenicity:
``Carcinogenicity
    4-Nitropyrene is reasonably anticipated to be a human carcinogen
based on sufficient evidence of malignant tumor formation at multiple
tissue sites in multiple species of experimental animals (IARC 1989).
Intraperitoneal injections of 4-nitropyrene caused an increased
incidence of liver tumors in male mice, lung tumors in male and female
mice (Wislocki et al. 1986), and mammary adenocarcinomas in female rats
(Imaida et al. 1991). When administered by subcutaneous injections, 4-
nitropyrene induced sarcomas at the injection site, and increased
incidences of mammary adenocarcinomas, leukemia, and tumors of the
Zymbal gland in female rats (Imaida et al. 1995, IARC 1989). In two
studies, female rats receiving mammary gland injections of 4-
nitropyrene showed an increased incidence of mammary tumors (Imaida et
al. 1991, El-Bayoumy et al. 1993).
    No data were available to evaluate the carcinogenicity of 4-
nitropyrene in humans.

Additional Information Relevant to Carcinogenicity
    Although not as reactive or potent as some of the mononitro- or
dinitropyrenes, 4-nitropyrene is genotoxic in bacterial cells and
induces cell transformation in BALB cells in vitro. Metabolic pathways
for 4-nitropyrene, leading to mutagenic and likely DNA adducts, have
also been described (IARC 1989).
    No data were available that would suggest that the mechanisms
thought to account for tumor induction by 4-nitropyrene in experimental
animals would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for 4-nitropyrene and
agrees that 4-nitropyrene can reasonably be anticipated to cause cancer
in humans. EPA believes that the evidence is sufficient for listing 4-
nitropyrene in the PACs category on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
    e. Nitroarene persistence and bioaccumulation data. The above four
nitroarenes are being proposed for addition to the PACs category, the
members of which have been classified as PBT chemicals with lower
reporting thresholds (October 29, 1999, 64 FR 58666). For purposes of
EPCRA section 313 reporting, EPA established persistence half-life
criteria for PBT chemicals of 2 months in water/sediment and soil and
2-days in air, and established bioaccumulation criteria for PBT
chemicals as a bioconcentration factor (BCF) or bioaccumulation factor
(BAF) of 1,000 or higher. Chemicals meeting the PBT criteria were
assigned 100 pound reporting thresholds. With regards to setting the
EPCRA section 313 reporting thresholds, EPA set lower reporting
thresholds (10 pounds) for those PBT chemicals with persistence half-
lifes of 6 months or more in water/sediment or soil and with BCF or BAF
values of 5,000 or higher, these chemicals were considered highly PBT
chemicals. At the time of the lowering of the thresholds for the PACs
category, the persistence and bioaccumulation data for the current
members in the category showed variation in these characteristics
(October 29, 1999, 64 FR 58713). The PACs persistence data included air
half-lifes of 2 hours to 4 days, surface water half-lifes of 79 days to
44 years, and soil half-lifes of 20 days to 14.6 years. The PACs
bioaccumulation data ranged from BCFs of 800 to 31,440. EPA determined
that while there was variation in the persistence and bioaccumulation
data for the members of the PACs category, the best way to report these
chemicals was as one single category (October 29, 1999, 64 FR 58725).
While much of the persistence and bioaccumulation data for the PACs
chemicals exceeded what EPA classified as highly persistent and
bioaccumulative for setting reporting thresholds, EPA decided not to
assign the PACs category the lower 10 pound reporting threshold because
of the variability of the persistence and bioaccumulation data across
members of the category (October 29, 1999, 64 FR 58726).
    Since little data is available on the persistence of the four
nitroarenes being proposed for listing, the data for 1-nitropyrene, a
member of the PACs category, was used to estimate the persistence
properties of the four nitroarenes (Ref. 21). 1-nitropyrene is a
structural isomer of 4-nitropyrene and very close chemical analog of
the other nitroarenes. The persistence data for 1-nitropyrene cited in
the PBT chemical rule included air half lives of 10 hours to 4 days and
surface water half lives of 16 to 44 years (October 29, 1999, 64 FR
58713). Based on EPA's assessment (Ref. 21), the four nitroarenes are
expected to have similar persistence properties due to structural
similarities and comparability of the available data.
    Most of the bioaccumulation data for the members of the PACs
category were calculated using a regression-derived equation (Ref. 22).
The regression equation used to estimate the BCF values for the PACs
category members for PBT chemical rule was: log BCF = 0.77 log Kow -
0.70 + correction factor. The estimated BCF value for 1-nitropyrene
cited in the PBT rule was 908 (Ref. 22). The most recent equations for
BCF calculations use the equation: log BCF = 0.6598 log Kow - 0.333 +
correction factor (Ref. 21). The results using results both equations
to calculate BCF values for the four nitroarenes are as follows: The
calculated BCF values for 1,6- and 1,8-dinitropyrene ranged from 480-
660, for 6-nitrochrysene they ranged from 1600 to 2600, and for 4-
nitropyrene they ranged from 630-910 (Ref. 21).
    EPA believes that the persistence and bioaccumulation data for the
four nitroarenes is sufficiently similar to that for the current
members of the PACs category that they should be included in the PACs
category with the current 100 pound category reporting threshold.
    8. o-Nitroanisole (CAS No. 91-23-6) (Refs. NTP Profile/Background
document (Refs. 23 and 24)). The National Toxicology Program has
classified o-nitroanisole as ``reasonably anticipated to be a human
carcinogen.'' The classification is based on sufficient evidence of
carcinogenicity in experimental animals. The NTP substance profile for
o-nitroanisole (Ref. 23) included the following summary information of
the evidence of carcinogenicity:
``Carcinogenicity
    o-Nitroanisole is reasonably anticipated to be a human carcinogen
based on sufficient evidence of malignant tumor formation at multiple
tissue sites in multiple species of experimental animals (NTP 1993).
    When administered in the diet to male and female rats, o-
nitroanisole induced increased incidences of mononuclear cell leukemia
and neoplasms of the urinary bladder, kidney, and large intestine. When
administered in the diet to mice, o-nitroanisole induced increased
incidences of benign and malignant hepatocellular neoplasms in males
and increased incidences of hepatocellular adenomas in females.
    No adequate human studies of the relationship between exposure to
o-nitroanisole and human cancer have been reported (IARC 1996).
Additional Information Relevant to Carcinogenicity
    o-Nitroanisole is genotoxic in a wide variety of bacteria and
mammalian cellular assays, and mutagenic and carcinogenic metabolites
have been described (NTP 1993, IARC 1996).
    No data were available that would suggest that the mechanisms
thought to account for tumor induction by o-nitroanisole in
experimental animals would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for o-nitroanisole and
agrees that o-nitroanisole can reasonably be anticipated to cause
cancer in humans. EPA believes that the evidence is sufficient for
listing o-nitroanisole on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
    9. Nitromethane (CAS No. 75-52-5) (Refs. NTP Profile/Background
document (Refs. 25 and 26)). The National Toxicology Program has
classified nitromethane as ``reasonably anticipated to be a human
carcinogen.'' The classification is based on sufficient evidence of
carcinogenicity in experimental animals. The NTP substance profile for
nitromethane (Ref. 25) included the following summary information of
the evidence of carcinogenicity:

``Carcinogenicity
    Nitromethane is reasonably anticipated to be a human carcinogen
based on sufficient evidence of carcinogenicity in experimental
animals. When administered by inhalation, nitromethane significantly
increased the combined incidences of benign and malignant tumors at
three tissue sites in mice and at a different tissue site in rats. In
mice, nitromethane caused harderian gland and lung tumors in both sexes
and liver tumors in females. In rats, nitromethane caused mammary gland
tumors in female F344/N rats but did not cause any increased tumors in
Long-Evans rats (exposed to lower levels) (NTP 1997). The International
Agency for Research on Cancer (2000) also has concluded that there was
sufficient evidence for the carcinogenicity of nitromethane in
experimental animals.
    No studies evaluating the carcinogenicity of nitromethane in humans
were found in the published literature.
Additional Information Relevant to Carcinogenicity
    The mechanism by which nitromethane causes cancer is not known.
Nitromethane did not cause mutations in bacteria and does not appear to
cause genetic damage in mammalian test systems. In cultured mammalian
cells, nitromethane did not cause chromosomal aberrations (changes in
chromosome structure or number), sister chromatid exchange, or
micronucleus formation (a sign of chromosome damage or loss).
Inhalation exposure of mice to nitromethane did not cause micronucleus
formation in the erythrocytes (red blood cells), in either bone marrow
or peripheral (circulating) blood (IARC 2000). In cultured Syrian
hamster embryo cells, nitromethane induced cell transformation (a step
in tumor formation) (Kerckaert et al. 1996, NTP 2002).
    Nitromethane appears to be absorbed by inhalation; the available
data suggest that dermal absorption is negligible. Metabolism of
nitromethane by experimental animals in vivo has not been
characterized. Metabolism of nitromethane by liver microsomes from
Fischer 344 rats resulted in formation of only trace amounts of
formaldehyde (IARC 2000).''
    EPA has reviewed the NTP cancer assessment for nitromethane and
agrees that nitromethane can reasonably be anticipated to cause cancer
in humans. EPA believes that the evidence is sufficient for listing
nitromethane on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
    10. Phenolphthalein (CAS No. 77-09-8) (Refs. NTP Profile/Background
document (Refs. 27 and 28)). The National Toxicology Program has
classified phenolphthalein as ``reasonably anticipated to be a human
carcinogen.'' The classification is based on sufficient evidence of
carcinogenicity in experimental animals. The NTP substance profile for
phenolphthalein (Ref. 27) included the following summary information of
the evidence of carcinogenicity:
``Carcinogenicity
    Phenolphthalein is reasonably anticipated to be a human carcinogen
based on sufficient evidence of increased incidence of malignant and/or
combination of malignant and benign tumors in multiple tissue sites and
in multiple species (IARC 2000). In a two-year B6C3F1 mouse
carcinogenicity study, NTP (1996) concluded that phenolphthalein,
administered in feed, induced significant increases in the incidence of
histiocytic sarcoma and lymphomas of thymic origin in males and females
and malignant lymphoma (all types) and benign ovarian sex cord stromal
tumors in females. In the corresponding Fischer 344 rat dietary
carcinogenicity study, phenolphthalein induced significant increases in
the incidence of benign pheochromocytoma of the adrenal medulla in
males and females and renal tubule adenoma in males (NTP 1996). In a 6-
month dietary study with female heterozygous p53-deficient transgenic
mice, phenolphthalein induced a significant increase in the incidence
of malignant lymphoma of thymic origin (Dunnick et al. 1997).
    A few epidemiological studies have investigated the association
between the use of phenolphthalein-containing laxatives and colon
cancer or adenomatous colorectal polyps. No consistent association was
found. Cancers at other sites have not been investigated in humans
(IARC 2000).
Additional Information Relevant to Carcinogenicity
    The malignant thymic lymphomas induced by phenolphthalein in female
heterozygous p53-deficient transgenic mice exhibited a loss of the
normal p53 allele, suggesting the involvement of a mutagenic mechanism
in tumor induction and/or progression (Dunnick et al. 1997).
    Phenolphthalein causes enhanced oxygen radical production in in
vitro systems. In vivo, reduction of phenoxyl radicals could allow
reformation of phenolphthalein, establishing a futile cycle of
oxidation and reduction, thereby generating more free radical species.
Thus, phenolphthalein may be a significant source of oxidative stress
in physiological systems.
    Although negative for mutagenicity and DNA damage in bacteria,
phenolphthalein exhibits genetic activity in several in vitro and in
vivo mammalian assays. Phenolphthalein was positive for the induction
of chromosomal aberrations in cultured Chinese hamster ovary cells in
the presence of metabolic activation and induced hprt gene mutations,
chromosomal aberrations, and morphological transformation in Syrian
hamster embryo cells. Phenolphthalein was also positive for the
induction of micronucleated erythrocytes in mice following multiple,
but not single, treatments administered by gavage or dosed feed.
Phenolphthalein also induced micronuclei in female heterozygous p53-
deficient transgenic mice exposed via dosed feed for 26 weeks. Abnormal
sperm were induced in male mice, but not male rats, treated with
phenolphthalein via dosed feed for 13 weeks. Phenolphthalein was
negative for Na/K ATPase gene mutations and aneuploidy in Syrian
hamster embryo cells.
    No data were available that would suggest that the mechanisms
thought to account for tumor induction by phenolphthalein in
experimental animals would not also operate in humans. Phenolphthalein
causes oxidative stress and also demonstrates the capability to alter
tumor suppressor gene pathways, which are both mechanisms believed to
be involved in human cancer.''
    EPA has reviewed the NTP cancer assessment for phenolphthalein and
agrees that phenolphthalein can reasonably be anticipated to cause
cancer in humans. EPA believes that the evidence is sufficient for
listing phenolphthalein on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.
    11. Tetrafluoroethylene (CAS No. 116-14-3) (Refs. NTP Profile/
Background document (Refs. 29 and 30)). The National Toxicology Program
has classified tetrafluoroethylene as ``reasonably anticipated to be a
human carcinogen.'' The classification is based on sufficient evidence
of carcinogenicity in experimental animals. The NTP substance profile
for tetrafluoroethylene (Ref. 29) included the following summary
information of the evidence of carcinogenicity:

``Carcinogenicity
    Tetrafluoroethylene (TFE) is reasonably anticipated to be a human
carcinogen based on sufficient evidence of malignant tumor formation at
multiple sites in multiple species of experimental animals (NTP 1997).
When administered by inhalation to F344 rats, TFE induced renal tubule
neoplasms, hepatocellular neoplasms, liver hemangiosarcoma, and
mononuclear cell leukemia. When administered by inhalation to
B6C3F1 mice, TFE induced liver hemangiomas and
hemangiosarcomas, hepatocellular neoplasms, and histiocytic sarcomas.
    No adequate human studies of the relationship between exposure to
TFE and human cancer have been reported (IARC 1999).
Additional Information Relevant to Carcinogenicity
    In prokaryotic systems, TFE was negative for the induction of gene
mutations in Salmonella typhimurium with and without S9 activation. In
mammalian systems in vitro, TFE was also negative for the induction of
gene mutations in Chinese hamster ovary cells (HSDB 2001). No increases
in the frequency of micronucleated erythrocytes were observed in
peripheral blood samples obtained from TFE-exposed mice (NTP 1997).
    The frequency of H-ras codon 61 mutations observed in TFE-induced
hepatocellular neoplasms (15%) was significantly less than the
corresponding frequency (56 to 59%) in spontaneous liver neoplasms of
B6C3F1 mice, suggesting that TFE induces liver neoplasms via
a ras-independent pathway (NTP 1997).
    The kidney-specific toxicity and carcinogenicity of TFE is most
likely related to the selective uptake and subsequent processing of
TFE-glutathione conjugates by renal [beta]-lyase (Miller and Surh 1994,
Anders et al. 1988). In rats, a TFE cysteine conjugate is bioactivated
in the kidney to a difluorothionacetyl fluoride, the putative reactive
metabolite for TFE-induced nephrotoxicity (NTP 1997).
    No data were available that would suggest that the mechanisms
thought to account for tumor induction by TFE in experimental animals
would not also operate in humans.''
    EPA has reviewed the NTP cancer assessment for tetrafluoroethylene
and agrees that tetrafluoroethylene can reasonably be anticipated to
cause cancer in humans. EPA believes that the evidence is sufficient
for listing tetrafluoroethylene on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
    12. Tetranitromethane (CAS No. 509-14-8) (Refs. NTP Profile/NTP
study (Refs. 31 and 32)). The National Toxicology Program has
classified tetranitromethane as ``reasonably anticipated to be a human
carcinogen.'' The classification is based on sufficient evidence of
carcinogenicity in experimental animals. The NTP substance profile for
tetranitromethane (Ref. 31) included the following summary information
of the evidence of carcinogenicity:
``Carcinogenicity
    Tetranitromethane is reasonably anticipated to be a human
carcinogen based on sufficient evidence of carcinogenicity in
experimental animals. Exposure to tetranitromethane in a two-year
inhalation bioassay caused a dose-related increase in alveolar/
bronchiolar neoplasms to nearly all mice and rats exposed to
concentrations of 2 and 5 ppm respectively. The incidences of these
neoplasms in lower exposure concentration groups (2 ppm for rats and
0.5 ppm for mice) were 66% and 44% in male and female rats,
respectively, and 54% and 48% in male and female mice, respectively
(NTP 1990). The majority of animals with alveolar/bronchiolar neoplasms
had neoplasms diagnosed as carcinomas, and these neoplasms frequently
metastasized to a variety of organs. Squamous cell carcinomas of the
lung were also markedly increased in rats exposed to 5 ppm. This
particular type of neoplasm has been found in only 3 of approximately
1,600 untreated control male rats and in none of a similar number of
untreated female controls (NTP 1990).
    No adequate human studies of the relationship between exposure to
tetranitromethane and human cancer have been reported (IARC 1996).''
    EPA has reviewed the NTP cancer assessment for tetranitromethane
and agrees that tetranitromethane can reasonably be anticipated to
cause cancer in humans. EPA believes that the evidence is sufficient
for listing tetranitromethane on EPCRA section 313 pursuant to EPCRA
section 313(d)(2)(B) based on the available carcinogenicity data for
this chemical.
    13. Vinyl Fluoride (CAS No. 75-02-5) (Refs. NTP Profile/Background
document (Refs. 33 and 34)). The National Toxicology Program has
classified vinyl fluoride as ``reasonably anticipated to be a human
carcinogen.'' The classification is based on sufficient evidence of
carcinogenicity in experimental animals. The NTP substance profile for
vinyl fluoride (Ref. 33) included the following summary information of
the evidence of carcinogenicity:
``Carcinogenicity
    Vinyl fluoride is reasonably anticipated to be a human carcinogen
based on sufficient evidence of carcinogenicity in experimental
animals. Both male and female rats exposed to vinyl fluoride by
inhalation showed increased incidences of hepatic hemangiosarcoma,
hepatocellular adenoma or carcinoma, and Zymbal gland carcinoma. Both
male and female mice exposed to vinyl fluoride by inhalation showed
increased incidences of hepatic hemangiosarcoma, bronchiolar-alveolar
adenoma or adenocarcinoma, hepatocellular adenoma, and harderian gland
adenoma. Female mice also showed an increased incidence of mammary
gland adenocarcinoma (Bogdanffy et al. 1995, IARC 1995).
    The tumor responses of laboratory animals to vinyl fluoride are
similar to their responses to vinyl chloride, a known human carcinogen
(IARC 1987), and to vinyl bromide, a probable human carcinogen (IARC
1986). A unique feature of vinyl chloride carcinogenicity is that vinyl
chloride induces rare hepatic hemangiosarcomas in experimental animals
and is causally associated with excess risk of liver hemangiosarcoma in
epidemiological studies of exposed workers. The fact that vinyl
fluoride, vinyl chloride, and vinyl bromide all induce rare
hemangiosarcomas of the liver in experimental animals and induce the
formation of similar DNA adducts suggests a possible common mechanism
of carcinogenicity for all three of these chemicals.
    No adequate human studies of the relationship between exposure to
vinyl fluoride and human cancer were found.
Additional Information Relevant to Carcinogenicity
    Vinyl fluoride is mutagenic in Salmonella typhimurium with the
addition of a rat liver homogenate metabolic activation system. In
addition, vinyl fluoride induces gene mutations and chromosomal
aberrations in Chinese hamster ovary cells (with metabolic activation),
sex-linked recessive lethal mutations in Drosophila melanogaster, and
micronuclei in bone marrow cells of female mice (IARC 1995).
    Vinyl fluoride likely is metabolized in a manner similar to vinyl
chloride: Oxidation via cytochrome P450 to fluoroethylene oxide,
followed by

rearrangement to 2-fluoroacetaldehyde, which is oxidized to
fluoroacetic acid. Human, rat, and mouse liver microsomes metabolize
vinyl fluoride at similar rates (Cantoreggi and Keller 1997). Vinyl
fluoride metabolites form covalent DNA adducts. Inhalation exposure of
rats and mice to vinyl fluoride produced a dose-related increase in the
formation of the promutagenic adduct N \2\,3- ethenoguanine in their
liver DNA (Swenberg et al. 1995).
    No available data suggest that mechanisms by which vinyl fluoride
induces tumors in experimental animals would not also operate in
humans.''
    EPA has reviewed the NTP cancer assessment for vinyl fluoride and
agrees that vinyl fluoride can reasonably be anticipated to cause
cancer in humans. EPA believes that the evidence is sufficient for
listing vinyl fluoride on EPCRA section 313 pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for this
chemical.

V. Rationale for Listing

    The NTP RoC document undergoes significant scientific review and
public comment. The NTP review mirrors the review EPA has historically
done to assess chemicals for listing under EPCRA section 313 on the
basis of carcinogenicity. The conclusions regarding the potential for
chemicals in the NTP RoC to cause cancer in humans are based on
established sound scientific principles. EPA believes that the NTP RoC
is an excellent and reliable source of information on the potential for
chemicals covered in the NTP RoC to cause cancer in humans. Based on
EPA's review of the data contained in the 11th NTP RoC, EPA has
determined that the chemicals in this proposed rule can reasonably be
anticipated to cause cancer. Therefore, EPA believes that the evidence
is sufficient for listing all of the chemicals in this proposed rule on
the EPCRA section 313 toxic chemical list pursuant to EPCRA section
313(d)(2)(B) based on the available carcinogenicity data for these
chemicals as presented in the 11th RoC.
    EPA considers chemicals that can reasonably be anticipated to cause
cancer to have moderately high to high chronic toxicity. EPA does not
believe that it is appropriate to consider exposure for chemicals that
are moderately high to highly toxic based on a hazard assessment when
determining if a chemical can be added for chronic effects pursuant to
EPCRA section 313(d)(2)(B) (see 59 FR 61440-61442). Therefore, in
accordance with EPA's standard policy on the use of exposure
assessments (59 FR 61432), EPA does not believe that an exposure
assessment is necessary or appropriate for determining whether any of
the chemicals in this proposed rule meet the criteria of EPCRA section
313(d)(2)(B).

VI. References

    EPA has established an official public docket for this action under
Docket ID No. EPA-HQ-TRI-2010-0006. The public docket includes
information considered by EPA in developing this action, including the
documents listed below, which are electronically or physically located
in the docket. In addition, interested parties should consult documents
that are referenced in the documents that EPA has placed in the docket,
regardless of whether these referenced documents are electronically or
physically located in the docket. For assistance in locating documents
that are referenced in documents that EPA has placed in the docket, but
that are not electronically or physically located in the docket, please
consult the person listed in the above FOR FURTHER INFORMATION CONTACT
section.
    1. NTP, 2005. National Toxicology Program. Introduction: Report on
Carcinogens, Eleventh Edition. Released January 31, 2005. U.S.
Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709.
    2. USEPA. Guidelines for Carcinogen Risk Assessment. Risk
Assessment Forum, U.S. Environmental Protection Agency, Washington, DC,
March 2005.
    3. USEPA, OEI. Economic Analysis of the Proposed Rule to add 16
Chemicals to the EPCRA Section 313 List of Toxic Chemicals. February
16, 2010.
    4. USEPA, OEI. Memorandum from Mark Miller, PhD, Toxicologist,
Analytical Support Branch to Nicole Paquette, PhD, Chief, Analytical
Support Branch. January 28, 2010. Subject: Review of National
Toxicology Program (NTP) Cancer Classification Data for Sixteen
Chemicals.
    5. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--1-Amino-2,4-dibromoanthraquinone Substance Profile.
Released January 31, 2005. U.S. Department of Health and Human
Services, Public Health Service, National Toxicology Program, Research
Triangle Park, NC 27709.
    6. NTP, 2002. Report on Carcinogens Background Document for 1-
Amino-2,4-dibromoanthraquinone. September 19, 2002. Prepared for, U.S.
Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709. Prepared
by, Technology Planning and Management Corporation Canterbury Hall,
Suite 310, 4815 Emperor Blvd., Durham, NC 27703. Contract Number N01-
ES-85421.
    7. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--2,2-bis(Bromomethyl)-1,3-propanediol Substance Profile.
Released January 31, 2005. U.S. Department of Health and Human
Services, Public Health Service, National Toxicology Program, Research
Triangle Park, NC 27709.
    8. NTP. Report on Carcinogens Background Document for 2,2-
bis(Bromomethyl)-1,3-propanediol (Technical Grade). Prepared for, U.S.
Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709. Prepared
by, Technology Planning and Management Corporation, Canterbury Hall,
Suite 310, 4815 Emperor Blvd., Durham, NC 27703. Contract Number N01-
ES-85421.
    9. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Furan Substance Profile. Released January 31, 2005. U.S.
Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709.
    10. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for Furan. March 1999. Prepared for, November 18-
19, 1996, Meeting of the Report on Carcinogens Subcommittee of the
Board of Scientific Counselors. Prepared by, Integrated Laboratory
Systems, Research Triangle Park, NC 27709. NIEHS Contract No. N01-ES-
25346.
    11. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Glycidol Substance Profile. Released January 31, 2005.
U.S. Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709.
    12. NTP, 1990. Toxicology and Carcinogenesis Studies of Glycidol
(CAS No. 556-52-5) In F344/N Rats and B6C3F1 Mice (Gavage Studies).
Technical Report Series No. 374. NIH Publication No. 90-2829, March
1990. National Toxicology Program, Research Triangle Park, NC. 229 pp.
    13. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Isoprene Substance Profile. Released January 31, 2005.
U.S. Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709.

    14. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for Isoprene. March 1999. Prepared for, December 2-
3, 1998, Meeting of the Report on Carcinogens Subcommittee of the NTP
Board of Scientific Counselors. Prepared by, Integrated Laboratory
Systems, Research Triangle Park, NC 27709. NIEHS Contract No. N01-ES-
25346.
    15. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Methyleugenol Substance Profile. Released January 31,
2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    16. NTP, 2000. Report on Carcinogens Background Document for
Methyleugenol. December 13-14, 2000, Meeting of the NTP Board of
Scientific Counselors Report on Carcinogens Subcommittee. Prepared for,
U.S. Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709. Prepared
by, Technology Planning and Management Corporation, Canterbury Hall,
Suite 310, 4815 Emperor Blvd., Durham, NC 27703. Contract Number N01-
ES-85421.
    17. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Nitroarenes (Selected) Substance Profile. Released January
31, 2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    18. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for 1,6-Dinitropyrene and 1,8-Dinitropyrene. Final
March 1999. Prepared for, November 18-19, 1996, Meeting of the Report
on Carcinogens Subcommittee of the NTP Board of Scientific Counselors.
Prepared by, Integrated Laboratory Systems, Research Triangle Park, NC
27709. NIEHS Contract No. N01-ES-25346.
    19. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for 6-Nitrochrysene. Final March 1999. Prepared
for, November 18-19, 1996, Meeting of the Report on Carcinogens
Subcommittee of the NTP Board of Scientific Counselors. Prepared by,
Integrated Laboratory Systems, Research Triangle Park, NC 27709. NIEHS
Contract No. N01-ES-25346.
    20. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for 4-Nitropyrene. Final March 1999. Prepared for,
November 18-19, 1996, Meeting of the Report on Carcinogens Subcommittee
of the NTP Board of Scientific Counselors. Prepared by, Integrated
Laboratory Systems, Research Triangle Park, NC 27709. NIEHS Contract
No. N01-ES-25346.
    21. USEPA/OEI. Technical Support Document: Bioaccumulation and
Persistence Data for Selected Nitroarenes. Office of Environmental
Information, Environmental Analysis Division, Analytical Support
Branch, November 2009.
    22. USEPA/OPPT. Technical Support Document for Determination of
Bioaccumulation (BAF) and Bioconcentration (BCF) Values for Persistent
Bioaccumulative Toxic (PBT) Chemicals and for Identification of PBT
Chemicals. Jerry Smrchek, PhD, Biologist, Existing Chemicals Assessment
Branch, Risk Assessment Division. September 1998.
    23. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--o-Nitroanisole Substance Profile. Released January 31,
2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    24. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for o-Nitroanisole. Final March 1999. Prepared for,
November 18-19, 1996, Meeting of the Report on Carcinogens Subcommittee
of the NTP Board of Scientific Counselors. Prepared by, Integrated
Laboratory Systems, Research Triangle Park, NC 27709. NIEHS Contract
No. N01-ES-25346.
    25. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Nitromethane Substance Profile. Released January 31, 2005.
U.S. Department of Health and Human Services, Public Health Service,
National Toxicology Program, Research Triangle Park, NC 27709.
    26. NTP, 2002. Final Report on Carcinogens Background Document for
Nitromethane. March 25, 2002. Prepared for, U.S. Department of Health
and Human Services, Public Health Service, National Toxicology Program,
Research Triangle Park, NC 27709. Prepared by, Technology Planning and
Management Corporation, Canterbury Hall, Suite 310, 4815 Emperor Blvd.,
Durham, NC 27703. Contract Number N01-ES-85421.
    27. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Phenolphthalein Substance Profile. Released January 31,
2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    28. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for Phenolphthalein. Final March 1999. Prepared
for, October 30-31, 1997, Meeting of the Report on Carcinogens
Subcommittee of the NTP Board of Scientific Counselors. Prepared by,
Integrated Laboratory Systems, Research Triangle Park, NC 27709. NIEHS
Contract No. N01-ES-25346.
    29. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Tetrafluoroethylene Substance Profile. Released January
31, 2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    30. NTP, 1999. National Toxicology Program Report on Carcinogens
Background Document for Tetrafluoroethylene. Final March 1999. Prepared
for, October 30-31, 1997, Meeting of the Report on Carcinogens
Subcommittee of the NTP Board of Scientific Counselors. Prepared by,
Integrated Laboratory Systems, Research Triangle Park, NC 27709. NIEHS
Contract No. N01-ES-25346.
    31. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Tetranitromethane Substance Profile. Released January 31,
2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    32. NTP, 1990. Toxicology and Carcinogenesis Studies of
Tetranitromethane (CAS No. 509-14-8) in F344/N Rats and B6C3F1 Mice
(Inhalation Studies). Technical Report Series No. 386. NIH Publication
No. 90-2841. Research Triangle Park, NC and Bethesda, NC: National
Toxicology Program. 207 pp.
    33. NTP, 2005. National Toxicology Program. 11th Report on
Carcinogens--Vinyl Fluoride Substance Profile. Released January 31,
2005. U.S. Department of Health and Human Services, Public Health
Service, National Toxicology Program, Research Triangle Park, NC 27709.
    34. NTP. Final Report on Carcinogens Background Document for Vinyl
Fluoride. Meeting of the NTP Board of Scientific Counselors Report on
Carcinogens Subcommittee. Prepared for, U.S. Department of Health and
Human Services, Public Health Service, National Toxicology Program,
Research Triangle Park, NC 27709. Prepared by, Technology Planning and
Management Corporation, Canterbury Hall, Suite 310,

4815 Emperor Blvd, Durham, NC 27703. Contract Number N01-ES-85421.

VIII. Statutory and Executive Order Reviews Associated With This
Action?

A. Executive Order 12866, Regulatory Planning and Review

    This action is not a ``significant regulatory action'' under the
terms of Executive Order (EO) 12866 (58 FR 51735, October 4, 1993) and
is therefore not subject to review under the EO.

B. Paperwork Reduction Act

    This proposed rule does not contain any new information collection
requirements that require additional approval by the Office of
Management and Budget (OMB) under the Paperwork Reduction Act (PRA), 44
U.S.C. 3501 et seq. Currently, the facilities subject to the reporting
requirements under EPCRA 313 and PPA 6607 may use either the EPA Toxic
Chemicals Release Inventory Form R (EPA Form 1B9350-1), or the EPA
Toxic Chemicals Release Inventory Form A (EPA Form 1B9350-2). The Form
R must be completed if a facility manufactures, processes, or otherwise
uses any listed chemical above threshold quantities and meets certain
other criteria. For the Form A, EPA established an alternative
threshold for facilities with low annual reportable amounts of a listed
toxic chemical. A facility that meets the appropriate reporting
thresholds, but estimates that the total annual reportable amount of
the chemical does not exceed 500 pounds per year, can take advantage of
an alternative manufacture, process, or otherwise use threshold of 1
million pounds per year of the chemical, provided that certain
conditions are met, and submit the Form A instead of the Form R. In
addition, respondents may designate the specific chemical identity of a
substance as a trade secret pursuant to EPCRA section 322 42 U.S.C.
11042: 40 CFR part 350.
    OMB has approved the reporting and recordkeeping requirements
related to Form R, supplier notification, and petitions under OMB
Control number 2070-0093 (EPA Information Collection Request (ICR) No.
1363.15); those related to Form A under OMB Control number 2070-0143
(EPA ICR No. 1704.09); and those related to trade secret designations
under OMB Control number 2070-0078 (EPA ICR No. 1428). As provided in 5
CFR 1320.5(b) and 1320.6(a), an Agency may not conduct or sponsor, and
a person is not required to respond to, a collection of information
unless it displays a currently valid OMB control number. The OMB
Control numbers relevant to EPA's regulations are listed in 40 CFR part
9, 48 CFR chapter 15, and displayed on the information collection
instruments (e.g., forms, instructions).
    For Form R, EPA estimates the industry reporting and recordkeeping
burden for collecting this information to average, in the first year,
approximately $4,615 per Form R (for a total first year cost of
$858,299 based on 16,069 total burden hours). In subsequent years, the
burden for collecting this information is estimated to average $1,553
per Form R (for a total cost of $288,902 based on 5,517 total burden
hours). These estimates include the time needed to become familiar with
the requirement (first year only); review instructions; search existing
data sources; gather and maintain the data needed; complete and review
the collection information; and transmit or otherwise disclose the
information. The actual burden on any facility may be different from
this estimate depending on the complexity of the facility's operations
and the profile of the releases at the facility. Upon promulgation of a
final rule, the Agency may determine that the existing burden estimates
in the ICRs need to be amended in order to account for an increase in
burden associated with the final action. If so, the Agency will submit
an information collection worksheet (ICW) to OMB requesting that the
total burden in each ICR be amended, as appropriate.
    The Agency would appreciate any comments or information that could
be used to: (1) Evaluate whether the proposed collection of information
is necessary for the proper performance of the functions of the Agency,
including whether the information will have practical utility; (2)
evaluate the reasonableness of the Agency's estimate of the burden of
the proposed collection of information, including the validity of the
methodology and assumptions used; (3) enhance the quality, utility, and
clarity of the information to be collected; and (4) minimize the burden
of the collection of information on those who are to respond, including
through the use of appropriate automated electronic, mechanical, or
other technological collection techniques or other forms of information
technology, e.g., permitting electronic submission of responses. Please
submit your comments within 90 days as specified at the beginning of
this proposal. Copies of the existing ICRs may be obtained from Rick
Westlund, Collection Strategies Division, U.S. Environmental Protection
Agency (2822T), 1200 Pennsylvania Ave., NW., Washington, DC 20460 or by
calling<PHONE_NUMBER>.

C. Regulatory Flexibility Act (RFA), as Amended by the Small Business
Regulatory Enforcement Fairness Act of 1996 (SBREFA), 5 U.S.C. 601 et
seq.

    The RFA generally requires an agency to prepare a regulatory
flexibility analysis of any rule subject to notice and comment
rulemaking requirements under the Administrative Procedure Act or any
other statute unless the agency certifies that the rule will not have a
significant economic impact on a substantial number of small entities.
Small entities include small businesses, small organizations, and small
governmental jurisdictions. For purposes of assessing the impacts of
today's rule on small entities, small entity is defined as: (1) A
business that is classified as a ``small business'' by the Small
Business Administration at 13 CFR 121.201; (2) a small governmental
jurisdiction that is a government of a city, county, town, school
district or special district with a population of less than 50,000; and
(3) a small organization that is any not-for-profit enterprise which is
independently owned and operated and is not dominant in its field.
    Of the 109 entities estimated to be impacted by this proposed rule,
41 are small businesses. Of the affected small businesses, all 41 have
cost impacts of less than 1% in both the first and subsequent years of
the rulemaking. No small businesses are projected to have a cost impact
of 1% or greater. In the first year, of the 41 estimated cost impacts,
there is a maximum impact of 0.616% and a minimum impact of less than
0.001%. Facilities eligible to use Form A (those meeting the
appropriate activity threshold which have 500 pounds per year or less
of reportable amounts of the chemical) will have a lower burden. No
small governments or small organizations are expected to be affected by
this action. Thus this rule is not expected to have a significant
adverse economic impact on a substantial number of small entities. A
more detailed analysis of the impacts on small entities is located in
EPA's economic analysis support document (Ref. 3).
    After considering the economic impacts of today's rule on small
entities, I certify that this action will not have a significant
economic impact on a substantial number of small entities. We continue
to be interested in the potential impacts of the proposed rule on small
entities and welcome comments on issues related to such impacts.

D. Unfunded Mandates Reform Act

    This rule does not contain a Federal mandate that may result in
expenditures of $100 million or more for State, local, and tribal
governments, in the aggregate, or the private sector in any one year.
EPA's economic analysis indicates that the total cost of this rule is
estimated to be $859,072 in the first year of reporting. Thus, this
rule is not subject to the requirements of sections 202 or 205 of UMRA.
    This rule is also not subject to the requirements of section 203 of
UMRA because it contains no regulatory requirements that might
significantly or uniquely affect small governments. Small governments
are not subject to the EPCRA section 313 reporting requirements.

E. Executive Order 13132 (Federalism)

    This action does not have federalism implications. It will not have
substantial direct effects on the States, on the relationship between
the national government and the States, or on the distribution of power
and responsibilities among the various levels of government, as
specified in Executive Order 13132. This action relates to toxic
chemical reporting under EPCRA section 313, which primarily affects
private sector facilities. Thus, Executive Order 13132 does not apply
to this action.
    In the spirit of Executive Order 13132, and consistent with EPA
policy to promote communications between EPA and State and local
governments, EPA specifically solicits comment on this proposed action
from State and local officials.

F. Executive Order 13175: Consultation and Coordination With Indian
Tribal Governments

    This action does not have tribal implications, as specified in
Executive Order 13175 (65 FR 67249, November 9, 2000). This action
relates to toxic chemical reporting under EPCRA section 313, which
primarily affects private sector facilities. Thus, Executive Order
13175 does not apply to this action. In the spirit of Executive Order
13175, and consistent with EPA policy to promote communications between
EPA and Indian Tribal Governments, EPA specifically solicits additional
comment on this proposed action from tribal officials.

G. Executive Order 13045: Protection of Children From Environmental
Health Risks and Safety Risks

    This action is not subject to EO 13045 (62 FR 19885, April 23,
1997) because it is not economically significant as defined in EO
12866, and because the Agency does not believe the environmental health
or safety risks addressed by this action present a disproportionate
risk to children. This action relates to toxic chemical reporting under
EPCRA section 313, which primarily affects private sector facilities.

H. Executive Order 13211: Actions Concerning Regulations That
Significantly Affect Energy Supply, Distribution, or Use

    This action is not subject to Executive Order 13211 (66 FR 28355
(May 22, 2001)), because it is not a significant regulatory action
under Executive Order 12866.

I. National Technology Transfer and Advancement Act

    Section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (``NTTAA''), Public Law 104-113, 12(d) (15 U.S.C. 272 note)
directs EPA to use voluntary consensus standards in its regulatory
activities unless to do so would be inconsistent with applicable law or
otherwise impractical. Voluntary consensus standards are technical
standards (e.g., materials specifications, test methods, sampling
procedures, and business practices) that are developed or adopted by
voluntary consensus standards bodies. NTTAA directs EPA to provide
Congress, through OMB, explanations when the Agency decides not to use
available and applicable voluntary consensus standards.
    This proposed rulemaking does not involve technical standards.
Therefore, EPA is not considering the use of any voluntary consensus
standards.

J. Executive Order 12898: Federal Actions To Address Environmental
Justice in Minority Populations and Low-Income Populations

    Executive Order (EO) 12898 (59 FR 7629 (Feb. 16, 1994)) establishes
Federal executive policy on environmental justice. Its main provision
directs Federal agencies, to the greatest extent practicable and
permitted by law, to make environmental justice part of their mission
by identifying and addressing, as appropriate, disproportionately high
and adverse human health or environmental effects of their programs,
policies, and activities on minority populations and low-income
populations in the United States.
    EPA has determined that this proposed rule will not have
disproportionately high and adverse human health or environmental
effects on minority or low-income populations because it does not
affect the level of protection provided to human health or the
environment. This proposed rule adds additional chemicals to the EPCRA
section 313 reporting requirements. By adding chemicals to the list of
toxic chemicals subject to reporting under section 313 of EPCRA, EPA
would be providing communities across the United States (including
minority populations and low income populations) with access to data
which they may use to seek lower exposures and consequently reductions
in chemical risks for themselves and their children. This information
can also be used by government agencies and others to identify
potential problems, set priorities, and take appropriate steps to
reduce any potential risks to human health and the environment.
Therefore, the informational benefits of the proposed rule will have a
positive impact on the human health and environmental impacts of
minority populations, low-income populations, and children.

List of Subjects in 40 CFR Part 372

    Environmental protection, Community right-to-know, Reporting and
recordkeeping requirements, and Toxic chemicals.

    Dated: March 31, 2010.
Lisa P. Jackson,
Administrator.
    Therefore, it is proposed that 40 CFR part 372 be amended as
follows:

PART 372--[AMENDED]

    1. The authority citation for part 372 continues to read as
follows:

    Authority:  42 U.S.C. 11023 and 11048.

Sec.  372.28  [Amended]

    2. In Sec.  372.28, the table in paragraph (a)(2) under the heading
``Polycyclic aromatic compounds (PACs): (This category includes only
those chemicals listed below)'' is amended by adding four new entries
in alphabetical order to read as follows:

Sec.  372.28  Lower thresholds for chemicals of special concern.

    (a) * * *
    (2) * * *

------------------------------------------------------------------------
                                                             Reporting
                      Category name                          threshold
------------------------------------------------------------------------

                                * * * * *
Polycyclic aromatic compounds (PACs): (This category                 100
 includes only those chemicals listed below)............

                                * * * * *
42397-64-8 1,6-Dinitropyrene............................
42397-65-9 1,8-Dinitropyrene............................

                                * * * * *
07496-02-8 6-Nitrochrysene..............................

                                * * * * *
57835-92-4 4-Nitropyrene................................
------------------------------------------------------------------------

Sec.  372.65  [Amended]

    3. Section 372.65 is amended as follows:
    a. In the table to paragraph (a) by adding new entries in
alphabetical order.
    b. In the table to paragraph (b) by adding new entries in numerical
order.
    c. In the table to paragraph (c) under the heading ``Polycyclic
aromatic compounds (PACs): (This category includes only those chemicals
listed below)'' by adding four entries in alphabetical order.

Sec.  372.65  Chemicals and chemical categories to which the part
applies.

* * * * *
    (a) * * *

------------------------------------------------------------------------
                                                              Effective
              Chemical name                    CAS No.           date
------------------------------------------------------------------------

                              * * * * * * *
1-Amino-2,4-dibromoanthraquinone........         00081-49-2         1/11

                              * * * * * * *
2,2-bis(Bromomethyl)-1,3-propanediol....        003296-90-0         1/11

                              * * * * * * *
Furan...................................         00110-00-9         1/11

                              * * * * * * *
Glycidol................................         00556-52-5         1/11

                              * * * * * * *
Isoprene................................         00078-79-5         1/11

                              * * * * * * *
Methyleugenol...........................         00093-15-2         1/11

                              * * * * * * *
o-Nitroanisole..........................         00091-23-6         1/11

                              * * * * * * *
Nitromethane............................         00075-52-5         1/11

                              * * * * * * *
Phenolphthalein.........................         00077-09-8         1/11

                              * * * * * * *
Tetrafluoroethylene.....................         00116-14-3         1/11

                              * * * * * * *
Tetranitromethane.......................         00509-14-8         1/11

                              * * * * * * *
Vinyl Fluoride..........................         00075-02-5         1/11

                              * * * * * * *
------------------------------------------------------------------------

    (b) * * *

------------------------------------------------------------------------
                                                              Effective
             CAS No.                     Chemical name           date
------------------------------------------------------------------------

                               * * * * * *
00075-02-5.......................  Vinyl Fluoride..........         1/11

                               * * * * * *
00075-52-5.......................  Nitromethane............         1/11

                               * * * * * *
00077-09-8.......................  Phenolphthalein.........         1/11

                               * * * * * *
00078-79-5.......................  Isoprene................         1/11

                               * * * * * *
00081-49-2.......................  1-Amino-2,4-                     1/11
                                    dibromoanthraquinone.

                               * * * * * *
00091-23-6.......................  o-Nitroanisole..........         1/11

                               * * * * * *
00093-15-2.......................  Methyleugenol...........         1/11

                               * * * * * *
00110-00-9.......................  Furan...................         1/11

                               * * * * * *
00116-14-3.......................  Tetrafluoroethylene.....         1/11

                               * * * * * *
00509-14-8.......................  Tetranitromethane.......         1/11

                               * * * * * *
00556-52-5.......................  Glycidol................         1/11

                               * * * * * *
03296-90-0.......................  2,2-bis(Bromomethyl)-1,3-        1/11
                                    propanediol.

                               * * * * * *
------------------------------------------------------------------------

    (c) * * *

------------------------------------------------------------------------
                                                              Effective
                       Category name                             date
------------------------------------------------------------------------

                               * * * * * *
Polycyclic aromatic compounds (PACs): (This category
 includes only those chemicals listed below)...............

                               * * * * * *
42397-64-8 1,6-Dinitropyrene...............................         1/11
42397-65-9 1,8-Dinitropyrene...............................         1/11

                               * * * * * *
07496-02-8 6-Nitrochrysene.................................         1/11

                               * * * * * *
57835-92-4 4-Nitropyrene...................................         1/11
------------------------------------------------------------------------

[FR Doc. 2010-7756 Filed 4-5-10; 8:45 am]
BILLING CODE 6560-50-P