Supporting Documents for Initial Risk-Based Prioritization of High Production Volume Chemicals m-Diisopropenylbenezene (CASRN 3748-13-8) (9th CI and CA Index Name: Benzene, 1,3-bis(1-methylethenyl)-)


U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization

September 2008

Supporting Documents for Initial Risk-Based Prioritization of
High Production Volume Chemicals

m-Diisopropenylbenezene (CASRN 3748-13-8)

(9th CI and CA Index Name: Benzene, l,3-bis(l-methylethenyl)-)

Contents:

•	Page 2: Background

•	Page 4: Screening-Level Risk Characterization: September 2008

•	Page 8: Screening-Level Hazard Characterization: September 2008

•	Page 16: Screening-Level Exposure Characterization: September 2008

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BACKGROUND

Screening-level hazard, exposure and risk characterizations for high production volume chemicals (HPV)
are important contributions to the chemicals cooperation work being done in North America1 through the
EPA Chemical Assessment and Management Program (ChAMP)2. These screening-level
characterizations are developed by EPA for individual chemicals or chemical categories to support initial
Risk-Based Prioritizations (RBPs) for HPV chemicals. These screening-level characterizations are
technical documents intended primarily to inform the Agency's internal decision-making process.
Accordingly, they are written for assessment professionals and assume a degree of technical
understanding. Each of the support documents is described below.

The Risk-Based Prioritizations are found in an accompanying document and are written for a general
audience. They present EPA's initial thinking regarding the potential risks presented by these chemicals
and future possible actions that may be needed.

Hazard Characterizations for HPV Chemicals

EPA's screening-level hazard characterizations are based primarily on the review of the summaries of
studies and other information submitted by the chemical sponsor(s) under the HPV Challenge Program3.
These studies included in the scope of the HPV Challenge comprise the Screening Information Data Set
(SIDS) of the Organization for Economic Cooperation and Development (OECD)4, an internationally
recognized battery of tests that provides the basic data necessary to make an initial evaluation of a
chemical's hazards and fate. In preparing the initial hazard characterizations, EPA also consulted a
variety of reliable sources5 for additional relevant information and considered its own comments and
public comments on the original submission as well as the sponsor's responses to comments and revisions
made to the submission. In order to determine whether any new hazard information was developed since
the time of an HPV submission, EPA also searched publicly available databases6 for information entered
from one year prior to the HPV submission through May 2008. The screening-level hazard
characterization is performed according to established EPA guidance7. A more detailed description of the
hazard characterization process is available on the EPA website8.

With respect to chemicals for which internationally-accepted OECD SIDS Initial Assessment Profiles
(SIAP) and Initial Assessment Reports (SIAR) were available, EPA did not generate its own screening-
level hazard characterization, but did check for and incorporate updated information in the risk
characterization.

Exposure Characterizations for HPV Chemicals

EPA recently received exposure-related data on chemicals submitted in accordance with the requirements
of Inventory Update Reporting (IUR)9. The 2006 IUR submissions pertain to chemicals manufactured in

1 U.S. EPA - U.S. Commitments to North American Chemicals Cooperation:
http://www.epa.gov/hpv/pubs/general/sppframework.htm.

2 U.S. EPA - ChAMP information: http://www.epa.gov/champ/.

3 U.S. EPA - HPV Challenge Program information: http://www.epa.gov/hpy.

4 U.S. EPA - Technical Guidance Document, OECD SIDS Manual Sections 3.4 and 3.5:
http://www.epa.gov/chemrtk/pubs/general/sidsappb.htm.

5 U.S. EPA - Public Database Hazard Information: http://www.epa.gov/hpvis/hazardinfo.htm.

6 U.S. EPA - Public Database Update Information: http://www.epa.gov/chemrtk/hpvis/updateinfo.htm.

7 U.S. EPA - Risk Assessment Guidelines: http://cfpub.epa.gov/ncea/raf/rafguid.cfm.

8 U.S. EPA - About HPV Chemical Hazard Characterizations: http://www.epa.gov/hpvis/abouthc.htm.

9 U.S. EPA - Basic IUR Information: http://www.epa.gov/opptintr/iur/pubs/guidance/basic-infonnation.h1m.

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(including imported into) the U.S. during calendar year 2005 in quantities of 25,000 pounds or more at a
single site. The reports include the identity, the quantity, and the physical form of the chemical
manufactured or imported, and the number of workers reasonably likely to be exposed during
manufacture of the chemical. For chemicals manufactured or imported in quantities of 300,000 pounds or
more at a single site, additional reported information includes: the industrial processing and uses of the
chemical; the number of industrial processing sites and workers reasonably likely to be exposed to the
chemical at those sites; the consumer and commercial uses of the chemical; and an indication whether the
chemical was used in products intended for use by children under 14 years of age.

EPA's screening-level exposure characterizations are based largely on the information submitted under
the IUR reporting, although other exposure information submitted to the Agency (for example, in HPV
submissions) or readily available through a limited set of publicly accessible databases10 was also
considered. The screening-level exposure characterizations identify a potential (high, medium, or low)
that each of five populations - the environment, the general population, workers, consumers, and children
- might be exposed to the chemical. In most cases, this potential doesn't address the quantity, frequency,
or duration of exposure, but refers only to the likelihood that an exposure could occur.

In many instances EPA is not able to fully disclose to the public all the IUR exposure-related data
reviewed or relied upon in the development of the screening-level documents because some of the
material was claimed as confidential business information (CBI) when it was submitted to the Agency.
These CBI claims do limit the Agency's ability to be completely transparent in presenting some
underlying exposure and use data for chemicals in public documents. EPA does consider all data,
including data considered to be CBI, in the screening-level exposure and risk characterization process,
and endeavors whenever possible to broadly characterize supporting materials claimed as confidential in
ways that do not disclose actual CBI.

Risk Characterizations for HPV Chemicals

EPA combines the information from the screening-level exposure characterization with the screening-
level hazard characterization to develop a qualitative screening-level risk characterization, as described in
the Agency's guidance on drafting risk characterizations11. These screening-level risk characterizations
are technical documents intended to support subsequent priority-setting decisions and actions by OPPT.
The purpose of the qualitative screening-level risk characterization is two-fold: to support initial risk-
based decisions to prioritize chemicals, identify potential concerns, and inform risk management options;
and to identify data needs for individual chemicals or chemical categories.

These initial characterization and prioritization documents do not constitute a final Agency determination
as to risk, nor do they determine whether sufficient data are available to characterize risk. Recommended
actions reflect EPA's relative judgment regarding this chemical or chemical category in comparison with
others evaluated under this program, as well as the uncertainties presented by gaps that may exist in the
available data.

10 U.S. EPA - Summary of Public Databases Routinely Searched:
http://www.epa.gov/chemrtk/hpvis/pubdtsum.htm.

11 U.S. EPA - Risk Characterization Program: http://www.epa.gov/osa/spc/2riskchr.htm.

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QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS

SPONSORED CHEMICAL

m-Diisopropenylbenzene (CAS No. 3748-13-8)
[9th CI Name: Benzene, l,3-bis(l-methylethenyl)-]

September 2008

Prepared by

Risk Assessment Division
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

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QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION FOR
m-Diisopropenylbenzene (CAS No. 3748-13-8)

1. Physical-Chemical Properties and Environmental Fate

w-Diisopropenylbenzene is a liquid with low water solubility and moderate vapor pressure. It is
expected to have moderate mobility in soil. Volatilization of w-diisopropenylbenzene is
considered moderate based on its Henry's Law constant. The rate of hydrolysis is considered
negligible, since w-diisopropenylbenzene does not contain functional groups that are subject to
hydrolysis under environmental conditions. The rate of atmospheric photooxidation is
considered rapid. w-Diisopropenylbenzene is expected to be moderately persistent (P2) and
have a moderate bioaccumulation potential (B2).

2. Hazard Characterization

Aquatic Organism Toxicity. The acute toxicity of w-diisopropenylbenzene to fish, aquatic
invertebrates and aquatic plants is moderate.

Human Health Toxicity. The acute inhalation toxicity of w-diisopropenylbenzene in rats is
moderate. The acute oral and dermal toxicity of w-diisopropenylbenzene to rats and rabbits is
low. w-Diisopropenylbenzene is slightly irritating to rabbit eyes and skin and is a dermal
sensitizer in guinea pigs. An oral combined repeated-dose/reproductive/developmental toxicity
study in rats showed no systemic, reproductive or developmental toxicity. An inhalation
repeated-dose toxicity study in rats showed moderate toxicity. w-Diisopropenylbenzene was not
mutagenic and did not induce chromosomal aberrations.

3. Exposure Characterization

w-Diisopropenylbenzene has an aggregated production/import volume in the United States of 1
million to 10 million pounds. Non-confidential information in the Inventory Update Reporting
(IUR) indicates that the industrial processing and uses of the chemical are as intermediates in the
manufacturing of other basic organic chemicals. The High Production Volume (HPV)
submission for m-diisopropenylbenzene, also referred to as benzene, l,3-bis(l-methylethenyl)-,
states that the chemical is primarily used as an industrial intermediate in the production of
diisocyanate monomer.

Potential Exposure to the General Population and the Environment: Based on use information,
there is potential for environmental releases during manufacturing, processing, and use. m-
Diisopropenylbenzene is expected to be moderately persistent in the environment (P2) and the
bioaccumulation potential is moderate (B2). Based on the information considered, including
environmental fate, known uses, and the Agency's expert judgment, EPA identifies, for the
purposes of risk-based prioritization, a medium potential that the general population and the
environment might be exposed to m-diisopropenylbenzene.

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Potential Exposure to Workers: Based on the information considered, including IUR and HPV
submissions, in combination with the Agency's professional judgment, EPA identifies, for the
purposes of prioritization, a low relative ranking for potential worker exposure. This low
ranking is based primarily on the moderate volatility, the uses of the chemical, the production
volume, and the number of potentially exposed workers.

Potential Exposure to Consumers: No consumer uses are reported in the IUR submissions, nor
were any found in other data sources. EPA identifies, for the purposes of risk-based
prioritization, a low potential that consumers might be exposed to w-diisopropenylbenzene.

Potential Exposure to Children: No uses in products intended to be used by children are
reported in the IUR, nor are any found in other data sources. EPA identifies, for the purposes of
risk-based prioritization, that the potential for exposures to children is low.

4. Risk Characterization

The statements and rationale provided below are intended solely for the purpose of this
screening-level and qualitative risk characterization and will be used for prioritizing substances
for future work in the U.S. Chemical Assessment and Management Program (ChAMP).

Risk Statement and Rationale

Potential Risk to Aquatic Organism from Environmental Releases: (MEDIUM
CONCERN). EPA identifies a medium potential that aquatic organisms might be
exposed from environmental releases. w-Diisopropenylbenzene has a moderate potential
for both bioaccumulation and persistence. These characteristics in combination with the
moderate toxicity to fish, aquatic invertebrates and plants indicate a medium concern for
potential risk to fish, aquatic invertebrates and plants.

Potential Risk to the General Population from Environmental Releases: (LOW
CONCERN). EPA identifies a medium potential that the general population might be
exposed from environmental releases. The potential human health hazard is expected to
be low from oral exposure and medium from inhalation exposure. Based on rapid
photodegradation in air, EPA assumes that air exposures to the general population will be
low. Therefore, the available information suggests a low concern for potential risk to the
general population from environmental releases.

Potential Risk to Workers: (LOW CONCERN). EPA identifies a low relative ranking
for potential worker exposure. The potential health hazard is expected to be moderate by
the inhalation route. w-Diisopropenylbenzene is slightly irritating to the eyes and skin
and is a dermal sensitizer. Adherence to standard good industrial hygiene practices
(gloves, respirators, goggles, and other protective clothing) will limit the exposure to
workers. Therefore, taken together, the available information suggests a low concern for
potential risks to workers.

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Potential Risk to Consumers: (LOW CONCERN). No consumer uses are reported in the
IUR submissions, nor were any found in other data sources. w-Diisopropenylbenzene is
primarily used as an industrial intermediate. EPA identifies a low potential that
consumers might be exposed. The potential health hazard is expected to be low by the
oral route and moderate by the inhalation route. Therefore, taken together, the available
information suggests a low concern for potential risks to consumers.

Potential Risk to Children: (LOW CONCERN). No uses in products intended to be used
by children are reported in the IUR submissions, nor were any found in other data
sources. EPA identifies a low potential that children might be exposed. There was no
toxicity in an animal study with exposures during early life stages. Therefore, taken
together, the available information suggests a low concern for potential risks to children.

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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization

September 2008

SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS

SPONSORED CHEMICAL

m-Diisopropenylbenzene (CAS No. 3748-13-8)
[9th CI Name: Benzene, l,3-bis(l-methylethenyl)-]

September 2008

Prepared by

Risk Assessment Division
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization

September 2008

SCREENING-LEVEL HAZARD CHARACTERIZATION
»i-Diisopropenylbenzene (CAS No. 3748-13-8)

Introduction

The sponsor, Cytec Industries Inc., submitted a Test Plan and Robust Summaries to EPA for
«/-diisopropenylbenzene (CAS No. 3748-13-8; 9th CI name: benzene, l,3-bis(l-methylethenyl)-) on December 18,
2002. EPA posted the submission on the ChemRTK HPV Challenge website on January 16, 2003
(http://www.epa.gov/oppt/chemrtk/pubs/summaries/mdiisopr/cl4136tc.htm). EPA comments on the original
submission were posted to the website on May 13, 2003. Public comments were also received and posted to the
website. The sponsor submitted updated/revised documents on July 8, 2003 and December 10, 2004, which were
posted to the ChemRTK website on July 25, 2003 and February 3, 2005 respectively.

This screening level hazard characterization is based primarily on the review of the test plan and robust summaries
of studies submitted by the sponsor(s) under the HPV Challenge Program. In preparing the hazard characterization
EPA considered its own comments and public comments on the original submission as well as the sponsor's
responses to comments and revisions made to the submission. In order to determine whether any new hazard
information was developed since the time of the HPV submission a search of the following databases was made
from 2004 to May 2008: the NLM databases (ChemID to locate available data sources including Medline/PubMed,
Toxline, HSDB, IRIS, NTP, ATSDR, EXTOXNET, EPA SRS, etc.), STN/CAS online databases (Registry file for
locators, ChemAbs for toxicology data, RTECS, Merck, etc.) and Science Direct. A summary table of SIDS
endpoint data with the structure(s) of the sponsored chemical(s) is included in the appendix. The screening-level
hazard characterization for environmental and human health effects is based largely on SIDS endpoints and is
described according to established EPA or OECD effect level definitions and hazard assessment practices.

Hazard Characterization

w-Diisopropenylbenzene is a liquid with low water solubility and moderate vapor pressure. It is expected to have
moderate mobility in soil. Volatilization of w;-diisopropenylbenzene is considered moderate based on its Henry's
Law constant. The rate of hydrolysis is considered negligible, since w;-diisopropenylbenzene does not contain
functional groups that are subject to hydrolysis under enviromnental conditions. The rate of atmospheric
photooxidation is considered rapid. w-Diisopropenylbenzene is expected to be moderately persistent (P2) and have
a moderate bioaccumulation potential (B2).

The acute toxicity of w;-diisopropenylbenzene to fish, aquatic invertebrates and aquatic plants is moderate.

The acute inhalation toxicity of w;-diisopropenylbenzene in rats is moderate. The acute oral and dermal toxicity of
»/-diisopropenylbenzene to rats and rabbits is low. w-Diisopropenylbenzene is slightly irritating to rabbit eyes and
skin and is a dermal sensitizer in guinea pigs. An oral combined repeated-dose/reproductive/developmental toxicity
study in rats showed no systemic, reproductive or developmental toxicity. An inhalation repeated-dose toxicity
study in rats showed moderate toxicity. w-Diisopropenylbenzene was not mutagenic and did not induce
chromosomal aberrations.

No data gaps were identified under the HPV Challenge Program.

1. Physical-Chemical Properties and Environmental Fate

The physical-chemical properties of m-diisopropenylbenzene are summarized in Table la, while its enviromnental
fate properties are provided in Table lb. The structure of the compound is provided in the Appendix.

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Physical-Chemical Properties Characterization

m-Diisopropenylbenzene is a liquid with low water solubility and moderate vapor pressure. The water solubility
value of ca. 5.6 mg/L does not agree with the value of a close analog, diisopropylbenzene (CA 25321-09-9), which
has a water solubility of 0.072 mg/L.

Table la. Phvsical-Chcmical Properties of m-Diisopropcnvlhcnzcne1

Property

Value

CAS No.

3748-13-8

Molecular Weight

158

Physical State

Liquid

Melting Point

-38 to -40°C (measured)

Boiling Point

231°C (measured)

Vapor Pressure

2.3 mm Hg at 69°C (measured)
0.16 mm Hg at 25°C (extrapolated)

Water Solubility

ca. 5.6 mg/L at 25°C (measured)

0.072 mg/L for diisopropylbenzene (analog)

Dissociation constants (pKa)

Not applicable

Henry's Law constant

3.48 x 10"3 atm-m3/mole (estimated)2

Log Kow

4.89 (estimated)2

1 Cytec Industries, Inc. December 10, 2004. Revised Robust Summary and Test Plan for m-

Diisopropenylbenzene, http://www. epa. gov/hpv/pubs/summaries/mdiisopr/c 14136tc.htm.

2US EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v3.20. United States

Environmental Protection Agency, Washington, DC, USA.

http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

Environmental Fate Characterization

/w-Diisopropenylbenzene is expected to have moderate mobility in soil. No biodegradation of m-
diisopropenylbenzene was observed over the course of a 28 day incubation period using an activated sludge
inoculum and a closed bottle (OECD 30 ID) test. These results are consistent with the results of a ready
biodegradation test for alpha-methylstyrene (CAS No. 98-83-9). Alpha-methylstyrene achived 0% of its theoretical
BOD using an activated sludge inoculum and the modified MITI test (OECD 301C) over a 2 week incubation
period. The rate of volatilization of /w-diisopropenylbenzene from water and moist soil is considered moderate
given its estimated Henry's Law constant. The rate of atmospheric photooxidation is considered rapid. The rate of
hydrolysis is considered negligible, since /w-diisopropenylbenzene does not contain functional groups that are
subject to hydrolysis under environmental conditions. /w-Diisopropenylbenzene is moderately persistent (P2) and
has a moderate bioaccumulation potential (B2).

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Table lb. Environmental Fate Characteristics of m-Diisopropenylbenzene1

Property

Value

Photodegradation Half-life

1.2 hours (estimated; assumes 12-hour day and 1.5 xlO6 hydroxyl
radicals/cm3)

Hydrolysis Half-life

Negligible

Biodegradation

0% in 28 days;

0% in 14 days (alplia-methylstyrene)3

Bioconcentration

BCF = 1166 (estimated)2

Direct Photolysis

Not Applicable

Log Koc

3.606 (estimated)

Fugacity

(Level III Model)

Air = 0.24%
Water = 24.9%
Soil = 63.9%
Sediment = 11.0%

Persistence

P2 (moderate)4

Bioaccumulation

B2 (moderate)4

1 Cytec Industries, Inc. 2004. Revised Robust Summary and Test Plan for m-Diisopropenylbenzene,
http://www.epa.gov/lipv/pubs/summaries/mdiisopr/cl4136tc.htm.

2US EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Enviromnental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.

3 National Institute of Technology and Evaluation Biodegradation and Bioconcentration of the Existing Chemical
Substances. Accessed July 9, 2008. http://www.safe.nite.go.ip/englisli/kizon/KIZON start hazkizon.html.
4Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.

Conclusion: w-Diisopropenylbenzene is a liquid with low water solubility and moderate vapor pressure. It is
expected to have moderate mobility in soil. Volatilization of w-diisopropenylbenzene is considered moderate based
on its Henry's Law constant. The rate of hydrolysis is considered negligible, since w-diisopropenylbenzene does
not contain functional groups that are subject to hydrolysis under enviromnental conditions. The rate of atmospheric
photooxidation is considered rapid. w-Diisopropenylbenzene is moderately persistent (P2) and has a moderate
bioaccumulation potential (B2).

2. Environmental Effects - Aquatic Toxicity

Acute Toxicity to Fish

Fathead minnows (Pimephales promelas) were exposed to w-diisopropenylbenzene at nominal concentrations of
0.60, 1.2, 2.5, 5.0, 10 or 20 mg/L under static conditions for 96 hours. At 5 mg/L, mortality was 10% and 20% at 72
and 96 hours, respectively. At 10 mg/L, 0, 50, 90 and 100% of fish had died at 24, 48, 72 and 96 hours,
respectively. At 20 mg/L, mortality was 0, 40, 70 and 100% at 24, 48, 72 and 96 hours, respectively.

96-h LC50 = 6.2 mg/L

Acute Toxicity to Aquatic Invertebrates

Water fleas (Daphnia magna) were exposed to w-diisopropenylbenzene at nominal concentrations of 1.0, 1.8, 3.2,
5.6 or 10 mg/L under static conditions for 48 hours. None of the daplinids exposed to 0, 1.0 or 1.8 mg/L died during
the study. At 3.2 mg/L mortality was 10%. At 5.6 mg/L, 9 out of 10 daplinids died within 24 hours and all died by
48 hours. All daplinids exposed to 10 mg/L died within 24 hours.

48-h LC50=4.0 mg/L

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Toxicity to Aquatic Plants

Green algae (Pseudokirchneriella subcapitata) were exposed to /w-diisopropenylbenzene at nominal concentrations
of 0, 1.8, 3.2, 5.6, 10 or 18 mg/L under static conditions for 96 hours. Inhibition of cell growth (compared with
control growth) was noted at concentrations >3.2 mg/L and was observed as early as 48 hours for cells exposed to
10 and 18 mg/L. Cell counts (and percent inhibition) of cells exposed to 10 mg/L at 72 and 96 hours were 10 (87%)
and 12 (95%). No growth occurred in cells exposed to 18 mg/L for 72 or 96 hours.

72-h EC50 (growth) = 4.93 mg/L
96-h EC50 (growth) = 4.92 mg/L

Conclusion: The acute toxicity of /w-diisopropenylbenzene to fish, aquatic invertebrates and aquatic plants is
moderate.

3. Human Health Effects
Acute Oral Toxicity

(1) Sprague-Dawley rats (5/sex/dose) were administered /w-diisopropenylbenzene via gavage at 0, 8.0, 10.0, 12.6,
15.8 or 20.0 mL/kg-bw (0, 7400, 9250, 11,655, 14,615 or 18,500 mg/kg-bw based on density) and observed for up
to 15 days. None of the animals treated with 0 (control) or 8 mL/kg-bw died. Mortality occurred at 10.0, 12.6, 15.8
and 20.0 mL/kg-bw.

LDS0 = 12,200 mg/kg-bw

(2) Sprague-Dawley rats (5/sex/dose) were administered /w-diisopropenylbenzene at 5000 mg/kg-bw and observed
for 14 days. Mortality occurred at this dose level. Labored breathing was observed in these rats just prior to death.
Pathological findings included red hepatization and expended lungs, indicative of acute pneumonia or pneumonitis
unrelated to treatment. Gross necropsies of survivors were unremarkable.

LDS0 > 5000 mg/kg-bw

Acute Inhalation Toxicity

Sprague-Dawley rats (5/sex/dose) were exposed to of /w-diisopropenylbenzene at nominal concentrations of 3 or 15
mg/L for 6 hours and observed for 5 days post-exposure. The mean actual exposure concentrations (± standard
deviation) were 0.545 ± 0.062 and 5.576 ± 0.417 mg/L. At 5.576 mg/L, signs of toxicity such as wet fur, red
perinasal wetness, lacrimation, whole body tremors, dermal irritation, hyperactivity, ataxia and mouth breathing
were observed during the first 90 minutes of exposure. A complete loss of motor activity was observed in these
animals for the remainder of the exposure period and all animals eventually died. After exposure, all animals
exhibited absent toe, tail pinch and surface righting reflexes, hypothermia, respiratory difficulties, wet fur and
dermal irritation. One high-concentration female had eye opacity. Necropsies of the dead animals revealed
discoloration of the lungs and kidneys and wet fur.

0.54 mg/L < LC50 < 5.6 mg/L

Acute Dermal Toxicity

New Zealand White rabbits (5/sex/dose) were administered /w-diisopropenylbenzene at 2 g/kg-bw to abraded skin
under occluded conditions for 24 hours. After exposure, the excess material was wiped off and animals were
observed for signs of toxicity for 14 days post-dosing. No animals died during the observation period.

LDS0 > 2000 mg/kg-bw

Repeated-Dose Toxicity

(1) In a combined repeated-dose/reproductive/developmental toxicity study, Sprague-Dawley rats (10/sex/dose)
were administered /w-diisopropenylbenzene via gavage at nominal doses of 0 (vehicle), 100, 300 or 1000 mg/kg-
bw/day for up to 53 days. Administration to F0 males and females began 14 days prior to mating and continued
through mating. Females continued receiving /w-diisopropenylbenzene until postnatal day 5. All F0 females were

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allowed to deliver naturally and rear the pups to postnatal day 5, the scheduled day of necropsy. Histopathological
examinations of the F0 rats were restricted to the following in the control and high-dose groups: coagulating glands,
epididymides, prostate, seminal vesicles, testes, ovaries, uterus/cervix, vagina and stomach. The study did not
include hematology, clinical chemistry. One high-dose female exhibited hunched posture, tiptoe gait and excessive
grooming 1 hour after dosing on one occasion. An additional high-dose female had similar signs on several
occasions and exhibited signs of lethargy, piloerection, decreased respiration and ptosis on one occasion. Several
findings noted in various organs and tissues of one or two treated animals of each dose were comparable with those
with the controls. None of the gross lesions observed were attributed to administration of test material. No
treatment-related histopathological changes were observed.

NOAEL = 1000 mg/kg-bw/day (highest dose tested)

(2) Sprague-Dawley rats (5/sex/dose) were exposed to /w-diisopropenylbenzene vapor via inhalation at nominal
concentrations of 0 (air only), 100, 500 or 1000 mg/m3 for 6 hours/day, 5 consecutive days/week for 4 weeks.

During the fourth week, all animals were exposed for 4 days and euthanized on the 5th day. The mean actual
exposure concentrations (± standard deviation) were 107 ± 13, 510 ± 29 and 970 ± 54 mg/m3 or 0.107, 0.510 and
0.970 mg/L/day for the nominal concentrations of 100, 500 and 1000 mg/m3. None of the animals died. Average
body weights and weight gains of males exposed to 510 and 970 mg/m3 were lower than controls, but the robust
summary did not report the magnitude of this effect. Increases in absolute (females only) and relative (to body
weight) liver weights were observed in high-dose animals (males and females). Total urine volume of males
exposed to 510 and 970 mg/m3 was different from controls. High-dose males also had increased relative (but not
absolute) brain, adrenal and testes weights. Males exposed to 510 mg/m3 also had increased relative liver weight.
The biological significance of the organ weight changes is unknown as there were no histopathological lesions.
LOAEL = 0.970 mg/L/day (based on body weight)

NOAEL = 0.510 mg/L/day

Reproductive/Developmental Toxicity

In the combined repeated-dose/reproductive/developmental toxicity study in Sprague-Dawley rats described above,
the clinical signs were hunched posture, tiptoe gait and excessive grooming in females at 1000 mg/kg-bw/day 1 hour
after dosing on one occasion, lethargy, piloerection, decreased respiration and ptosis. All animals recovered shortly
after treatment. There was no effect on body weights and organ weights. There were no effects of treatment on
fertility or mating performance. There was no effect of treatment on gestation length and no significant (p < 0.05)
effect of treatment on the number of implantation sites. There were no significant (p < 0.05) effects of treatment on
live birth or viability index, litter size, litter weight, pinna unfolding, surface righting reflex or sex ratio. Gross
examinations were normal, with the exception of pale kidneys in more than one pup in all groups (one control, one
low-dose, two mid-dose and four high-dose litters).

NOAEL (systemic toxicity) = 1000 mg/kg-bw/day (highest dose tested)

NOAEL (reproductive toxicity) = 1000 mg/kg-bw/day (highest dose tested)

NOAEL (developmental toxicity) = 1000 mg/kg-bw/day (highest dose tested)

Genetic Toxicity - Gene Mutation

In vitro

(1) Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 were exposed to /w-diisopropenylbenzene
at concentrations of 0, 1.5, 5, 15, 50, 150, 500, 1500 or 5000 |.ig/platc in the presence and absence of metabolic
activation. Positive controls were tested concurrently and produced an appropriate response. Signs of cytotoxicity
were apparent at concentrations of 500 |.ig/platc and higher.

wi-Diisopropenylbenzene was not mutagenic in this assay.

(2) Escherichia coli strain WP2uvrA- was exposed to /w-diisopropenylbenzene at concentrations of 0, 50, 150, 500,
1500 or 5000 |.ig/platc in the presence and absence of activation. Positive controls were tested concurrently and
produced an appropriate response. A preliminary toxicity study found no evidence for cytotoxicity at the highest
concentration tested.

wi-Diisopropenylbenzene was not mutagenic in this assay.

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September 2008

Genetic Toxicity - Chromosomal Aberrations
In vitro

Chinese hamster ovary (CHO) cells were exposed to /w-diisopropenylbenzene at concentrations of 0 - 49.38 |ag/mL
in the absence of metabolic activation and 0 - 197.5 |ag/mL in the presence of metabolic activation. Tested
concentrations were selected based on results from a preliminary cytotoxicity test. Positive controls were tested
concurrently and produced an appropriate response.

wi-Diisopropenylbenzene did not induce chromosomal aberrations in this assay.

Additional Information
Skin Irritation

New Zealand White rabbits were administered /w-diisopropenylbenzene to abraded skin at a dose of 2 g/kg-bw under
occlusive conditions for 24 hours and observed for 14 days. The only effect of treatment was slight dermal
irritation.

m-Diisopropeny I benzene was slightly irritating to rabbit skin in this assay.

Eye Irritation

New Zealand White rabbits (9 males) were administered /w-Diisopropenylbenzene (0.1 mL) via instillation into the
cupped lower lid of the right eye. Thirty seconds after treatment, the eyes of three animals were rinsed with water
for 60 seconds; no further treatment was conducted on the other six animals. The animals were observed for 13
days. No irritation to the cornea or iris was observed at any time point. Discharge, chemosis and/or redness of the
conjunctivae were observed in most animals. Nasal discharge was observed in one animal with unwashed eyes on
day 2 and two animals with unwashed eyes on day 3.

wi-Diisopropenylbenzene was slightly irritating to the rabbit eye in this assay.

Sensitization

Guinea pigs (7-8 per sex) were administered /w-diisopropenylbenzene dermally to a shaved patch of the dorsal
surface at a concentration of 100% during the induction phase. The test material was applied to the test site 3
times/week on alternating days until a total of 10 applications were made. Fourteen days after the last induction
dose, animals were challenged with the test substance at a concentration of 100%. All animals induced and
challenged with test material were rechallenged with test material 11 days after the original challenge with
concentrations of 12.5, 25, 50 or 100% test material. Positive control tests were conducted concurrently.
m-Diisopropeny I benzene was sensitizing in this assay.

Conclusion: The acute inhalation toxicity of /w-diisopropenylbenzene in rats is moderate. The acute oral and
dermal toxicity of /w-diisopropenylbenzene to rats and rabbits is low. /w-Diisopropenylbenzene is slightly irritating
to rabbit eyes and skin and is a dermal sensitizer in guinea pigs. An oral combined repeated-
dose/reproductive/developmental toxicity study in rats showed no systemic reproductive or developmental toxicity.
An inhalation repeated-dose toxicity study in rats showed moderate toxicity. /w-Diisopropenylbenzene was not
mutagenic and did not induce chromosomal aberrations.

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APPENDIX

Summary Tabic of the Screening Information Data Set
as Submitted under the U.S. HPV Challenge Program

Endpoints

SPONSORED CHEMICAL
/w-Diisopropcnylbcnzcnc
(3748-13-8)

Structure



Summary of Environmental Effects - Aquatic Toxicity Data

Fish

96-h LCS0 (mg/L)

6.2

Aquatic Invertebrates
48-h ECS0 (mg/L)

4.0

Aquatic Plants
72-h ECS0 (mg/L)
(growth)

4.93

Summary of Human Health Data

Acute Oral Toxicity
LDS0 (mg/kg-bw)

>5000

Acute Inhalation Toxicity

LCS0 (mg/L)

0.54-5.6

Acute Dermal Toxicity
LDS0 (mg/kg-bw)

>2000

Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)

NOAEL = 1000 (53-d)

Repeated-Dose Toxicity
NOAEL/LOAEL
Inhalation (mg/L/day)

NOAEL = 0.970 (4-wk)
1 .OAF.I. = 0.510 (4-wk)

Reproductive/Developmental Toxicity

NOAEL/LOAEL

Oral (mg/kg-bw/day)

Systemic/Reproductive/Developmental Toxicity

NOAEL = 1000 (53-d)

Genetic Toxicity - Gene Mutation
In vitro

Negative

Genetic Toxicity - Chromosomal Aberrations
In vitro

Negative

Additional Information
Skin Irritation
Eye Irritation
Skin Sensitization

Slightly irritating
Slightly irritating
Sensitizing

15

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Screening Level Exposure Characterization for HPV Challenge

Chemical

m-Diisopropenylbenzene (CAS No. 3748-13-8)
[9th CI Name: Benzene, l,3-bis(l-methylethenyl)-]

September 2008

Prepared by

Exposure Assessment Branch
Chemical Engineering Branch
Economics, Exposure and Technology Division
Office of Pollution Prevention and Toxics
Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460-0001

16

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September 2008

Screening Level Exposure Characterization
m-Diisopropenylbenzene (CAS No. 3748-13-8)
[9th CI Name: Benzene, l,3-bis(l-methylethenyl)-]

Non-CBI Executive Summary

Potential Exposure to the General Population and the Environment: Based on use information,
there is potential for environmental releases during manufacturing, processing, and use. m-
Diisopropenylbenzene is expected to be moderately persistent in the environment (P2) and the
bioaccumulation potential (B2) is moderate. Based on the information considered, including
environmental fate, known uses, and the Agency's expert judgment, EPA identifies, for the
purposes of risk-based prioritization, a medium potential that the general population and the
environment might be exposed to m-diisopropenylbenzene.

This exposure characterization was completed using both public, non-confidential sources, and
one or more IUR submissions that were available as of this writing.

12 Cytec, 2004. Test Plan for m-diisopropenylbenzene (CAS No. 3748-13-8). Cytec Industries Inc. DIPEB Test
Plan, Final Revision. November 17, 2004. Accessed, 7/16/08.
http://www.epa.gov/chemrtk/pubs/summaries/mdiisopr/cl4136rtl.pdf

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Volume and Use Information

w-Diisopropenylbenzene (CAS #3748-13-8) has an aggregated production and/or import volume
in the United States of 1 million to 10 million pounds.13 Non-confidential information in the
IUR indicates that this chemical was manufactured and/or imported at the following companies
and sites: Deltech Corporation/Baton Rouge, LA. There may be other companies and sites that
are claimed confidential. Persons submitting IUR information for 2005 asserted that some or all
of the information was confidential. Only non-confidential versions of reported IUR data are
included in this summary. A pre-manufacture notification for this chemical was submitted to
EPA and contains data and information that are claimed confidential.

The non-confidential industrial processing use (IPU) reported in IUR submissions for this
chemical is processing as a reactant/intermediate in basic organic chemical manufacturing.

There may be other IPUs that are claimed confidential. No commercial/consumer uses are
reported in IUR submissions.

The HPV submission for this chemical states that the chemical is used as an industrial
intermediate in the production of diisocyanate monomer, with about one percent of this chemical
being shipped to another facility in the United States for use as an intermediate in optical
products, and about five percent of this chemical is exported.14

Environmental Releases

Environmental releases may impact general population and environmental exposures. Factors
affecting releases include volumes produced, processed and used; numbers of sites; and
processes of manufacture, processing, and use.

Based on IUR data, the maximum total number of industrial sites for manufacturing, processing,
or using this chemical is confidential.

Many chemicals used as reactants/intermediates have industrial releases that are a relatively low
percentage of the volume. Lower percentage releases occur when a high percentage of the
chemical reacts without excess loss during its use as an intermediate. The actual percentage and
quantity of release of the reported chemical associated with this use are not known.

The chemical is not on the Toxics Release Inventory.15

Experience has shown that air releases due to volatilization have not been an issue for chemicals
with vapor pressures below 0.01 mm Hg. This chemical has a vapor pressure of 0.16 mm Hg at

13 USEPA, 2006. Partial Updating of TSCA Chemical Inventory, http://www.epa.gov/oppt/iur/tools/data/20Q2-
vol.htm.

14 Cytec Industries, Inc., 2004. Test Plan for m-Diisopropenylbenzene (CAS No. 3748-13-8).
http://www.epa.gov/chemrtk/pubs/summaries/mdiisopr/cl4136tp.pdf.

15 USEPA, 2006. Toxic Release Inventory. Accessed, 7/16/08. http://www.epa.gov/tri/.

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September 2008

25°C (extrapolated from a measured value).16 This chemical's vapor pressure could result in air
releases.

Exposures to the General Population and the Environment

Based on the available information, it is assumed that there could be releases to various media,
including air, during manufacturing, processing, and use. A search of additional relevant
databases did not provide any further information on releases of this chemical.

The IUR ranking for general population and the environment is medium since there may
exposure from releases of this chemical based on the reported uses in the IUR data (see Table 1).

Persistence and bioaccumulation ratings for this chemical are P2 and B2.17 These ratings suggest
that this chemical is very persistent in the environment; and is bioaccumulative. m-
Diisopropenylbenzene is a liquid with moderate water solubility and moderate vapor pressure. It
is expected to have moderate mobility in soil. Volatilization of w-diisopropenylbenzene is
considered moderate based on its Henry's Law constant. The rate of hydrolysis is considered
negligible, since w-diisopropenylbenzene does not contain functional groups that are subject to
hydrolysis under environmental conditions. The rate of atmospheric photooxidation is
considered rapid.

Based on the information considered, including environmental fate, known uses, and the
Agency's expert judgment, EPA identifies, for the purposes of risk-based prioritization, a
medium potential that the general population and the environment might be exposed to m-
diisopropenylbenzene.

Exposures to Workers

Based on the information considered (including IUR data and information from other selected
data sources including HPV submission), in combination with the Agency's professional
judgment, EPA identifies, for the purposes of risk-based prioritization, a low relative ranking for
potential worker exposure. This low ranking is based primarily on the moderate volatility, the
uses of the chemical, the production volume, and the number of potentially exposed workers.
The following is a summary of relevant information affecting occupational exposure.

16 USEPA, 2008. Screening-Level Hazard Characterization for High Production Chemical, m-diisopropenylbenzene
(CAS No. 3748-13-8) (9th CI Name: Benzene, l,3-bis(l-methylethenyl)-.

17 USEPA, 2008. Screening-Level Hazard Characterization for High Production Chemical, m-diisopropenylbenzene
(CAS No. 3748-13-8) (9th CI Name: Benzene, l,3-bis(l-methylethenyl)-.

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Summary of Parameters affecting Worker Exposure

Parameter

Volume *

1 million to 10 million pounds

Physical Form(s) *

Liquid

Vapor Pressure

0.16 mm Hg at 25°C (extrapolated from a
measured value)

Concentration*

Greater than 90% by weight

Number of Industrial Workers *

between 100 and 999

Uses* (including both IUR and HPV)

Intermediates

Key MSDS Info

combustible liquid; wear respirator, goggles,
and gloves

* Only non-confidential IUR data are included for these parameters.

Based on IUR data, the maximum total number of workers reasonably likely to be exposed to
this chemical during manufacturing and industrial processing and use may be between 100 and
999. There may be additional potentially exposed industrial workers who are not included in this
estimate since not all submitters were required to report on industrial processing and use and/or
there is at least one submission that contains a "Not Readily Obtainable" (NRO) response for the
number of workers, for at least one use. This estimate does not include potentially exposed
commercial workers. However, based on the IUR, there may not be any workers in commercial
businesses who are exposed to this chemical. The National Occupational Exposure Survey
(NOES) has no data for the total number of workers potentially exposed to this chemical.18

Based on IUR data, the chemical is manufactured in liquid forms, and worker exposures are
possible for this chemical in these forms. There may be other physical forms that are claimed
confidential. Also, the non-confidential maximum concentration is up to 100%. There may be
other concentrations that are claimed confidential. This chemical has a vapor pressure of 0.16
mm Hg at 25°C (extrapolated from a measured value).19 Experience has shown that worker
exposures to vapors have not been an issue for chemicals with vapor pressures below 0.001 mm
Hg. This chemical's vapor pressure could result in worker exposures to vapors if workers are
proximal to the liquid.

This chemical does not have OSHA Permissible Exposure Limits (PELs).20
Exposures to Consumers

No uses in consumer products were reported in the IUR.

18NIOSH, 1983. National Occupational Exposure Survey (NOES, 1981-1983). Accessed, 7/16/08.
http ://www .cdc. gov/noes/

19 USEPA, 2008. Screening-Level Hazard Characterization for High Production Chemical, m-diisopropenylbenzene
(CAS No. 3748-13-8) (9th CI Name: Benzene, l,3-bis(l-methylethenyl)-.

20 NIOSH, 1988. OSHA PEL Project Documentation, http://www.cdc.gov/niosh/pel88/npelcas.html. Accessed,
7/16/08.

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EPA identifies, for the purposes of risk-based prioritization, a low potential for exposures to
consumers from products containing this chemical based on the IUR data.

Exposures to Children

No uses in products intended to be used by children were reported in the IUR, nor were any
found in other data sources. EPA identifies, for the purposes of risk-based prioritization, that the
potential for exposures to children is low.

Non Confidential IUR Data Summary: w-Diisopropenylbenzene
Manufacturing/Import Information

Production and import volume:	1 million to 10 million pounds

List of non-CBI companies/ sites*:	Deltech Corporation / Baton Rouge, LA

Highest non-CBI maximum concentration*: up to 100% by weight

Non-CBI physical forms*:	liquid

*Note: There may be other companies/ sites, concentrations, and physical forms that are claimed
as confidential business information (CBI).



Table 1



Industrial Processing and Use Information



Reported in 2006 IUR



Processing

Industrial

Function in

Activity

Sector

Ind. Sector

Processing as a reactant

Other Basic Organic Chemical

Intermediates



Manufacturing



Additional line item(s) may be claimed as CBI



Table 2





Commercial/ Consumer Uses



Reported in 2006 IUR



Commercial/ Consumer

Highest maximum concentration

Use in Children's Products

Product Category Description

range



None reported





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