United States
Environmental Protection
1=1 m m Agency
EPA/690/R-09/013F
Final
9-17-2009
Provisional Peer-Reviewed Toxicity Values for
?7-Decane
(CASRN 124-18-5)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
Commonly Used Abbreviations
BMD
Benchmark Dose
IRIS
Integrated Risk Information System
IUR
inhalation unit risk
LOAEL
lowest-observed-adverse-effect level
LOAELadj
LOAEL adjusted to continuous exposure duration
LOAELhec
LOAEL adjusted for dosimetric differences across species to a human
NOAEL
no-ob served-adverse-effect level
NOAELadj
NOAEL adjusted to continuous exposure duration
NOAELhec
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-ob served-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
RfC
inhalation reference concentration
RfD
oral reference dose
UF
uncertainty factor
UFa
animal to human uncertainty factor
UFC
composite uncertainty factor
UFd
incomplete to complete database uncertainty factor
UFh
interhuman uncertainty factor
UFl
LOAEL to NOAEL uncertainty factor
UFS
subchronic to chronic uncertainty factor
1

-------
FINAL
9-17-2009
PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
n-DECANE (CASRN 124-18-5)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (U.S. EPA) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1)	U.S. EPA's Integrated Risk Information System (IRIS).
2)	Provisional Peer-Reviewed Toxicity Values (PPRTVs) used in U.S. EPA's Superfund
Program.
3)	Other (peer-reviewed) toxicity values, including
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in U.S. EPA's IRIS. PPRTVs are developed according to a
Standard Operating Procedure (SOP) and are derived after a review of the relevant scientific
literature using the same methods, sources of data, and Agency guidance for value derivation
generally used by the U.S. EPA IRIS Program. All provisional toxicity values receive internal
review by two U.S. EPA scientists and external peer review by three independently selected
scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multiprogram consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all U.S. EPA programs, while PPRTVs are developed
specifically for the Superfund Program.
Because new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. Once an IRIS
value for a specific chemical becomes available for Agency review, the analogous PPRTV for
that same chemical is retired. It should also be noted that some PPRTV documents conclude that
a PPRTV cannot be derived based on inadequate data.
Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and Resource Conservation and Recovery Act (RCRA) program offices are advised to
carefully review the information provided in this document to ensure that the PPRTVs used are
appropriate for the types of exposures and circumstances at the Superfund site or RCRA facility
in question. PPRTVs are periodically updated; therefore, users should ensure that the values
contained in the PPRTV are current at the time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV document and understand the strengths
1

-------
FINAL
9-17-2009
and limitations of the derived provisional values. PPRTVs are developed by the U.S. EPA
Office of Research and Development's National Center for Environmental Assessment,
Superfund Health Risk Technical Support Center for OSRTI. Other U.S. EPA programs or
external parties who may choose of their own initiative to use these PPRTVs are advised that
Superfund resources will not generally be used to respond to challenges of PPRTVs used in a
context outside of the Superfund Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the U.S. EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
INTRODUCTION
//-Decane (CASRN 124-18-5) is a high production volume (HPV) chemical constituent of
the paraffin fraction of petroleum and natural gas. A very small volume (estimated at less than
20,000 pounds) is produced in pure form for use as a laboratory reagent. There are no known
consumer product applications for pure //-decane, but, their large production volumes and wide
usage make the petroleum distillates the primary sources of exposure. Toxicity information is
scant, and there is a paucity of quantitative reference values in the //-decane literature. No RfD,
RfC, or carcinogenicity assessment for «-decane is available on IRIS (U.S. EPA, 2008).
«-Decane is not included on the Health Effects Assessment Summary Tables (HEAST;
U.S. EPA, 1997), the Drinking Water Standards and Health Advisory list (U.S. EPA, 2006), or
the Chemical Assessments and Related Activities (CARA) list (U.S. EPA, 1991, 1994). The
Agency for Toxic Substances and Disease Registry (ATSDR, 2008) has not produced a
Toxicological Profile for //-decane. Toxicological Profiles for mixtures containing //-decane,
such as Total Petroleum Hydrocarbons (TPH) (ATSDR, 1999) and Stoddard Solvent (a low
aromatic hydrocarbon solvent containing C10-C14 n-, iso-, and cycloalkanes) (ATSDR, 1995),
do exist, but they do not derive oral or inhalation MRLs for any of the individual compounds.
Staats Creative Sciences (SCS) for the United States Air Force (Staats, 1994) derived a chronic
oral RfD of 1.332 mg/kg-day based on a route-to-route extrapolation from an inhalation NOAEL
of 540 ppm, which, in turn, was derived from a subchronic inhalation study in rats by Nau (1966)
described below.
No Environmental Health Criteria Document is available for //-decane from the World
Health Organization (WHO, 2008). The Occupational Safety and Health Administration
(OSHA, 2008), the National Institute for Occupational Safety and Health (NIOSH, 2008), and
the American Conference for Governmental Industrial Hygienists (ACGIH, 2007) have not
established occupational health standards for //-decane. The carcinogenicity of //-decane has not
been assessed by the International Agency for Research on Cancer (IARC, 2008) or the National
Toxicology Program (NTP) (2005, 2008). NTP has conducted subchronic inhalation and
carcinogenicity studies in rats and mice on Stoddard Solvent (mixture containing //-decane, as
mentioned above), but they did not evaluate the individual compounds (NTP, 2004).
2

-------
FINAL
9-17-2009
To identify toxicological information pertinent to the derivation of provisional toxicity
values for //-decane, a literature search was conducted through December 2008 using the
following databases: MEDLINE, TOXLINE (Special), BIOSIS, TSCATS 1/TSCATS2, CCRIS,
DART/ETIC, GENETOX, HSDB, RTECS, and Current Contents. Additionally, a Voluntary
Children's Chemical Evaluation Program (VCCEP) Tier-1 Pilot Submission on the n-Alkane
Categories of decane, undecane, and dodecane (CASRNs 124-18-5, 1120-21-4, and 112-40-3),
from the American Chemistry Council //-Alkane VCCEP Consortium (ACCVC, 2004), was
reviewed.
REVIEW OF PERTINENT DATA
Human Studies
No information was located regarding the subchronic or chronic oral or inhalation
toxicity of //-decane in humans. Some information is available for several complex mixtures, for
example, white spirits, or Stoddard solvent (ATSDR, 1995), but none of these are directly
applicable here because of the problems inherent in dealing with complex mixtures of variable
composition.
Animal Studies
Oral Exposure
Data on the effects of repeated oral exposure to //-decane in animals are available from a
single study, initially submitted on behalf of Sasol North America, Inc., under the Toxic
Substances Control Act to the U.S. EPA Office of Pollution Prevention and Toxics, evaluating
the effects of commercial //-decane on general, reproductive, and developmental toxicity
(Sasol NA, 1995). This study is also included as Maraschin et al. (1995) in the VCCEP Tier-1
Pilot Submission for the «-alkane category as a robust summary (ACCVC, 2004). Sasol NA
(1995) treated groups of 20 Sprague-Dawley rats (10/sex) with doses of 0, 25, 150, or
1000 mg/kg-day (10 mL/kg dosing volume) of commercial //-decane (Linpar 10; approximately
97% //-decane) in 0.5% methylcellulose aqueous solution by gavage. Dosing was conducted
7 days/week from Day 14 prior to mating through to the end of the mating phase for males for a
total duration of approximately 4 weeks, and through Day 4 of lactation for females for a total
duration of up to approximately 8 weeks. The dosages were established in accordance with the
sponsorship of Italy in the Organization for Economic Co-operation and Development Screening
Information Datasets (OECD SIDS) program; further detail on how the dose levels were chosen
is not reported. The study authors determined pregnancy based on the presence of spermatozoa
in vaginal smears collected. For females demonstrating a positive smear that did not give birth,
treatment was continued until presumed Day 27 of pregnancy when these rats were then
sacrificed. For females that did not demonstrate positive smears, treatment continued up until
Day 27 after the end of the mating period when these rats were then sacrificed. Initial body
weights were 0.20-0.225 kg for female rats and 0.275-0.30 kg for male rats. Rats were allowed
free access to food and water and were housed two to a cage by sex prior to mating, one to a cage
after mating and gestation, and dams were housed in a cage with their litter through the first
4 days of lactation. A control group consisted of 10 males and 10 females treated with
0.5% methylcellulose following the same treatment schedule as described above. Each animal
3

-------
FINAL
9-17-2009
was fasted for about 16 hours overnight before killing and the fasted body weight was recorded.
Male rats were killed the day after the end of the mating period, and dams and pups were killed
on Day 5 of lactation.
Effects on general toxicity, neurobehavioral activity (startle reflex, grip reflex, and open
field tests performed in five adult males and females of each group), clinical chemistry (glucose,
urea, creatinine, alanine aminotransferase [ALT, formerly serum glutamic oxalacetic
transaminase, or SGOT], and aspartate aminotransferase [AST, formerly serum glutamic pyruvic
transaminase, or SGPT], total cholesterol, total protein, protein electrophoresis, albumin/globulin
[A/G] ratio, sodium, potassium, and bile acids examined in five adult males and females of each
group) and hematology (erythrocytes, total and differential leukocytes, and platelet count, as well
as measures of hemoglobin volume, mean corpuscular volume [MCV], mean corpuscular
hemoglobin concentration [MCHC], mean corpuscular hemoglobin [MCH], and prothrombin
time in five adult male and female rats of each group) were evaluated (Sasol NA, 1995).
Urinalysis (diuresis and specific gravity, semiquantitative examination for leukocytes, nitrites,
pH, protein, glucose, ketone bodies, urobilinogen, and bilirubin), and blood and microscopic
examination (for epithelial cells, leukocytes, erythrocytes, crystals, casts, bacteria, and other
abnormal components) was only conducted in males that were also used for blood collection.
Reproductive and developmental effects were evaluated by measuring mating, fertility, gestation,
and birth indices, conception, gestation length, litter size, offspring survival, pup body weight,
sex ratio, and developmental abnormalities in pups at birth. Gross necropsies, including
examination of the external surface of the body, all orifices and the cranial, thoracic, and
abdominal cavities and their contents, were conducted on each adult rat. Whenever possible, the
study authors examined the dead pups externally and internally in an attempt to determine the
cause of death. In the adults of the high-dose group, the study authors conducted
histopathological examination of tissues (bladder, prostate, testes, epididymides, seminal
vesicles, uterus, ovaries, spleen, stomach, intestine, mesenteric lymph nodes, liver, kidneys,
adrenals, submandibular lymph nodes, sternum, heart, thymus, lungs, trachea, brain, peripheral
nerve, spinal cord, and gross lesions). In the adults of the low- and intermediate-dose groups, the
study authors evaluated the male reproductive tract, the stomach, kidneys, and gross lesions.
The study authors noted no mortalities, clinical signs, or treatment-related changes in
behavior or body weight were observed throughout the study in parental rats (Sasol NA, 1995).
There were no differences in the functional neurobehavioral tests (startle reflex, forelimb grip
strength, open field test) between treated and control rats. The study authors noted no significant
urological findings in male rats (not examined in female rats). Hematology and serum chemistry
parameters in treated animals were comparable to controls. Although serum creatinine in male
rats exhibited a trend towards an increase in all treated groups, it is not statistically significant.
This change is considered incidental because (1) it was slight in degree, (2) not clearly
dose-related, and (3), while some individual values were above the range for controls, the values
were still within the normal clinical ranges. Female rats exhibited a nonsignificant trend towards
an increase in total cholesterol across all treated groups, indicating a possible dose-response
relationship (very slight variation, compared to controls, at the low dose and of moderate degree
at the highest dose); some individual animals given the intermediate dose (Group 3 female
number 51) and the highest does (Group 4 females 72 and 80) showed concentrations above
100 mg/dL. Except for the slight changes noted in the nonglandular stomach mucosa of treated
rats (data presented in Table 1), no changes in organ weights or gross pathology were observed.
Upon gross examination, thickening of the nonglandular mucosa of the stomach was noted in
4

-------
FINAL
9-17-2009
rats from the 150-mg/kg-day (3/20) and 1000-mg/kg-day (10/20) dose groups. Some of the
animals in these groups also demonstrated slight erosion of the nonglandular mucosa and/or
thickening of the cuticular ridge. Sasol NA (1995) considered these findings to be related to the
bolus dosing method. Histopathology confirmed treatment-related slight-to-moderate
hyperplasia of the nonglandular mucosa of the stomach associated with degeneration,
hyperkeratosis, and submucosal subacute inflammation (see Table 1). The authors reported that
these changes of the nonglandular mucosa of the stomach were not dose-related in degree,
frequency, or diffusion (i.e., focal, multifocal, or diffuse) (diffusion data are presented in the
Sasol NA [1995] Appendix and are not shown in Table 1). Sasol NA (1995) considered the
additional findings observed upon gross or microscopic examination to be incidental and not
related to treatment. Despite the author's statements, there does appear to be a dose related
increase in incidence, though not severity of these lesions.
Table 1. Stomach Gross Pathology and Histology Incidence and Severitya'b
Pathology
Dose (mg/kg-day)
0
25
150
1000
Male
Female
Male
Female
Male
Female
Male
Female
Gross Pathology
Nonglandular mucosa,
erosion
0/10
0/10
2/10
(1.5)
0/10
2/10
(1.0)
1/10(1.0)
1/10
(2.0)
1/10(1.0)
Nonglandular mucosa,
thickened
0/10
0/10
0/10
0/10
2/10
(1.0)
1/10(1.0)
6/10
(1.0)
4/10(1.3)
Histology
Nonglandular mucosa,
degeneration
0/5
0/5
5/5 (1.0)
1/5 (2.0)
4/5
(1.5)
5/5 (1.6)
7/7
(1.6)
6/6 (1.3)
Nonglandular mucosa,
erosion
0/5
0/5
1/5 (2.0)
0/5
0/5
2/5 (1.5)
1/7
(2.0)
1/6 (2.0)
Nonglandular mucosa,
hyperkeratosis
0/5
0/5
3/5 (1.0)
1/5 (1.0)
4/5
(1.0)
5/5 (1.0)
7/7
(1.1)
5/6 (1.2)
Nonglandular mucosa,
hyperplasia
0/5
0/5
5/5 (1.8)
2/5 (1.0)
5/5
(1.8)
5/5 (1.2)
7/7
(1.8)
6/6 (2.2)
Nonglandular submucosa,
Inflammation-subacute
0/5
0/5
3/5 (1.7)
1/5 (1.0)
5/5
(1.4)
5/5 (1.2)
7/7
(1.1)
5/6 (1.8)
aSasol NA, 1995
incidence (mean severity); Severity: 0 (very slight), 1 (slight), 2 (moderate), 3 (severe)
The mean mating time of rats in the high-dose group was slightly longer than that of the
control group, but this difference was still within the normal range of variability for this strain of
rat according to Sasol NA (1995). A decrease in fertility—evaluated as a decreased fertility
index in all treated rats—was observed compared to controls (see data presented in Table 2).
However, the differences between the treated and control rats are not statistically significant and
there is not a clear dose-response relationship among these data.
5

-------
FINAL
9-17-2009
Table 2. Fertility Index3
Dose

(mg/kg-day)
Incidence of Gravid Females
0
7/10
25
5/10
150
6/10
1000
4/10
aSasol NA, 1995
Sasol NA (1995) noted that the decrease in fertility index occurred in the absence of any
adverse effects on reproductive organs and considered that this effect may be related to stomach
irritation in treated rats, as described above. No other treatment-related effects on any of the
reproductive parameters are noted; there are no treatment-related effects at any dose level on any
of the developmental parameters evaluated in this study.
Based on the findings described above, the NOAEL was the highest dose of
1000 mg/kg-day.
Inhalation Exposure
Data on the subchronic inhalation effects of //-decane in animals come from a single,
poorly reported subchronic study by Nau (1966). Nau (1966) exposed groups of 43 rats (strain
and sex not specified) to 540 ppm (3140 mg/m3) //-decane (purity not reported) via whole-body
inhalation in an exposure chamber for 18 hours per day, 7 days per week, for up to 91 days. The
study authors measured vapor concentrations via a sampling port in the chamber each hour
during exposure to ensure that the rats were exposed to a constant concentration of //-decane.
Some rats (number not specified) were set aside without additional exposure for 32 days, while
the rest of the animals were presumably sacrificed immediately following the exposure period—
although details of animal treatment are lacking. Nau (1966) does not discuss how the exposure
concentration of 540 ppm was chosen and reports the tested concentration inconsistently in the
text and tables of the report as 540 ppm and 560 ppm (3260 mg/m3). The number of rats
exposed is also inconsistently reported as 43 rats and 41 rats in different tables of the report.
Study details regarding maintenance of the rats during the experiment are not reported. Initial
average rat body weight was 301 ± 40 grams. In addition to the inhalation exposures in rats
using //-decane, Nau (1966) also exposed rats via inhalation to benzene and other aromatic-rich
fractions of reformed naphthas for 105 days. A control group of 20 rats was maintained
simultaneously through 105 days (longer than the 91-day exposure of //-decane treated rats) for
comparison to all of the exposure groups evaluated by this study.
Nau (1966) monitored rats for changes in general appearance and behavior, body-weight
gain, organ weights (specific organs not specified), limited hematology (total leukocytes,
polymorphonuclear-lymphocyte ratio, and total lymphocytes), and changes in bone marrow
(myelocytic and erythrocytic activity). Gross necropsies and histopathological examination of
the tissues were conducted following inhalation exposure. However, in their report, the study
authors did not disclose which specific tissues were evaluated following exposure to //-decane.
6

-------
FINAL
9-17-2009
Significant gains in body weight were observed during exposure in comparison to
controls (p < 0.001) (Nau 1966). Methods of statistical analysis performed by Nau (1966) are
not reported. Table 3 shows the changes in body weight over the exposure period in comparison
to the control group. After 57 days of exposure, the mean body weight of the treated rats was
approximately 36% higher than the control rats. However, at the end of the 91-day exposure
period the mean body weight of the treated rats was only about 12% higher than that of the
control rats, suggesting that this response may be reversible. Nau (1966) reported that the
increase in weight gain among treated rats compared to the control rats was maintained through
the 32-day recovery period, although the magnitude of the increase is not reported and neither is
the mean body weight of the treated rats at the end of recovery period.
Table 3. Body Weights in Rats Following Inhalation of «-Decanea
Exposure Period
0 ppm
540 ppm
N Rats
Mean ± SD (g)
N Rats
Mean ± SD (g)
Preexposure
20
295 ± 33
43
301 ±40
End of 57 days
20
335 ± 94
31
456 ± 26c
End of 91 daysb
17
423 ± 23
18
476 ± 38c
aNau, 1966
bend of 105 days for control rats
Significantly different from controls (p < 0.001)
SD-standard deviation
Table 4 presents changes in hematology (Nau, 1966). After 57 days of exposure, mean
counts of total leukocytes were significantly decreased in the treated rats (p < 0.001). However,
by the end of the 91-day exposure, the mean number of total leukocytes measured in treated rats
was significantly increased compared to controls. No significant changes were observed in
numbers of lymphocytes or polymorphonuclear-lymphocyte ratio. Although specific data are not
reported, Nau (1966) states that there were no significant gross or microscopic changes or
changes in bone marrow observed in rats exposed to 540-ppm «-decane for 91 days. Organ
weight results are not reported.
The only changes associated with exposure to //-decane in rats reported in this study are
increased body weight and altered total leukocyte counts (decreased at 57 days, increased at
91 days) (Nau, 1966). Neither of these changes was considered toxicologically significant by the
authors. Due to the limited endpoints examined and the poor reporting of methods and results,
this study is considered inadequate for identification of effect levels.
7

-------
FINAL
9-17-2009
Table 4. Hematological Changes in Rats Following Inhalation of «-Decanea
Hematology Measure
Exposure Period
0 ppm
540 ppm
N Rats
Mean ± SD
N Rats
Mean ± SD
Total leukocytes
Preexposure
20
22,760 ± 3060
43
21,490 ±730
End of 57 days
20
21,055 ± 1610
31
17,765 ± 1600c
End of 91 daysb
17
20,510 ±2120
18
22,815 ± 1530c
Poly, leukocytes
Preexposure
20
16 ±5
43
18 ±8
End of 57 days
20
18 ±8
31
22 ±6
End of 91 daysb
17
22 ±7
18
28 ± 14
Total lymphocytes
Preexposure
20
82 ±6
43
81± 8
End of 57 days
20
81 ± 9
31
76 ±6
End of 91 daysb
17
77 ±6
18
72 ± 14
aNau, 1966
bhematology values at the end of 105 days for the control rats (0 ppm)
Significantly different from controls (p < 0.001)
Other Studies
Acute Studies
Petresa (1984) reported an acute oral LD50 value of >5000 mg/kg. The study authors
derived this value from a single dosing of 5 male and 5 female Sprague-Dawley rats by gavage
with 5000 mg/kg //-decane. During a 3-day observation period, no deaths were recorded.
Terminal necropsy findings are reported as normal. The study authors noted piloerection shortly
following treatment in all animals. External appearance and behavior appeared normal by the
end of the study.
Nau (1966) exposed 25 CFW mice for 3.75 hours to 540 ppm (3140 mg/m3) «-decane
vapor and notes that all mice survived the exposure period and through the next 24 hours
postexposure, but 4 mice died before the end of the fourth day after the exposure. Nilsen et al.
(1988) exposed 10 male Sprague-Dawley rats to //-decane near the saturation concentration at
1368 ppm (7967 mg/m3) for 8 hours and did not observe any signs of toxicity (no deaths or
adverse behavioral effects and no pathological changes), resulting in an 8-hour acute LC50 in rats
of >1368 ppm (7967 mg/m3). Carreon (2001) reported a 2-hour LC50 of 12,400 ppm
"3
(72,300 mg/m ) in mice. Based on the saturation concentration for //-decane reported by
Nilsen et al. (1988), it is unclear how the value reported in Carreon (2001) was achieved, and
details of the methodology used to derive the 2-hour LC50 value of 12,400 ppm (72,300 mg/m )
are unavailable. Thus, confidence in the 2-hour LC50 value is low.
8

-------
FINAL
9-17-2009
Dermal Studies
Nau (1966) applied 0.1 to 0.15 g of «-decane to the skin of 65 male C3H mice 3 times per
week on alternate days for a total of 16.53 g per mouse over the course of approximately 150
applications. The mice demonstrated gross and microscopic evidence of skin irritation and
kidney and lung hemorrhage, pigmentation, and inflammation. The study authors observed no
significant changes in body weight gain or hematology, and they reported no skin tumors.
Absorption through the skin is negligible; studies have shown that alkanes having eight or more
carbons penetrate the skin with difficulty (Tsuruta, 1982).
Toxicokinetics
Zahlsen et al. (1992) studied the inhalation kinetics of «-decane by exposing male
Sprague-Dawley rats to an average of 100 ppm for 3 consecutive days and measuring the
concentration in blood, brain, liver, kidney, and peripheral fat. The study authors concluded that
//-alkanes show very low concentrations in the blood, but //-alkanes do have relatively elevated
concentrations in the brain and exhibit a potential for accumulation in fat with repeated
exposures. The acute neurotoxicity study described below (TNO, 1999) reports that the
concentration of //-decane in the brain was approximately 12- to 23-fold higher than the
concentration in blood following a single 8-hour exposure. This is corroborated by
Lammers et al. (2007), which studied blood and brain levels of //-decane after inhalation
exposure to white spirits (nondearomatized). The brain:blood ratio was 15 for a single 8-hour
exposure (ratio not dose dependent) and 16 after 3 consecutive days of 8-hour exposures (ratio
not dose dependent). The blood levels of human subjects were similar to that of rats exposed to
similar concentrations (adjusted for slight differences in dosing). Peak blood concentrations in
the Lammers et al. (2007) study decrease after the initial exposures, which is consistent with the
explanation that exposures induce metabolism in the treated animals. A physiologically based
pharmacokinetic (PBPK) model (for inhalation exposures [not oral]) exists (Hissink et al., 2007)
for «-decane that allows predictions of blood, expired air, and brain levels. The model predicts
an //-decane level that is 20% lower in the human brain than the rat brain at a dose near the
no-effect level for inhalation exposures.
Neurotoxicity
TNO (1999) exposed rats for 8 hours each day for 3 successive days to «-decane at
concentrations of 85, 260, and 860 ppm (0.5, 1.5, and 5 g/m respectively). The study authors
evaluated the rats for neurobehavioral changes including functional observational battery (gait,
arousal and convulsive behavior, sensory reactivity, grip strength, and landing foot splay)
immediately prior to exposure, and 30 minutes after exposure on each of the 3 days and 24 hours
after the last exposure. In a separate study, the study authors evaluated response speed and
accuracy in separate groups of rats using a discrete trial operant visual discrimination task
(water-deprived rats were trained to depress the lever to obtain a reward). //-Decane treatment
produced a small reduction in forelimb—but not hind limb—grip strength at the top
concentration. This decrease was noted only after the third day of exposure. The effect was not
apparent 24 hours after the last exposure. There was also a temporal, but not dose-related,
decrease in the visual discrimination test. All effects were normal on the day following
exposure, suggesting that there was no cumulative neurotoxic effect. The NOAEL for
"3
behavioral effects is reported to be 1.5 g/m . In the Maraschin et al. (1995) rat subchronic oral
study of commercial decane, startle reflex, an open field test, and forelimb grip strength were
examined. The study authors reported no effects at any dose up to 1000 mg/kg-day.
9

-------
FINAL
9-17-2009
Mutagenicity
Genotoxicity studies summarized by ACCVC (2004) indicate that the potential for
//-decane to induce any significant mutagenic or cytogenetic activity is low. n-Decane produced
uniformly negative results in bacteria assays—including negative results in TA1535, 1537, 97,
98, and 100 ± S9 (rat, hamster) (Petresa, 1985; Zeiger, 1992). Negative results have also been
obtained in mammalian systems including gene mutation studies in Chinese hamster lung
V79 cells, both with or without metabolic activation (enhanced mutant frequency of
methylazoxy-methanol (Lankas et al., 1978), and in cytogenetic studies involving chromosomal
aberrations with or without metabolic activation (Sasol Italy, 1994) in V79 Chinese hamster lung
cells in vitro. «-Decane also failed to induce DNA adducts in P-32 postlabeling studies in the
skin of treated mice (Shell, 1998). In the mouse micronuclei assay, mice given up to 5.0 g/kg in
corn oil gavage showed no increase in micronuclei/PCE in bone marrow (ExonMobil Biomedical
Science Inc., 1991). One additional in vitro study on V79 Chinese hamster cells showed that n-
decane, as a component of mineral spirits, could be considered a tumor promoter because the
frequency of mutations caused by methylazoxymethanol, a complete carcinogen in several
species, increased in the presence of «-decane (ATSDR, 1995). This however, appears to be
related to its efficacy as a solvent and primary irritant (see text below).
Carcinogenicity
Little information is available on the carcinogenic potential for //-decane. //-Decane did
not produce skin tumors when tested alone in initiation/promotion studies conducted in mice
(Van Duuren and GoldSchmitt, 1976). //-Decane does not promote morphological
transformation or inhibit intercellular communication in primary Syrian hamster embryo cells in
culture (Rived et al., 1992).
There is, however, evidence for a cocarcinogenic effect with some agents. Bingham and
Nord (1977) compared the effects of repeated topical applications to mice of 3 //-paraffins
(//-decane, //-dodecane, and //-tetradecane) on the carcinogenic potential of UV light at
3 wavelength regions: 254 nm, 290-320 nm, and greater than 350 nm. All three //-alkanes had a
cocarcinogenic effect at 254 nm, whereas only //-dodecane was effective from 290 to 320 nm.
Radiation at wavelengths longer than 350 nm, generally considered noncarcinogenic, produced
tumors on the backs of mice treated with //-decane or //-tetradecane. According to Horton et al.
(1957) //-decane can also act as a cocarcinogen with agents such as 3-methylcholanthrene or
benzo[a]pyrene. For example, solutions of polycyclic carcinogens in solvents having long-chain
structures (e.g., w-dodecane and dodecylbenzene) induce tumors of the skin of mice at a much
higher rate for a given concentration of carcinogen than do solutions in hydrocarbon solvents of
lower molecular weight. Solutions in such accelerating solvents also show an unusual capacity to
spread upon the skin. An additional study, Nessel et al. (1999), provides evidence that the
skin-tumor-promoting effects of C10-C14 normal alkanes is secondary to skin irritation by
showing that undiluted C10-C14 alkanes produced irritation and significant increases in tumor
incidence in dimethylbenzanthracene pretreated mice. When applied in mineral oil diluent, skin
irritation was ameliorated and tumor incidence dropped to an insignificant level. The available
evidence indicates that these solvents, when free of polycyclic impurities, are not carcinogenic
for the skin of mice, although they are primary irritants.
10

-------
FINAL
9-17-2009
FEASIBILITY OF DERIVING OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfD VALUES FOR n-DECANE
Sasol NA (1995) is the only study located that reports data on the toxicity of //-decane
following repeated oral exposure. As this study was not reported in the peer-reviewed literature,
but rather as an industry study reported to EPA, any reference values derived from it must be
used only as screening values (see Appendix).
FEASIBILITY OF DERIVING PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfC VALUES FOR n-DECANE
Nau (1966) is the only study that reports data on the subchronic inhalation toxicity of
//-decane. This is a poorly reported study that features investigation of limited endpoints. The
only reported changes (increased body-weight gain and variable alterations in total leukocyte
count) were not considered to be toxicologically significant. Thus, this study is inadequate to
identify a point of departure for derivation of p-RfC values.
PROVISIONAL CARCINOGENICITY ASSESSMENT
FOR n-DECANE
Weight-of-Evidence Descriptor
Studies evaluating the carcinogenic potential of oral or inhalation exposure to //-decane in
humans or animals are not available. Mutagenicity data suggest that the potential for //-decane to
induce any significant mutagenic or cytogenetic activity is low. Under the 2005 Guidelines for
Carcinogen Risk Assessment (U.S. EPA, 2005), there is "Inadequate Information to Assess the
Carcinogenic Potential" of //-decane.
Quantitative Estimates of Carcinogenic Risk
The lack of suitable data precludes derivation of quantitative estimates of cancer risk.
REFERENCES
ACCVC (American Chemistry Council n-Alkane VCCEP Consortium). 2004. Voluntary
children's chemical evaluation program (VCCEP) tier 1 pilot submission on the //-alkane
category: decane, undecane, dodecane (CAS Nos. 124-18-5, 1120-21-4, 112-40-3). Docket
Number OPPTS-00274D.
ACGIH (American Conference of Governmental Industrial Hygienists). 2007. 2007 Threshold
limit values for chemical substances and physical agents and biological exposure indices.
ACGIH, Cincinnati, OH.
11

-------
FINAL
9-17-2009
ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological profile for
Stoddard solvent. U.S. Department of Health and Human Services, Public Health Service.
Online, http://www.atsdr.cdc.gov/toxprofiles/tp79.html.
ATSDR (Agency for Toxic Substances and Disease Registry). 1999. Toxicological profile for
total petroleum hydrocarbons (TPH). U.S. Department of Health and Human Services, Public
Health Service. Online, http://www.atsdr.cdc.gov/toxprofiles/tpl23.pdf.
ATSDR (Agency for Toxic Substances and Disease Registry). 2008. Toxicological profile
information sheet. U.S. Department of Health and Human Services, Public Health Service.
Online, http://www.atsdr.cdc.gov/toxpro2.html.
Bingham, E. and P.J. Nord. 1977. Cocarcinogenic Potential of //-alkanes and ultraviolet light on
mice. J. Natl. Cancer Inst. 58(4): 1099-1101.
Carreon, T. 2001. Aliphatic hydrocarbons. In: Patty's industrial hygiene and toxicology.
G.D. Clayton and F.E. Clayton, (ed.). New York, NY: John Wiley and Sons.
ExxonMobil Biomedical Science Inc. 1991. 90—day Subchronic and Chronic Oral Toxicity
Study in Rats. Study Nos. 158270 and 186870. (Unpublished report—summarized in VCCEP
«-alkane Appendix B, 2004).
Grice, 1988. Safety evaluation of butylated hydroxytoluene from the perspective of effects on
forestomach and oesophageal squamous epithelium. Food Chem Toxicol. Aug 26(8):717-723.
Hissink A.M., J. Krase, B.N. Kulig et al. 2007. PBPK Modeling of white spirit constituents as a
tool for integrating animal and human test data. Neurotoxicology 28:751-760.
Horton, W., D.T. Denman and R.P. Trosset. 1957. Carcinogenesis of the skin: the accelerating
properties of aliphatic and related hydrocarbons. Cancer Res. 17:758-766.
IARC (International Agency for Research on Cancer). 2008. Search IARC monographs.
Online. http://monographs.iarc.fr/ENG/Monographs/allmonos90.php.
Lammers, J.H.C.M., H.H. Emmen, H. Muijser et al. 2007. Model studies for evaluating the
neurobehavioral effects of complex hydrocarbon mixtures. Neurotoxicology 28:736-750.
Lankas, G.R., C.S. Baxter and R.T. Christian. 1978. Effect of alkane tumor-promoting agents
on chemically induced mutagenesis in cultured V79 Chinese hamster cells. J. Toxicol. Environ.
Health. 4:37-41. (As cited in ACCVC, 2004).
Maraschin, R., L. Comotto and A. Conz. 1995. LINPAR 10: Combined repeated-dose toxicity
study with the reproduction/developmental screening test in Crl:CD (SD) BR male and female
rats, Sprague Dawley rats of the test article LINPAR 10 administered by oral route at the dosages
of 0, 25, 150 and 1000 mg/kg/day. Report of Medici del Vascello. 20138- Milano (Italy),
Instituto di Ricerche Biomediche "Antoine Marxer" RBM S.p. A. for the Enichem Augusta
Industriale (Currently Sasol Italy). (Cited as an unpublished report provided as a robust
summary RPTD-2 in n-Alkane VCCEP Submission June 2004).
12

-------
FINAL
9-17-2009
Nau, C.A. 1966. C9-C12 fractions obtained from petroleum distillates: An evaluation of their
potential toxicity. Arch. Environ. Health. 12:382-393.
Nessel, C., J., Freeman, R. Forgash, and R. McKee. 1999. The role of dermal irritation in the
skin tumor promoting activity of petroleum middle distillates. Toxicol. Sci. 49:48-55.
Nilsen, O.G., O.A. Haugen, K. Zahlsen et al. 1988. Toxicity of n-C9 to n-C13 alkanes in the rat
on short term inhalation. Pharmacol. Toxicol. 62:259-266. (Cited as a robust summary ACTI-2
in «-Alkane VCCEP Submission June 2004).
NIOSH (National Institute for Occupational Safety and Health). 2008. NIOSH Pocket Guide to
Chemical Hazards. Index by CASRN. Online, http://www2.cdc.gov/nioshtic-2/nioshtic2.htm.
NTP (National Toxicology Program). 2004. NTP technical report on the toxicology and
carcinogenesis studies of Stoddard solvent IIC (CAS No. 64742-88-7) in F344/N rats and
B6C3F1 mice (inhalation studies). U.S. Department of Health and Human Services, Public
Health Service, National Institutes of Health, Research Triangle Park, NC. September 2004.
NTP (National Toxicology Program). 2005. 11th Report on carcinogens. U.S. Department of
Health and Human Services, Public Health Service, National Institutes of Health, Research
Triangle Park, NC. Online, http://ntp-server.niehs.nih.gov.
NTP (National Toxicology Program). 2008. Management Status Report. Online, http://
ntp.niehs.nih.gov/index.cfm?objectid=78CC7E4C-FlF6-975E-72940974DE301C3F.
OSHA (Occupational Safety and Health Administration). 2008. OSHA standard 1910.1000
table Z-l. Part Z, toxic and hazardous substances. Online, http://www.osha-slc.gov/
OshStd data/1910 1000 TABLE Z-l.html.
Petresa (Petroquimia Espanola S.A.). 1984. Acute oral toxicity to rats of Petrepar® n-CIO
(C10). (Cited as a robust summary ACTO-1 in n-Alkane VCCEP Submission June 2004).
Petresa (Petroquimia Espanola S.A.). 1985. Ames metabolic activation test to assess the
potential mutagenic effect of PETREPAR C10 (1-decane). Huntingdon Research Centre, Ltd.
(Cited as a robust summary GTVT-3 in n-Alkane VCCEP Submission June 2004).
Rivedal E., S.O. Mikalsen, L.E. Roseng, T. Sanner and I. Eide. 1992. Effects of hydrocarbons
on transformation and intercellular communication in Syrian hamster embryo cells. Laboratory
for Environmental and Occupational Cancer, Norwegian Radium Hospital, Montebello, Oslo.
Pharmacol Toxicol. 71(1):57—61.
Sasol Italy (Enichem Augusta). 1994. Study of the capacity of the test article LINPAR 10 to
induce chromosome aberrations in V79 Chinese hamster lung cells. (Cited as a robust summary
GTVT-4 in n-Alkane VCCEP Submission June 2004).
Sasol NA. 1995. Initial submission: Combined repeated dose toxicity study w/the reproductive/
developmental toxicity screening test in rats by oral route, with cover letter dated 121801.
TSCATS Section 8E. OTS0574257.
13

-------
FINAL
9-17-2009
Shell Chemicals Europe. 1998. Toxicology report C.A. 98.20387. «-Decane and «-dodecane:
DNA adduct detection in mouse skin exposed in vivo, using the 32P-postlabeling test. Shell
Research and Technology Centre, Amsterdam. (As cited in ACCVC 2004).
Staats, D.A. 1994. Development of a human health oral risk factor for long chain petroleum
hydrocarbons. Report prepared by Staats Creative Sciences for Armstrong Laboratory,
Occupational and Environmental Health Directorate, Toxicology Division, Human Systems
Center, Air Force Materiel Command, Wright-Patterson AFB, OH. AL/OE-TR-1995-0007.
October 1994.
TNO Nutrition and Food Research Institute. 1999. Model studies for evaluating the behavioral
effects of petroleum solvents and the role of toxicokinetic factors: the effects of //-decane on
behavior in the rat. TNO Nutrition and Food Research Institute. Project No. 804518/014.
(Cited as an unpublished report provided as a robust summary Other-2 in n-Alkane VCCEP
Submission June 2004).
Tsuruta, H. 1982. Percutaneous absorption of organic solvents. III. On the penetration rates of
hydrophobic solvents through the excised rat skin. Ind. Health. 20:335-345.
U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. Prepared by
the Office of Research and Development, National Center for Environmental Assessment,
Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC. July.
EPA/540/R-97/036. NTIS PB97-921199.
U.S. EPA. 2005. Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection
Agency, Risk Assessment Forum, Washington, DC. EPA/630/P-03/001B. Online. http://www.
thecre.com/pdf/20050404 cancer.pdf.
U.S. EPA. 2006. Edition of the Drinking Water Standards and Health Advisories. Office of
Water, Washington, DC. EPA 822-R-06-013. Online, http://www.epa.gov/waterscience/
drinkina/standards/dwstandards.pdf.
U.S. EPA. 2008. Integrated Risk Information System (IRIS). Online. Office of Research and
Development, National Center for Environmental Assessment, Washington, DC.
http ://www. epa. gov/iris/.
Van Duuren, B.L. and B.M. Goldshmidt. 1976. Cocarcinogenic and tumor-promoting agents in
tobacco carcinogenesis. J. Natl. Cancer Inst. 56(6): 1237-1242.
Wester P.W., Kroes R. 1988. Forestomach carcinogens: Pathology and relevance to man.
Toxicol. Pathol. (1988) 16(2): 168-171.
14

-------
FINAL
9-17-2009
WHO (World Health Organization). 2008. Online catalogs for the Environmental Health
Criteria Series. Online, http://www.who.int/ipcs/publications/ehc/ehc alphabetical/en/
index.html.
Zahlsen, K., I. Eide, A.M. Nilsen et al. 1992. Inhalation kinetics of C6-C10 aliphatic, aromatic
and naphthenic hydrocarbons in rat after repeated exposures. Pharmacol. Toxicol.
71(2): 144-149.
Zeiger, E., B. Anderson, S. Haworth et al. 1992. Salmonella mutagenicity tests: V. Results
from the testing of 311 chemicals. Environ. Mol. Mutagen. 19(Suppl 21):2—13. (Cited as a
robust summary GTVT-2 in n-Alkane VCCEP Submission June 2004).
15

-------
FINAL
9-17-2009
APPENDIX. DERIVATION OF A SCREENING p-RfD VALUE
FOR n-DECANE (CASRN 124-18-5)
For reasons noted in the main PPRTV document, it is inappropriate to derive provisional
toxicity values for //-decane. However, information is available for this chemical which,
although insufficient to support derivation of a provisional oral or inhalation toxicity values,
under current guidelines, may be of limited use to risk assessors. In such cases, the Superfund
Health Risk Technical Support Center summarizes available information in an Appendix and
develops a "screening value." Appendices receive the same level of internal and external
scientific peer review as the PPRTV documents to ensure their appropriateness within the
limitations detailed in the document. Users of screening toxicity values in an appendix to a
PPRTV assessment should understand that there is considerably more uncertainty associated
with the derivation of an appendix screening toxicity value than for a value presented in the body
of the assessment. Questions or concerns about the appropriate use of screening values should
be directed to the Superfund Health Risk Technical Support Center.
Sasol NA (1995) is the only study located that reports data on the toxicity of //-decane
following repeated oral exposure. As this study was not reported in the peer-reviewed literature,
but rather as an industry study reported to EPA, any reference values derived from it must be
used only as screening values. This study found hyperplastic changes of the nonglandular
mucosa of the stomach in male and female rats treated by daily gavage with commercial
//-decane (approximately 97% //-decane) for 4-8 weeks. The effects were not statistically
significant although there was a trend. No other systemic effects are reported. Although there is
some indication of reduced fertility in treated rats, the differences from controls are not
statistically significant, the observations are not clearly related to dose, and there are no
corresponding histological changes in the reproductive organs. Therefore, a NOAEL of
1000 mg/kg-day, the highest dose tested, is identified for repeated-dose toxicity in this study.
Screening Subchronic p-RfD Value
Although the duration of oral exposure in the Sasol NA (1995) study is only 4-8 weeks,
10 rats of each sex were tested at multiple doses and evaluated for multiple endpoints, as
described above. The NOAEL of 1000 mg/kg-day in rats from Sasol NA (1995) is used to
calculate a screening subchronic value for //-decane. The only other data regarding oral toxicity
of //-decane come from an acute study that derived an LD50 value of >5000 mg/kg based on the
absence of mortality in rats treated with a single dose of «-decane at 5000 mg/kg (Petresa, 1984).
A screening subchronic screening p-RfD of 1 mg/kg-day is derived by dividing the
NOAEL of 1000 mg/kg-day by an UF of 1000, as shown below:
Screening Subchronic p-RfD Value = NOAEL ^ composite UF
= 1000 mg/kg-day -H000
= 1.0 mg/kg-day
16

-------
FINAL
9-17-2009
The composite UF of 1000 encompasses the following:
•	A UF of 10 is applied for interspecies extrapolation to account for potential
pharmacodynamic and pharmacokinetic differences between rodents and humans.
•	A UF of 10 is applied for intraspecies differences to account for potentially
susceptible individuals in the absence of quantitative information or information
on the variability of response in humans.
•	A UF of 10 is applied for database insufficiencies. A single, short-term-oral
toxicity study in one animal species (rat) is available (Sasol NA, 1995). Although
the principal study (Sasol NA, 1995) did evaluate systemic, neurological,
reproductive, and developmental effects, the database lacks studies of subchronic
and chronic toxicity, a study in another species, a supporting developmental
toxicity study, and a multigenerational reproduction study.
Confidence in the principal study (Sasol NA, 1995) is moderate because, despite
investigation of multiple endpoints at multiple dose levels with sample sizes of 10 rats/sex/dose,
the experiment only lasted 4 to 8 weeks depending on the sex of the rat. Confidence in the
database is low because the data set includes only short-term and acute animal studies.
Reflecting medium confidence in the principal study and low confidence in the database,
confidence in the subchronic value is low to medium.
Screening Chronic Value
A chronic p-RfD is not derived from the previous data due to the lack of any data on the
effects of longer-term exposure. The only repeated-dose oral study is the 4-8 week study in rats
(Sasol NA, 1995), which is used to derive the subchronic screening value. While repeat dosing
induces metabolism, and blood and brain levels decline relatively quickly, the compound does
partition to fat, and levels there accumulate with time in repeat dosing experiments
(Lammers et al., 2007).
17

-------