[Federal Register Volume 70, Number 113 (Tuesday, June 14, 2005)]
[Proposed Rules]
[Pages 34437-34440]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-11664]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 372

[TRI-2005-0004; FRL-7532-4]
RIN 2025-AA17


Addition of Diisononyl Phthalate Category; Community Right-to-
Know Toxic Chemical Release Reporting; Notice of Data Availability

AGENCY: Environmental Protection Agency (EPA).

ACTION: Proposed rule, notice of data availability.

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SUMMARY: On September 5, 2000, EPA issued a proposed rule, in response 
to a petition filed under section 313(e)(1) of the Emergency Planning 
and Community Right-to-Know Act (EPCRA), to add a diisononyl phthalate 
(DINP) category to the list of toxic chemicals subject to the reporting 
requirements under EPCRA section 313 and section 6607 of the Pollution 
Prevention Act (PPA). EPA proposed to add this chemical category to the 
EPCRA section 313 toxic chemical list pursuant to its authority to add 
chemicals and chemical categories because EPA believes this category 
meets the EPCRA section 313(d)(2)(B) toxicity criterion. The purpose of 
today's action is to inform interested parties that, in an effort to 
ensure adequate opportunities for input from all affected parties, EPA 
is making available for public comment a revised hazard assessment for 
DINP.

DATES: Comments must be received on or before September 12, 2005.

ADDRESSES: Submit your comments, identified by Docket ID No. TRI-2005-
0004, by one of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the on-line instructions for submitting comments.
     Agency Web site: http://www.epa.gov/edocket. EDOCKET, 
EPA's electronic public docket and comment system, is EPA's preferred 
method for receiving comments. Follow the on-line instructions for 
submitting comments.
     E-mail: [email protected].
     Mail: Office of Environmental Information (OEI) Docket, 
Environmental Protection Agency, Mail Code: 28221T, 1200 Pennsylvania 
Ave., NW., Washington, DC, 20460, Attention Docket ID No. TRI-2005-
0004.
     Hand Delivery: EPA Docket Center, (EPA/DC) EPA West, Room 
B102, 1301 Constitution Ave., NW., Washington, DC, 20004, telephone: 
202-566-1744, Attention Docket ID No. TRI-2005-0004. 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. TRI-2005-0004. 
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.epa.gov/edocket, 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 EDOCKET, regulations.gov, or e-
mail. The EPA EDOCKET and the Federal regulations.gov Web sites are 
``anonymous access'' systems, 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 EDOCKET or 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, any form of encryption, and be free of 
any defects or viruses.
    Docket: All documents in the docket are listed in the EDOCKET index 
at: http://www.epa.gov/edocket. Although listed in the index, some 
information is not publicly available, i.e., CBI or other information 
whose disclosure is restricted by statute. Certain other material, such 
as copyrighted material, is not placed on the Internet and will be 
publicly available only in hard copy form. Publicly available docket 
materials are available either electronically in EDOCKET or in hard 
copy at the OEI Docket, EPA/DC, EPA West, Room B102, 1301 Constitution 
Ave., NW., Washington, DC. The Public Reading Room 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 202-566-1744, and the 
telephone number for the OEI Docket is 202-566-1752.

FOR FURTHER INFORMATION CONTACT: Daniel R. Bushman, Toxics Release 
Inventory Program Division, Office of Information Analysis and Access 
(2844T), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460; telephone number: 202-566-0743; fax number: 202-
566-0741; e-mail: [email protected], for specific 
information on this proposed rule, or for more information on EPCRA 
section 313, the Emergency Planning and Community Right-to-Know 
Hotline, Environmental Protection Agency, Mail Code 5101, 1200 
Pennsylvania Ave., NW., Washington, DC 20460, Toll free: 1-800-424-
9346, in Virginia and Alaska: 703-412-9810 or Toll free TDD: 1-800-553-
7672.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does This Notice Apply To Me?

    You may be potentially affected by this notice if you manufacture, 
process, or otherwise use DINP. Potentially affected categories and 
entities may include, but are not limited to:

[[Page 34438]]



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                      Category                                 Examples of potentially affected entities
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Industry............................................  SIC major group codes 10 (except 1011, 1081, and 1094); 12
                                                       (except 1241); or 20 through 39; or industry codes 4911
                                                       (limited to facilities that combust coal and/or oil for
                                                       the purpose of generating power for distribution in
                                                       commerce); or 4931 (limited to facilities that combust
                                                       coal and/or oil for the purpose of generating power for
                                                       distribution in commerce); or 4939 (limited to facilities
                                                       that combust coal and/or oil for the purpose of
                                                       generating power for distribution in commerce); or 4953
                                                       (limited to facilities regulated under the Resource
                                                       Conservation and Recovery Act, subtitle C, 42 U.S.C.
                                                       section 6921 et seq.); or 5169; or 5171; or 7389 (limited
                                                       to facilities primarily engaged in solvent recovery
                                                       services on a contract or fee basis).
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. 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 information that you consider to be CBI 
electronically through EPA's electronic public docket or by e-mail. 
Commenters wishing to submit proprietary information for consideration 
must clearly distinguish such information from other comments and 
clearly label it as CBI. Send submissions containing such proprietary 
information directly to the following address only, and not to the 
public docket, to ensure that proprietary information is not 
inadvertently placed in the docket: Attention: OEI Document Control 
Officer, Mail Code: 2822T, U.S. EPA, 1200 Pennsylvania Ave., NW., 
Washington, DC, 20460. You may claim information that you submit to EPA 
as CBI by marking any part or all of that information as CBI (if you 
submit CBI on disk or CD ROM, 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 CBI). The EPA will disclose information 
claimed as CBI only to the extent allowed by the procedures set forth 
in 40 CFR part 2.
    In addition to one complete version of the comment that includes 
any 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 and EPA's electronic public docket. If you submit 
the copy that does not contain CBI on disk or CD ROM, mark the outside 
of the disk or CD ROM clearly that it does not contain CBI. Information 
not marked as CBI will be included in the public docket and EPA's 
electronic public docket without prior notice. If you have any 
questions about CBI or the procedures for claiming CBI, please consult 
the person identified in the FOR FURTHER INFORMATION CONTACT section.

II. What Did EPA Propose and What Is the Purpose of This Notice?

    In response to a petition to add diisononyl phthalate (DINP) to the 
EPCRA section 313 list of toxic chemicals, EPA published a proposed 
rule to add a DINP category to the EPCRA section 313 list (65 FR 53681, 
September 5, 2000). The proposed rule was based on information 
contained in the hazard assessment for DINP that was developed in 
response to the petition (Ref. 1). In response to comments on the 
proposal, EPA revised its hazard assessment for DINP. The purpose of 
this notice is to allow the public an opportunity to comment on a 
revised hazard assessment that EPA has developed for DINP (Ref. 2).

A. What Preliminary Determinations Did EPA Reach in the Proposed Rule?

    After a review of the data available at the time, the Agency 
preliminarily determined that there was sufficient evidence to support 
the conclusion that DINP can reasonably be anticipated to cause 
carcinogenicity and liver, kidney, and developmental toxicity. The 
preliminary findings were summarized as follows.

    DINP has been shown to cause developmental toxicity in prenatal 
rats. This developmental toxicity included significant decreases in 
the mean body weight of pups from two generations which may result 
in serious developmental delays in growth throughout the lifetime. 
In addition, skeletal variations were observed which may interfere 
with normal nerve function and blood flow. Kidney effects in fetuses 
were observed which might lead to progressive kidney damage and 
impaired kidney function.
    DINP has been shown to cause chronic liver and kidney toxicity 
in rats and mice. The liver effects are indicators of the serious 
liver damage produced by DINP and are early indicators of the tissue 
damage which leads to DINP-induced tumors. In addition to chronic 
liver toxicity, biochemical indicators of chronic kidney toxicity 
were evident in male and female rats. Also, chronic progressive 
irreversible kidney damage (nephropathy) occurred in female mice 
which lead to early mortality.
    DINP has been shown to be a liver carcinogen in rats and mice, 
to induce kidney tumors in male rats, and to increase the incidence 
of mononuclear cell leukemia. (65 FR 53686, September 5, 2000).

EPA EAPA also stated that:

    EPA currently believes that it is reasonable to anticipate that 
all members of the DINP category as described will exhibit 
carcinogenicity and liver, kidney, and developmental toxicity in 
humans and that creating a category of DINP is the most appropriate 
way to list this class of chemicals. (65 FR 53686, September 5, 
2000).

B. Why Has EPA Issued This Notice?

    EPA received significant comments on its original hazard assessment 
for DINP both during the comment period for the proposed rule and in 
later submissions to the Agency. Based on the comments EPA received, 
the Agency decided to revise the DINP hazard assessment and subject the 
document to a peer review process. The revised DINP hazard assessment 
was reviewed by experts within EPA and then by a group of external peer 
reviewers. Based on these reviews EPA made additional revisions to the 
DINP hazard assessment. The comments received from the external peer 
reviewers and EPA's responses to those comments have been placed in the 
docket for this notice (Ref. 3). The revisions to the hazard assessment 
have an impact on the preliminary conclusions that EPA reached in the 
proposed rule. Therefore, EPA is making the revised DINP hazard 
assessment available for public comment through the publication of this 
notice.

III. How Has the Hazard Assessment Changed?

    The original DINP hazard assessment has been updated to include the 
most recent data available on the toxicity of DINP and has been revised 
based on public comments and on feedback from internal and external 
peer reviewers. Based on public comment, the revised hazard assessment 
has been expanded

[[Page 34439]]

to include a more extensive discussion of each human health endpoint of 
concern. The significant substantive changes to the hazard assessment 
are discussed in the following sections.

A. What Changes Have Been Made to the Discussion of Carcinogenicity?

    1. Liver Cancer. In the original DINP hazard assessment (Ref. 1), 
EPA stated that DINP was a liver carcinogen in rats and mice and could 
reasonably be anticipated to cause cancer in humans. Liver tumors were 
demonstrated in three independent chronic studies in rats and mice 
(Refs. 4, 5, and 6). At that time, EPA acknowledged that there was an 
ongoing scientific discussion regarding the role of peroxisome 
proliferation and peroxisome proliferation activating receptor-/ (PPAR/
) activation in rodent liver tumors and its relevance to human cancer.
    In accordance with EPA's cancer guidelines (Ref. 7), however, the 
data were considered insufficient to demonstrate that a response in 
animals was not relevant to any human situation. Therefore, the default 
assumption that positive effects in animal studies indicate that DINP 
could have carcinogenic potential in humans was warranted. Based on 
this default assumption, EPA's position in the original hazard 
assessment was that DINP could reasonably be anticipated to cause 
cancer in humans.
    Recently, the Office of Prevention, Pesticides and Toxics 
Substances (OPPTS) presented a draft of a proposed OPPTS science policy 
on PPAR[alpha]mediated hepatocarcinogenicity to the Federal 
Insecticide, Fungicide, and Rodenticide Act (FIFRA) Science Advisory 
Panel (SAP), a Federal advisory committee. The SAP serves as the 
primary scientific peer review mechanism of OPPTS under Section 25(d) 
of FIFRA. The guidance document described an approach OPPTS proposed to 
use to evaluate the scientific information regarding the mode of action 
of PPAR/ activating chemicals, such as DINP, in rodent liver tumors and 
the relevance of this mode of action for human liver cancer. EPA is 
currently reviewing the responses from the FIFRA SAP and will notify 
the public on a science policy decision. EPA therefore reserves 
judgment on whether DINP can reasonably be anticipated to cause liver 
cancer in humans, pending the results of this EPA review. The revised 
DINP hazard assessment has been updated to include a discussion of 
EPA's ongoing review.
    2. Mononuclear Cell Leukemia. In the original DINP hazard 
assessment (Ref. 1), EPA stated that there were clear, statistically 
significant increases in the incidences of mononuclear cell leukemia 
(MNCL) in two independent chronic oral studies using Fischer rats. 
Fischer rats (F-344) had an increased mortality due to MNCL in DINP-
treated rats suggesting that DINP is associated with the elevated 
incidence, progression and severity of MNCL. The tumor findings may be 
biologically significant because the time to onset of tumor was shorter 
and the disease was more severe in treated animals compared to the 
timing of onset and severity in control animals. EPA believes that it 
is therefore highly unlikely that these findings were unrelated to 
treatment. EPA notes, however, that there are several sources of 
uncertainty in the interpretation of the MNCL data. These include a 
high and variable background rate of MNCL and a lack of information on 
the mode of action for induction of MNCL. Furthermore, some scientists 
believe that MNCL may be a rodent-specific cancer of unclear relevance 
to human cancer. EPA is reviewing the scientific question of the 
biological relevance of MNCL and human cancer. As a result of these 
scientific uncertainties, EPA reserves judgment on the human 
significance of MNCL and whether DINP can reasonably be anticipated to 
cause cancer in humans.
    Because the data currently available do not permit a clear 
conclusion on the relevance of DINP-induced liver tumors and MNCL at 
this time, EPA reserves judgment on whether DINP can reasonably be 
anticipated to cause cancer in humans.

B. What Changes Have Been Made to the Discussion of Chronic Liver 
Toxicity?

    In the original DINP hazard assessment (Ref. 1), EPA stated that 
DINP could reasonably be anticipated to cause chronic liver toxicity 
based on increased liver weight, increased liver enzyme activities, and 
chronic liver lesions based on two chronic studies in rats (Refs. 4 and 
5). In the revised hazard assessment, the chronic liver lesion is 
described in more detail and identified as spongiosis hepatis. The 
incidence of spongiosis hepatis was dose-related and significantly 
elevated in male rats chronically treated with DINP in two independent 
studies conducted by different laboratories. The incidence of 
spongiosis hepatis was not elevated in female rats or in male or female 
mice. Based on the available data, the Agency has identified a No 
Observed Adverse Effect Level (NOAEL) of 15 milligrams per kilogram per 
day (mg/kg/day) and a Lowest Observed Adverse Effect Level (LOAEL) of 
152 mg/kg/day for the Lington et al. study (Ref. 4) and a NOAEL of 88 
mg/kg/day and a LOAEL of 359 mg/kg/day for the Moore study (Ref. 5), 
based on indications of serious liver damage (i.e., a statistically 
significant increased incidence of spongiosis hepatis and increased 
liver weight and liver enzyme activities) in male rats chronically 
exposed to DINP for two years.
    The Agency believes that the existing data support the conclusion 
that the increased incidence of spongiosis hepatis in dosed rats is 
clearly related to DINP treatment. In further evaluating the data for 
hepatic spongiosis, the Agency considered (1) The possibility that the 
occurrence of spongiosis hepatis and induction of peroxisome 
proliferation were related; (2) the possibility that the occurrence of 
spongiosis hepatis was a consequence of MNCL; (3) the relationship of 
spongiosis hepatis to hepatocellular cancer; and (4) the human 
relevance of hepatis spongiosis.
    EPA believes that the occurrence of spongiosis hepatis is not 
likely to be related to the occurrence of peroxisome proliferation, 
hepatocellular cancer, or MNCL. Spongiosis hepatis is a lesion of the 
perisinusoidal cells of the liver (the Ito cells) whereas the 
carcinogenic and other toxic effects of DINP on the liver involved 
hepatocytes, which are the predominant cell type in the liver. This 
lesion has been found in livers of rodents and fish following exposure 
to substances (e.g., nitrosamines) that induce cancer in these species 
(Ref. 8). Both chronic studies of DINP (Refs. 4 and 5) reported 
increased incidences of treated male rats with spongiosis hepatis. EPA 
has determined that spongiosis hepatis is relevant to human health and 
that determination is discussed in detail in the revised hazard 
assessment (Ref. 2, section II.E.1).
    Spongiosis hepatis was also considered to be a significant finding 
by the authoritative scientific panel, the U.S. Consumer Product Safety 
Commission's (CPSC) Chronic Hazard Advisory Panel (CHAP) on DINP in 
their final report (Ref. 9). In addition to the CPSC panel report, a 
Histopathology Peer Review and Pathology Working Group convened by 
Experimental Pathology Laboratories (ELP) (Ref. 10) independently 
evaluated the liver slides from rats chronically treated with DINP and 
confirmed that the spongiosis hepatitis was increased in male rats of 
both chronic rodent studies. These findings support EPA's position that 
chronic liver toxicity is an endpoint of concern for DINP. At the time 
of the development of the original DINP hazard assessment, EPA had not

[[Page 34440]]

reviewed the ELP report (Ref. 10), or seen the CHAP report (Ref. 9) 
that discusses the ELP report conclusions because the final CHAP report 
was not available.

IV. How Does the Revised Hazard Assessment Impact EPA's Previous 
Conclusions About the Toxicity of DINP?

    In the previous DINP hazard assessment (Ref. 1), carcinogenicity 
was determined to be a significant concern for DINP. However, based on 
the revised hazard assessment (Ref. 2), at this time EPA reserves 
judgment on whether cancer is an endpoint of concern for DINP. This 
conclusion may change in the future depending on how EPA resolves the 
issues concerning the human relevance of the types of tumors that DINP 
has been shown to cause. The revised hazard assessment also provides a 
more detailed and specific discussion about the ability of DINP to 
cause chronic liver toxicity than that contained in the previous hazard 
assessment. The revised discussion on chronic liver toxicity provides 
additional support to the previous conclusion that DINP causes chronic 
liver toxicity.
    The revised DINP hazard assessment does not affect the previous 
conclusions from the original DINP hazard assessment that developmental 
and chronic kidney toxicity are endpoints of concern for DINP. In 
addition, nothing in the revised DINP hazard assessment affects EPA's 
previous conclusion that the addition of DINP as a category of 
chemicals, rather than individual chemical listings, would be 
appropriate.

V. What Type of Comments Is EPA Interested In Receiving?

    EPA is requesting comments on all parts of the revised hazard 
assessment. However, EPA is specifically interested in comments on the 
sections of the revised hazard assessment that deal with 
carcinogenicity and chronic liver toxicity. EPA also requests 
commenters to provide any additional data or information on the human 
relevance of any of the adverse effects discussed in the revised hazard 
assessment.

VI. References

    EPA has established an official public docket for this action under 
Docket ID No. TRI-2005-0004. The previous docket number for the 
proposed rule was OEI-100004 and was assigned prior to the development 
of EPA's electronic public docket and comment system. Therefore, EPA is 
creating a new electronic docket number for this action. All the 
materials submitted to docket number OEI-100004 have been transferred 
to docket number TRI-2005-0004. The public docket includes information 
considered by EPA in developing this proposed rule, 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. USEPA, OEI. 2000. Technical Review of Diisononyl Phthalate. 
Office of Environmental Information, Becki Madison, Christine 
Augustyniak, Ron Bloom, Candace Brassard, Ossi Meyn, Nicole Paquette, 
Pam Russell, and John Scalera.
    2. USEPA, OEI. 2005. Revised Technical Review of Diisononyl 
Phthalate, March 4, 2005. Office of Environmental Information, 
Environmental Analysis Division, Analytical Support Branch. Amy Newman, 
Candace Brassard, Kathryn Montague, Nicole Paquette, Ph.D., and John 
Scalera.
    3. USEPA, OEI. 2005. Response to External Peer Review Comments on 
the Revised Technical Review for Diisononyl Phthalate, April 2005.
    4. Lington, A.W.; Bird M.G.; Plutnick, R.T.; Stubblefield, W.A.; 
and Scala, RA. 1997. Chronic toxicity and carcinogenic evaluation of 
diisononyl phthalate in rats. Fundam. Appl. Toxicol 36: 79-89.
    5. Moore, M.R., 1998. Oncogenicity study in rats with 
di(isononyl)phthalate including ancillary hepatocellular proliferation 
and biochemical analyses. TSCATS Doc 89980000308. Old Doc 
8EHQ099813083. Fiche  OTS05562832. Submitted by Aristech 
Chemical Corporation. Produced by Covance Laboratories 2598-104.
    6. Moore M.R., 1998. Oncogenicity study in mice with 
di(isononyl)phthalate including ancillary hepatocellular proliferation 
and biochemical analyses. TSCATS Doc 89990000046. Old Doc 
8EHQ119813083. Fiche  OTS05562833. Submitted by Aristech 
Chemical Corp. Produced by Covance 2598-105.
    7. USEPA. 1999. Draft Revised Guidelines for Carcinogen Risk 
Assessment. NCEA-F-0644, July 1999.
    8. Stoebel, P.; Mayer, F.; Zerban, H., Bannasch, P. 1995. 
Spongiotic pericytoma: a benign neoplasm deriving from the 
perisinusoidal cells in rat liver. Am. J. Pathol. 146:903-913.
    9. Chronic Hazard Advisory Panel on Diisononyl Phthalate. Report to 
the U.S. Consumer Product Safety Commission. June 2001. U.S. Consumer 
Product Safety Commission, Bethesda, MD.
    10. Experimental Pathology Laboratories, 1999. Histology peer 
review and pathology working group review of selected lesions of the 
liver and spleen in male and female F344 rats exposed to DINP. EPL 
Project number 303-013, Pathology Report.

List of Subjects in 40 CFR Part 372

    Environmental protection, Chemicals, Community right-to-know, 
Hazardous substances, Intergovernmental relations, Reporting and 
recordkeeping requirements, Superfund.

    Dated: June 7, 2005.
Kimberly T. Nelson,
Assistant Administrator for Office of Environmental Information and 
Chief Information Officer.
[FR Doc. 05-11664 Filed 6-13-05; 8:45 am]
BILLING CODE 6560-50-P