Screening-Level Hazard Characterization Monoterpene Hydrocarbons Category d-Limonene (CASRN 5989-27-5) dl-Limonene (CASRN 138-86-3) Terpinolene (CASRN 586-62-9) Myrcene (CASRN 123-35-3) Dihydromyrcene (CASRN 2436-90-0) Hydrocarbons, terpene processing by-products (CASRN 68956-56-9) Orange peel oil, sweet (Citrus sinensis (L.) Osbeck) (CASRN 8008-57-9) Terpenes & terpenoids, sweet orange oil (CASRN 68647-72-3) Terpenes & terpenoids, limonene fraction (CASRN 65996-98-7) Terpenes & terpenoids, turpentine oil, limonene fraction (CASRN 65996-99-8)


U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
SCREENING-LEVEL HAZARD CHARACTERIZATION
Monoterpene Hydrocarbons Category
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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
123-35-3
Registry Number
138-86-3
(CASRN)
586-62-9

2436-90-0

5989-27-5

8008-57-9

68647-72-3

68956-56-9

65996-98-7

65996-99-8
Chemical Abstract Index
1, 6-Octadiene, 7-methyl-3-methylene-
Name
Cyclohexene, l-methyl-4-(l-methylethenyl-

Cyclohexene, l-methyl-4-(l-methylethylidene-

1, 6-Octadiene, 3,7-dimethyl-

Cyclohexene, l-methyl-4-(l-methylethenyl)-, (4R)-

Oils, orange, sweet

Terpenes and Terpenoids, sweet orange-oil

Hydrocarbons, terpene processing by-products

Terpenes and Terpenoids, limonene fraction

Terpenes and Terpenoids, turpentine-oil, limonene fraction
Structural Formula
See Section 1

Summary
Members of the monoterpene hydrocarbons category are liquids with moderate water solubility
and moderate to high vapor pressure. The monoterpene hydrocarbons are expected to have
moderate mobility in soil. Volatilization of the monoterpene hydrocarbons is considered high
based on their Henry's Law constants. The rate of hydrolysis is considered negligible since the
monoterpene hydrocarbons lack functional groups that hydrolyze under environmental
conditions. The rate of atmospheric photooxidation is considered moderate to rapid. All the
chemicals in the monoterpene hydrocarbons category are expected to have low persistence (PI).
The bioaccumulation potentials for members of this category are expected to be low (Bl) to
moderate (B2).

The acute toxicity of the monoterpene hydrocarbons category members is low via the oral (rats
and mice) and dermal (rabbits) routes of exposure. CASRN 5989-27-5 is an eye irritant
(rabbits), skin irritant (rabbits and humans) and skin sensitizer (guinea-pigs and humans).
Repeated oral exposures in rats and mice with CASRN 123-35-3 showed hematological effects
as well as splenic atrophy in rats, and histopathological changes in the liver of mice, at 1000
mg/kg-bw/day. The NOAEL was 500 mg/kg-bw/day in rats and mice. Repeated oral exposures
in rats and mice with CASRN 5989-27-5 showed decreasing body weights followed by mortality
at 2400 and 2000 mg/kg-bw/day, respectively. In male rats, nephropathy associated with
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alpha2u-globulin formation was the primary systemic effect. The NOAEL was 1200 mg/kg/bw
in rats and 1000 mg/kg-bw/day in mice. Repeated oral exposures in rats with CASRN 8008-57-9
showed clinical chemistry effects and lesions in the stomach at 1500 mg/kg-bw/day. In male
rats, nephropathy associated with alpha2u-globulin formation was the primary systemic effect.
The NOAEL was 600 mg/kg-bw/day. CASRN 8008-57-9 did not elicit an immune response in
vitro up to 2500 mg/kg-bw/day.
No studies that specifically address the reproductive toxicity endpoint were available for CASRN
5989-27-5; however, the evaluation of the reproductive organs in the 13-week repeated-dose
studies showed no treatment-related effects. In a modified oral developmental toxicity study in
rats with CASRN 123-35-3, effects on the fertility of female off-spring were observed at 1000
mg/kg-bw/day. The NOAEL for reproductive toxicity was 500 mg/kg-bw/day. In the same
study, maternal body weights were decreased and perinatal mortality, delayed postnatal
development and decreased pup body weights were observed at 1000 and 500 mg/kg-bw/day,
respectively. The NOAEL for maternal and developmental toxicity was 500 and 250 mg/kg-
bw/day, respectively. In an oral combined reproductive/developmental toxicity study in rats with
CASRN 123-35-3, no adverse effects on reproduction were observed. The NOAEL for
reproductive toxicity was 500 mg/kg-bw/day. In the same study, skeletal abnormalities were
observed at 500 mg/kg-bw/day and the NOAEL for developmental toxicity was 300 mg/kg-
bw/day; the NOAEL for maternal toxicity was 500 mg/kg-bw/day. In an oral combined
reproductive/developmental toxicity screening test with CASRN 8008-57-9 in rats, still births
and pup mortality were observed at 1500 mg/kg-bw/day. The NOAEL for reproductive and
developmental toxicity was 750 mg/kg-bw/day. The NOAEL for maternal toxicity was 1500
mg/kg-bw/day. Prenatal oral developmental toxicity studies with CASRN 5989-27-5 showed
decreased fetal body weights and delayed ossification in rats and mice at 2869 and 2363 mg/kg-
bw/day, respectively. Mortality was observed in the adult rats and mice at 2869 and 2363
mg/kg-bw/day, respectively. The NOAEL for maternal and developmental toxicity was 591
mg/kg-bw/day for both species. In rabbits, maternal body weight gain was reduced but no
developmental toxicity was observed at 500 mg/kg-bw/day. The NOAEL for maternal and
developmental toxicity was 250 and 1000 mg/kg-bw/day, respectively.
CASRN 5989-27-5 and CASRN 8008-57-9 did not induce gene mutations in vitro. CASRN
5989-27-5 and CASRN 123-35-3 did not induce chromosomal aberrations in vitro or in vivo.
CASRN 5989-27-5 induced tumors in male rats via a mode of action not considered relevant to
humans, and did not induce tumors in female rats and mice.
The acute hazard to fish is based on the toxicity values for CASRN 586-62-9 of 1.21 mg/L and
CASRN 5989-27-5 of 0.7 mg/L. The acute hazard to aquatic invertebrates is based on the
toxicity values for CASRN 586-62-9 of 1.38 mg/L and CASRN 5989-27-5 of 0.421 mg/L. The
acute hazard to aquatic plants is based on the toxicity values for CASRN 586-62-9 of
>3.38 mg/L and CASRN 5989-27-5 of >1.81 mg/L.
The chronic toxicity to aquatic invertebrates for CASRN 2436-90-0 remains as a data gap under
the HPV Challenge Program.	
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The Flavor and Fragrance High Production Volume Consortia submitted a Test Plan and Robust
Summaries to EPA for the Monoterpene Hydrocarbon category on May 21, 2002. EPA posted
the submission on the ChemRTK HPV Challenge website on June 14, 2002,
(http://www.epa.gov/oppt/chemrtk/pubs/summaries/monoterp/cl3756tc.htm). EPA comments
on the original submission were posted to the website November 6, 2002. Public comments
were also received and posted to the website. The sponsor submitted updated/revised documents
on September 27, 2006 which were posted to the ChemRTK website on November 13, 2006. The
monoterpene hydrocarbons category consists of 10 substances described in Figure 1.
Category Justification
The category justification is based on structural similarity, similar molecular weights and
functional groups and the expectation that inherent physicochemical, environmental and
toxicological properties are predicted to be similar. Five members of the monoterpene
hydrocarbon category (V-limonene (CASRN 5989-27-5), t/Z-limonene, (CASRN
138-86-3), terpinolene (CASRN 586-62-9), myrcene (CASRN 123-35-3) and dihydromyrcene
(CASRN 2436-90-0) are monoterpene hydrocarbons. Three complex mixtures (orange peel oil,
sweet (CASRN 8008-57-9), terpenes and terpenoids, sweet orange oil (CASRN 68647-72-3),
and terpenes and terpenoids, limonene fraction (CASRN 65996-98-7) each contain greater than
90% monoterpene hydrocarbons, and inclusion in this category is justified by the fact that they
are expected to have physicochemical, environmental and toxicological properties similar to the
major components of each mixture, namely limonene and myrcene. Hydrocarbons, terpene
processing by-products (CASRN 68956-56-9) and terpenes and terpenoids, turpentine oil,
limonene fraction (CASRN 65996-99-8) are composed of 67-95% monoterpene hydrocarbons.
The inclusion of these mixtures in this category is also reasonable.
Two proposed category members are mixtures that contain 5-10% unspecified terpene
hydrocarbons and additional information regarding the unspecified substances is needed to better
understand the chemical composition of these mixtures and potentially different expected
toxicity.
EPA does not accept the inclusion of terpenes and terpenoids, turpentine oil limonene fraction
and distillation residue (CASRN 68334-40-7) and terpenes and terpenoids, turpentine-oil residue
(CASRN 68938-00-1) in this category as these mixtures are composed predominantly of non-
monoterpene hydrocarbons. These chemicals will be reviewed separately and are excluded from
this assessment.
t/-Limonene has been evaluated by EPA under the IRIS program and the assessment can be
found at the following link: http://www.epa.gov/ncea/iris/subst/0682.htm.
1 Chemical Identity
1.1 Identification and Purity
The following description is taken from the final Test Plan (2006):
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The chemical category includes five simple monoterpene hydrocarbons (V-limonene, dl-
limonene, terpinolene, beta-myrcene and dihydromyrcene) and five mixtures comprised
primarily of the five terpene hydrocarbons. In plants, monoterpene hydrocarbons are produced
by the isoprene pathway. They have a chemical formula of CioHi6, or if partly or completely
saturated, Ci0Hi8 or Ci0H2o. Monoterpene hydrocarbons are ubiquitous in food given that they
are present in varying degrees in all plants. Being volatile constituents of plants, they are also
normal components of the atmosphere. They are mainly released by coniferous woodland such
as pine trees, cedars, redwood and firs. To a lesser extent, they are also produced and released by
deciduous plants. They are common components of traditional foods occurring in essentially all
fruits and vegetables.
t/-Li m on en e and terpinolene are monocyclic monounsaturated terpenes. J-Limonene is (R)-l-
methyl-4-(l-methylethenyl)-cyclohexene, 6//-limonene is an equal mixture of (R)- and (S)-l-
methyl-4-(l-methylethenyl)-cyclohexene while terpinolene is l-methyl-4-(l-methylethylidene)-
cyclohexene. Myrcene is commonly recognized as beta-myrcene, the isomeric form that
predominates in nature, beta-Myrcene is an acylclic monounsaturated isomer of limonene. The
alpha isomer, 2-methyl-6-methylene-l,7-octadiene is not found in nature and is of no
commercial importance, beta-Myrcene is 7-methyl-3-methylene-l,6-octadiene while
dihydromyrcene is 3,7-dimethyl-l,6-octadiene. The chemical constituents of the mixtures are
listed in Table 1.
Table 1. Chemical Structures of Monoterpene Hydrocarbons
CASRN
Chemical Name
Structure
5989-27-5
t/-Limonene
-c~
138-86-3
6//-Limonene

586-62-9
Terpinolene

123-35-3
Myrcene
=CK
2436-90-0
Dihydromyrcene

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Table 1. Chemical Structures of Monoterpene Hydrocarbons
CASRN
Chemical Name
Structure
68956-56-9
Hydrocarbons, terpene
processing by-
products
Limonene: 22-34%
Terpinolene: 22-33%
Myrcene: 5-10%
Limonene isomers: 18%
Other terpene hydrocarbons:
10%
8008-57-9
Orange peel oil, sweet
(Citrus sinensis (L.)
Osbeck)
Limonene: 91-94%
Myrcene: 2.0-2.1%
68647-72-3
Terpenes &
terpenoids, sweet
orange oil
J-Limonene: 91-95%
Myrcene: 2.0-2.1%
alpha-Pinene: 1-2%
65996-98-7
Terpenes and
terpenoids, limonene
fraction
^/-Limonene: 96-98%
Myrcene: 1-2%
Other terpene hydrocarbons: 5-
10%
65996-99-8
Terpenes and
terpenoids, turpentine
oil, limonene fraction
^/-Limonene: 59-64%
&eta-Phellandrene: 14-18%
beta-Pinene: 4-11%
Other terpene hydrocarbons: 5-
10%
1.2 Physical-Chemical Properties
The physical-chemical properties of the monoterpene hydrocarbons category are summarized in
Table 2. Members of the monoterpene hydrocarbons category are liquids with moderate water
solubility and moderate to high vapor pressure.
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Table 2. P
lysical-Chemical Properties of Monoterpene Hydrocarbons Category1
Property
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Table 2. P
lysical-Chemical Properties of Monoterpene Hydrocarbons Category1
Property
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2 General Information on Exposure
2.1 Production Volume and Use Pattern
The Monoterpene Category Chemicals have an aggregated production and/or import volume in
the United States of 66 million to 210.5 million pounds during calendar year 2005.
CASRN
5989-27-5
Less than 500,000 pounds
CASRN
138-86-3
1 to 10 million pounds
CASRN
586-62-9
1 to 10 million pounds
CASRN
123-35-3
10 to 50 million pounds
CASRN
2436-90-0
1 to 10 million pounds
CASRN
68956-56-9
50 to 100 million pounds
CASRN
8008-57-9
1 to 10 million pounds
CASRN
68647-72-3
1 to 10 million pounds
CASRN
65996-98-7
1 to 10 million pounds
Non-confidential information in the IUR4 indicated that the industrial processing and uses of
these chemicals include processing as intermediates and odor agents, and solvents in cleaning
and degreasing. Non-confidential information in the IUR indicated that the commercial and
consumer products containing these chemicals include soaps and detergents; automotive care
products; rubber and plastic products; and polishes and sanitation goods. The HPV submission
for the Monoterpene Hydrocarbons Category states that the chemicals are typically used as
flavoring substances.5 The Hazardous Substances Data Bank (HSDB) states that CASRN 8008-
57-9 is used as a flavoring agent in soaps, cosmetics, lotions and perfumes; CASRN 5989-27-5 is
used in flavorings, fragrances, cosmetics solvents, wetting agents, insecticide, insect repellant,
animal repellant, and the manufacture of resins; CASRN 138-86-3 is used in flavorings,
perfumes, pesticides, paint brush cleansers and preservatives, solvents, wetting and dispersing
agents, air fresheners, cleaning compounds, lubricating oil additives and as monomer in resins;
CASRN 586-62-9 is used in flavorings, fragrances, and as solvents in the manufacture of
synthetic resins; and CASRN 123-35-3 is used in perfumes, flavorings, insect repellents, and
detergents.6
2.2 Environmental Exposure and Fate
No quantitative information is available on environmental releases of these chemicals to the
environment.
The environmental fate properties are provided in Table 3. The monoterpene hydrocarbons are
expected to have moderate mobility in soil. CASRN 5989-27-5 was completely biodegraded in
4	USEPA, 2006. Inventory Update Reporting Database, v. 1.02
5	The Flavor and Fragrance High Production Volume Consortia and The Terpene Consortium, 2006. Revised Test
Plan for Monoterpene Hydrocarbons. Accessed: 01/14/09.
http://www.epa.gov/chemrtk/pubs/summaries/monoterp/cl3756rt.pdf
6	HSDB, 2008. Hazardous Substances Data Bank. CASRN 8008-57-9, 5989-27-5, 138-86-3, 586-62-9, and 123-35-
3. Accessed, 01/21/09. http://toxnet.nlm.nih.gov/
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8 days in a laboratory study using unacclimated soil obtained from a coniferous forest. It was
also shown to be readily biodegradable using the modified MITI test (OECD 301C).
CASRN 586-62-9 was shown to be readily biodegradable using a modified Sturm test (OECD
301B), although it did not pass the readily biodegradable criteria using the manometric
respirometry test (OECD 301F). CASRN 80-56-8, a minor constituent of several of the mixtures
contained in the monoterpene hydrocarbons category, was shown to be readily biodegradable
using the modified MITI test (OECD 301C). Based on the biodegradation data of these
chemicals and the structural similarity and makeup of the mixtures in the monoterpene
hydrocarbons category, all of the constituents are expected to biodegrade in the environment.
Volatilization of the monoterpene hydrocarbons is considered high based on their Henry's Law
constants. The monoterpene hydrocarbons are not expected to hydrolyze since they lack
functional groups that hydrolyze under environmental conditions. The rate of atmospheric
photooxidation is considered moderate to rapid. Based on these data, all the chemicals in the
monoterpene hydrocarbon category are expected to have low persistence (PI). The
bioaccumulation potentials for members of this category are expected to range from low (Bl) to
moderate (B2).
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Table 3. Environmental Fate Characteristics of Monoterpene Hydrocar
)ons Category1
Property
^/-Limonene
dl-
Limoncnc
Terpinolene
Mvrccnc
Dihydro-
mvrccnc
Hydrocar
bons,
terpene
proccssin
S by-
products
Orange
peel oil,
sweet
(Citrus
sinensis (L)
Osbeck)
Tcrpcncs
and
Terpenoids,
sweet
orange-oil
Tcrpcncs
and
Terpenoids,
limonene
fraction
Tcrpcncs and
Terpenoids,
turpcntinc-oil
limonene fraction
CASRN
5989-27-5
138-86-3
586-62-9
123-35-3
2436-90-0
68956-56-
9
8008-57-9
68647-72-3
65996-98-7
65996-99-8
Photodegra
dation Half-
life
0.884 hours
(estimated)
0.64 hours
(estimated)
0.66 hours
(estimated)
1.02 hours
(estimated)2
0.884 hours (estimated value for limonene);
0.64 hours (estimated value for terpinolene);
0.66 hours (estimated value for myrcene);
1.4 hours (estimated value for alpha-pmenof ;
2.2 hours (estimated value for beta-pinene)2;
1.5 hours (estimated value for 6eta-phellandrene)2
Hydrolysis
Half-life
Stable
Biodegradat
ion
Complete
biodegradation in
8 days using
unacclimated soil;
41-98% in 14 days
(readily
biodegradable)3
51-80% in
28 days
(readily
biodegrad-
able)
82-92% in
28 days
(readily
biodegrad-
able)4
82-92% in
28 days
(readily
biodegrad-
able)4
41-98%) in 14 days (readily biodegradable) (data for limonene);
51-80%) in 28 days (readily biodegradable) (data for
terpinolene);
91-95%o in 28 days (readily biodegradable) (data for alpha-
pinene)3
Bioaccumul
ation Factor
BAF =
761 (estimated)2
BAF =
3,506
(estimated)2
BAF = 739
(estimated)2
BAF =1,398
(estimated)2
BAF = 761 (estimated value for limonene)2;
BAF = 3,506 (estimated value for terpinolene)2;
BAF = 739 (estimated value for myrcene)2;
BAF = 3,072 (estimated value for alpha-pmenef;
BAF = 923 (estimated value for beta-pinene)2;
BAF = 976 (estimated value for &eta-phellandrene)2
Log Koc
3.1 (estimated)2
3.1
(estimated)2
3.1
(estimated)2
3.1
(estimated)2
3.1 (estimated values for limonene, terpinolene, myrcene,
alpha-pmenQ, beta-pinene, and &eta-phellandrene)2
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Table 3. Environmental Fate Characteristics of Monoterpene Hydrocar
)ons Category1
Property
^/-Limonene
dl-
Limoncnc
Tcrpinolcnc
Mvrccnc
Dihydro-
mvrccnc
Hydrocar
bons,
terpene
proccssin
S by-
products
Orange
peel oil,
sweet
(Citrus
sinensis (L)
Osbeck)
Tcrpcncs
and
Terpenoids,
sweet
orange-oil
Tcrpcncs
and
Terpenoids,
limonene
fraction
Tcrpcncs and
Terpenoids,
turpentinc-oil
limonene fraction
CASRN
5989-27-5
138-86-3
586-62-9
123-35-3
2436-90-0
68956-56-
9
8008-57-9
68647-72-3
65996-98-7
65996-99-8
Fugacity
(Level III
Model)
Air (%)
Water (%)
Soil (%)
Sediment(
%)
0.145
32.1
64.4
3.38
0.034
20.3
58.4
21.2
0.0606
25.9
62.8
11.2
0.226
32.1
53.8
13.9
0.034-1.73
20.3-44.5
38.5-64.4
3.38-34.3
(estimated values for limonene, terpinolene, myrcene, alpha-
pinene, beta-pinene, and &eta-phellandrene)2
Persistence5
PI (low)
PI (low)
PI (low)
PI (low)
PI (low)
Bioaccumul
ation5
B1 (low)
B2
(moderate)
B1 (low)
B2
(moderate)
B1 (low) - B2 (moderate)
'The Flavor and Fragrance High Production Volume Consortia. The Terpene Consortium. November 1, 2006. Robust Summary and Test Plan for Monoterpene
Hydrocarbons Category (posted November 13, 2006). http://www.epa.gov/oppt/chemrtk/pubs/summaries/monoterp/cl3756tc.htm.
2USEPA. 2009. Estimation Programs Interface Suite™ for Microsoft® Windows, v4.0. U.S. Environmental Protection Agency, Washington, DC, USA.
http://www.epa.gov/opptintr/exposure/pubs/episuite.htm.
3National Institute of Technology and Evaluation. 2002. Biodegradation and Bioaccumulation of the Existing Chemical Substances under the Chemical Substances
Control Law. http://www.safe.nite.go.ip/english/kizon/KIZON start hazkizon.html.
4Wilson, D. and Hrutfiord, B. 1975. The fate of turpentine in aerated lagoons. Pulp Pap. Can. 76:91-93.
5Federal Register. 1999. Category for Persistent, Bioaccumulative, and Toxic New Chemical Substances. Federal Register 64, Number 213 (November 4, 1999) pp.
60194-60204.
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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
d-Limonene (CASRN 5989-27-5)
(1)	Wistar rats (10/sex/dose) were administered d-Limonene in Arabic gum/water via gavage at
1500, 1900, 2500, 3300, 4300, 4400, 5200, 5600, 7300, 9400, 12,200 or
15,900 mg/kg-bw. Observation period not reported.
LD50 (males) = 4400 mg/kg-bw
LD50 (females) = 5200 mg/kg-bw
(2)	Mice (10/sex/dose, strain not specified) were administered d-Limonene in Arabic gum/water
via gavage at 3000, 3500, 4300, 5300, 5600, 6600, 7000, 7500, 8300, or
10,000 mg/kg-bw. Observation period not reported.
LD50 (males) = 5600 mg/kg-bw
LD50 (females) = 6600 mg/kg-bw
Terpinolene (CASRN 586-62-9)
Rats (10/dose group, strain and sex not reported) were administered terpinolene via gavage at
3.0, 3.5, 4.0 and 5.0 ml/kg-bw (corresponding to 2500, 3000, 3464 and 4300 mg/kg-bw).
Observation period not reported. A dose dependent increase in the number of deaths was
observed with zero deaths at 3.0 ml/kg-bw, 1 death at 3.5 ml/kg-bw, 5 deaths at 4.0 ml/kg-bw
and 6 deaths at 5.0 ml/kg-bw.
LD50 = 3800 mg/kg-bw
Myrcene (CASRN 123-35-3)
(1)	Male and female Albino Swiss mice (1/sex/dose or 3/sex/dose) were administered myrcene in
corn oil via gavage at 670, 1000, 2250, 3250, 5060, 7590 or 11,390 mg/kg-bw and observed for
14 days. There were no mortalities up to 3250 mg/kg-bw. At 5060 mg/kg-bw 2/3 (males) and
3/3 (females) died, at 7590 mg/kg-bw 3/3(males) and 2/3 (females) died and both animals died at
11,390 mg/kg-bw.
LD50 = 5060 mg/kg-bw
(2)	Wistar rats (1/sex/dose at three lower doses and 2/sex/dose at the three higher doses) were
administered myrcene in corn oil via gavage at 0, 670, 1000, 1500, 2250, 3250, 5060, 7590 and
11,390 mg/kg-bw and observed for 14 days. No deaths were observed.
LD50 > 11,390 mg/kg-bw
Dihydromyrcene (CASRN 2436-90-0)
Wistar rats (10 males) were administered dihydromyrcene via gavage at 5000 mg/kg-bw and
observed for 14 days. One animal died.
LD50 (male) > 5000 mg/kg-bw
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Orange peel oil, sweet (Citrus sinensis (L.) Osbeck) (CASRN 8008-57-9)
Wistar rats (10 males) were administered orange peel oil, sweet via gavage at 5000 mg/kg-bw
and observed for 14 days. No deaths were reported.
LD50 (male) > 5000 mg/kg-bw
Acute Dermal Toxicity
d-Limonene (CASRN 5989-27-5)
New Zealand White rabbits (10, sex not reported) were administered J-Limonene dermally at
5000 mg/kg-bw on to their clipped, abraded abdominal skin for 24 hours and observed for 7
days. There were no mortalities.
LD50 > 5000 mg/kg-bw
Terpinolene (CASRN 586-62-9)
Rats (4, species and sex not reported) were administered terpinolene dermally at 5 ml/kg-bw
(corresponding to 4330 mg/kg-bw). There were no mortalities.
LD50 > 4330 mg/kg-bw
Myrcene (CASRN 123-35-3)
New Zealand White rabbits (10, sex not reported) were administered myrcene dermally at 5000
mg/kg-bw on to their clipped, abraded abdominal skin for 24 hours and observed for 7 days.
There were no mortalities.
LD50 > 5000 mg/kg-bw
Dihydromyrcene (CASRN 2436-90-0)
New Zealand White rabbits (10 males) were administered dihydromyrcene dermally at 5000
mg/kg-bw on to their clipped, abraded abdominal skins for 24 hours and observed for 14 days.
One rabbit died.
LD50 (male) > 5000 mg/kg-bw
Orange peel oil, sweet (Citrus sinensis (L.) Osbeck) (CASRN 8008-57-9)
New Zealand White rabbits (10, sex not reported) were administered orange peel oil, sweet
dermally at 5000 mg/kg-bw on to their clipped, abraded abdominal skin for 24 hours and
observed for 7 days. There were no mortalities.
LD50 > 5000 mg/kg-bw
Repeated-Dose Toxicity
d-Limonene (CASRN 5989-27-5)
(1) In a 13-week National Toxicology Program (NTP) study, F344/N rats (10/sex/dose) were
administered J-limonene in corn oil via gavage at 0, 150, 300, 600, 1200 and 2400 mg/kg-
bw/day, 5 days/week. Mortality was seen in 9/10 females and 5/10 males at the highest dose.
Male rats showed a decrease in relative and absolute body weight gain. At the three highest
doses, final body weights were decreased by 6%, 12% and 23%, respectively, compared to the
controls. In males, a dose dependent increase in the severity of nephropathy, characterized by
15
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September, 2009
epithelial degeneration in the convoluted tubules, granular casts with tubular lumens and tubular
epithelium regeneration associated with hyaline droplet formation and alpha2u-globulin
formation was observed. Nephropathy associated with alpha2u-globulin formation in male rats is
not considered relevant to humans (US EPA, 1991). Rough hair coats, lethargy and excessive
lacrimation were observed for all animals at the two highest doses.
LOAEL = 2400 mg/kg-bw/day (based on mortality)
NOAEL = 1200 mg/kg-bw/day
(2) In a 13-week NTP study, B6C3F1 mice (10/sex/dose) were administered J-limonene in corn
oil via gavage at 0, 125, 250, 500, 1000 and 2000 mg/kg-bw/day, 5 days/week. Mortality was
observed at 2000 mg/kg-bw/day (1/10 males and 2/10 females) and 500 mg/kg-bw/day (1/10
females). In males a 10% decrease in body weight gain was observed at the two highest doses.
Rough hair coats and decreased activity were observed at the two highest doses in both sexes.
There were no treatment-related histopathologic lesions in either sex.
LOAEL = 2000 mg/kg-bw/day (based on mortality)
NOAEL = 1000 mg/kg-bw/day
Myrcene (CASRN123-35-3)
(1)	In a 13-week NTP study, F344/N rats (10/sex/dose) were administered beta-myrcene in corn
oil via gavage at 0, 250, 500, 1000, 2000 or 4000 mg/kg-bw/day for 5 days/week. Right kidneys
of male rats were frozen while left kidneys were processed for investigation of alpha2u-globulin.
Additionally, special study groups (SSG) (10/dose/sex) were administered three doses of beta-
myrcene daily for 23 days. The left kidneys were frozen and the right kidneys were processed
and microscopically examined for the presence of hyaline droplets. At 4000 mg/kg-bw/day, all
animals in the core and SSG died. At 2000 mg/kg-bw/day, mortality was 20% in the core and
40% in the SSG. The mean body weight gain decreased by >10% in males at 1000, 2000 and
4000 mg/kg- bw/day. At 2000 mg/kg-bw/day, there was a decrease in white blood cells (27%
and 24%) and lymphocytes (35% and 25%) in males and females. Reticulocytes were increased
in males at the 1000 and 2000 mg/kg bw/day. No treatment-related effects on clinical chemistry
parameters were observed. A dose-dependent increase in absolute and relative liver and kidney
weights was observed in male and female rats. A dose-dependent decrease in mean thymus
weight was seen in males at and above 500 mg/kg-bw/day and at 2000 mg/kg-bw/day in females.
All test groups showed evidence of renal tubular degeneration while dose levels of 1000
mg/kg-bw/day and above exhibited splenic atrophy, olfactory epithelial degeneration and chronic
nasal irritation.
LOAEL = 1000 mg/kg-bw/day (based on splenic atrophy, blood effects and body weight
changes)
NOAEL = 500 mg/kg-bw/day
(2)	In a 13-week NTP study, B6C3F1 mice (10/sex/dose) were administered beta-myrcene at 0,
250, 500, 1000, 2000 or 4000 mg/kg-bw/day in corn oil via gavage for 5 days/week. All animals
at 4000 mg/kg bw/day died and 1/10 males and 2/10 females died at 2000 mg/kg-bw/day. At
1000 mg/kg-bw/day, group mean body weight gains were depressed for males (22.5%) and
females (2.4%): mean female body weight gains were significantly depressed. For males,
relative liver weights were increased at 1000 and 2000 mg/kg-bw/day, while in females a dose
related increase in liver weights was observed at 500 mg/kg-bw/day and above. At 1000 mg/kg-
16
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September, 2009
bw/day small hematologic changes (3-6%), decrease in red blood cells, hemoglobin and
hematocrit, and increase in mean corpuscular volume and hemoglobin, were seen—these
changes were more pronounced (5-43%) at 2000 mg/kg-bw/day in both sexes. No treatment-
related effects on clinical chemistry parameters were observed. In females, centrilobular
hypertrophy and necrosis of the liver and irritation of forestomach were observed at 2000 and
4000 mg/kg-bw/day. In males, centrilobular hypertrophy was observed at all doses and liver
necrosis was observed at 1000 and 2000 mg/kg-bw/day.
LOAEL = 1000 mg/kg-bw/day (based on effects on liver, blood and body weight)
NOAEL = 500 mg/kg-bw/day
Orange peel oil, sweet (Citrus sinensis (L.) Osbeck) (CASRN 8008-57-9)
In a 28-day study, Sprague Dawley rats (10/sex/dose) were administered orange peel oil, sweet,
in 1% methyl cellulose, via gavage at 0, 240, 600 or 1500 mg/kg-bw/day. No treatment-related
effects were reported on survival, body weights or food consumption. Treatment-related
decreases in glucose were observed in males at the high dose and in females at the mid- and high
dose. Increases (significance not reported) in serum albumin and total serum protein were
observed in all treated females and in the high dose males. Kidney and liver weights were
increased in the treated male groups and in the high dose female groups. Treatment-related
lesions were observed in the nonglandular stomach of the high dose males and females, and in
the kidney of all treated males, characteristic of hyaline droplet formation and alpha2u-globulin
accumulation. Nephropathy associated with alpha2u-globulin formation in male rats is not
considered relevant to humans (US EPA, 1991).
LOAEL = 1500 mg/kg-bw/day (based on lesions in the stomach and clinical chemistry)
NOAEL = 600 mg/kg-bw/day
Reproductive Toxicity
d-Limonene (CASRN 5989-27-5)
There were no studies specifically designed to assess the reproductive toxicity endpoint available
for 6/-limonene. Evaluation of reproductive organs in repeated-dose studies were used to address
the reproductive toxicity endpoint for the purposes of the HPV Challenge Program.
Myrcene (CASRN 123-35-3)
(1)	In a combined reproductive/developmental toxicity study, Wistar rats, male (15/dose) and
female (45/dose) were administered beta-myrcene via gavage at 0, 100, 300 or 500 mg/kg-
bw/day. Males were exposed to myrcene for 91 days prior to and during mating, and females
were exposed for 21 days before and during mating, pregnancy and throughout lactation up to
postnatal day 21. Except for a slight increase in liver and kidney weights, no other signs of
toxicity were observed in either sex. No morphological changes in the liver or testes were
observed. The mating and pregnancy indices were comparable to controls. No signs of maternal
toxicity were observed at any dose.
NOAEL (reproductive toxicity) = 500 mg/kg-bw/day (based on no adverse effects at the
highest dose tested)
(2)	In a modified prenatal developmental toxicity study, pregnant Wistar rats (number not stated)
were administered beta-myrcene via gavage at 0, 250, 500, 1000 or 1500 mg/kg-bw/day from
17
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September, 2009
gestation day 15 until postnatal day 21. Reproductive capacity was assessed in the exposed
offspring upon reaching maturity (120 days). At 1500 mg/kg-bw/day, mortality was observed in
the dams (5/15). A decrease in body weight (significance not stated) was also observed at the
two high doses. Fertility was impaired in the female offspring at 1000 and 1500 mg/kg-bw/day.
LOAEL (maternal toxicity) = 1000 mg/kg-bw/day (based on decrease in body weight)
NOAEL (maternal toxicity) = 500 mg/kg-bw/day
LOAEL (female reproductive toxicity) = 1000 mg/kg-bw/day (based on effects on fertility)
NOAEL (female reproductive toxicity) = 500 mg/kg-bw/day
Orange peel oil, sweet (Citrus sinensis (L.)Osbeck) (CASRN 8008-57-9)
In a combined reproductive/developmental toxicity screening test, female Sprague-Dawley rats
(10/dose) were administered orange peel oil, sweet via gavage at 0, 375, 750 or 1500 mg/kg-
bw/day for 7 days prior to and through mating, gestation, delivery and four days of lactation.
Treated animals had decreased weight gains, and significantly decreased absolute and relative
food consumption at 750 and 1500 mg/kg-bw/day during the seven day pre-mating period. No
treatment related effects on mating performance or fertility were observed at any dose level. A
significant number of stillbirths and pup deaths were observed at 1500 mg/kg-bw/day. No other
treatment-related effects on offspring were observed.
LOAEL (reproductive toxicity) = 1500 mg/kg-bw/day (based on stillbirths and pup mortality)
NOAEL (reproductive toxicity) = 750 mg/kg-bw/day
Developmental Toxicity
d-Limonene (CASRN 5989-27-5)
(1)	Pregnant Wistar rats (20/dose) were administered J-limonene via gavage at doses of 0, 591 or
2869 mg/kg-bw/day during days 9-15 of gestation. At 2869 mg/kg-bw/day, maternal mortality
and decrease in maternal body weights (significance not stated) were observed. At the high
dose, there was also a decrease in fetal body weights (significance not stated), a delay in
ossification of fetal metacarpal bones and proximal phalanx, and decreased weights of thymus,
spleen and ovaries (significance not stated).
LOAEL (maternal toxicity) = 2869 mg/kg-bw/day (based on mortality and decreased body
weights)
NOAEL (maternal toxicity) = 591 mg/kg-bw/day
LOAEL (developmental toxicity) = 2869 mg/kg-bw/day (based on decreased fetal
bodyweights and delayed ossification)
NOAEL (developmental toxicity) = 591 mg/kg-bw/day
(2)	Pregnant Japanese White rabbits (number not stated) were administered J-limonene via
gavage at 0, 250, 500 or 1000 mg/kg-bw/day during days 6-18 of gestation. Increased maternal
mortality was observed at 1000 mg/kg-bw/day and significant decreases in maternal body weight
gain and food consumption were observed at 500 and 1000 mg/kg-bw/day. No treatment related
effects were observed in offspring.
LOAEL (maternal toxicity) = 500 mg/kg-bw/day (based on decreased body weight gain)
NOAEL (maternal toxicity) = 250 mg/kg-bw/day
NOAEL (developmental toxicity) = 1000 mg/kg-bw/day (based on no adverse effects at the
highest dose tested)
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September, 2009
(3) Pregnant ICR mice (number not stated) were administered J-limonene via gavage at 0, 591 or
2363 mg/kg-bw/day during days 7-12 of gestation. A significant decrease in maternal body
weight gain was observed at 2363 mg/kg-bw/day. In the offspring, an increased incidence of
fused ribs compared to that of controls, delayed ossification of some bones and decreased body
weight gain were reported at the highest dose.
LOAEL (maternal toxicity) = 2363 mg/kg-bw/day (based on decreased body weight gain)
NOAEL (maternal toxicity) = 591 mg/kg-bw/day
LOAEL (developmental toxicity) = 2363 mg/kg-bw/day (based on delayed ossification,
incidence of fused ribs and decreased body weight gain)
NOAEL (developmental toxicity) = 591 mg/kg-bw/day
Myrcene (CASRN123-35-3)
(1)	In a combined reproductive/developmental toxicity study, described above, Wistar rats, were
administered beta-myrcene via gavage at 0, 100, 300 or 500 mg/kg-bw/day. No signs of
maternal toxicity and no increase in externally visible malformations were observed at any dose.
A slight increase (significance not stated) in the resorption rate and a higher frequency of fetal
skeletal anomalies (dislocated sternum and lumbar extra ribs) were observed at 500 mg/kg-
bw/day. No adverse effect on postnatal weight gain was noted. The appearance of primary coat,
incisor eruption and eye opening were slightly delayed in the exposed offspring.
NOAEL (maternal toxicity) = 500 mg/kg-bw/day (based on no adverse effects at the highest
dose tested)
LOAEL (developmental toxicity) = 500mg/kg-bw/day (based on skeletal abnormalities)
NOAEL (developmental toxicity) = 300mg/kg-bw/day
(2)	In a modified prenatal developmental toxicity study described above, pregnant Wistar rats
(number not stated) were administered beta-myrcene via gavage at 0, 250, 500, 1000 or 1500
mg/kg-bw/day from gestation day 15 until postnatal day 21. At 1500 mg/kg-bw/day, mortality
was observed in the dams (5/15). A decrease in body weight (significance not stated) was also
observed at the two high doses. At 500, 1000 and 1500 mg/kg-bw/day, there was perinatal
mortality, delayed developmental landmarks and decreased pup body weights (significance not
stated).
LOAEL (maternal toxicity) = 1000 mg/kg-bw/day (based on decrease in body weight)
NOAEL (maternal toxicity) = 500 mg/kg-bw/day
LOAEL (developmental toxicity) = 500 mg/kg-bw/day (based on perinatal mortality, delayed
postnatal development and decreased pup body weight)
NOAEL (developmental toxicity) = 250 mg/kg-bw/day
(3)	Pregnant Wistar rats (number not stated) were administered beta-myrcene via gavage at 0,
250, 500 or 1200 mg/kg-bw/day during days 6-15 of gestation. At 1200 mg/kg-bw/day, there
was one maternal death. Decreased maternal weight gain (significance not stated) was also
reported. Increased fetal skeletal malformations were reported at 1200 mg/kg-bw/day.
LOAEL (maternal toxicity) = 1200 mg/kg-bw/day (based on mortality and decreased body
weight gain)
NOAEL (maternal toxicity) = 500 mg/kg-bw/day
LOAEL (developmental toxicity) = 1200 mg/kg-bw/day (based on skeletal malformations)
NOAEL (developmental toxicity) = 500 mg/kg-bw/day
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Hazard Characterization Document
September, 2009
Orange peel oil, sweet (Citrus sinensis (L.) Osbeck) (CASRN 8008-57-9)
In a reproductive/developmental toxicity screening test described above, female Sprague-Dawley
rats (10/dose) were administered orange peel oil, sweet via gavage at 0, 375, 750 or 1500
mg/kg-bw/day for 7 days prior to and through mating, gestation, delivery and four days of
lactation. Treated animals had decreased weight gains, and significantly decreased absolute and
relative food consumption at 750 and 1500 mg/kg-bw/day during the seven day pre-mating
period. A significant number of stillbirths and pup deaths were observed at 1500 mg/kg-bw/day.
No other treatment-related effects on offspring were observed.
NOAEL (maternal toxicity) = 1500 mg/kg-bw/day (based on no adverse effects at the highest
dose tested)
LOAEL (developmental toxicity) = 1500 mg/kg-bw/day (based on pup mortality)
NOAEL (developmental toxicity) = 750 mg/kg-bw/day
Genetic Toxicity — Gene Mutation
In vitro
d-Limonene (CASRN 5989-27-5)
(1)	In several reverse-mutation assays, Salmonella typhimurium strains (TA98, TA100, TA102,
TA1535, TA1537 or TA1538) were exposed to J-limonene at concentrations up to 150 mg/plate
in the presence and absence of metabolic activation. Positive controls responded appropriately,
t/-Li m on en e did not increase the number or revertants with or without metabolic activation.
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September, 2009
Genetic Toxicity - Chromosomal Aberrations
In vitro
d-Limonene (CASRN 5989-27-5)
Chinese hamster ovary cells were exposed to J-limonene at concentrations of 50 - 500 |ag/mL in
the presence and absence of metabolic activation. A negative solvent control was used. No
treatment-related increase in number of aberrant cells was observed.
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Myrcene (CASRN123-35-3)
(1)	In an in vitro SCE assay, human lymphocytes were exposed to beta-myrcene at
concentrations up to 1000 |ag/m L for a period of 24 hrs (without metabolic activation) or 2 hrs
(with metabolic activation). There was no increase in the frequency of sister chromatid
exchange with or without metabolic activation.
beta-Myrcene did not induce sister chromatid exchange in this assay.
(2)	In another in vitro SCE assay, Chinese hamster ovary V79 (with and without metabolic
activation) and hepatic tumor cells (HTC) were exposed to beta-myrcene at concentrations up to
500 |ig/mL, for 3 and 20 hrs, respectively. There was no increase in the frequency of sister
chromatid exchange with or without metabolic activation.
beta-Myrcene did not induce sister chromatid exchange in this assay.
Additional Information
Eye Irritation
d-Limonene (CASRN 5989-27-5)
d-Limonene is an eye irritant in rabbits. No study details were provided
(http://www.inchem.Org/documents/cicads/cicads/cicad05.htm#SectionNumber:8.2).
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September, 2009
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response to sheep erythrocytes was used to measure humoral immunity. Body weights,
lymphoid organ weights and spleen cellularity were also evaluated. In the absence of
modulation of the PFC response, these effects were not considered as indicators of
immunotoxicity. Orange oil had no effects on cell-mediated or humoral immune response at any
dose level tested.
NOAEL = 2500 mg/kg-bw/day (based on no effects at the highest dose tested)
Conclusion: The acute toxicity of the monoterpene hydrocarbons category members is low via
the oral (rats and mice) and dermal (rabbits) routes of exposure. CASRN 5989-27-5 is an eye
irritant (rabbits), skin irritant (rabbits and humans) and skin sensitizer (guinea-pigs and humans).
Repeated oral exposures in rats and mice with CASRN 123-35-3 showed hematological effects
as well as splenic atrophy in rats, and histopathological changes in the liver of mice, at 1000
mg/kg-bw/day. The NOAEL was 500 mg/kg-bw/day in rats and mice. Repeated oral exposures
in rats and mice with CASRN 5989-27-5 showed decreasing body weights followed by mortality
at 2400 and 2000 mg/kg-bw/day, respectively. In male rats, nephropathy associated with
alpha2u-globulin formation was the primary systemic effect. The NOAEL was 1200 mg/kg/bw
in rats and 1000 mg/kg-bw/day in mice. Repeated oral exposures in rats with CASRN 8008-57-9
showed clinical chemistry effects and lesions in the stomach at 1500 mg/kg-bw/day. In male
rats, nephropathy associated with alpha2u-globulin formation was the primary systemic effect.
The NOAEL was 600 mg/kg-bw/day. CASRN 8008-57-9 did not elicit an immune response in
vitro up to 2500 mg/kg-bw/day. No studies that specifically address the reproductive toxicity
endpoint were available for CASRN 5989-27-5; however, the evaluation of the reproductive
organs in the 13-week repeated-dose studies showed no treatment-related effects. In a modified
oral developmental toxicity study in rats with CASRN 123-35-3, effects on the fertility of female
off-spring were observed at 1000 mg/kg-bw/day. The NOAEL for reproductive toxicity was 500
mg/kg-bw/day. In the same study, maternal body weights were decreased and perinatal
mortality, delayed postnatal development and decreased pup body weights were observed at
1000 and 500 mg/kg-bw/day, respectively. The NOAEL for maternal and developmental
toxicity was 500 and 250 mg/kg-bw/day, respectively. In an oral combined
reproductive/developmental toxicity study in rats with CASRN 123-35-3, no adverse effects on
reproduction were observed. The NOAEL for reproductive toxicity was 500 mg/kg-bw/day. In
the same study, skeletal abnormalities were observed at 500 mg/kg-bw/day and the NOAEL for
developmental toxicity was 300 mg/kg-bw/day; the NOAEL for maternal toxicity was 500
mg/kg-bw/day. In an oral combined reproductive/developmental toxicity screening test with
CASRN 8008-57-9 in rats, still births and pup mortality were observed at 1500 mg/kg-bw/day.
The NOAEL for reproductive and developmental toxicity was 750 mg/kg-bw/day. The NOAEL
for maternal toxicity was 1500 mg/kg-bw/day. Prenatal oral developmental toxicity studies with
CASRN 5989-27-5 showed decreased fetal body weights and delayed ossification in rats and
mice at 2869 and 2363 mg/kg-bw/day, respectively. Mortality was observed in the adult rats and
mice at 2869 and 2363 mg/kg-bw/day, respectively. The NOAEL for maternal and
developmental toxicity was 591 mg/kg-bw/day for both species. In rabbits, maternal body
weight gain was reduced but no developmental toxicity was observed at 500 mg/kg-bw/day. The
NOAEL for maternal and developmental toxicity was 250 and 1000 mg/kg-bw/day, respectively.
CASRN 5989-27-5 and CASRN 8008-57-9 did not induce gene mutations in vitro. CASRN
5989-27-5 and CASRN 123-35-3 did not induce chromosomal aberrations in vitro or in vivo.
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U.S. Environmental Protection Agency	September, 2009
Hazard Characterization Document
CASRN 5989-27-5 induced tumors in male rats via a mode of action not considered relevant to
humans, and did not induce tumors in female rats and mice.
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Table 4: Summary of Human Health Data
Knd points
<1 1 i 111 Oil IIH'
(CASRN
5989-27-5)
<11 I imiiiHiH1
(CASRN
138-86-3)
Tcrpinolcnc
(CASRN
586-62-9)
Myrcene
(CASRN
123-35-3)
Dihydromyrccnc
(CASRN
2436-90-0)
Ilyd rocarbons.
terpene
processing by-
prod ucts
(CASRN
68956-56-9)
Orange peel oil.
sweet (Citrus
sinensis (L.)
Osbeck)
(CASRN
8008-57-9)
Tcrpenes
and
terpenoids.
sweet
orange oil
(CASRN
68647-72-3)
Tcrpcncs and
terpenoids.
Mmoncnc
traction
(CASRN
65996-98-7)
Tcrpcncs and
terpenoids,
turpentine
oil.
limoncnc
fraction
(CASRN
65996-98-7)
Acute Oral
toxicity
LDso
(mg/kg-bw)
4400 (m)
5200 (f)
No Data
4400 (m)
5200 (f)
(RA)
3800
5060
> 5000(m)
No Data
4400(m)
5200 (f)
(RA)
> 5000(m)
No Data
>5000
(RA)
No Data
4400(m)
5200 (f)
(RA)
No Data
4400 (m)
5200 (f)
(RA)
Acute Dermal
toxicity
LD50
(mg/kg-bw)
>5000
No Data
> 5000
(RA)
>4330
>5000
>5000
No Data
>5000
(RA)
>5000
No Data
>5000
(RA)
No Data
> 5000
(RA)
No Data
>5000
(RA)
Oral Repeated -
Dose T oxicity
NOAEL/
LOAEL
(mg/kg-bw/day)
NOAEL =
1200
LOAEL =
2400
No Data
NOAEL = 1200
LOAEL = 2400
(RA)
No Data
NOAEL =
1200
LOAEL =
2400
(RA)
NOAEL = 500
LOAEL =
1000
No Data
NOAEL = 500
LOAEL = 1000
No Data
NOAEL = 1200
LOAEL = 2400
(RA)
NOAEL = 600
LOAEL = 1500
No Data
NOAEL =
600
LOAEL=
1500
(RA)
No Data
NOAEL =
1200
LOAEL =
2400
(RA)
No Data
NOAEL =
1200
LOAEL =
2400
(RA)

NOAEL =
1000
LOAEL =
2000
NOAEL = 1000
LOAEL = 2000
(RA)
NOAEL =
1000
LOAEL =
2000
(RA)


NOAEL = 1000
LOAEL = 2000
(RA)


NOAEL =
1000
LOAEL =
2000
(RA)
NOAEL =
1000
LOAEL =
2000
(RA)
Reproductive
Toxicity
NOAEL/
LOAEL
(mg/kg-bw/day)
No effects
were seen
following
evaluation of
reproductive
organs in 13-
week oral
repeated-
dose toxicity
studies in
rats and
mice.
No Data
No effects were seen following
evaluation of reproductive
organs in 13-week oral
repeated-dose toxicity studies
in rats and mice.
(RA)
NOAEL =
500
(hdt)
NOAEL(f) =
500
LOAEL(f) =
1000
No Data
NOAEL =
500
(RA)
No Data
NOAEL(f) =
500
LOAEL(f) =
1000
(RA)
No Data
No effects
were seen
following
evaluation of
reproductive
organs in 13-
week oral
repeated-dose
toxicity studies
in rats and
mice.
(RA)
NOAEL = 750
LOAEL=
1500
No Data
NOAEL =
750
LOAEL =
1500
(RA)
No Data
No effects were seen
following evaluation of
reproductive organs in 13-
week oral repeated-dose
toxicity studies in rats and
mice.
(RA)
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Hazard Characterization Document
September, 2009
Table 4: Summary of Human Health Data
End points
<1 I i 111 Oil 1IH'
<11 I imiiiHiH1
Tcrpinolcnc
Myrcene
Dilmlromyrccne
Ilyd rocarbons.
Orange peel oil.
Terpenes
Terpenes iiml
Terpenes and

(CASRN
(CASRN
(CASRN
(CASRN
(CASRN
terpene
sweet (Citrus
iiml
terpenoids.
terpenoids.

5989-27-5)
138-86-3)
586-62-9)
123-35-3)
2436-90-0)
processing bv-
sinensis (L.)
terpenoids.
limonene
turpentine






prod ucts
Osbeck)
sweet
fraction
oil.






(CASRN
(CASRN
orange oil
(CASRN
limonene






68956-56-9)
8008-57-9)
(CASRN
65996-98-7)
fraction








68647-72-3)

(CASRN










65996-98-7)
Developmental










Toxicity










NOAEL/










LOAEL










(mg/kg-bw/day)








No Data
No Data


No Data
No Data

No Data
No Data


(rat, mice)
(rat, mice)
Maternal
(rat, mice)
(rat, mice)
(rat, mice)
(rat)
(rat)
(rat, mice)

No Data
NOAEL =
NOAEL =
Toxicity
NOAEL =
NOAEL = 591
NOAEL =
NOAEL =
NOAEL = 500
NOAEL = 591
NOAEL=
NOAEL =
591
591

591
LOAEL =
591
500
LOAEL = 1000
LOAEL =
1500 (hdt)
1500
LOAEL =
LOAEL =

LOAEL =
2869
LOAEL =
LOAEL =

2869

(RA)
2869
2869

2869

2869
1000














No Data
NOAEL =
NOAEL =
Developmental
NOAEL =
NOAEL = 591
NOAEL =
NOAEL =
NOAEL = 250
NOAEL = 591
NOAEL = 750
NOAEL =
591
591
T oxicity
591
LOAEL =
591
250
LOAEL =500
LOAEL =
LOAEL
750
LOAEL =
LOAEL =

LOAEL =
2869
LOAEL =
LOAEL
(RA)
2869
=1500
LOAEL =
2869
2869

2869
(RA)
2869
=500

(RA)

1500
(RA)
(RA)



(RA)




(RA)




No Data
No Data

No Data
No Data


No Data
No Data
Maternal
T AYirifv
(rabbit)
(rabbit)
(rabbit)
(rat)
(rat)
(rabbit)


(rabbit)
(rabbit)

NOAEL =
NOAEL = 250
NOAEL =
NOAEL =
NOAEL = 500
NOAEL = 250


NOAEL =
NOAEL =

250
LOAEL = 500
250
500
LOAEL = 1200
LOAEL = 500


250
250

LOAEL =

LOAEL =
LOAEL =




LOAEL =
LOAEL =

500

500
1200




500
500
Developmental
NOAEL
NOAEL
NOAEL
NOAEL =
NOAEL = 500
NOAEL


NOAEL
NOAEL
T oxicity
=1000 (hdt)
=1000
=1000
500
LOAEL = 1200
= 1000


=1000
= 1000


(RA)
(RA)
LOAEL =
(RA)
(RA)


(RA)
(RA)




1200






27
-------
U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 4: Summary of Human Health Data
Knd points
^/-Limoncnc
(CASRN
5989-27-5)
til I imiiiHiH1
(CASRN
138-86-3)
Tcrpinolcne
(CASRN
586-62-9)
Myrccnc
(CASRN
123-35-3)
Dilmlronivrccnc
(CASRN
2436-90-0)
Ilyd rocarbons.
terpene
processing bv-
prod ucts
(CASRN
68956-56-9)
Orange peel oil.
sweet (Citrus
sinensis (L.)
Osbock)
(CASRN
8008-57-9)
Terpenes
and
terpenoids.
sweet
orange oil
(CASRN
68647-72-3)
Terpenes and
terpenoids,
limoncnc
frsiction
(CASRN
65996-98-7)
Terpenes and
terpenoids,
turpentine
oil.
limoncnc
fraction
(CASRN
65996-98-7)
Maternal
Toxicity



NOAEL =
500 (hdt)
No Data
NOAEL = 500



No Data
NOAEL =
500
No Data
NOAEL =
500
Developmental
Toxicity



NOAEL =
300
LOAEL =
500
NOAEL = 300
LOAEL = 500
(RA)



NOAEL =
300
LOAEL =
500
(RA)
NOAEL =
300
LOAEL =
500
(RA)
Genetic
Toxicicty — Gene
Mutation
In Vitro
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
Genetic Toxicity
Chromosomal
Aberrations
In vitro
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
Negative
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
No Data
Negative
(RA)
Genetic
Toxicicty — Gene
Mutation
In Vivo
Negative
**
**
Negative
**
**
**
**
**
**
Genetic Toxicity










Other effects
Sister chromatid
exchange
Negative
**
**
Negative
**
**
**
**
**
**
Eye irritant
Positive
**
**
**
**
**
**
**
**
**
Skin irritant
Positive
**
**
**
**
**
**
**
**
**
Skin sensitizer
Positive
**
**
**
**
**
**

**
**
Carcinogenicity
Negative
**
**
**
**
**


**
**
Measured data in bold text; (RA) = read across; NE = not established; (m) = male; (f) = female; hdt = highest dose tested; **_ - endpoint not addressed for this
chemical
28
-------
U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
4 Hazards 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
d-Limonene (CASRN 5989-27-5)
Fathead minnows (Pimephalespromelas) were exposed to J-limonene at measured
concentrations (<0.05, 0.25, 0.56, 0.96, 1.38, and 1.89 mg/L) under flow-through conditions for
96 hours (Geiger et al., 1990).
96-h LC50 = 0.7 mg/L
Terpinolene (CASRN 586-62-9)
Fathead minnows (Pimephalespromelas) were exposed to terpinolene at measured
concentrations (<0.03, 0.27, 0.65, 0.90, 1.36, and 1.67 mg/L) under flow-through conditions for
96 hours (Geiger et al., 1990).
96-h LC50 = 1.21 mg/L
Acute Toxicity to Aquatic Invertebrates
d-Limonene (CASRN 5989-27-5)
Daphnia magna were exposed to J-limonene at measured concentrations (<50, 287, 619, 932,
1190, and 1630 mg/L) under flow through conditions for 48 hours.
48-h EC50 = 0.421 mg/L
Terpinolene (CASRN 586-62-9)
Daphnia magna were exposed to terpinolene at measured concentrations (<30, 910, 1960, and
2930 mg/L) under flow through conditions for 48 hours.
48-h EC50 = 1.38 mg/L
Toxicity to Aquatic Plants
d-Limonene (CASRN 5989-27-5)
Green algae (Selenastrum capricornutum) were exposed to J-limonene under static conditions
for 96 hours.
48-h EC50 > 1.81 mg/L
Terpinolene (CASRN 586-62-9)
Green algae (Selenastrum capricornutum) were exposed to terpinolene under static conditions
for 96 hours.
48-h EC50 > 3.38 mg/L
29
-------
U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Chronic Toxicity to Aquatic Invertebrates
Dihydromyrcene (CASRN 2436-90-0)
Given the log Kow range of 4.8 to 5.3 for this category, EPA recommended the chronic daphnia
21- day test for the most hydrophobic chemical, dihydromyrcene.
Data Gap
Conclusion: The acute hazard to fish is based on the toxicity values for CASRN 586-62-9 of
1.21 mg/L and CASRN 5989-27-5 of 0.7 mg/L. The acute hazard to aquatic invertebrates is
based on the toxicity values for CASRN 586-62-9 of 1.38 mg/L and CASRN 5989-27-5 of 0.421
mg/L. The acute hazard to aquatic plants is based on the toxicity values for CASRN 586-62-9
of >3.38 mg/L and CASRN 5989-27-5 of >1.81 mg/L.
The chronic toxicity to aquatic invertebrates for CASRN 2436-90-0 remains as a data gap under
the HPV Challenge Program.
30
-------
U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
Table 5. Summary of Environmental Effects - Aquatic Toxicity Data
Endpoints
<1I imiiiHiH1
(CASRN
5989-27-5)
<11 I imiiiHiH1
(CASRN
138-86-3)
Terpinolene
(CASRN
586-62-9)
Mvrcene
(CASRN
123-35-3)
Dilmlronivrcene
(CASRN
2436-90-0)
Ilyd rocsirbons.
terpene
processing by-
prod ucts
(CASRN
68956-56-9)
Orange peel
oil. sweet
(( itrus
sinensis (1,.)
Osbeck)
(CASRN
8008-57-9)
Terpenes
smd
terpenoids.
sweet
orsinge oil
(CASRN
68647-72-3)
Terpenes mid
terpenoids,
limonene
frsiction
(CASRN
65996-98-7)
Terpenes mid
terpenoids,
turpentine oil.
limonene
frsiction
(CASRN
65996-99-8)
Fish
96-h LCS0
(mg/L)
0.7
No Data
0.7
(RA)
1.21
No Data
0.7
(RA)
No Data
0.7
(RA)
No Data
0.7
(RA)
No Data
0.7
(RA)
No Data
0.7
(RA)
No Data
0.7
(RA)
No Data
0.7
(RA)
Aquatic
Invertebrates
48-h ECS0
(mg/L)
0.421
No Data
0.421
(RA)
1.38
No Data
0.421
(RA)
No Data
0.421
(RA)
No Data
0.421
(RA)
No Data
0.421
(RA)
No Data
0.421
(RA)
No Data
0.421
(RA)
No Data
0.421
(RA)
Aquatic
Plants
96-h ECS0
(mg/L)
>1.81
No Data
>1.81
(RA)
>3.38
No Data
>1.81
(RA)
No Data
>1.81
(RA)
No Data
>1.81
(RA)
No Data
>1.81
(RA)
No Data
>1.81
(RA)
No Data
>1.81
(RA)
No Data
>1.81
(RA)
Aquatic
Invertebrates
21-day ECS0
(mg/L)
Data Gap
Measured data (i.e. derived from testing) are in bold; (e) = estimated data (i.e., derived from modeling); (RA) = read across
31
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U.S. Environmental Protection Agency
Hazard Characterization Document
September, 2009
5 References
Geiger, D.L., L.T. Brooke, and D.J. Call. (1990) Acute Toxicities of Organic Chemicals to
Fathead Minnows (Pimephalespromelas), Volume 5. Ctr.for Lake Superior Environ.Stud.,
Univ.of Wisconsin-Superior, Superior, WI :332 p.
US EPA (1991) Alpha2u-Globulin: Association with Chemically Induced Renal Toxicity and
Neoplasia in the Rat, EPA/625/3-91/019F.
32
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