United States
kS^laMIjk Environmental Protection
^J^iniiil m11 Agency
EPA/690/R-15/005F
Final
7-30-2015
Provisional Peer-Reviewed Toxicity Values for
1 -Chlorooctadecane
(CASRN 3386-33-2)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Dan D. Petersen, PhD. DABT
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY
National Center for Environmental Assessment, Cincinnati, OH
This document was externally peer reviewed under contract to
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the contents of this document may be directed to the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center (513-569-7300).

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TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS AND ACRONYMS	iv
BACKGROUND	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVs	 1
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (NONCANCER AND CANCER)	4
DERIVATION 01 PROVISIONAL VALUES	4
DERIVATION 01 ORAL REFERENCE DOSES	4
Feasibility of Deriving Subchronic and Chronic p-RfDs	4
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS	4
Feasibility of Deriving Subchronic and Chronic Provisional Reference Concentrations
(p-RfCs)	4
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR	4
MODE-OF-ACTION (MOA) DISCI SSION	5
ALTERNATIVE METHODS	5
REFERENCES	6

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COMMONLY USED ABBREVIATIONS AND ACRONYMS
a2u-g
alpha 2u-globulin
MN
micronuclei
ACGIH
American Conference of Governmental
MNPCE
micronucleated polychromatic

Industrial Hygienists

erythrocyte
AIC
Akaike's information criterion
MOA
mode of action
ALD
approximate lethal dosage
MTD
maximum tolerated dose
ALT
alanine aminotransferase
NAG
N-acetyl-P-D-glucosaminidase
AST
aspartate aminotransferase
NCEA
National Center for Environmental
atm
atmosphere

Assessment
ATSDR
Agency for Toxic Substances and
NCI
National Cancer Institute

Disease Registry
NOAEL
no-observed-adverse-effect level
BMD
benchmark dose
NTP
National Toxicology Program
BMDL
benchmark dose lower confidence limit
NZW
New Zealand White (rabbit breed)
BMDS
Benchmark Dose Software
OCT
ornithine carbamoyl transferase
BMR
benchmark response
ORD
Office of Research and Development
BUN
blood urea nitrogen
PBPK
physiologically based pharmacokinetic
BW
body weight
PCNA
proliferating cell nuclear antigen
CA
chromosomal aberration
PND
postnatal day
CAS
Chemical Abstracts Service
POD
point of departure
CASRN
Chemical Abstracts Service Registry
PODadj
duration-adjusted POD

Number
QSAR
quantitative structure-activity
CBI
covalent binding index

relationship
CHO
Chinese hamster ovary (cell line cells)
RBC
red blood cell
CL
confidence limit
RDS
replicative DNA synthesis
CNS
central nervous system
RfC
inhalation reference concentration
CPN
chronic progressive nephropathy
RfD
oral reference dose
CYP450
cytochrome P450
RGDR
regional gas dose ratio
DAF
dosimetric adjustment factor
RNA
ribonucleic acid
DEN
diethylnitrosamine
SAR
structure activity relationship
DMSO
dimethylsulfoxide
SCE
sister chromatid exchange
DNA
deoxyribonucleic acid
SD
standard deviation
EPA
Environmental Protection Agency
SDH
sorbitol dehydrogenase
FDA
Food and Drug Administration
SE
standard error
FEV1
forced expiratory volume of 1 second
SGOT
glutamic oxaloacetic transaminase, also
GD
gestation day

known as AST
GDH
glutamate dehydrogenase
SGPT
glutamic pyruvic transaminase, also
GGT
y-glutamyl transferase

known as ALT
GSH
glutathione
SSD
systemic scleroderma
GST
glutathione-S-transferase
TCA
trichloroacetic acid
Hb/g-A
animal blood-gas partition coefficient
TCE
trichloroethylene
Hb/g-H
human blood-gas partition coefficient
TWA
time-weighted average
HEC
human equivalent concentration
UF
uncertainty factor
HED
human equivalent dose
UFa
interspecies uncertainty factor
i.p.
intraperitoneal
UFh
intraspecies uncertainty factor
IRIS
Integrated Risk Information System
UFS
subchronic-to-chronic uncertainty factor
IVF
in vitro fertilization
UFd
database uncertainty factor
LC50
median lethal concentration
U.S.
United States of America
LD50
median lethal dose
WBC
white blood cell
LOAEL
lowest-observed-adverse-effect level


iv

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PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
1-CHLOROOCTADECANE (CASRN 3386-33-2)
BACKGROUND
A Provisional Peer-Reviewed Toxicity Value (PPRTV) is defined as a toxicity value
derived for use in the Superfund Program. PPRTVs are derived after a review of the relevant
scientific literature using established Agency guidance on human health toxicity value
derivations. All PPRTV assessments receive internal review by a standing panel of National
Center for Environment Assessment (NCEA) scientists and an independent external peer review
by three scientific experts.
The purpose of this document is to provide support for the hazard and dose-response
assessment pertaining to chronic and subchronic exposures to substances of concern, to present
the major conclusions reached in the hazard identification and derivation of the PPRTVs, and to
characterize the overall confidence in these conclusions and toxicity values. It is not intended to
be a comprehensive treatise on the chemical or toxicological nature of this substance.
The PPRTV review process provides needed toxicity values in a quick turnaround
timeframe while maintaining scientific quality. PPRTV assessments are updated approximately
on a 5-year cycle for new data or methodologies that might impact the toxicity values or
characterization of potential for adverse human health effects and are revised as appropriate. It is
important to utilize the PPRTV database flittp://hhpprtv.ornl.gov) to obtain the current
information available. When a final Integrated Risk Information System (IRIS) assessment is
made publicly available on the Internet (http://www.epa.eov/iris). the respective PPRTVs are
removed from the database.
DISCLAIMERS
The PPRTV document provides toxicity values and information about the adverse effects
of the chemical and the evidence on which the value is based, including the strengths and
limitations of the data. All users are advised to review the information provided in this
document to ensure that the PPRTV used is appropriate for the types of exposures and
circumstances at the site in question and the risk management decision that would be supported
by the risk assessment.
Other U.S. Environmental Protection Agency (EPA) programs or external parties who
may choose to use PPRTVs are advised that Superfund resources will not generally be used to
respond to challenges, if any, of PPRTVs used in a context outside of the Superfund program.
QUESTIONS REGARDING PPRTVs
Questions regarding the contents and appropriate use of this PPRTV assessment should
be directed to the EPA Office of Research and Development's National Center for
Environmental Assessment, Superfund Health Risk Technical Support Center (513-569-7300).
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INTRODUCTION
1-Chlorooctadecane (CASRN 3386-33-2) is a high production volume chemical used as a
solvent and an intermediate in the manufacture of surfactant, pharmaceuticals, and other organic
compounds. The molecular formula of 1-chlorooctadecane is CH3(CH2)i7Cl (see Figure 1). A
list of physicochemical properties is provided in Table 1.
Figure 1. 1-Chlorooctadecane (CASRN 3386-33-2) Structure
Table 1. Physicochemical Properties of 1-Chlorooctadecane (CASRN 3386-33-2)a
Property (Unit)
Value
Boiling point (C)
348
Melting point (C)
28.6
Density (g/cm3 at 20C)
ND
Vapor pressure (mm Hg at 25C)
1.71 x 10"5
pH (unitless)
ND
Solubility in water (mg/L at 25 C)
1.25 x 1(T4
Relative vapor density (air = 1)
ND
Molecular weight (g/mol)
288.943
TliemTDnliis (2013 V
ND = no data.
Table 2 provides a summary of available toxicity values for 1-chlorooctadecane
from EPA and other regulatory agencies or organizations.
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Table 2. Summary of Available Toxicity Values for
1-Chlorooctadecane (CASRN 3386-33-2)
Sou rce/Parameterab
Value (Applicability)
Reference
Noncancer
ACGIH
NA
ACGIH (2013)
ATSDR
NA
ATSDR (2013)
Cal/EPA
NA
(Cal/EPA); Cal/EPA (2014)c
NIOSH
NA
NIOSH (2010)
OSHA
NA
OSHA (2011); OSHA (2006)
IRIS
NA
(U.S. EPA)
DWSHA
NA
U.S. EPA (2012a)
HEAST
NA
U.S. EPA (2011)
CARA HEEP
NA
U.S. EPA (1994)
WHO
NA
(WHO)
Cancer
IRIS
NA
(U.S. EPA)
HEAST/WOE
NA
U.S. EPA (2011)
IARC
NA
(IARC)
NTP
NA
NTP (2014)
Cal/EPA
NA
(Cal/EPA): Cal/EPA (2015a): Cal/EPA (2011)
aSources: ACGIH = American Conference of Governmental Industrial Hygienists; ATSDR = Agency for Toxic
Substances and Disease Registry; Cal/EPA = California Environmental Protection Agency; CARA = Chemical
Assessments and Related Activities; DWSHA = Drinking Water Standards and Health Advisories; HEAST =
Health Effects Assessment Summary Tables; HEEP = Health and Environmental Effects Profile; IARC =
International Agency for Research on Cancer; IRIS = Integrated Risk Information System; NIOSH = National
Institute for Occupational Safety and Health; NTP = National Toxicology Program; OSHA = Occupational
Safety and Health Administration; WHO = World Health Organization.
' Parameters: Cancer weight of evidence (WOE) (U.S. EPA. 1986).
The Cal/EPA Office of Environmental Health Hazard Assessment (OEHHA) Toxicity Criteria Database
(httn://oehha.ca.gov/tcdb/index.asp) was also reviewed and found to contain no information on
1 -chlorooctadecane.
NA = not available.
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Literature searches were conducted on sources published from 1900 through
February 2015 for studies relevant to the derivation of provisional toxicity values for
1-chlorooctadecane (CASRN 3386-33-2). The following databases were searched by chemical
name, synonyms, or CASRN: ACGIH, ANEUPL, AT SDR, BIOSIS, Cal/EPA, CCRIS, CD AT,
ChemlDplus, CIS, CRISP, DART, EMIC, EPIDEM, ETICBACK, FEDRIP, GENE-TOX,
HAPAB, HERO, HMTC, HSDB, IARC, INCHEM IPCS, IP A, ITER, IUCLID, LactMed,
NIOSH, NTIS, NTP, OSHA, OPP/RED, PESTAB, PPBIB, PPRTV, PubMed
(toxicology subset), RISKLINE, RTECS, TOXLINE, TRI, U.S. EPA IRIS, U.S. EPA HEAST,
U.S. EPA HEEP, U.S. EPA OW, and U.S. EPA TSCATS/TSCATS2. The following databases
were searched for toxicity values or exposure limits: ACGIH, ATSDR, Cal EPA, U.S. EPA IRIS,
U.S. EPA HEAST, U.S. EPA HEEP, U.S. EPA OW, U.S. EPA TSCATS/TSCATS2, NIOSH,
NTP, OSHA, and RTECS.
REVIEW OF POTENTIALLY RELEVANT DATA
(NONCANCER AND CANCER)
The available data on 1-chlorooctadecane primarily focuses on its biodegradation,
biotransformation by marine creatures, incorporation into the fatty acids of microorganisms, and
usage in the development of analytical methods. No usable information is available regarding
repeated-dose oral or inhalation exposure of humans or animals to 1-chlorooctadecane.
DERIVATION OF PROVISIONAL VALUES
DERIVATION OF ORAL REFERENCE DOSES
Feasibility of Deriving Subchronic and Chronic p-RfDs
No sub chronic-duration, chronic-duration, developmental toxicity, reproductive toxicity,
or carcinogenicity studies on 1-chlorooctadecane via the oral route were identified. Thus, no oral
reference doses could be derived. However, as noted below, a computational toxicological
surrogate approach was attempted.
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS
Feasibility of Deriving Subchronic and Chronic Provisional Reference Concentrations
(p-RfCs)
No sub chronic-duration, chronic-duration, developmental toxicity, reproductive toxicity,
or carcinogenicity studies on 1-chlorooctadecane via the inhalation route were identified. Thus,
no inhalation reference doses could be derived. However, as noted below, a computational
toxicological surrogate approach was attempted.
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR
Limitations in the available data preclude development of a weight-of-evidence (WOE)
descriptor.
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MODE-OF-ACTION (MOA) DISCUSSION
Limitations in the available data preclude determination of a mode-of-action (MOA)
discussion.
ALTERNATIVE METHODS
The surrogate approach allows for the use of data from related compounds to calculate
screening values when data for the compound of interest are limited or unavailable. Details
regarding searches and methods for surrogate analysis are presented in Wang et al. (2012). Three
types of potential surrogates (structural, metabolic, and toxicity) are identified to facilitate the final
surrogate chemical selection. The surrogate approach may or may not be route-specific or applicable
to multiple routes of exposure. All information was considered together as part of the final
weight-of-evidence (WOE) approach to select the most suitable surrogate both toxicologically and
chemically.
An initial surrogate search focused on the identification of structurally similar chemicals with
toxicity values from the Integrated Risk Information System (IRIS), PPRTV, and Health Effects
Assessment Summary Tables (HEAST) databases to take advantage of the well-characterized
chemical-class information. This was accomplished by searching the US EPA's DSSTox database
(DSSTox. 2012) at similarity levels >60%, and the National Library of Medicine's ChemID/;/.v
database (ChemlDplus. 2013) at similarity levels >80%. There were 20 compounds identified in
DSSTox and 76 compounds identified in ChemlDp/ws, for a total of 69 unique compounds. The
larger number of compounds identified in ChemID/;///.s largely reflects its inclusion of other
halogen substituted (fluorinated or brominated) compounds. However, there was no in vivo
repeated-dose information on any of these related compounds. Due to a lack of repeat-dose
toxicity information for any of the potential structural surrogates, derivation of risk values
(e.g., RfD, RfC, and oral cancer slope factor) based on the computational toxicological surrogate
approach (Wane et al.. 2012) is not feasible for 1 -chlorooctadecane.
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REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2013). 2013 TLVs and
BEIs. Based on documentation of the threshold limit values for chemical substances and
physical agents and biological exposure indices. Cincinnati, OH.
AT SDR (Agency for Toxic Substances and Disease Registry). (2013). Minimal risk levels
(MRLs) for hazardous substances. Atlanta, GA: Agency for Toxic Substances and
Disease Registry (ATSDR). Retrieved from http://www.atsdr.cdc.gov/mrls/index.asp
Cal/EPA (California Environmental Protection Agency). (201 1). Hot spots unit risk and cancer
potency values. Appendix A. Sacramento, CA: Office of Environmental Health Hazard
Assessment, http://www.oehha.ca.gov/air/hot spots/2009/AppendixA.pdf
Cal/EPA (California Environmental Protection Agency). (2014). All OEHHA acute, 8-hour and
chronic reference exposure levels (chRELs) as of June 2014. Sacramento, CA: Office of
Health Hazard Assessment, http://www.oehha.ca.gov/air/allrels.html
Cal/EPA (California Environmental Protection Agency). (2015a). Chemicals known to the state
to cause cancer or reproductive toxicity, May 11, 2015. Proposition 65 list. Sacramento,
CA: Office of Environmental Health Hazzard Assessment.
http://oehha.ca.gov/prop65/prop65 list/Newlist.html
Cal/EPA (California Environmental Protection Agency). (2015b). OEHHA toxicity criteria
database [Database], Sacramento, CA: Office of Environmental Health Hazard
Assessment. Retrieved from http://www.oehha.ca.gov/tcdb/
ChemlDplus. (2013). 1 -Chloroctadecane. Bethesda, MD: Department of Health and Human
Services, National Library of Medicine. Retrieved from
http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.isp
DSSTox (Distributed Structure-Searchable Toxicity). (2012). DSSTox database network.
Washington, DC: U.S. Environmental Protection Agency, National Center for
Computational Toxicology. Retrieved from http://www.epa.gov/ncct/dsstox/
I ARC (International Agency for Research on Cancer). (2015). I ARC Monographs on the
evaluation of carcinogenic risk to humans. Available online at
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NIOSH (National Institute for Occupational Safety and Health). (2010). N10SH pocket guide to
chemical hazards. Index of chemical abstracts service registry numbers (CAS No.).
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id=10286
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U.S. EPA (U.S. Environmental Protection Agency). (1986). Guidelines for carcinogen risk
assessment [EPA Report], (EPA/630/R-00/004). Washington, DC: U.S. Environmental
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