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
Sponsored Chemical
3-Methyl benzonitrile (CASRN 620-22-4)
(9th CI and CA Index Name: Benzonitrile, 3-methyl-)
Supporting Chemical
Benzonitrile (CASRN 100-47-0)
Contents:
• Page 2: Background
• Page 4: Screening-Level Risk Characterization: September 2008
• Page 7: Screening-Level Hazard Characterization: September 2008
• Page 14: Screening-Level Exposure Characterization: September 2008
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
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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Supporting Documents for Risk-Based Prioritization
September 2008
(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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Supporting Documents for Risk-Based Prioritization
September 2008
QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
3-Methyl Benzonitrile (CAS No. 620-22-4)
[9th CI Name: Benzonitrile, 3-methyl-]
SUPPORTING CHEMICAL
Benzonitrile (CAS No. 100-47-0)
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
QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION FOR
3-Methyl Benzonitrile (CAS No. 620-22-4)
1. Physical-Chemical Properties and Environmental Fate
3-Methylbenzonitrile is a clear, colorless liquid at room temperature. It is estimated to have
moderate water solubility and vapor pressure. It has moderate mobility in soil and moderate
volatility. 3-Methylbenzonitrile undergoes atmospheric photooxidation at a rate that is
considered slow. No biodegradation or stability in water (hydrolysis) data for 3-
methylbenzonitrile were submitted; however, EPA located ready biodegradability studies on
related substances indicating that the substances were readily biodegradable. Based on this
information and modeling, the environmental persistence of this substance is expected to be low
(PI). An estimated BCF of 8 suggests that 3-methylbenzonitrile has a low bioaccumulation
potential (Bl).
2. Hazard Characterization
Aquatic Organism Toxicity. The acute aquatic toxicity of 3-methylbenzonitrile to fish, aquatic
invertebrates and plants is expected to be low based on data for the supporting chemical
benzonitrile (CAS No. 100-47-0).
Human Health Toxicity. The acute oral toxicity of 3-methylbenzonitrile is low. 3-
Methylbenzonitrile is slightly irritating to rabbit skin and severely irritating to rabbit eyes.
Repeated-dose and reproductive toxicity data were not required for the HPV Challenge Program
because 3-methylbenzonitrile is a closed-system intermediate. 3-Methylbenzonitrile did not
induce gene mutations.
3. Exposure Characterization
There are no 2006 Inventory Update Rule submissions for this chemical. Information submitted
as part of the HPV Challenge Program indicates that this chemical is used as a process
intermediate in the synthesis of a fungicide.
Potential for Exposures to Human and the Environment:
Based on information from the HPV Challenge Program and in combination with Agency's
professional judgment, EPA identifies, for the purposes of risk-based prioritization, a low
relative ranking for each of the potentially exposed groups, including workers, general
population, consumers and children, and the environment. In 2007, the Agency reviewed the
information in the HPV submission or test plan and determined that the HPV chemical satisfies
the guidance to demonstrate that the chemical is a closed system intermediate. The chemical is
manufactured and processed in systems that are expected to reduce the potential for worker
exposure and environmental releases that could lead to other human and environmental
exposure. The guidance for identifying this chemical substance as a closed-system intermediate
was satisfied at all sites reporting this chemical in accordance with IUR requirements. No
information on commercial/consumer uses were found in the IUR or other data sources.
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
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 Chemical Assessment and Management Program (ChAMP).
Risk Statement and Rationale
The Agency has reviewed the information in the HPV submission or test plan and determined
that the HPV chemical satisfies the guidance to demonstrate that the chemical is a closed system
intermediate (CSI). 3-Methylbenzonitrile is manufactured and processed in closed systems that
are expected to significantly reduce the potential for worker exposure and environmental releases
that could lead to other human and environmental exposure. Therefore, there is a low concern
for potential risks to aquatic organisms and the general population from environmental releases,
and also to workers, consumers, and 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
3-Methyl Benzonitrile (CAS No. 620-22-4)
[9th CI Name: Benzonitrile, 3-methyl-]
SUPPORTING CHEMICAL
Benzonitrile (CAS No. 100-47-0)
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
3-Methyl Benzonitrile (CAS No. 620-22-4)
Introduction
The sponsor, Syngenta Crop Protection, Inc., submitted a Test Plan and Robust Summaries to EPA for 3-methyl
benzonitrile (CAS No. 620-22-4; 9th CI name: benzonitrile, 3-methyl-) on January 05, 2006. EPA posted the
submission on the ChemRTK HPV Challenge Web site on February 22, 2006
(http://www.epa.gov/chemrtk/pubs/summaries/3methbnz/cl6166tc.htm'). EPA comments on the original submission
were posted to the website on August 16, 2007. Public comments were also received and posted to the website.
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 any sponsors
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.
The sponsor proposed reduced health effects testing claiming that 3-methyl benzonitrile is a closed-system
intermediate (CSI). EPA's evaluation of the original information indicated that the chemical meets the guidance to
support the CSI claim for this chemical. 3-methyl benzonitrile is formed as an intermediate during the synthesis of
isophthalonitrile (IPN) which is subsequently used on-site to produce the FIFRA regulated fungicide,
Chlorothalonil. Transport of 3-methyl benzonitrile to other sites does not occur. Therefore, EPA has determined
that the chemical qualifies for reduced testing and waiving of repeated-dose and reproductive toxicity testing for the
purposes of the HPV Challenge Program.
EPA has identified that data for benzonitrile (CAS No. 100-47-0) can be used to address the ecotoxicity endpoints
for the purposes of the HPV Challenge Program. Benzonitrile is structurally similar to 3-methyl benzonitrile and
has similar physical-chemical properties.
Il;i/;ii'(l ( liiii'iiclori/iilion
'-\1elh\ Iheii/ouiiiile is a clear, colorless liquid al mom temperature ll is estimated in ha\e moderate water
soliihiliis and \ apor pressure ll has moderate niohihts in soil and moderale \ olalihts '-\leth\ Iheii/ouiiiile
undergoes aluiospheric phoioo\idaliou al a rale llial is considered slow \u esiimaled I >(T' of S suuuesis ilial
'-niclliv Ihcu/ouiiiilc has a low hioaccuniulalioii potential < 151) \o hiodemadaliou or stahilils mi waler < hulroK sis)
dala lor "-mclh\ Iheii/ouiiiile were subniiiied. howe\er. ~ '\ located reads hiodemadahilits studies on related
substances uidicaliuu that the substances were readils hiodeumdahle l!ased on this information and niodehuu. the
eu\ irounieuial persistence of this substance is e\pccled to he low il'l >
I lie acute aquatic lo\icil> of '-nielh\ Ihcu/ouiiiilc to fish, aquatic imeriehrales and plants is e\pccled to he low
hased on dala lor the supportiiiu chemical heii/ouitrile ((' \S \o |uo-4~-t>)
I lie acute oral lo\icil> of '-nielhv Iheii/ouiiiile is low '-\lelh\ Iheu/oiiiirile is shuhik iiriialiim to rahhit skin and
sc\crcl> ii'iiialiim to rahhit e\es Repeated-dose and rcpi'oducli\ e lo\icil> dala were not required fur the lll'V
Challeime I'lourani because '-nielhv Ihcu/ouiiiilc is a closcd-sssieni iiiierniediale '-\lelh\ Iheu/oiiiiiilc did not
induce ueiie miiialions
Vapor pressure, water soliihihts. reads hiodem.idatiou. de\ clopnieuial to\icil>. and chromosomal aberration assa\ s
were identified as dala uaps under the 111 J\ Challenge hourani
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
1. Physical-Chemical Properties and Environmental Fate
The physical-chemical properties of 3-methylbenzonitrile are summarized in Table la, while its environmental fate
properties are given in Table lb. The structure of the compound is provided in the Appendix.
Physical-Chemical Properties Characterization
3-Methylbenzonitrile is liquid that has moderate water solubility and moderate vapor pressure based on estimated
values. Estimated values for vapor pressure and water solubility were provided by the sponsor for 3-methyl-
benzonitrile and used to characterize these endpoints. However, estimated values for these endpoints are not
adequate for the HPV Challenge Program unless the solubility is <1 ppb and the vapor pressure is lower than 1 x 10"5
Pa.
Table la. Phvsical-Chcmical Properties of 3-IVlcthvl hen/on it rile'
Property
Value
CAS No.
620-22-4
Molecular Weight
117.15
Physical State
Liquid
Melting Point
-23 °C (measured)
Boiling Point
213°C (measured)
Vapor Pressure
0.187 mm Hg (estimated)2
Henry's Law Constant
4.8xlO"5 atm-m3/mole (estimated)2
Water Solubility
921.2 mg/L (estimated)2
Log Kow
2.087 (estimated)2
'Syngcnta Crop Protection Inc. 2005. Robust Summary and Test Plan for 3-Methylbenzonitrile.
http://www.epa.gov/chemrtk/pubs/summaries/3methbnz/cl6166tc.htm.
2USEPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
Environmental Fate Characterization
3-Methylbenzonitrile is expected to partition primarily to soil and water according to the results of a Level III
fugacity model that assumes equal emissions to air, water, and soil. 3-Methylbenzonitrile is expected to possess
moderate mobility in soil. 3-Methylbenzonitrile undergoes atmospheric photooxidation with photochemically
generated hydroxyl radicals at a rate that is considered slow. An estimated BCF of 8 suggests that 3-
methylbenzonitrile has a low bioaccumulation potential (Bl). No biodegradation or stability in water (hydrolysis)
data for 3-methylbenzonitrile were submitted; however, EPA located ready biodegradability data for benzonitrile
and 4-hydroxybenzonitrile indicating that they are both readily biodegradable. The combination of these measured
values and modeling lead to the conclusion that the environmental persistence of 3-methylbenzonitrile will be low
(PI). Measured ready biodegradation and hydrolysis data were not submitted and are therefore considered data gaps
under the HPV Challenge Program.
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Supporting Documents for Risk-Based Prioritization
September 2008
Table lb. Environmental Fate Characteristics of 3-Mcthvlbcnzonitrilc1
Property
Value
Photodegradation Half-life
13.3 days (estimated)
Biodegradation
Data Gap
Readily biodegradable based on analogs2 and modeling3
Hydrolysis Half-life
Data Gap
Bioconcentration
BCF = 8 (estimated)3
Koc
2.17 (estimated)3
Fugacity
(Level III Model)2
Air =8.1%
Water =28.5%
Soil = 63.3%
Sediment = 0.1%
Persistence3
PI (low)
Bioaccumulation3
Bl (low)
'Syngcnta Crop Protection Inc. 2005. Robust Summary and Test Plan for 3-Methylbenzonitrile.
http://www.epa.gov/chemrtk/pubs/summaries/3methbnz/cl6166tc.htm.
^National Institute of Technology and Evaluation, Tokyo, Japan. 2002. Biodegradation and Bioconcentration of
the Existing Chemical Substances under the Chemical Substances Control Law. CAS Numbers 100-47-0 and
767-00-0. http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html.
3USEPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States
Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
3Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal
Register 64, Number 213 (November 4, 1999) pp. 60194-60204.
Conclusion: 3-Methylbenzonitrile is a clear, colorless liquid at room temperature. It is estimated to have moderate
water solubility and vapor pressure. It has moderate mobility in soil and moderate volatility. 3-Methylbenzonitrile
undergoes atmospheric photooxidation at a rate that is considered slow. No biodegradation or stability in water
(hydrolysis) data for 3-methylbenzonitrile were submitted; however, EPA located ready biodegradability studies on
related substances indicating that the substances were readily biodegradable. Based on this information and
modeling, the environmental persistence of this substance is expected to be low (PI). An estimated BCF of 8
suggests that 3-methylbenzonitrile has a low bioaccumulation potential (Bl).
2. Environmental Effects - Aquatic Toxicity
Acute toxicity to Fish
3-Methyl benzonitrile(CAS No. 620-22-4)
Acute toxicity to fish from 3-methyl benzonitrile was estimated using ECOSAR.
96-h LCS0 = 71.5 mg/L
Benzonitrile (CAS No. 100-47-0, Supporting Chemical)
Fish (several species) were exposed to benzonitrile in 16 studies reported in EPA's ECOTOX database.
96-h LCS0 = 54 - 400 mg/L
Acute Toxicity to Aquatic Invertebrates
3-Methyl benzonitrile (CAS No. 620-22-4)
Acute toxicity to aquatic invertebrates from 3-methyl benzonitrile was estimated using ECOSAR.
48-h LCS0 = 11A mg/L
Benzonitrile (CAS No. 100-47-0, Supporting Chemical)
Water fleas (Daphnia magna) were exposed to benzonitrile in three studies reported in EPA's ECOTOX database.
24-h ECS0 = 30.9 - 200 mg/L
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September 2008
Toxicity to Aquatic Plants
3-Methyl benzonitrile (CAS No. 620-22-4)
Toxicity to aquatic plants from 3-methyl benzonitrile was estimated using ECOSAR.
96-h ECS0 (growth) = 48.4 mg/L
Benzonitrile (CAS No. 100-47-0, Supporting Chemical)
Aquatic plants (several species) were exposed to benzonitrile in 13 studies reported inEPA's ECOTOX database.
72-h EC50 (growth) = 30 mg/L
Conclusion: No adequate aquatic toxicity data were submitted for 3-methyl benzonitrile. Based on ECOSAR
estimations for 3-methyl benzonitrile and available toxicity data for the supporting substance benzonitrile (CAS No.
100-47-0), the acute toxicity to fish and aquatic invertebrates and toxicity to aquatic plants is expected to be low.
3. Human Health Effects
Acute Oral Toxicity
Sprague-Dawley rats (sex, number not stated) were administered 3-methyl benzonitrile via gavage at 3000 mg/kg-
bw/day (in tragarth) and observed for 7 days. No further details were provided in the summary. Although the
sponsor rated the study invalid, the results indicate the potential acute toxicity of the test substance.
LDS0 > 3000 mg/kg-bw/day
Repeated-Dose Toxicity
No repeated-dose toxicity data were provided. EPA has determined that 3-methyl benzonitrile meets the guidance to
support a CSI claim and has waived the requirement for repeated-dose toxicity testing for the purposes of the HPV
Challenge Program.
Reproductive Toxicity
No reproductive toxicity data were submitted. EPA has determined that 3-methyl benzonitrile meets the guidance to
support a CSI claim and has waived the requirement for reproductive toxicity testing for the purposes of the HPV
Challenge Program.
Developmental Toxicity
No developmental toxicity test data were submitted. Data gap
Genetic Toxicity - Gene Mutations
In Vitro
In an NTP study, Salmonella typhimurium strains TA97, TA98, TA100 and TA1535 were exposed to 3-methyl
benzonitrile up to 3333 |ig/plate in the presence and absence of metabolic activation. Positive and negative controls
gave the appropriate response. Cytotoxicity was observed at concentrations >1000 ng/plate. No mutagenicity was
observed.
3-Methylbenzonitrile was not mutagenic in this assay.
Genetic Toxicity - Chromosomal Aberrations
No chromosomal aberration test data were submitted. Data gap
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Additional Information
Skin Irritation
White rabbits (strain and number not specified) were administered 3-methyl benzonitrile dermally on to their backs
on cotton pads saturated with the test substance. After 15 minutes, the pads were removed and the application area
was washed with undiluted polyethylene glycol 400 (PEG 400) and then with a 50% solution of PEG 400. After 20
hours, the skin was not washed. Skin reactions were scored immediately after pad removal and after 1,3, and 8 days
until the skin changes had disappeared. At 15 minutes slight vascular injection and at 20 hours, significant vascular
injection was seen. Although the sponsor rated the study invalid, the results do provide indication of the potential
irritating properties of the test substance.
3-Methyl benzonitrile was slightly irritating to rabbit skin.
Eye Irritation
Rabbits (strain and number not specified) were instilled 3-methyl benzonitrile into the conjunctival sac and spread
over the upper eye. The reactions were scored after 10 minutes, 1 and 24 hours, 3 and 8 days and until the signs of
irritation disappeared. 3-Methyl benzonitrile caused necrosis to the rabbit eye. Although the sponsor rated the study
invalid, the results do provide indication of the potential irritating properties of the test substance.
3-Methyl benzonitrile was severely irritating to rabbit eyes in this study.
Conclusion: The acute oral toxicity of 3-methylbenzonitrile is low. 3-Methylbenzonitrile is slightly irritating to
rabbit skin and severely irritating to rabbit eyes. Repeated-dose and reproductive toxicity data were not required for
the HPV Challenge Program because 3-methylbenzonitrile is a closed-system intermediate. 3-Methylbenzonitrile
did not induce gene mutations.
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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
3-Methyl ben/onitrile
(620-22-4)
SUPPORTING CHEMICAL
Bcnzonitrilc
(100-47-0)
Structure
CN
X
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
71.5
(estimate)
54 - 400
Aquatic Invertebrates
48-h ECS0 (mg/L)
77.1
(estimate)
30.9-200 (24-h)
Aquatic Plants
72-h ECS0 (mg/L)
48.4 (96-h)
(estimate)
30.0
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
>3000
*
Repeated-Dose Toxicity
NOAEL/LOAEL
Endpoint waived because the
chemical is a closed system
intermediate.
*
Reproductive Toxicity
NOAEL/LOAEL
Endpoint waived because the
chemical is a closed system
intermediate.
*
Developmental Toxicity
NOAEL/LOAEL
Data Gap
*
Genetic Toxicity - Gene Mutation
Negative
*
Genetic Toxicity - Chromosomal
Aberrations
Data Gap
*
Additional Information
Skin Irritation
Eye Irritation
Slightly irritating
Severely irritating
**
— indicates that endpoint was not addressed for this chemical; * indicates endpoint not necessary for supporting
chemical; ** indicates endpoints that are not part of the base Screening Information Data Set (SIDS).
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Screening Level Exposure Characterization for HPV Challenge
Chemical
Benzonitrile, 3-methyl
CAS # 620-22-4
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
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September 2008
Screening Level Exposure Characterization
Benzonitrile, 3-methyl (CAS # 620-22-4)
Non-CBI Executive Summary
There are no 2006 Inventory Update Rule submissions for this chemical.
Information submitted as part of the HPV Challenge Program indicates that this chemical is used
as a process intermediate in the synthesis of a fungicide.12
Potential for Exposures to Human and the Environment:
Based on information from the HPV Challenge Program and in combination with Agency's
professional judgment, EPA identifies, for the purposes of risk-based prioritization, a low
relative ranking for each of the potentially exposed groups, including workers, general
population, consumers and children, and the environment. In 2007, the Agency reviewed the
information in the HPV submission or test plan and determined that the HPV chemical satisfies
the guidance to demonstrate that the chemical is a closed system intermediate.13 The chemical is
manufactured and processed in systems that are expected to reduce the potential for worker
exposure and environmental releases that could lead to other human and environmental
exposure. No information on commercial/consumer uses were found in the IUR or other data
sources.
12 Syngenta Crop Protection, Inc. 2005. Robust Summary and Test Plan for 3-Methylbenzonitrile.
http://www.epa.gov/chemrtk/pubs/summaries/3methbnz/cl6166tc.htm.
13 USEPA, 2007. EPA Comments on Chemical RTK HPV Challenge Submission. Letter dated November, 2007.
http://www.epa.gov/chemrtk/pubs/summaries/3methbnz/c 16166ct.pdf. Accessed June 20, 2008.
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