U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Alkyl Sulfides Category
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, l-(ferf-dodecylthio)
CASRN 67124-09-8
Subcategory II: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized
CASRN 68511-50-2
Pentene, 2,4,4-trimethyl-, sulfurized
CASRN 68515-88-8
Alkenes, C15-C18 alpha-, sulfurized
CASRN 67762-55-4
The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary
initiative aimed at developing and making publicly available screening-level health and
environmental effects information on chemicals manufactured in or imported into the United
States in quantities greater than one million pounds per year. In the Challenge Program,
producers and importers of HPV chemicals voluntarily sponsored chemicals; sponsorship
entailed the identification and initial assessment of the adequacy of existing toxicity
data/information, conducting new testing if adequate data did not exist, and making both new
and existing data and information available to the public. Each complete data submission
contains data on 18 internationally agreed to "SIDS" (Screening Information Data Set1'2)
endpoints that are screening-level indicators of potential hazards (toxicity) for humans or the
environment.
The Environmental Protection Agency's Office of Pollution Prevention and Toxics (OPPT) is
evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored
chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of
the quality and completeness of the data set provided in the Challenge Program submissions.
They are not intended to be definitive statements regarding the possibility of unreasonable risk of
injury to health or the environment.
The evaluation is performed according to established EPA guidance2'3 and is based primarily on
1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.
2 U.S. EPA. HPV Challenge Program - Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.
3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
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hazard data provided by sponsors; however, 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 one year prior to the date of the HPV
Challenge submission to the present: (ChemID to locate available data sources including
Medline/PubMed, Toxline, HSDB, IRIS, NTP, AT SDR, IARC, EXTOXNET, EPA SRS, etc.),
STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS,
Merck, etc.) and Science Direct. OPPT's focus on these specific sources is based on their being
of high quality, highly relevant to hazard characterization, and publicly available.
OPPT does not develop HCs for those HPV chemicals which have already been assessed
internationally through the HPV program of the Organization for Economic Cooperation and
Development (OECD) and for which Screening Initial Data Set (SIDS) Initial Assessment
Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These documents are
presented in an international forum that involves review and endorsement by governmental
authorities around the world. OPPT is an active participant in these meetings and accepts these
documents as reliable screening-level hazard assessments.
These hazard characterizations are technical documents intended to inform subsequent decisions
and actions by OPPT. Accordingly, the documents are not written with the goal of informing the
general public. However, they do provide a vehicle for public access to a concise assessment of
the raw technical data on HPV chemicals and provide information previously not readily
available to the public.
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Chemical Abstract Service
Registry Number
(CASRN)
67124-09-8
68511-50-2
68515-88-8
67762-55-4
Chemical Abstract Index
Name
2-Propanol, l-(ferf-dodecylthio)
1-Propene, 2-methyl-, sulfurized
Pentene, 2,4,4-trimethyl-, sulfurized
Alkenes, Cis-is .alpha.-, sulfurized
Structural Formula
See Section 1
Summary
These category members are viscous liquids with estimated negligible to moderate water
solubility and negligible to low vapor pressure. They are expected to have low to moderate
mobility in soil. Volatilization of these category members is considered to be low to moderate
based upon their estimated Henry's Law constants. The rate of hydrolysis is considered
negligible. The rate of atmospheric photooxidation is considered moderate. These category
members are expected to have moderate persistence (P2) and low to moderate bioaccumulation
potential (B1-B2).
Subcategory I (CASRN 67124-09-8)
The acute oral and dermal toxicity for CASRN 67124-09-8 in rats and rabbits are low and the
acute inhalation toxicity in rats is moderate. An oral repeated-dose toxicity study in rats showed
liver effects at 100 mg/kg/day. The NOAEL was not established. A one-generation reproductive
toxicity study in rats showed decreased body weight and an increase in mean liver and kidney
weights in adult males and hematology changes in dams at 167 mg/kg-bw/day via the oral route;
the NOAEL was 50 mg/kg-bw/day. A developmental toxicity showed a decrease in mean pup
weight at 67 mg/kg-bw/day; the NOAEL was 50 mg/kg/day. No reproductive toxicity effects
were seen at 500 mg/kg-bw/day (highest dose tested). This chemical did not induce gene
mutation or chromosomal aberration in vitro.
The evaluation of available toxicity data for aquatic organisms for CASRN 67124-09-8 indicates
that the 96-h LC 50 for fish is 0.42 mg/L, the 48-h EC 50 for aquatic invertebrates is 1.3 mg/L
and the 96-hour EC50 for aquatic plants is "no effects at saturation." The estimated 21-d chronic
toxicity value for aquatic invertebrates using ECOSAR is 0.036 mg/L.
The chronic aquatic invertebrate toxicity endpoint for CASRN 67124-09-8 remains a data gap
under the HPV Challenge Program.
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Subcategory II (CASRNs 68511-50-2, 68515-88-8, and 67762-55-4)
The acute oral toxicity of CASRNs 68511-50-2 and 68515-88-2 in rats is low. The acute
inhalation toxicity of CASRN 68515-88-8 in mice, guinea pigs and rats is moderate. The acute
dermal toxicity of CASRNs 68515-88-8 and 67762-55-4 is low.
In a dermal repeated-dose toxicity study in rats, CASRN 68511-50-2 showed a decrease in body
weight gain in male rats and hematological effects in both sexes at 250 mg/kg/day; the NOAEL
was 100 mg/kg/day. Female rats exposed to CASRN 68515-88-8 via aerosol inhalation, showed
increased hemoglobin levels and relative liver-to-body weight ratios at 150 mg/kg/day; the
NOAEL was 50 mg/kg-bw/day. In the same study, liver effects were seen in male rats at 150
mg/kg-bw/day. The NOAEL for male rats was not established. CASRNs 68511-50-2 and
68515-88-8 were irritating to rat and rabbit skin in dermal repeated-dose studies.
CASRNs 68511-50-2 and 68515-88-8 did not induce gene mutations in vitro or chromosomal
aberrations in vivo. CASRN 67762-55-4 did not induce gene mutations in vivo.
The evaluation of available toxicity data to aquatic organisms for all subcategory II members
indicates that for the acute hazard to fish, aquatic invertebrates and aquatic plants, there are "no
effects at saturation".
Reproductive and developmental toxicity were identified as data gaps for all subcategory
members under the HPV Challenge program.
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The sponsor, The American Chemistry Council, Petroleum Additives Panel, Health,
Environmental and Regulatory Task Group (HERTG), submitted a Test Plan and Robust
Summaries to EPA for the alkyl sulfides category on March 28, 2000. EPA posted the
submission on the ChemRTK HPV Challenge website on June 13, 2000
http://www.epa.gov/chemrtk/pubs/summaries/alkylsul/cl2549tc.htm. EPA comments on the
original submission were posted to the website on October 6, 2000. Public comments were also
received and posted to the website. The sponsor submitted updated/re vised documents on May
18, 2005, which were posted to the ChemRTK website on June 7, 2005.
Category Justification
The sponsor proposes a category of four alkyl sulfide substances that are used as petroleum
lubricant additives. One of the sponsored mixtures, 2-propanol, (fe/7-dodecylthio)- (CASRN
67124-09-8), is a hydroxyalkyl monosulfide. Two of the sponsored mixtures, 1-propene, 2-
methyl-, sulfurized (CASRN 68511-50-2) and pentene, 2,4,4-trimethyl, sulfurized (CASRN
68515-88-8), are highly branched alkyl sulfide chains that contain varying numbers of repeated
units. The fourth sponsored mixture, alkenes C15 - 18 alpha-, sulfurized (CASRN 67762-55-4),
contains both cyclic and non-cyclic alkyl sulfide structures with long chain alkyl groups that can
be either linear or branched. Structures of these three alkyl sulfides indicate that their
components may contain mono- through penta- sulfide units.
The sponsor's proposed grouping of these alkyl sulfides into a single category was based on the
structural similarity, limited reactivity, low biological activity, very low water solubility and low
vapor pressure. EPA, for this phase of review, considers these chemicals as two subcategories:
(1) Hydroxyalkyl Monosulfide consisting of 2-propanol, (fe/7-dodecylthio)- (CASRN 67124-09-
8) and (2) Alkyl Polysulfides consisting of 1-propene, 2-methyl-, sulfurized (CASRN 68511-50-
2), pentene, 2,4,4-trimethyl, sulfurized (CASRN 68515-88-8) and alkenes CI5 - 18 alpha-,
sulfurized (CASRN 67762-55-4). This is primarily based on the fact that 2-propanol, (tert-
dodecylthio)- is the only sponsored chemical that contains a hydroxyl group which may cause it
to be metabolized and excreted differently from the remaining sponsored chemicals. It is the
only sponsored chemical that is exclusively a monosulfide, and its molecular weight appears to
be much lower than the components that make up the other three sponsored mixtures.
In addition, based on the sponsor's descriptions, pentene, 2,4,4-trimethyl, sulfurized and alkenes
CI5 - 18 alpha-, sulfurized, are not expected to contain lower molecular weight components and,
therefore, would have aquatic toxicity similar to that of 1-propene, 2-methyl-, sulfurized. Thus,
grouping of the sponsored mixtures 1-propene, 2-methyl-, sulfurized, pentene, 2,4,4-trimethyl,
sulfurized and alkenes C15 - 18 alpha-, sulfurized appears to be supported for evaluation of
physicochemical and aquatic toxicity endpoints. In contrast, 2-propanol, (fert-dodecylthio)- has
a low molecular weight (260.5) and is expected to have different physicochemical properties
(lower log Kow and higher water solubility) than the higher molecular weight mixtures.
Furthermore, aquatic toxicity data provided for 2-propanol, (/^/'/-dodecylthio)- showed evidence
of toxicity that is consistent with its lower molecular weight. Thus, these physicochemical and
aquatic toxicity data support evaluation of 2-propanol, (te/7-dodecylthio)- separately from the
other sponsored mixtures.
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Overall, structural considerations and the physicochemical, aquatic toxicity and health data that
allow comparisons among the sponsored chemicals support evaluation of 2-propanol, (tert-
dodecylthio)- in one subcategory and the three sponsored mixtures in a separate subcategory.
Therefore, in this hazard characterization assessment, 2-propanol, (/^/'/-dodecylthio)- will be
considered alone in Subcategory I (hydroxyalkyl monosulfide), whereas 1-propene, 2-methyl-,
sulfurized, pentene, 2,4,4-trimethyl, sulfurized and alkenes CI5 - 18 alpha-, sulfurized will be
considered together in Subcategory II (alkyl polysulfides).
1. Chemical Identity
1.1 Identification and Purity
All four substances are derived from similar starting materials (i.e., alkenes and sulfur), and all
contain similar chain length olefinic hydrocarbons linked by sulfur to form linear, branched, or cyclic
structures. Commercial alkyl sulfides are manufactured by reacting olefins (linear or branched) with
sulfur in a controlled exothermic reaction and then sparged with nitrogen to remove hydrogen
sulfide. The 1-propene, 2-methyl- and Pentene, 2,4,4-trimethyl derivatives require a pre-step where
an adduct of the olefin and sulfur is first produced and then further reacted with additional sulfur to
create the final product. Three substances include saturated long-chain hydrocarbons. Two of the
substances contain mixtures of linear and cyclic alkyl sulfides. These substances can also contain
cyclic structures made up of sulfur and carbon, and the alkyl groups can be linear or branched.
Table 1. Sponsored Chemicals
Chemical Name
CASRN
Chemical Structure
2-Propanol, 1 -{teri-
dodecylthio)-
67124-09-8
?H3 CH3
Ho^srx>:
H3C H3C CH3 CH3
1-Propene, 2-methyl-,
sulfurized
68511-50-2
h3c ch3
H3\ /Sx^/^sx^^CH3
/\h ^CHiy
H3C 3 CH3
x=l-5
y=l-20
Pentene, 2,4,4-trimethyl-,
sulfurized
68515-88-8
CH,
H3C\PCH3
h3c /CH3
H3C/\ H3C CH3 x=4-5
ch3
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1.2 Physical-Chemical Properties
The physical-chemical properties of the alkyl sulfides are summarized in Table 2. The alkyl
sulfides are viscous liquids with estimated negligible to moderate water solubility and negligible
to low vapor pressure.
2. General Information on Exposure
2.1 Production Volume and Use Pattern
The alkyl sulfides category chemicals had an aggregated production and/or import volume in the
United States of 52 to 120.5 million pounds during calendar year 2005. The volumes for the
category members are as follows:
CASRN 67124-09-8
CASRN 68511-50-2
CASRN 68515-88-8
CASRN 67762-55-4
1 to 10 million pounds
50 to 100 million pounds
1 to 10 million pounds
<500,000 pounds
Non-confidential information in the IUR indicates that the industrial processing and uses of these
chemicals include lubricants and functional fluids. Non-confidential information in the IUR
indicates that the commercial and consumer products containing these chemicals include
lubricants, greases, and fuel additives.
The HPV submission for this category states that these chemicals are used as high temperature
and anti-wear inhibitors in the formulation of engine oils, industrial and metal working
lubricating oils and greases. Alkyl sulfides are generally sold to finished oil blenders contained
in additive packages; these additive packages are then blended into finished oils.
2.2 Environmental Exposure and Fate
No quantitative information is available on releases of this chemical category to the environment.
The environmental fate properties are provided in Table 3. The alkyl sulfides are expected to
have low to moderate mobility in soil. Two category members, 2-propanol, 1 -(VtrZ-dodecylthio)-
and 1-propene, 2-methyl-, sulfurized were not readily biodegradable using the manometric
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respirometry (OECD 301F) and modified Sturm (OECD 301B) tests; however, alkyl sulfides are
typically not recalcitrant in the environment. The rate of volatilization of the alkyl sulfides from
water and moist soil is considered low to moderate based on their estimated Henry's Law
constants. The rate of hydrolysis is considered negligible under environmental conditions. The
alkyl sulfides are expected to have moderate persistence (P2) and low to moderate
bioaccumulation potential (B1-B2).
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Table 2. Physical-Chemica
Properties of Alkyl Sulfides Category1
Property
2-Propanol, 1-
1-Propene, 2-
Pentene, 2,4,4-
Alkenes, C15-18 .alpha.-, sulfurized
(ftrf-dodecylthio)-
niethyl-, sulfurized
tri-methyl-,
sulfurized
CASRN
67124-09-8
68511-50-2
68515-88-8
67762-55-4
Molecular Weight
260
160-1,600 (mean
molecular weight of
480)
594-658
520 (mean molecular weight)
Physical State
Viscous liquid
Viscous liquid
Viscous liquid
Viscous liquid
Melting Point
No data2
No data2
No data2
No data2
Boiling Point
Decomposes at
>200°C without
Decomposes at
>200°C without
Decomposes at
>200°C without
Decomposes at >200°C without boiling
boiling
boiling
boiling
Vapor Pressure
l.lxlO"4mm Hg3
0.02 to <7.5xl0"8
mm Hg3
<7.5 xlO"8 mm Hg3
<7.5xlO"8mm Hg3
Dissociation
Constant (pKa)
Not applicable
Not applicable
Not applicable
Not applicable
Henry's Law
l.lxl0"6atm-
6
>6
>6
American Chemistry Council. May 19, 2005. Revised Robust Summary and Test Plan for Alkyl Sulfides Category.
htto://www.et>a.eov/chemrtk/t>ubs/summaries/alkvlsul/cl2549tc.htm.
Estimated melting points were provided in the Test Plan that conflicted with the physical state of the substance.
3U.S. EPA. 2008. Estimation Programs Interface Suite™ for Microsoft® Windows, v 3.20. United States Environmental Protection Agency, Washington,
DC, USA. lUtD:/Avww.CDa.aoY/oDDtintr/c\DOSiirc/Dubs/cDisuitc.htm.
m=measured data; e=estimated
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Table 3. Environment;!
Fate Characteristics of Alkyl Sulfides Category1
Property
2-Propanol, 1-
(tert-
dodecylthio)-
1-Propene, 2-
methyl-, sulfurized
Pentene, 2,4,4-
tri-methyl-,
sulfurized
Alkenes, Cis-is .alpha.-,
sulfurized
CASRN
67124-09-8
68511-50-2
68515-88-8
67762-55-4
Photodegradati on
Half-life
5.51 hours
1.42-3.60 hours
2.75-6.78 hours
1.66-22.63 hours
Hydrolysis Half-
life
Stable
Stable
Stable
Stable
Biodegradation
5.9% after 28
days (not readily
biodegradable)
0.3% after 28 days
(not readily
biodegradable)
Not readily
biodegradable
based on
comparisons with
other category
members
Not readily
biodegradable based on
comparisons with other
category members
Bi oconcentrati on
BCF= 3,020
BCF=3.16-2,818
BCF=3.16
BCF=3.16
Log Koc
3.0
6.12-11.98
6.49-12.74
9.50-9.77
Fugacity
(Level I Model)
Air = 0.265%
Water = 0.407%
Soil = 97.1%
Sediment =
2.158%
Air = <0.1%
Water = <0.1%
Soil = 97.7%
Sediment = 2.172%
Air = <0.1%
Water = <0.1%
Soil = 97.7%
Sediment =
2.172%
Air = <0.1%
Water = <0.1%
Soil = 97.8%
Sediment = 2.112%
Persistence2
P2 (moderate)
P2 (moderate)
P2 (moderate)
P2 (moderate)
Bi oaccumul ati on2
B2 (moderate)
B1-B2 (low-
moderate)
BI (low)
BI (low)
American Chemistry Council. May 19, 2005. Revised Robust Summa
lUtD:/Avww.CDa.aoY/chcmrtk/Diibs/summarics/alkYlsul/c 12549tc.htm.
ry and Test Plan for Alkyl Sulfides Category.
Toxic New Chemical Substances. Federal Register
2Federal Register. 1999. Category for Persistent, Bioaccumulative, and
64, Number 213 (November 4, 1999) pp. 60194-60204.
m=measured data; e=estimated
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3. Human Health Hazard
A summary of health effects data submitted for SIDS endpoints is provided in Table 4. The table
also indicates where data for tested category members are read-across (RA) to untested members
of the category.
Acute Oral Toxicity
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)- (CASRN 67124-09-8)
Fasted male Sprague-Dawley rats (5/sex/dose) were administered 2-propanol, (fert-dodecylthio)-
in mineral oil via oral gavage at 5000 mg/kg-bw and observed for 14 days following dosing.
Mortality was observed in one rat within 48 hours. No treatment related histopathological
changes or microscopic lesions were observed.
LD50 > 5000 mg/kg-bw
Subcategory 2: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
Fasted male Sherman/Wistar rats (5/sex/dose) were administered 1-propene, 2-methyl-,
sulfurized via oral gavage at 2.0, 4.0, 8.0, 16.0 or 32.0 mL/kg (~ 2000, 4000, 8000, 16,000 or
32,000 mg/kg-bw) and observed for 14 days following dosing. Four/five deaths were observed
day 1 and one/five on day two at 8000 mg/kg-bw. Five/five deaths occured on day 1 at 16,000
and 32,000 mg/kg-bw. No histopathology or microscopic evaluations were performed.
1,1)511 = ~ 5700 mg/kg-bw
Pentene, 2,4,4-trimethyl, sulfurized (CASRN 68515-88-8)
Albino Sprague-Dawley rats (5/sex/dose) were administered pentene, 2,4,4-trimethyl, sulfurized
in a mineral oil based material via oral gavage at 5000 mg/kg-bw and observed for 15 days
following dosing. Clinical signs included decreased activity, salivation and urinary incontinence
in females and diarrhea and salivation in males. No mortality was observed. No treatment
related histopathological changes or microscopic lesions were observed.
LD50 > 5000 mg/kg-bw
Acute Inhalation Toxicity
Subcategory 2: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
Sprague-Dawley rats (10/sex/concentration) were exposed whole-body to 1-propene, 2-methyl-,
sulfurized vapor at 0.07 or 0.39 mg/L for 4 hours and observed for 14 days. Five males and five
females from each group were sacrificed 24 hours following exposure and the remaining animals
were observed for 14 days. Clinical signs included oral and ocular discharge, shallow respiration
(high dose) decreased response to stimuli. No mortality, treatment related histopathological
changes or microscopic lesions were observed.
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4-h LC50 > 0.39 mg/L
Pentene, 2,4,4-trimethyl, sulfurized (CASRN. 68515-88-8)
(1) CD-I mice and Hartley guinea pigs (5/sex/species/concentration) were exposed whole-body
to pentene, 2,4,4-trimethyl, sulfurized aerosol at 0 or 4.3 mg/L for 4 hours, observed every 15
minutes during/after dosing and for 14 days following. Ano-genital staining was observed in
guinea pigs during week two. One death occurred that was not attributed to treatment. No
treatment related histopathological changes or microscopic lesions were observed.
4-h LC50 (mice and guinea pigs) > 4.3 mg/L
(2) Sprague-Dawley rats, CD-I mice and Hartley guinea pigs (5/sex/species/concentration) were
exposed whole-body to pentene, 2,4,4-trimethyl, sulfurized aerosol at concentrations of 0 or 4.3
mg/L for 4 hours, observed every 15 minutes during/after dosing and for 14 days following. One
female rat died within 2 hours, and three female rats died within one day of dosing. An
additional two rats (sex not stated) were found dead the morning after dosing. A single male
mouse and a single male guinea pig also died on test days 7 and 9, respectively. A significant
decrease in body weight was seen in all three species.
4-h LC50 (mice and guinea pigs) > 4.3 mg/L
4-h LC50 (rat) < 4.3 mg/L
(3) Sprague-Dawley rats, (5/sex/concentration) were exposed whole-body to pentene, 2,4,4-
trimethyl, sulfurized as an aerosol at concentrations of 1.5, 2.5 or 5.6 mg/L for 4 hours and
observed for 14 days following dosing. Three/five females exposed to 1.5 mg/L died on day 2,
4/5 females exposed to 2.5 mg/L died on day 2, 3/5 females exposed to 5.6 mg/L died on day 2
with an additional death on day six. Male rats showed a decrease in body weight at 2.5 and 5.6
mg/L (significance not specified). No mortality, treatment related histopathological changes or
microscopic lesions were observed in males.
4-h LC50 (males) > 5.6 mg/L
4-h LC50 (females) = 2.2 mg/L
Acute Dermal Toxicity
Subcategory 1: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)-(CASRN 67124-09-8)
New Zealand White rabbits (5/sex) were administered 2-propanol, (fe/7-dodecylthio)- in a
mineral oil-based material dermally on unabraded shaved skin at 2000 mg/kg-bw under occluded
conditions for 24 hours and observed for 14 days following dosing. Blistering and blanching at
the site of application was observed. No mortalities were observed. Gross pathological
examination revealed no abnormal findings.
LD50 > 2000 mg/kg-bw
Subcategory II: Alkyl Polysulfides
Pentene, 2,4,4-trimethyl, sulfurized (CASRN 68515-88-8)
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New Zealand White rabbits (5/sex) were administered pentene, 2,4,4-trimethyl, sulfurized in a
mineral oil-based material dermally on unabraded shaved skin at 2000 mg/kg-bw under occluded
conditions for 24 hours and observed for 14 days following dosing. One male rabbit died on day
14. Mild skin erythema and mild-to-moderate edema was observed in both sexes within 24
hours. By day 7, slight to mild skin irritation was noted and was completely resolved by day 14.
LD50 > 2000 mg/kg-bw
Alkenes C15 - 18 alpha-, sulfurized (CASRN 67762-55-4)
New Zealand White rabbits (5/sex) were administered alkenes CI5 - 18 alpha-, sulfurized
dermally on clipped dorsa skin at 2000 mg/kg-bw under unspecified occlusion for 24 hours and
observed for 14 days following dosing. Erythema and edema was seen at the application site on
day one. Gross pathological examination revealed no abnormal findings. No mortality was
observed.
LD50 > 2000 mg/kg-bw
Repeated-Dose Toxicity
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)- (CASRN 67124-09-8)
Sprague-Dawley rats (5/sex/dose) were administered 2-propanol, (tert-dodecylthio)- in corn oil
via gavage at 0, 100, 300 or 1000 mg/kg-bw/day 7 days/week for 28 days, and observed 14 days
post exposure. Additional high-dose and control animals (5/sex/group) were observed for a 14-
day recovery period. No mortalities were observed. Body weight gain was decreased in high-
dose males during the first week of the study. A decrease in hemoglobin and hematocrit values
was observed in high-dose females following exposure; however, values returned to normal
during the recovery period. Gross pathological examination of the liver revealed an accentuated
lobular pattern in the mid- and high-dose females following treatment, which resolved during the
recovery period. Increased kidney weights and kidney/body weight ratios were noted in high-
dose males following treatment and throughout recovery. Dose-related increases in mean liver
weights and/or liver/body weight ratios were seen at study termination in males at all dose levels
and in females at the mid- and high-dose levels. Recovery was apparent during the 2-week
recovery period for the high-dose group. Histopathological effects included hepatocellular
hypertrophy of the liver at all dose levels following the treatment period and throughout the
recovery period as well as increased incidences of globular casts and hyaline droplets in all
treated males. Hyaline droplets in the proximal tubules were seen only at dosing termination.
The nephropathy in males is consistent with the alpha 2 |i-globul in-mediated mechanism that is
male rat-specific. EPA's Risk Assessment Forum has outlined the key events and the data that
are necessary to demonstrate this mode of action (Alpha 2|i-Globulin: Association with
Chemically Induced Renal Toxicity and Neoplasia in the Rat, EPA/625/3-91/019F).
LOAEL = 100 mg/kg-bw/day (based on liver effects)
NOAEL = not established
Subcategory II: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
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(1) Sprague-Dawley rats (10/sex/dose) were administered 1-propene, 2-methyl-, sulfurized
dermally onto clipped intact skin at 0, 500 or 2000 mg/kg-bw/day undiluted and at 0, 10, 50,
100, 250 or 500 mg/kg-bw/day diluted in mineral oil, respectively, under non-occluded
conditions 5 days/week for 13 weeks. Rats were fitted with Elizabethan collars to minimize
ingestion of test material. Male rats treated with diluted doses at > 250 mg/kg-bw/day exhibited
a 15% decrease in body weight gain. At doses > 250 mg/kg-bw/day, both sexes had decreased
levels of red blood cells and increased levels of neutrophils in circulation, increased spleen size
and increased pigment and red pulp in the spleen. There was increased production of white
blood cells in the spleen and bone marrow at >100 mg/kg-bw/day. Mean liver to body weight
ratios were increased in male rats at > 250 mg/kg-bw/day and in females at > 500 mg/kg-bw/day.
Male rats treated with undiluted doses at 500 or 2000 mg/kg-bw/day had increased kidney
weights correlating with dose-related increases in hyaline droplet formation indicative of hyaline
droplet nephropathy. Administration of 1-propene, 2-methyl-, sulfurized undiluted at doses of
500 and 2000 mg/kg-bw/day and diluted in mineral oil at doses of 250 and 500 mg/kg-bw/day
induced moderate to severe reactions in the skin, characterized by erythema, edema and
increased thickness and stiffness; these effects were more severe at 500 mg/kg-bw/day.
Microscopic examination revealed hyperkeratosis, hyperplasia of sebaceous gland, increased
mitosis in the epidermis and dermal abscesses. Virtually no irritation was observed in the
vehicle control group or in dose groups of 10, 50 or 100 mg/kg-bw/day. No effects on sperm
motility or morphology were observed in rats treated at 2000 mg/kg-bw/day. The relative weight
increases in livers of higher dose animals of both sexes had no microscopic correlation and is
considered by the authors as an adaptive response to treatment. The increase in kidney weight
and hyaline droplet formation in male rats is indicative of hyaline droplet nephropathy.
Although many changes in hematology parameters can be associated with infections that can
occur with severe skin irritation, increased dose related neutrophil production was observed in
animals with minimal skin irritation and can be considered a direct effect of the test material.
LOAEL = 250 mg/kg-bw/day (based on decreased bodyweight gain in males, and
hematological effects)
NOAEL= 100 mg/kg-bw/day
(2) Albino rabbits (6/sex/dose) were administered 1-propene, 2-methyl-, sulfurized dermally,
onto intact or abraded skin (3/sex/group) at 0, 200 or 2000 mg/kg-bw/day under occluded
conditions, 6 hours/day, 5 days/week for 4 weeks (20 applications). One high-dose male died.
Decreased body weight was noted in high-dose males during the latter half of the study, and
weight gain in five/six females at the high-dose. Severe skin irritation was observed at both dose
levels and abrasion of the skin increased the degree of irritation at the low-dose level (sex not
stated). Hematological and clinical chemistry effects included increased monocytes at the high
dose, increased chloride and decreased albumin at the low dose and increased chloride and
globulin and decreased alkaline phosphatase activity at the high dose. Gross and
histopathological examination revealed no treatment-related findings.
LOAEL = 2000 mg/kg-bw/day (based on hematological effects)
NOAEL = 200 mg/kg-bw/day
(3) New Zealand White rabbits (10/dose) were administered 1-propene, 2-methyl-, sulfurized
dermally undiluted at 0 mg/kg-bw/day (5/sex), 140 mg/kg-bw/day (seven males, three females),
560 mg/kg-bw/day (eight males, two females) or 2240 mg/kg-bw/day (six males, four females)
under non-occluded conditions, 5 days/week for 3 weeks (15 applications). Rabbits were fitted
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with Elizabethan collars to minimize ingestion of test material. No mortalities or effects on body
weight were observed. All animals exhibited lethargy, ptosis, gastrointestinal disturbances, nasal
and ocular discharges and respiratory distress, all more often in the second and third weeks with
no discernible pattern of response. Skin reactions included mild to moderate erythema and mild
edema during week 1 for all treated groups. During week 2, reactions in all treated groups
included moderate to severe erythema with additional signs of cracked skin, bleeding and
discoloration. Edema was mild at the low-dose and mild to moderate at higher doses. During
week 3, all treated animals exhibited severe erythema with cracked and bleeding skin, eschar and
discoloration and slight to moderate edema. Hematology, clinical chemistry and urinalysis
revealed no treatment-related effects. At necropsy, sporadic occurrences of dark lungs and liver,
red and bloated intestines, pale kidney coloration and small or gray coloration of the spleen were
observed, but were not considered to be treatment-related. Epithelial hyperplasia of the treated
skin was observed in all rabbits with the treated groups exhibiting slightly more severe grades of
hyperplasia than the control group. With no discernable pattern of response in both test and
control groups, observed clinical signs are considered to be related to handling. The occurrence
of hyperplasia in all groups suggests a relationship to clipping rather to test material
administration. Six errors in sex determination was discovered which resulted in uneven sex
distribution within groups.
NOAEL = 2240 mg/kg-bw/day (based on no systemic toxicity at the highest dose tested))
Pentene, 2,4,4-trimethyl, sulfurized (CASRN 68515-88-8)
(1) Sprague-Dawley rats (10/sex/concentration) were exposed (whole-body) to pentene, 2,4,4-
trimethyl, sulfurized aerosol at 0, 15, 50 or 150 mg/mL for 6 hours/day, 5 days/week for 4 weeks
(20 applications). Additional control and high-dose animals (5 males and 10 females/group)
were observed over a 3-week recovery period. Convulsive behavior was observed in one high-
dose female on day 3 followed by death on day 4, due to undetermined causes. A trend toward
lower body weight gains was noted in males at all dose levels and in females at the two highest
dose levels; however, statistical significance was not achieved. Hematological effects included a
significant increase in hemoglobin concentration in high-dose females. Gross pathological
examination revealed a significant increase in kidney weights in mid- and high-dose males and
increased spleen, adrenal and liver weights/relative liver-to-body weight ratios in high-dose
animals of both sexes. Post-recovery increases in testes, heart, lung and spleen weights were
noted at unspecified dose levels. Histopathological examination revealed treatment-related
effects in the kidneys of males at all dose levels and included globular casts at the
corticomedulary junction, cortex and medulla as well as hyaline droplets in the proximal
convoluted tubule. These effects were also noted in high-dose males following the 3-week
recovery period. The nephropathy in males is consistent with the alpha 2|i-globulin-mediated
mechanism that is male rat-specific. EPA's Risk Assessment Forum has outlined the key events
and the data that are necessary to demonstrate this mode of action (Alpha 2|i-Globulin:
Association with Chemically Induced Renal Toxicity and Neoplasia in the Rat, EPA/625/3-
91/019F).
LOAEL (male) = 150 mg/kg-bw/day (based on liver effects)
NOAEL (male) = Not established
LOAEL (female) = 150 mg/kg-bw/day (based on increased hemoglobin levels and relative
liver-to body weight ratios)
NOAEL (female) = 50 mg/kg-bw/day
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(2) Sprague-Dawley rats (5 males/dose) were administered pentene, 2,4,4-trimethyl, sulfurized
dermally at 0 or 1000 mg/kg-bw/day under semi-occluded conditions, 6 hours/day, 5 days/week
for 4 weeks (20 applications). No mortality was observed and no changes in body weight were
noted. Treatment-related effects included weak to moderate irritation characterized by erythema,
eschar and flaking of the skin at the application site and persisting throughout the duration of
treatment.
NOAEL = 1000 mg/kg-bw/day (based on no systemic toxicity at the highest dose tested))
Reproductive/Developmental Toxicity
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)- (CASRN 67124-09-8)
Sprague-Dawley rats (28/sex/dose) were administered 2-propanol, (tert-dodecylthio)- in corn oil
via gavage at 0, 50, 167 or 500 mg/kg-bw/day once a day, 7 days/week for 14 days during
premating, 25 days during gestation and 20 days during lactation. Lower mean body weights (5
- 7% compared to controls) were noted in males at the high-dose level. There were no
treatment-related effects on food consumption mating and fertility indices, hematology data,
absolute and relative organ weights, sperm evaluation parameters or macro or microscopic
pathology. Dams at all dose levels exhibited reddish vaginal discharge, mammary gland
swelling and dark material around the eyes and nose. Two low-dose females delivered all
stillborn pups. Because this finding was not observed at any other dose level, it was not
considered to be a toxicologically significant effect. In the control, low-, mid- and high-dose
groups, the number of females with live born pups was 25, 24, 27 and 26, respectively. There
were no treatment-related effects on pre-coital intervals, gestation length or mean hematology
values. Gross pathological examination of one high-dose female sacrificed on post mating day
25 included dark red/brown fluid in the uterus and vagina as well as one small placenta and two
nonviable pups in the vagina. There were no treatment-related effects on total and mean number
of pups delivered, number of live pups/litter or sex ratio. A decrease in the number of live pups
was noted at the low-dose level; however, this was attributed to both litter losses at the lowest
dose and therefore not considered to be an adverse effect. Mean pup weights were decreased at
the mid-dose level on lactation day 14 and at the high-dose level on lactation days 14 and 21.
Necropsy of stillborn pups, pups found dead, pups culled on day 4 and pups sacrificed on
lactation day 21 revealed no treatment-related findings. In addition to the above findings,
increased mean liver weights were noted at the highest dose in adult males and females and at
the two highest doses in males only. Males also exhibited increased mean kidney weights at the
two highest dose levels accompanied by evidence of accumulation of alpha-2-[j,globulin in renal
hyaline droplets. The nephropathy in males is consistent with the alpha 2 |i-globul in-mediated
mechanism that is male rat-specific. EPA's Risk Assessment Forum has outlined the key events
and the data that are necessary to demonstrate this mode of action (Alpha 2|i-Globulin:
Association with Chemically Induced Renal Toxicity and Neoplasia in the Rat, EPA/625/3-
91/019F). (Summarized from TSCATS submission OTS0574387).
NOAEL (reproductive toxicity) = 500 mg/kg-bw/day (based on no effects at the highest dose
tested)
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LOAEL (systemic toxicity) = 167 mg/kg-bw/day (based on decreased body weight in males,
hematology changes in dams, increased mean liver and kidney weights males)
NOAEL (systemic toxicity) = 50 mg/kg-bw/day
LOAEL (developmental toxicity) = 167 mg/kg-bw/day (based on decreased mean pup weight)
NOAEL (developmental toxicity) = 50 mg/kg-bw/day
Subcategory II: Alkyl Polysulfides
No data
Genetic Toxicity — Gene Mutation
Subcategory I: Hydroxyalkyl Monosulfide
In vitro
2-Propanol, (tert-dodecylthio)-(CASRN 67124-09-8)
Salmonella strains TA98, TA100, TA1535, TA1537 and Escherichia coli strain WP-2 were
exposed to 2-propanol, (fert-dodecylthio)- in DMSO at 15, 50, 150, 500, 1500 or 5000 |ig/plate
in the presence and absence of metabolic activation. Positive and negative controls were
included and responded appropriately. Cytotoxicity was observed in Salmonella strain TA1537
at concentrations of 50, 500, 1500 and 5000 |ig/plate both with and without metabolic activation,
but the number of revertants was not increased in any strain.
2-Propanol, (terf-dodecylthio)- was not mutagenic in this assay.
Subcategory II: Alkyl Polysulfides
In vitro
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to
1-propene, 2-methyl-, sulfurized in DMSO at 0.01, 0.05, 0.1, 0.5 or 1 |iL/plate in the presence
and absence of metabolic activation. Positive and negative controls were included and
responded appropriately. Cytotoxicity was not noted. (This assay was conducted using very low
concentrations.)
1-Propene, 2-methyl-, sulfurized was not mutagenic in this assay.
Pentene, 2,4,4-trimethyl, sulfurized (CASRN 68515-88-8)
Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 were exposed to
pentene, 2,4,4-trimethyl, sulfurized in DMSO at 0.01, 0.03, 0.1, 0.3 or 1 |iL/plate in the presence
and absence of metabolic activation. Positive and negative controls were included and
responded appropriately. Cytotoxicity was not observed. (This assay was conducted using very
low concentrations.)
Pentene, 2,4,4-trimethyl, sulfurized was not mutagenic in this assay.
Alkenes CI5 — 18 alpha-, sulfurized (CASRN 67762-55-4)
Salmonella strains TA98, TA100, TA1535, TA1537, TA102 and Escherichia coli strain WP2
uvrA were exposed to alkenes C15 - 18 alpha-, sulfurized at 50, 167, 500, 1670, 5000 or 10,000
|ig/plate in the presence and absence of metabolic activation. Positive and negative controls
were included and responded appropriately. Cytotoxicity was not noted. The test substance was
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found to be incompletely soluble (droplets were observed) at all does levels under both treatment
conditions.
Alkenes C15 - 18 alpha-, sulfurized was not mutagenic in this assay.
Genetic Toxicity — Chromosomal Aberrations
Subcategory I: Hydroxyalkyl Monosulfide
In vitro
2-Propanol, (tert-dodecylthio)-(CASRN 67124-09-8)
Chinese hamster ovary (CHO) cells were exposed to 2-propanol, (fert-dodecylthio)- in DMSO at
0.05, 0.15, 0.5, 1.5, 5, 15, 50, 495, 1490 or 4950 |ig/mL and 0.05, 0.15, 0.5, 1.5, 15, 50 or 150
|ig/mL in the absence and presence of metabolic activation, respectively, for exposure periods of
10 or 20 hours each. Positive and negative controls were included and responded appropriately.
For the 20- and 10-hour exposure periods, cytotoxicity was observed at concentrations of > 15
and 50 |ag/m L in the absence of metabolic activation and >50 and 15 |ag/mL in the presence of
metabolic activation, respectively. A slight increase in the number of aberrant cells was
observed in the activated 10-hour exposure assay at 5 jag/mL; however, this increase did not
achieve statistical significance.
2-Propanol, (terf-dodecylthio)-did not induce chromosomal aberrations in this assay.
Subcategory II: Alkyl Polysulfides
In vivo
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
(1) B63CF1 mice (5/sex/dose) were administered 1-propene, 2-methyl-, sulfurized in Methocel
K4M Premium (hydroxypropyl methyl cellulose; Dow Chemical) via intraperitoneal injection at
3500 mg/kg-bw and sacrificed at 24-, 48- or 72-hour intervals. Positive and negative controls
were included and responded appropriately. Positive controls were sacrificed at the 24-hour
interval only. Cytotoxicity was not observed.
1-Propene, 2-methyl-, sulfurized did not induce micronuclei in this assay.
(2) In the 13-week dermal repeated-dose toxicity study in rats on 1-propene, 2-methyl-,
sulfurized described above, micronuclei were analyzed from femoral bone marrow samples taken
24 hours following the final dermal administration (5/sex/dose). A negative control was
included and responded appropriately; however, a positive control was not tested. Cytotoxicity
was not observed.
1-Propene, 2-methyl-, sulfurized did not induce micronuclei in this assay.
Pentene, 2,4,4-trimethyl, sulfurized (CASRN 68515-88-8)
B63CF1 mice (5/sex/dose) were administered pentene, 2,4,4-trimethyl, sulfurized via gavage at 5
mg/kg-bw and sacrificed at 18-, 24- or 48-hour intervals. Positive and negative controls were
included and responded appropriately. Positive control animals were treated via intraperitoneal
injection and sacrificed at the 24-hour interval only. Cytotoxicity was not observed.
Pentene, 2,4,4-trimethyl, sulfurized did not induce micronuclei in this assay.
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Conclusions:
Subcategory I (CASRN 67124-09-8)
The acute oral and dermal toxicity for CASRN 67124-09-8 in rats and rabbits are low and the
acute inhalation toxicity in rats is moderate. An oral repeated-dose toxicity study in rats showed
liver effects at 100 mg/kg/day. The NOAEL was not established. A one-generation reproductive
toxicity study in rats showed decreased body weight and an increase in mean liver and kidney
weights in adult males and hematology changes in dams at 167 mg/kg-bw/day via the oral route;
the NOAEL was 50 mg/kg-bw/day. A developmental toxicity showed a decrease in mean pup
weight at 67 mg/kg-bw/day; the NOAEL was 50 mg/kg/day. No reproductive toxicity effects
were seen at 500 mg/kg-bw/day (highest dose tested). This chemical did not induce gene
mutation or chromosomal aberration in vitro.
The evaluation of available toxicity data for aquatic organisms for CASRN 67124-09-8 indicates
that the 96-h LC 50 for fish is 0.42 mg/L, the 48-h EC 50 for aquatic invertebrates is 1.3 mg/L
and the 96-hour EC50 for aquatic plants is "no effects at saturation." The estimated 21-d chronic
toxicity value for aquatic invertebrates using ECOSAR is 0.036 mg/L.
The chronic aquatic invertebrate toxicity endpoint for CASRN 67124-09-8 remains a data gap
under the HPV Challenge Program.
Subcategory II (CASRNs 68511-50-2, 68515-88-8, and 67762-55-4)
The acute oral toxicity of CASRNs 68511-50-2 and 68515-88-2 in rats is low. The acute
inhalation toxicity of CASRN 68515-88-8 in mice, guinea pigs and rats is moderate. The acute
dermal toxicity of CASRNs 68515-88-8 and 67762-55-4 is low.
In a dermal repeated-dose toxicity study in rats, CASRN 68511-50-2 showed a decrease in body
weight gain in male rats and hematological effects in both sexes at 250 mg/kg/day; the NOAEL
was 100 mg/kg/day. Female rats exposed to CASRN 68515-88-8 via aerosol inhalation, showed
increased hemoglobin levels and relative liver-to-body weight ratios at 150 mg/kg/day; the
NOAEL was 50 mg/kg-bw/day. In the same study, liver effects were seen in male rats at 150
mg/kg-bw/day. The NOAEL for male rats was not established. CASRNs 68511-50-2 and
68515-88-8 were irritating to rat and rabbit skin in dermal repeated-dose studies.
CASRNs 68511-50-2 and 68515-88-8 did not induce gene mutations in vitro or chromosomal
aberrations in vivo. CASRN 67762-55-4 did not induce gene mutations in vivo.
The evaluation of available toxicity data to aquatic organisms for all subcategory II members
indicates that for the acute hazard to fish, aquatic invertebrates and aquatic plants, there are "no
effects at saturation".
Reproductive and developmental toxicity were identified as data gaps for all subcategory
members under the HPV Challenge program.
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Table 4. Summary of Human Health Data
Subcategory I
Subcategory II
Endpoints
2-Propanol, (tert-
dodecylthio)-
(67124-09-8)
1-Propene,
2-methyl, sulfurized
(68511-50-2)
Pentene, 2,4,4-trimethyl,
sulfurized
(68515-88-8)
Alkenes C15 - 18 alpha-
, sulfurized
(67762-55-4)
Acute Oral Toxicity
LD5o (mg/kg-bw)
>5000
-5700
>5000
No Data
>5000
(RA)
Acute Inhalation Toxicity
LC5o (mg/L)
Rat
Mouse and guinea pig
>0.39
>2.17
>4.3
No Data
>0.39
(RA)
Acute Dermal Toxicity
LD5o (mg/ kg-bw)
>2000
No Data
>2000
(RA)
>2000
>2000
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Table 4. Summary of Human Health Data
Endpoints
Subcategory I
Subcategory II
2-Propanol, (tert-
dodecylthio)-
(67124-09-8)
1-Propene,
2-methyl, sulfurized
(68511-50-2)
Pentene, 2,4,4-trimethyl,
sulfurized
(68515-88-8)
Alkenes C15 - 18 alpha-
, sulfurized
(67762-55-4)
Repeated-Dose Toxicity
Oral (mg/kg-bw/day)
LOAEL = 100
NOAEL = Not Est.
No Data
No Data
No Data
Repeated-Dose Toxicity
Inhalation (mg/L-bw/day)
No Data
LOAEL = 150
(RA)
LOAEL = 150 (male)
NOAEL = Not Est.
LOAEL = 150(female)
NOAEL = 50
No Data
LOAEL = 150
(RA)
Repeated-Dose Toxicity
Dermal (mg/kg-bw/day)
Rat
Rabbit
LOAEL = 250
NOAEL = 100
LOAEL = 2000
NOAEL = 200
NOAEL = 1000
(hdt)
No Data
LOAEL = 250
NOAEL = 100
LOAEL = 2000
NOAEL = 200
(RA)
Reproductive/Developmental
Toxicity (mg/kg-bw/day)
Systemic Toxicity
Developmental Toxicity
LOAEL = 167
NOAEL = 50
LOAEL = 167
No Data
No Data
No Data
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Table 4. Summary of Human Health Data
Subcategory I
Subcategory II
Endpoints
2-Propanol, (tert-
dodecylthio)-
(67124-09-8)
1-Propene,
2-methyl, sulfurized
(68511-50-2)
Pentene, 2,4,4-trimethyl,
sulfurized
(68515-88-8)
Alkenes C15 - 18 alpha-
, sulfurized
(67762-55-4)
Reproductive Toxicity
NOAEL = 50
LOAEL = 500
Genetic Toxicity -
Gene Mutation In vitro
Negative
Negative
Negative
Negative
Genetic Toxicity -
Chromosomal Aberrations
In vitro
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
Genetic Toxicity -
Chromosomal Aberrations
In vivo
Negative
Negative
No Data
Negative
(RA)
Measured data in bold text; (RA) = read across; - indicates that endpoint was not addressed for this chemical, (hdt) = highest dose tested.
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4. Hazard to the Environment
A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 5. The
table also indicates where data for tested category members are read-across (RA) to untested
members of the category.
Acute Toxicity to Fish
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)- (CASRN 67124-09-8)
Rainbow trout (Oncorhynchus mykiss) were exposed to 2-propanol, (fe/7-dodecylthio)- as water
accommodated fractions (WAFs) under semi-static conditions for 96 hours. The loading rates
were 0, 1, 1.8, 3.2, 5.6 or 10 mg/L. During the initial main study, mortality or sublethal effects
were observed at all concentrations; therefore, a second definitive study was conducted at 0,
0.32, 0.56, 1.0, 1.8 or 3.2 mg/L. Analytical monitoring was not conducted, but all of the loading
rates were below the reported measured water solubility for 2-propanol, (tert-dodecylthio)- (4.84
mg/L). At 0.56, 1, 1.8 and 3.2 mg/L, 100% mortality was noted at 96, 48, 24 and 24 hours,
respectively.
96-h LC50 = 0.42 mg/L
Subcategory II: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
(1) Fathead minnows (Pimephalespromelas) were exposed to 1-propene, 2-methyl-, sulfurized
as WAFs under static renewal conditions for 96 hours. The loading rates were 0, 100, 300 or
1000 mg/L, and no analytical measurements were made on the WAFs. At 1000 mg/L, all fish
were lethargic and exhibited erratic swimming by the end of the exposure period. The 96-hour
LC50 and NOEC values were > 1000 and 300 mg/L, respectively. EPA does not consider the
loading rate as the no-effect concentration when the concentration exceeds the water solubility of
the substance. Assuming that the exposure concentration in the WAF is the water solubility limit
(saturation) for 1-propene, 2-methyl-, sulfurized, the no-effect concentration would be
approximately 2.7 mg/L.
No effects at saturation.
(2) Sheepshead minnow (Cyprinodon variegatus) were exposed to 1-propene, 2-methyl-,
sulfurized as WAFs under static renewal conditions for 96 hours. The loading rates were 0 or
10,000 mg/L, and no analytical measurements were made on the WAFs. No effects were noted
at any of the WAF loading rates. The 96-hour LC50 and NOEC values were > 10,000 and
10,000 mg/L, respectively. EPA does not consider the loading rate as the no-effect concentration
when the concentration exceeds the water solubility of the substance. Assuming that the
exposure concentration in the WAF is the water solubility limit (saturation) for 1-propene, 2-
methyl-, sulfurized, the no-effect concentration would be approximately 2.7 mg/L.
No effects at saturation.
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Acute Toxicity to Aquatic Invertebrates
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)- (CASRN 67124-09-8)
Water fleas (Daphnia magna) were exposed to 2-propanol, (tert-dodecylthio)- as WAFs under
static conditions for 48 hours. The loading rates were 0, 1, 1.8, 3.2, 5.6, 10, 18, 32, 56 or 100
mg/L, and no analytical measurements were made on the WAFs. Within 24 hours, 100%
immobilization was noted at concentrations >1.8 mg/L. The 48-hour EC50 and NOEC values
were 1.3 and 1.0 mg/L, respectively. These concentrations are below the reported measured
solubility for 2-propanol, (tert-dodecylthio)- (4.84 mg/L).
48-h EC50 = 1.3 mg/L
Subcategory II: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
Water fleas (Daphnia magna) were exposed to 1-propene, 2-methyl-, sulfurized as WAFs under
static conditions for 48 hours. The loading rates were 0, 100, 300 or 1000 mg/L, and no
analytical measurements were made on the WAFs. No effects were noted at any of the WAF
loading rates. The 48-hour EC50 and NOEC values were > 1000 and 1000 mg/L, respectively.
EPA does not consider the loading rate as the no-effect concentration when the concentration
exceeds the water solubility of the substance. Assuming that the exposure concentration in the
WAF is the water solubility limit (saturation) for 1-propene, 2-methyl-, sulfurized the no-effect
concentration would be approximately 2.7 mg/L.
No effects at saturation.
Toxicity to Aquatic Plants
Subcategory I: Hydroxyalkyl Monosulfide
2-Propanol, (tert-dodecylthio)- (CASRN 67124-09-8)
Green algae (Scendesmus subspicatus) were exposed to 2-propanol, (tert-dodecylthio)- as WAF
under static conditions for 96 hours. The loading rates were 0 or 100 mg/L, and no analytical
measurements were made on the WAFs. No effects were noted for growth rate or biomass. The
96-hour EC50 and NOEC values were >100 and 100 mg/L for biomass and growth rate,
respectively. EPA does not consider the loading rate as the no-effect concentration when the
concentration exceeds the water solubility of the substance. Assuming that the exposure
concentration in the WAF is the water solubility limit (saturation) for 2-propanol, (tert-
dodecylthio)-, the no-effect concentration would be approximately 4.84 mg/L.
No effects at saturation.
Subcategory II: Alkyl Polysulfides
1-Propene, 2-methyl-, sulfurized (CASRN 68511-50-2)
Green algae (Pseudokirchneriella subcapitata) were exposed to 1-propene, 2-methyl-, sulfurized
as WAFs under static conditions for 96 hours. The loading rates were 0, 1,5, 10, 50 or 100
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Hazard Characterization Document
September, 2009
mg/L and no analytical measurements were made on the WAFs. The NOEC was 5 mg/L and 72-
hour EC50 was 26 mg/L (21-32 mg/L) for biomass and >100 mg/L for growth rate. EPA does
not consider the loading rate as the no-effect concentration when the concentration exceeds the
water solubility of the substance. Assuming that the exposure concentration in the WAF is the
water solubility limit (saturation) for 1-propene, 2-methyl-, sulfurized, the no-effect
concentration would be approximately 2.7 mg/L.
No effects at saturation.
Chronic Toxicity to Invertebrates
Subcategory I: Hydroxyalkyl Monosulfide
EPA recommended that the sponsor conduct chronic toxicity testing on invertebrates (i.e., the
daphnid 21-day reproduction test), but no chronic data has been submitted. The physical-
chemical properties of this chemical indicate that it is soluble in water at concentrations that
could cause chronic effects. The estimated toxicity based on ECOSAR (vl.00) is 0.036 mg/L.
Conclusions:
Subcategory I: Hydroxyalkyl Monosulfide
The aquatic toxicity data submitted were generated using the Water Accommodated Fraction
(WAF) method. The evaluation of available toxicity data for aquatic organisms for CASRN
67124-09-8 indicates that the potential acute hazard for fish is high, for aquatic invertebrates is
moderate and for aquatic plants is low. The potential chronic hazard is high based on the
estimated toxicity value using ECOSAR.
The chronic aquatic invertebrate toxicity endpoint for CASRN 67124-09-8 remains a data gap
under the HPV Challenge Program.
Subcategory II: Alkyl Polysulfides
The aquatic toxicity data submitted were generated using the WAF method. The evaluation of
available toxicity data to aquatic organisms for all subcategory II members indicates that the
potential acute hazard to fish, aquatic invertebrates and aquatic plants is low.
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Hazard Characterization Document
September, 2009
Table 5. Summary of Environmental Effects - Aquatic Toxicity Data
Subcategory I
Subcategory II
2-Propanol,
1-Propene, 2-
Pentene, 2,4,4-
Alkenes C15 - 18
(fcrt-dodecylthio)-
methyl, sulfurized
trimethyl,
sulfurized
alpha-,
sulfurized
Endpoints
(67124-09-8)
(68511-50-2)
(68515-88-8)
(67762-55-4)
Fish
No Data
No Data
96-h LCso
0.42 (m)
NES (m)
NES
NES
(mg/L)
(RA)
(RA)
Aquatic
No Data
No Data
Invertebrates
1.3 (m)
NES (m)
NES
NES
48-h ECso
(mg/L)
(RA)
(RA)
Aquatic Plants
No Data
No Data
72-h ECso
NES (m)
NES (m)
NES
NES
(mg/L)
(RA)
(RA)
Chronic
—
—
—
Toxicity to
Invertebrates
0.036 (e)*
21-day EC50
(mg/L)
m= measured; RA= Read Across; ~ indicates endpoint was not addressed for this chemical; NES= Measured data
with No Effects at Saturation *Testing was recommended for this endpoint.
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