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
Methallyloxyphenol (CASRN 4790-71-0)
(9th CI and CA Index Name: Phenol, 2-[(2-methyl-2-propen-l-yl)oxy]-)
Contents:
• Page 2: Background
• Page 4: Screening-Level Risk Characterization: September 2008
• Page 7: Screening-Level Hazard Characterization: September 2008
• Page 15: Screening-Level Exposure Characterization: September 2008
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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
Methallyloxyphenol (CAS No. 4790-71-0)
[9th CI Name: Phenol, 2-[(2-methyl-2-propenyl)oxy-]
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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September 2008
QUALITATIVE SCREENING-LEVEL RISK CHARACTERIZATION FOR
Methallyloxyphenol (CAS No. 4790-71-0)
1. Physical-Chemical Properties and Environmental Fate
Methallyloxyphenol is a liquid at room temperature with a moderate vapor pressure and high
water solubility. It is expected to partition primarily to water and soil in the environment. It is
moderately mobile in soil and moderately volatile from moist soil and water. Its rate of
hydrolysis is considered negligible under environmental conditions. The rate of vapor-phase
photooxidation in the ambient atmosphere is rapid with respect to the hydroxyl radical and
moderate with respect to ozone. It did not degrade in a ready biodegradation test; however,
based on estimated biodegradability and professional judgment, it is expected to have low
persistence in the environment (PI). The estimated bioconcentration factor (BCF) of 25.3
indicates that methallyloxyphenol has a low potential to bioaccumulate (Bl).
2. Hazard Characterization
Aquatic Organism Toxicity. Acute toxicity of methallyloxyphenol to fish and aquatic
invertebrates is high and to aquatic plants is low.
Human Health Toxicity. The acute oral toxicity of methallyloxyphenol to rats is low. Repeat-
dose and reproductive toxicity studies are not required for the HPV Challenge Program because
methallyloxyphenol is a closed-system intermediate (CSI). A combined
reproductive/developmental toxicity study in rats showed no reproductive, developmental, or
parental systemic toxicity. Methallyloxyphenol was mutagenic in vitro, but did not induce
chromosomal aberrations in vivo.
3. Exposure Characterization
There are no 2002 or 2006 Inventory Update Rule (IUR) submissions for methallyloxyphenol
(CAS #4790-71-0).
Potential for Exposures to Human and the Environment:
Based on the information considered and in combination with the 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 2003, EPA reviewed the information in the HPV submission
and test plan and determined that the HPV chemical satisfied the guidance to demonstrate that
the chemical is a closed system intermediate. The use of this chemical solely as an intermediate
to produce other chemicals in enclosed vessels is 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 is available in the IUR or any other
sources.
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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). Methallyloxyphenol 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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Supporting Documents for Risk-Based Prioritization
September 2008
SCREENING-LEVEL HAZARD CHARACTERIZATION
OF HIGH PRODUCTION VOLUME CHEMICALS
SPONSORED CHEMICAL
Methallyloxyphenol (CAS No. 4790-71-0)
[9th CI Name: Phenol, 2-[(2-methyl-2-propenyl)oxy-]
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
Methallyloxyphenol
(Phenol, 2-[(2-methyl-2-propenyl)oxy]- , CAS No. 4790-71-0)
Introduction
The sponsor, FMC Corporation, submitted a Test Plan and Robust Summaries to EPA for methallyloxyphenol (CAS
Number 4790-71-0, 9th CI Name: phenol, 2-[(2-methyl-2-propenyl)oxy) on December 28, 2001. EPA posted the
submission on the ChemRTK HPV Challenge Web site on January 3, 2002
(http://www.epa.gov/chemrtk/pubs/summaries/methYall/cl3458tc.htm'). EPA comments on the original submission
were posted to the website on were submitted on July 31, 2002. Public comments were also received and posted to
the website. The sponsor submitted updated/revised documents on July 8, 2002, September 29, 2002, and December
30, 2004, which were posted to the ChemRTK website on July 24, 2002, October 17, 2002, 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.
The sponsor proposed reduced health testing, claiming that methallyloxyphenol is a closed-system intermediate
(CSI). EPA's evaluation of the original and revised/updated information indicated that the chemical meets the
guidance to support the CSI claim for this chemical. Methallyloxyphenol is produced at a single site, is consumed in
the in-process reaction to make another substance, and there are no offsite shipment. Therefore, EPA has
determined that the chemical qualifies for reduced testing - waiving of repeated-dose and reproductive toxicity
testing for the purposes of the HPV Challenge Program.
Ha/ard Characterization
Methallyloxyphenol is a liquid at room temperature with a moderate vapor pressure and high water solubility. It is
expected to partition primarily to water and soil in the environment. It is moderately mobile in soil and moderately
volatile from moist soil and water. Its rate of hydrolysis is considered negligible under environmental conditions.
The rate of vapor-phase photooxidation in the ambient atmosphere is rapid with respect to the hvdroxyl radical and
moderate with respect to ozone. It did not degrade in a ready biodegradation test: however, based on estimated
biodcgradability and professional judgment, it is expected to have low persistence in the environment (PI). The
estimated bioconcentration factor (BCF) of 25.3 indicates that methallyloxyphenol has a low potential to
bioaccumulatc (B1).
Acute toxicity of mcthallyloxphenol to fish and aquatic invertebrates is high and to aquatic plants is low.
The acute oral toxicity of mcthallyloxphenol to rats is low. Repeal-dose and reproductive toxicity studies are not
required for the HPV Challenge Program because mcthallyloxphenol is a closed-system intermediate (CSI). A
combined reproductive/developmental toxicity study in rats showed no reproductive, developmental, or parental
systemic toxicity. Mcthallyloxphenol was mutagenic in vitro, but did not induce chromosomal aberrations in vivo.
Melting point was identified as a data gap under the HPV Challenge Program: however, mcthallyloxphenol is a
liquid at room temperature.
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September 2008
1. Physical-Chemical Properties and Environmental Fate
The physical-chemical properties of methallyloxyphenol 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
Methallyloxyphenol is a liquid at room temperature. It has a moderate vapor pressure and high water solubility.
Table la. Phvsical-Chcmical Properties of Mcthallvloxvphcnol1
Property
Value
CAS Reg. No.
4790-71-0
Molecular Weight
164.21
Physical State
Liquid
Melting Point
Liquid at room temperature
Boiling Point
Undergoes Claisen rearrangement before reaching boiling point at
atmospheric pressure
Vapor Pressure
0.02 mm Hg at 25°C (mathematical extrapolation from higher
temperature vapor pressure data)
Water Solubility
1830 mg/L at 20°C (measured)
Henry's Law Constant
2.36 x 10"3 atm-m3/mol (estimated)2
Log Kow
2.47 (measured)
1FMC Corporation. 2004. Revised Robust Summary and Test Plan for Methallyloxyphenol.
http://www.epa.gov/chemrtk/pubs/summaries/methvall/cl3458tc.htm.
2US EPA. 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
Methallyloxyphenol is expected to partition primarily to water and soil, according to the results of a Level III
fugacity model. It is moderately mobile in soil. The Henry's Law constant indicates that methallyloxyphenol is
moderately volatile from moist soil and water. Its rate of hydrolysis is considered negligible under environmental
conditions (pH 5-9). The rate of vapor-phase photooxidation in the ambient atmosphere is rapid with respect to the
hydroxyl radical and moderate with respect to ozone. The estimated bioconcentration factor (BCF) of 25.3 indicates
that methallyloxyphenol has a low potential to bioaccumulate (B1). It did not degrade in a ready biodegradation
test; however, based on estimated biodegradability and professional judgment, it is judged to have low persistence in
the environment (PI).
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Table lb. Environmental Fate Characteristics of Mcthallvloxvphcnol1
Property
Value
Photodegradation Half-Life
OH half-life =1.5 hours (estimated)
03 half-life = 22.9 hours (estimated)2
Hydrolysis Half-Life
184 days at 37°C and pH 1.2
534 days at 20°C and pH 9
100 days at 37°C and pH 9
Biodegradation
0 % after 28 days (not readily biodegradable)
Bioconcentration
BCF = 25.3 (estimated)2
Direct Photolysis
Not significant
Log Koc
2.1 (estimated)2
Fugacity
(Level III Model)
Air = 85 %
Water =8.4%
Soil = 5 %
Sediment = 47 %
Persistence3
PI (low)
Bioaccumulation3
Bl (low)
1FMC Corporation. 2004. Revised Robust Summary and Test Plan for Methallyloxyphenol.
http://www.epa.gov/chemrtk/pubs/summaries/methYall/cl3458tc.htm.
2US EPA. 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
3 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64,
Number 213 (November 4, 1999) Page 60194-60204.
Conclusion: Methallyloxyphenol is a liquid at room temperature with a moderate vapor pressure and high water
solubility. It is expected to partition primarily to water and soil in the environment. It is moderately mobile in soil
and moderately volatile from moist soil and water. Its rate of hydrolysis is considered negligible under
environmental conditions. The rate of vapor-phase photooxidation in the ambient atmosphere is rapid with respect
to the hydroxyl radical and moderate with respect to ozone. It did not degrade in a ready biodegradation test;
however, based on estimated biodegradability and professional judgment, it is expected to have low persistence in
the environment (PI). The estimated bioconcentration factor (BCF) of 25.3 indicates that methallyloxyphenol has a
low potential to bioaccumulate (Bl).
2. Environmental Effects - Aquatic Toxicity
Acute Toxicity to Fish
(1) Sheepshead minnow (Cyprinodon variegates, 10/replicate) were exposed to methallyoxyphenol at measured
concentrations of 0, 2.3, 4.4, 8.8, 18 or 38 mg/L under flow-through conditions for 96 hours. Mortality ranged from
5% at 4.4 mg/L to 100% at 18 and 38 mg/L.
96-h LCS0 = 9.8 mg/L
(2) Atlantic silverside (Menidia menidia, 10/replicate) were exposed to methallyoxyphenol at measured
concentrations of 0, 0.684, 1.42, 2.96, 6.16 or 11.6 mg/L under flow-through conditions for 96 hours. The mortality
was 5% at 0.684 mg/L and 100% at 11.6 mg/L.
96-h LCS0 = 4.6 mg/L
(3)Marine spot (Leiostomus xanthurus, 5/replicate) were exposed to methallyoxyphenol at nominal concentrations of
0, 0.065, 0.125, 0.25, 0.50 or 1.0 mg/L for 96 hours. Partial loss of equilibrium was noted in four out of ten fish at
1.0 mg/L at 24 hours. There was 100% mortality at 1.0 mg/L at 48 hours.
96-h LCS0 = 0.71 mg/L
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Acute Toxicity to Aquatic Invertebrates
(1) Mysidopsis bahia (10/replicate) were exposed to methallyoxyphenol at measured concentrations of 0, 527, 660,
1080, 1363 or 2307 |ig/L under flow-through conditions for 96 hours.
96-h LCS0= 1.327 mg/L
(2) Mysidopsis bahia (10/replicate) were exposed to methallyoxyphenol at measured concentrations of 0, 255, 417,
643, 880 and 2255 |ig/L under flow-through conditions for 96 hours.
96-h LCS0 = 1.130 mg/L
(3) Mysidopsis bahia (10/replicate) were exposed to methallyoxyphenol at measured concentrations of 67, 138, 257,
495 or 1053 |ig/L under flow-through conditions for 96 hours. After 96 hours, mortality ranged from 10% at 67
|ig/L to 100% at 1053 |ig/L. Partial loss of equilibrium was observed at the 24 hour observation period at 138 |ig/L.
48-h LCS0= 0.520 mg/L
96-h LCS0= 0.201 mg/L
{A) Mysidopsis bahia (10/replicate) were exposed to methallyoxyphenol at nominal concentrations of 0.23, 0.39,
0.65, 1.1, 1.8 or 3.0 mg/L under static conditions for 96 hours. After 96 hours, mortality ranged from 10% at and
below 0.39 mg/L to 100% at and above 1.8 mg/L.
96-h LCS0= 0.81 mg/L
Toxicity to Aquatic Plants
Skeletonema costatum were exposed to methallyloxyphenol (68% purity) at measured concentrations of 0, 3.45,
10.59, 19.43, 37.64 or 76.4 mg/L for 96 hours. Loss of color (chlorophyll) and general fading of cells (representing
disintegration of the cell wall and cell death) was noted only at 37.64 mg/L. No viable cell material was found at
74.6 mg/L.
96-h ECS0 (biomass) = 26.6 mg/L
Conclusion: The acute toxicity of methallyloxyphenol to fish and aquatic invertebrates is high and to aquatic plants
is low.
3. Human Health Effects
Acute Oral Toxicity
Sprague-Dawley rats (10/sex/dose) were administered single doses of methallyloxyphenol via gavage at 2000, 2500,
3000, 4000 or 4500 mg/kg-bw (males) or 2500, 2700, 3000 or 4500 mg/kg-bw (females) and observed for 14 days.
Predominant clinical signs included decreased locomotion, ataxia, recumbency, exophthalmos, hematuria,
lacrimation, oral discharge, and abdominogenital staining. Most signs of toxicity subsided by the 5th day of the
study. Gross necropsy findings among decedents included red fluid in the intestines and bladder of several rats. The
necropsy of survivals did not reveal any abnormalities.
LDS0 = 2943 mg/kg-bw
Repeated-Dose Toxicity
The requirement for repeated-dose toxicity endpoint was waived for the purposes of the HPV Challenge Program
because methallyloxyphenol is a closed system intermediate.
Reproductive Toxicity
The requirement for reproductive toxicity endpoint was waived for the purposes of the HPV Challenge Program
because methallyloxyphenol is a closed system intermediate. However, the sponsor submitted a combined
reproductive/developmental toxicity test which is described below in the Developmental Toxicity section.
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Developmental Toxicity
In a combined reproductive/developmental toxicity study, Sprague-Dawley rats (group size not indicated) were
administered methallyloxypehnol via gavage at 0, 60, 240 or 720 mg/kg-bw/day. Males were exposed from 2 weeks
before mating to end of mating (28 days) and females were exposed from 2 weeks before mating through gestation
to day 3 post partum (54 days). There was a high incidence of salivation in both sexes at 240 and 720 mg/kg-bw
doses. There were no treatment-related changes in body weight, food consumption, necropsy findings, and male
reproductive organ weights or histopathological findings. There were no treatment-related changes in precoital
time, mating index, fertility index, pregnancy index and reproductive and litter findings such as gestation length,
number of live and dead pups at birth, sex ratio, and body weights of live pups.
NOAEL for systemic/reproductive/developmental toxicity = 720 mg/kg-bw/day (based on no effects at the
highest dose tested)
Genetic Toxicity - Gene Mutation
In vitro
(1) In two separate assays, Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were
exposed to methallyloxyphenol at concentrations from 20 - 5000 ug/plate in the presence and absence of metabolic
activation. Mthallyloxyphenol was not mutagenic in any strain in the presence of metabolic activation, but caused
an increase in revertants/plate in TA1535 in the absence of metabolic activation. An increase in mutant frequency in
TA100 was observed in the absence of metabolic activation; however this increase did not meet the criterion for a
positive response due to the high background incidence in this strain. The positive and negative (DMSO) controls
were included in the assay and gave appropriate response.
Methallyloxyphenol was mutagenic in these assays.
(2) Salmonella typhimurium strain TA1535 was exposed to methallyoxyphenol at concentrations of 2.5, 12.5, 62.5,
312.5, 625, 1250, 2500, 5000 or 10,000 (ig/plate in the absence of metabolic activation in a modified Ames assay.
No positive controls were used. All concentrations induced an increase in the revertants per plate.
Methallyloxyphenol was mutagenic in this assay.
(3) Mouse lymphoma L5178Y cells were exposed to methallyloxyphenol (64% purity) in the presence and absence
of metabolic activation. Concentrations were 0.0006 - 0.0084 |iL/mL in the presence of metabolic activation and
0.0013 - 0.0075 |iL/mL in the absence of metabolic activation. In the absence of metabolic activation,
methallyloxyphenol induced an increase in mutant frequency. In the presence of metabolic activation, there was no
increase in mutant frequency.
Methallyloxyphenol was mutagenic in this assay.
(4) Mouse lymphoma L5178Y cells were exposed to methallyloxyphenol (64% purity) in the presence and absence
of metabolic activation. Concentrations tested were 0.2 - 3.3 (ig/mL in the presence of metabolic activation and
20.0 - 330 (ig/mL in the absence of metabolic activation. The test material induced significant increases in the
mutant frequency in both the presence and absence of metabolic activation in this assay at concentrations in which
cell survival was greater than 10%. The positive and negative (DMSO) controls were included in the assay and gave
appropriate response.
Methallyloxyphenol was mutagenic in this assay.
Genetic Toxicity - Chromosomal aberrations
In vivo
Sprague-Dawley rats (5 males/dose) were administered methallyloxyphenol via gavage at 0 (corn oil), 100, 300 or
1000 mg/kg-bw and were sacrificed 6, 24, and 48 hours later. A positive control group of 5 rats received 40 mg/kg-
bw cyclophosphamide and were sacrificed after 24 hours. Two hours prior to sacrifice, animals were given a single
intraperitoneal injection of 2.0 mg/kg colchicine to arrest cells in metaphase. Bone marrow was collected from both
femurs, cells were prepared and analyzed. The test material did not induce an increase in chromosomal aberrations
relative to the solvent control.
Methallyloxyphenol did not induce chromosomal aberrations in this assay.
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Genetic Toxicity - Other
In an unscheduled DNA synthesis assay, rat primary hepatocytes were exposed to methallyloxyphenol at 0.1, 0.5,
1.0, 5.0, 10, 50, 100 or 500 (ig/mL for 24 hours. There was no net increase in the mean net nuclear grain count in
cells treated with the test article compared to the solvent control (100 cells counted). The positive controls showed
the expected increase in net nuclear grain counts (50 cells counted). Higher doses (not specified) were cytotoxic.
Methallyloxyphenol did not induce unscheduled DNA synthesis in this assay.
Conclusion: The acute oral toxicity of methallyloxphenol to rats is low. Repeat-dose and reproductive toxicity
studies are not required for the HPV Challenge Program because methallyloxphenol is a closed-system intermediate
(CSI). A combined reproductive/developmental toxicity study in rats showed no reproductive, developmental, or
parental systemic toxicity. Methallyloxphenol was mutagenic in vitro, but did not induce chromosomal aberrations
in vivo.
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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
Mcthallyloxyphcnol
(4790-71-0)
Structure
OH //
c
Summary of Environmental Effects - Aquatic Toxicity Data
Fish
96-h LCS0 (mg/L)
0.71 mg/L (Marine spot)
4.6 (Atlantic silverslide)
9.8 (Sheepshead minnow)
Aquatic Invertebrates
48-h ECS0 (mg/L)
0.201 - 1.3 mg/L (Mysidopsis bahia)
Aquatic Plants
72-h ECS0 (mg/L)
(biomass)
26.6
Summary of Human Health Data
Acute Oral Toxicity
LDS0 (mg/kg-bw)
2943
Repeated-Dose Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
Data not required based on CSI.
Reproductive/Developmental Toxicity
NOAEL/LOAEL
Oral (mg/kg-bw/day)
Systemic/Reproductive/Developmental Toxicity
NOAEL = 720 (highest dose tested)
Genetic Toxicity - Gene Mutation
In vitro
Positive
Genetic Toxicity - Chromosomal Aberrations
In vitro
Negative
Genetic Toxicity - Other
Unscheduled DNA Synthesis
Negative
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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Screening Level Exposure Characterization for HPV Challenge
Chemical
Phenol, 2- [(2-methyl-2-propenyl)oxy] -
CAS # 4790-71-0
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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U.S. Environmental Protection Agency
Supporting Documents for Risk-Based Prioritization
September 2008
Screening Level Exposure Characterization
Phenol, 6-tert-butyl-3-(chloromethyl)-2,4-dimethyl (CAS # 4790-71-0)
Non-CBI Executive Summary
There are no 2002 or 2006 Inventory Update Rule (IUR) submissions for phenol, 6-tert-butyl-3-
(chloromethyl)-2,4-dimethyl (CAS # 4790-71-0). A pre-manufacture notification for this
chemical was submitted to EPA, and this notification contains data and information that are
claimed confidential.
Potential for Exposures to Human and the Environment:
Based on the information considered and in combination with the 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 2003, EPA reviewed the information in the HPV submission
and test plan and determined that the HPV chemical satisfied the guidance to demonstrate that
the chemical is a closed system intermediate.12 The use of this chemical solely as an
intermediate to produce other chemicals in enclosed vessels is expected to reduce the potential
for worker exposures. Wastewater containing the chemical is treated on-site before discharge to
a publicly-owned wastewater facility for further treatment. There are no 2002 or 2006 IUR
submissions for this chemical. No information on commercial/consumer uses is available in the
IUR or any other sources.
12 USEPA, 2003. EPA Comments on Chemical RTK HPV Challenge Submission. Letter dated July 24, 2002.
http://www.epa.gov/chemrtk/pubs/summaries/methYall/cl3458ct.pdf. Accessed June 20, 2008.
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