United States
Environmental Protection
1=1 m m Agency
EPA/690/R-12/037F
Final
11-29-2012
Provisional Peer-Reviewed Toxicity Values for
Tris( 1 -chloro-2-propyl)phosphate
(CASRN 13674-84-5)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Carrie R. Fleming, PhD
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY
ICF International
9300 Lee Highway
Fairfax, VA 22031
PRIMARY INTERNAL REVIEWERS
Zheng (Jenny) Li, PhD, DABT
National Center for Environmental Assessment, Washington, DC
Suryanarayana V. Vulimiri, BVSc, PhD, DABT
National Center for Environmental Assessment, Washington, DC
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 U.S. 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
COM MOM . Y USED ABBREVIATIONS	111
BACKGROUND	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVs	1
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	3
HUMAN STUDIES	7
Oral Exposures	7
Inhalation Exposures	7
ANIMAL STUDIES	7
Oral Exposures	7
Subchronic Studies	7
Chronic Studies	9
Developmental Studies	9
Reproductive Studies	10
Carcinogenicity Studies	10
Inhalation Exposures	10
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)	10
Tests Evaluating Carcinogenicity, Genotoxicity, and/or Mutagenicity	10
Other Toxicity Studies (Exposures Other Than Oral or Inhalation)	11
Short-term Studies	11
Metabolism/Toxicokinetic Studies	13
Mode-of-Action/Mechanistic Studies	13
Immunotoxicity	13
Neurotoxicity	13
DERIVATION OI PROVISIONAL VALUES	22
DERIVATION OI ORAL REFERENCE DOSES	22
Derivation of Subchronic Provisional RfD (Subchronic p-RfD)	22
Derivation of Chronic Provisional RfD (Chronic p-RfD)	23
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS	23
CANCER WEIGHT - OF-E VIDEN CE DESCRIPTOR	23
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES	23
APPENDIX A. PROVISIONAL SCREENING VALUES	25
APPENDIX B. DATA TABLES	28
APPENDIX C. BMD OUTPUTS	33
APPENDIX D. REFERENCES	40
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COMMONLY USED ABBREVIATIONS
BMC
benchmark concentration
BMCL
benchmark concentration lower bound 95% confidence interval
BMD
benchmark dose
BMDL
benchmark dose lower bound 95% confidence interval
HEC
human equivalent concentration
HED
human equivalent dose
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
POD
point of departure
p-OSF
provisional oral slope factor
p-RfC
provisional reference concentration (inhalation)
p-RfD
provisional reference dose (oral)
RfC
reference concentration (inhalation)
RfD
reference dose (oral)
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
WOE
weight of evidence
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PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
TRIS(l-CHLORO-2-PROPYL)PHOSPHATE (CASRN 13674-84-5)
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.gov/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
Tris(l-chloro-2-propyl)phosphate (TCPP) belongs to a class of chemicals known as
trisphosphates, more specifically, aliphatic halogenated trisphosphates (NICNAS, 2001).
Trisphosphates are primarily used industrially as flame retardants, plasticizers, and solvents
(NICNAS, 2001). TCPP is used as a flame retardant in polyurethane foam (OECD, 2000).
Figure 1 provides the chemical structure for TCPP. A table of physicochemical properties is
provided below (see Table 1).
ch3
I
CH—CH2C1
O — CH—CH2C1
I
ch3
ch2ci
Figure 1. Tris(l-chloro-2-propyl)phosphate Structure
Table 1. Physicochemical Properties for TCPP (CASRN 13674-84-5)a
Property (unit)
Value
Boiling point (°C)
Not available
Melting point (°C)
-40
"3
Density (g/cm )
1.29
Vapor pressure (Pa at 25°C)
<260
pH (unitless)
Not available
Solubility in water (g/L at 20°C)
1.6
Relative vapor density (air =1)
Not available
Molecular weight (g/mol)
327.6
aNICNAS (2001).
No Reference Dose (RfD), Reference Concentration (RfC), or cancer assessment for
TCPP is included on the EPA's Integrated Risk Information System (IRIS) database (U.S. EPA,
201 la) or on the Drinking Water Standards and Health Advisories List (U.S. EPA, 2009). No
RfD or RfC values were reported in the Health Effects Assessment Summary Tables (HEAST)
(U.S. EPA, 201 lb). The Chemical Assessments and Related Activities (CARA) list did not
include a Health and Environmental Effects Profile (HEEP) for TCPP (U.S. EPA, 1994a). The
0	—
1
o — P—
H3C—CH O
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Agency for Toxic Substances and Disease Registry (ATSDR) is in the process of reviewing the
toxicity of TCPP in conjunction with other phosphate ester flame retardants, and a draft
Toxicological Profile is available (ATSDR, 2009). No minimal risk levels were reported for
TCPP due to lack of adequate information. The World Health Organization (WHO) reviewed
the toxicity of TCPP in an Environmental Health Criteria document (IPCS, 1998) and indicated
that adverse health effects are negligible due to low exposure risk. The California
Environmental Protection Agency (CalEPA, 2008, 2009) has not derived toxicity values for
exposure to TCPP. No occupational exposure limits for TCPP have been derived or
recommended by the American Conference of Governmental Industrial Hygienists
(ACGIH, 2011), proposed by the National Institute of Occupational Safety and Health (NIOSH,
2011), or adopted by the Occupational Safety and Health Administration (OSHA, 2006).
The HEAST (U.S. EPA, 201 lb) does not report a cancer weight-of-evidence (WOE)
classification or an oral slope factor for TCPP. The International Agency for Research on
Cancer (IARC, 2011) has not reviewed the carcinogenic potential of TCPP. TCPP is not
included in the 12th Report on Carcinogens (NTP, 201 lc). CalEPA (2008) has not derived a
quantitative estimate of carcinogenic potential for TCPP.
Literature searches were conducted on sources published from 1900 through
September 13, 2011 for studies relevant to the derivation of provisional toxicity values for
tris(l-chloro-2-propyl)phosphate (TCPP), CAS No. 13674-84-5. Searches were conducted using
EPA's Health and Environmental Research Online (HERO) database of scientific literature.
HERO searches the following databases: AGRICOLA; American Chemical Society; BioOne;
Cochrane Library; DOE: Energy Information Administration, Information Bridge, and Energy
Citations Database; EBSCO: Academic Search Complete; GeoRef Preview; GPO: Government
Printing Office; Informaworld; IngentaConnect; J-STAGE: Japan Science & Technology;
JSTOR: Mathematics & Statistics and Life Sciences; NSCEP/NEPIS (EPA publications
available through the National Service Center for Environmental Publications [NSCEP] and
National Environmental Publications Internet Site [NEPIS] database); PubMed: MEDLINE and
CANCERLIT databases; SAGE; Science Direct; Scirus; Scitopia; SpringerLink; TOXNET
(Toxicology Data Network): ANEUPL, CCRIS, ChemlDplus, CIS, CRISP, DART, EMIC,
EPIDEM, ETICBACK, FEDRIP, GENE-TOX, HAPAB, HEEP, HMTC, HSDB, IRIS, ITER,
LactMed, Multi-Database Search, NIOSH, NTIS, PESTAB, PPBIB, RISKLINE, TRI; and
TSCATS; Virtual Health Library; Web of Science (searches Current Contents database among
others); World Health Organization; and Worldwide Science. The following databases outside
of HERO were searched for health information: ACGIH, ATSDR, CalEPA, EPA IRIS, EPA
HEAST, EPA HEEP, EPA OW, EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS.
REVIEW OF POTENTIALLY RELEVANT DATA
(CANCER AND NONCANCER)
Table 2 provides an overview of the relevant database for TCPP and includes all
potentially relevant repeated short-term-, subchronic-, and chronic-duration studies. Principal
studies are identified. The phrase "statistical significance," used throughout the document,
indicates ap-value of <0.05.
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Table 2. Summary of Potentially Relevant Data for TCPP (CASRN 13674-84-5)
Category
Number of
Male/Female, Strain,
Species, Study Type,
Study Duration
Dosimetry"
Critical Effects
NOAEL'
BMDL/
BMCLa
LOAELa
Reference (Comments)
Notesb
Human
1. Oral (mg/kg-d)
Subchronic
ND
Chronic
ND
Developmental
ND
Reproductive
ND
Carcinogenicity
ND
2. Inhalation (mg/m3)
Subchronic
ND
Chronic
ND
Developmental
ND
Reproductive
ND
Carcinogenicity
ND
Animal
1. Oral (mg/kg-d)
Subchronic
20/20, CD rat, diet,
90 d
Males: 0, 36, 112,337, 944;
Females: 0, 43, 120, 399,
1222°
(Adjusted)
Increased liver weight in
males'1
ND
NDr
36e
Freudenthal and
Henrich (1999)
Compound used was
70% TCPP; doses are
adjusted for TCPP
content.

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Table 2. Summary of Potentially Relevant Data for TCPP (CASRN 13674-84-5)
Category
Number of
Male/Female, Strain,
Species, Study Type,
Study Duration
Dosimetry"
Critical Effects
NOAEL'
BMDL/
BMCLa
LOAELa
Reference (Comments)
Notesb

10/10 B6C3F! mice,
diet, 14 wk
Males: 0,219,456, 737,
2470,4410
Females: 0,198,420,906,
1930,3590
(Adjusted)
Decreased terminal body
weight; increased relative
liver weight in males
Hepatocyte hypertrophy
in males
219
737
NDr
138
456
2470
NTP (2011a,b)
PS
Chronic
ND
Developmental
0/11-14, Wistar rat,
diet, GD 0-20
0, 6.7, 69, 670
tris(chloropropyl)phosphate
(Adjusted)
Missing 13 th rib in fetuses
69"
278
670
Kawasaki et al. (1982)f
Compound used was
tris(chloro-propyl)phos-
phate, a mixture that
contains TCPP. Doses
are not corrected for
TCPP content because
sufficient information
was not available.

Reproductive
ND
Carcinogenicity
ND
2. Inhalation (mg/m3)
Subchronic
ND
Chronic
ND
Developmental
ND
Reproductive
ND
Carcinogenicity
ND
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Table 2. Summary of Potentially Relevant Data for TCPP (CASRN 13674-84-5)
Category
Number of
Male/Female, Strain,
Species, Study Type,
Study Duration
Dosimetry3
Critical Effects
NOAEL3
BMDL/
BMCL3
LOAEL3
Reference (Comments)
Notesb
""Dosimetry: NOAEL, BMDL/BMCL, and LOAEL values are converted to an adjusted daily dose (ADD in mg/kg-d) for oral noncancer effects. All long-term exposure
values (4 wk and longer) are converted from a discontinuous to a continuous (weekly) exposure. Values from animal developmental studies are not adjusted to a
continuous exposure.
bNotes: PS = Principal study.
"Compound tested was administered in the diet and stated to contain 70% TCPP; therefore, doses are adjusted by the formula:
DoseADi = [Dose in ppm x Average Food Consumption per Day x (1 -f- Body Weight) x (Days Dosed ^ Total Days)] x 0.7.
dThe critical effect was not specified in the report, but the information provided indicates that it was liver weight.
"These values were not reported by the study authors but are determined by the data.
fThis was published in a foreign journal, but a translation was provided by the National Institute of Health Science (NIHS, 1994).
ND = No data, NDr = Not determined.
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HUMAN STUDIES
Oral Exposures
No human oral exposure studies on TCPP were identified.
Inhalation Exposures
No human inhalation exposure studies on TCPP were identified.
ANIMAL STUDIES
Oral Exposures
The effects of oral exposure of animals to TCPP have been evaluated in two subchronic
studies (Freudenthal and Henrich, 1999; NTP, 2011a,b) and one developmental study
(Kawasaki et al., 1982). Three short-term studies (Kawasaki et al., 1982; Bayer, 1993; Stauffer
Chemical Company, 1980a) were also identified and are summarized in the section titled
"OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS) "
Subchronic Studies
Freudenthal and Henrich, 1999
Freudenthal and Henrich (1999) conducted a subchronic study in rats. CD rats
(20/sex/treatment group) were administered 0-, 800-, 2500-, 7500-, or 20,000-ppm Fyrol PCF—
which was stated in the description of the 7-day Stauffer Chemical Company (1980a) study to
contain 70 ± 5% TCPP and 22 ± 5% 2-chloropropanol phosphate—via the diet for 13 weeks.
Average daily Fyrol PCF consumption was calculated by the study authors based on weekly food
consumption measurements; daily Fyrol PCF consumption in male rats was 0, 52, 160, 481, and
1349 mg/kg-day and in female rats it was 0, 62, 171, 570, and 1745 mg/kg-day. Because the
compound was stated to contain only 70% TCPP, average daily TCPP intakes were equivalent to
0, 36, 112, 337, and 944 mg/kg-day in males and 0, 43, 120, 399, and 1222 mg/kg-day in
females. Animals were examined for clinical signs of toxicity twice daily. Food consumption
and body weight were measured weekly. Hematology and clinical chemistry parameters were
measured in 10 males and 10 females per dose group at study initiation, mid-study, and
termination; parameters measured included hemoglobin, packed cell volume, total erythrocyte
count, total leukocyte count, total platelet count, mean corpuscular volume, differential
leukocytes, blood urea nitrogen, lactate dehydrogenase, glutamic pyruvic transaminase, glutamic
oxaloacetic transaminase, inorganic phosphates, alkaline phosphatase, creatinine, bilirubin,
cholesterol, glucose, albumin, total protein, sodium concentration, potassium concentration, and
chloride concentration. Urinalysis was performed mid-study and at termination and examined
color, turbidity, specific gravity, pH, glucose, and ketones; the study authors mention that other
endpoints were also measured but do not specify what they were. Cholinesterase activity was
determined in plasma and erythrocytes at study initiation, mid-study, and at termination, and in
brain at termination. Organ weights were obtained during necropsy for the brain, adrenals, heart,
liver, kidneys, gonads, and thymus. Histopathologic examination was performed on the adrenal
glands, brain, epididymides, esophagus, eyes, heart, intestine, kidneys, liver, lungs, lymph nodes,
mammary gland, sciatic nerve, ovaries, pancreas, pituitary gland, prostate, salivary glands, spinal
cord, stomach, spleen, testes, thymus, thyroid, tibiofemoral joint, trachea, urinary bladder, uterus,
and vagina.
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There were no effects on mortality, clinical signs of toxicity, food consumption,
hematology, clinical chemistry, urinary parameters, or cholinesterase activity. Body weight was
statistically significantly lower than controls in the high-dose group (944 mg/kg-day in males,
1222 mg/kg-day in females) during Weeks 4-12 for males and 6-12 for females (see Table B. 1);
only in females was this change greater than 10%. Absolute and relative liver weights were
increased 15-42% in all treated male rats (i.e., >36 mg/kg-day) and 17—33% in female rats at
>399 mg/kg-day (see Table B.2). In the high-dose group, swelling of the periportal hepatocytes
was observed in 9 male and 8 female rats; this change was only statistically significant for the
males due to elevated incidence in the control females (see Table B.3). The study authors
considered this change to be mild and of no toxicological significance. Relative kidney weights
were increased 13—16% in males at >337 mg/kg-day. Kidney weights were unaffected in
females. Histopathology of the kidney revealed mild cortical tubular degeneration in males at
>337 mg/kg-day and females at 1222 mg/kg-day; statistical significance of these changes was
not discussed (see Table B.3). Other histopathological changes noted included mild thyroid
follicular hyperplasia (males in all groups and Fyrol PCF-treated female rats); the study authors
considered this change nontreatment related due to its occurrence in male control rats (see
Table B.3). The study authors indicate a NOEL of 2500 ppm (112 mg/kg-day in males and
120 mg/kg-day in females); however, it is unclear what data this NOEL was based on. A
LOAEL of 36 mg/kg-day based on increased relative and absolute liver weights in male rats is
identified for this review. A NOAEL was not identified.
NTP, 2011 a,b
The study by NTP (201 la,b) is selected as the principal study for the derivation of
the screening subchronic p-RfD and the screening chronic p-RfD. The National Toxicology
Program conducted a 14-week study in mice (NTP, 201 la,b). At the time that this document
was prepared, the final report was not available from NTP. However, the study abstract and
summary tables were provided upon request for use in this review (NTP, 201 la). In addition,
detailed mortality and body weight tables from this study were available on the NTP Web site
(NTP, 201 lb). TCPP (95.7%) purity) was administered at concentrations of 0, 1250, 2500, 5000,
10,000, and 20,000 ppm in dosed feed to B6C3Fi mice (10/sex/group) for 14 weeks. Average
daily TCPP consumption was calculated based on average food consumption and body weight
values reported in the study; doses were 0, 219, 456, 737, 2470, and 4410 mg/kg-day for males,
and 0, 198, 420, 906, 1930, and 3590 mg/kg-day in females. Clinical observations, body
weights, and food consumption were recorded weekly and prior to study termination. For
females in the 0-, 906-, 1930- and 3590-mg/kg-day groups, vaginal smears were prepared on the
last 16 days of the study; for males in the 0-, 737-, 2470-, and 4410-mg/kg-day groups, sperm
motility and count were determined at necropsy. At termination, mice were necropsied and
examined for gross abnormalities, blood was drawn for hematology and micronuclei assay,
selected organs were weighed, and histopathological examinations were performed.
No treatment-related mortality or abnormal clinical signs occurred during the 14 weeks of
the study (NTP, 201 la). Body weights were decreased in males and females in a time- and
dose-dependent manner (NTP, 201 lb). In males, body weight was decreased relative to control
values by >10% from Weeks 2-14 at the highest dose (4410 mg/kg-day), from Weeks 6-14 at
2470 mg/kg-day, from Weeks 8-14 at 737 mg/kg-day, and on Week 10 and Weeks 12-14 at
456 mg/kg-day. At study termination, the average weight of the highest dose group was
approximately 29% lower than controls. In females, body weight was decreased relative to
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control values by >10% from Weeks 3-14 at the highest dose (3590 mg/kg-day); additional
decreases in body weight in excess of 10% occurred at Week 2 for the 420-mg/kg-day group and
the 906-mg/kg-day group and at Week 14 for the 198-mg/kg-day group. Average body weights
for males and females over the course of the study are presented in Tables B.4 and B.5,
respectively. These changes in body weight were not related to food consumption; food
consumption in TCPP treated groups was increased 3—15% over controls for females and 4-28%
over controls for males (see Table B.6) (NTP, 201 la).
Relative liver weight was statistically significantly increased at all doses in males and at
198, 906, 1830, and 3590 mg/kg-day in females (NTP, 201 la). Values were reported only as
average percent change from controls. Changes of greater than 10% occurred at
>456 mg/kg-day in males and >906 mg/kg-day in females (see Table B.6). No other changes in
organ weight were reported. Hepatocyte hypertrophy was observed in male mice at doses
>456 mg/kg-day and in female mice at doses >906 mg/kg-day, with changes reaching statistical
significance at >2470 mg/kg-day in males and >906 mg/kg-day in females. Incidence of
hepatocyte hypertrophy was dose related (see Table B.6). No other histopathological changes
were noted. The only noted changes in hematological parameters were decreases in leukocyte
counts of multiple lineages. These values were reported only as percent change from control
where statistically significant changes occurred. In females treated with 3590-mg/kg-day TCPP,
white blood cells (WBC) were decreased 19% relative to controls, lymphocytes (LYM) were
decreased 19%, neutrophils (SEG) were decreased 19%, and eosinophils (EOS) were decreased
13%). In males, WBC were decreased 10% at 2470 mg/kg-day and 48% at 4410 mg/kg-day,
LYM were decreased 6% at 2470 mg/kg-day and 51% at 4410 mg/kg-day, SEG were decreased
24%) at 2470 mg/kg-day and 30% at 4410 mg/kg-day, EOS were decreased 25% at
2470 mg/kg-day and 67% at 4410 mg/kg-day, and monocytes were decreased 70% at
4410 mg/kg-day.
Based on increased relative liver weight and decreased body weight in male mice, a
LOAEL of 456 mg/kg-day and a NOAEL of 219 mg/kg-day are identified.
Chronic Studies
There is no suitable information to provide in this regard.
Developmental Studies
Kawasaki et al., 1982
Kawasaki et al. (1982) conducted a developmental study in rats that was published in a
foreign journal in Japanese. NIHS (1994) provides a translation of the Japanese paper by
Kawasaki et al. (1982); however, the poor quality of the copy made data tables difficult to read.
The original source (Kawasaki et al., 1982) was unavailable for review at the time this review
was prepared. It is unknown if it was peer reviewed. Pregnant female Wistar rats were
administered diets containing 0, 0.01, 0.1, or 1.0% tris(chloropropyl)phosphate, which is
described by the study authors as a mixture of the following four products:
tris(l-chloromethylethyl)phosphate (a synonym for TCPP),
bis(l-chloromethyl)(2-chloropropyl)phosphate, bis(2-chloropropyl)(l-chloromethyl)phosphate,
and tris(2-chloropropyl)phosphate (relative abundance of each chemical species was not
indicated)—from Gestational Day (GD) 0 to GD 20. This is estimated to be equivalent to
approximately 0, 6.7, 69, or 670 mg/kg-day. This is based on the average food consumption
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provided by the study authors, which was used to calculate the grams of
tris(chloropropyl)phosphate consumed; however, the study authors did not provide body weight.
Because body weight gains were >100 g and animals were pregnant, use of the average body
weight provided by U.S. EPA (1994b) would be too low (i.e., 0.156 kg). To calculate the
estimated daily intake of tris(chloropropyl)phosphate, the initial body weight was assumed to be
equal to the control body weight in the 7-day experiment from the same study (0.212 kg). An
average weight over the course of the study was then calculated based on the reported weight
gains for each dose group and an assumption of a consistent rate of weight gain throughout the
20 days of the study. Dams (11-14/treatment) were sacrificed on GD 20. Dams were examined
for implantation, fetal sex ratio, and fetal mortality. Dam body weight was also measured. The
body weight of live fetuses was measured. Two thirds of the live fetuses from a litter were
prepared for skeletal examinations, and the remaining third were examined for visceral
abnormalities. Some dams (5-7) were allowed to deliver and litters were culled to eight pups.
The pups were weaned at 21 days and monitored for an additional 7 days (until 4 weeks of age).
Data tables were difficult to read due to the poor quality of the copy. There were no
treatment-related effects on body weight (only body weight gain was provided) or food
consumption. No effects on dams were noted. There was no increase in fetal mortality. There
were no statistically significant differences in the number of implantations, resorptions, or fetal
weight. Although there were no statistically significant increases in skeletal abnormalities,
treated animals had a low incidence (1-6%) of cervical ribs and missing 13th ribs that was
apparently dose dependent. There were no changes in visceral abnormalities. There were no
abnormalities noted in the animals observed for 4 weeks after delivery and there were no
changes in the pup growth rate. The study authors did not consider tris(chloropropyl)phosphate
to be teratogenic; however the dose-related 6% increase in the incidence of missing 13th ribs at
670 mg/kg-day is considered biologically significant. The NOAEL is considered to be
69 mg/kg-day with a LOAEL of 670 mg/kg-day.
Reproductive Studies
No reproductive toxicity studies on TCPP were identified.
Carcinogenicity Studies
No carcinogenicity studies on TCPP were identified.
Inhalation Exposures
No inhalation exposure studies on TCPP were identified.
OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS)
Tests Evaluating Carcinogenicity, Genotoxicity, and/or Mutagenicity
The majority of the genotoxicity and mutagenicity studies were negative (see Table 3A).
All studies in bacteria and yeast were negative (Stauffer Chemical Company, 1978a;
Nakamura et al., 1979; Mehlman et al., 1980; Zeiger et al., 1992; Follman and Wober, 2006).
One mouse lymphoma assay was negative (Stauffer Chemical Company, 1978b), while the other
was positive only in the presence of S9 (Mobil Oil Corporation, 1981). However, a memo from
Albright and Wilson Americas (1989) stated that this study was incomplete. Additionally, both
of these studies were conducted with industrial grade chemicals (two different sources) that are
only approximately 75 ± 10% TCPP (OECD, 2000); it is unknown how other chemical species
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or impurities in these mixtures impact toxicity. Three BALB/3T3 cell transformation assays
were conducted. One of the studies had a nondose-related increase in cell transformation at
concentrations of 0.039-0.312 |iL/mL with cytotoxicity observed at 0.625 |iL/mL (Stauffer
Chemical Company, 1978c), while two of the studies were negative with maximum
concentrations of 0.02-3.00 |iL/mL used (Stauffer Chemical Company, 1978d, 1980b). A comet
assay was also negative (Follman and Wober, 2006), but an unscheduled DNA test had
ambiguous and equivocal results (Stauffer Chemical Company, 1978e). Chromosomal
aberrations were also not induced in male Sprague-Dawley rats (Stauffer Chemical Company,
1978f).
Other Toxicity Studies (Exposures Other Than Oral or Inhalation)
The neutral red uptake test in V79 hamster fibroblast cells demonstrated that TCPP was
only cytotoxic at relatively high concentrations in the presence of S9 (Follman and Wober, 2006)
(see Table 3B). In the absence of S9, cytotoxicity was not observed with the highest
concentration tested (10 mM). TCPP was not found to have estrogenic or antiestrogenic
properties in vitro (Follman and Wober, 2006) (see Table 3B).
Short-term Studies
Kawasaki et al., 1982
Kawasaki et al. (1982) conducted a short-term study in rats that is published in a foreign
language journal in Japanese. The National Institute of Health Science (NIHS, 1994) provides a
translation of the Japanese paper by Kawasaki et al. (1982), however the poor quality of the copy
made data tables difficult to read. The original source (Kawasaki et al., 1982) was unavailable at
the time this review was prepared. It is unknown if it is peer reviewed, and the study does not
state whether it was Good Laboratory Practice (GLP) compliant. Female Wistar rats
(5/treatment group) were administered 0, 8, 40, 200, or 1000 mg/kg-day of
tris(chloropropyl)phosphate, which is described by the study authors as a mixture of the
following four products: tris(l-chloromethylethyl)phosphate (a synonym for TCPP),
bis(l-chloromethyl)(2-chloropropyl)phosphate, bis(2-chloropropyl)(l-chloromethyl)phosphate,
and tris(2-chloropropyl)phosphate (relative abundance of each chemical species was not
indicated)—in olive oil, presumably via gavage, for seven consecutive days (see Table 3B).
Animals were monitored for changes in body weight and general signs of distress during the
exposure (frequency not indicated), and body weight and organ weights were recorded on
necropsy at Day 7. There were no significant differences in body weight. There were no
abnormal clinical signs observed, but one 1000-mg/kg-day rat died. Only relative organ weights
were presented. Relative liver weights were stated to be statistically significantly increased
above the control in the 1000-mg/kg-day group by just under 10% (i.e., 9.7%). The study
authors report a statistically significant increase in relative kidney weight in the 200- and
1000-mg/kg-day groups, however the data table indicates that the 40-mg/kg-day group is also
statistically significantly higher than controls. Increases ranged from 9.8-20%) but were not dose
dependent, and the highest dose (i.e., 1000 mg/kg-day) was increased by less than 10%> (i.e.,
9.8%>). The type of statistical analysis performed was not specified. There was no
histopathology conducted; therefore, the significance of the organ-weight changes cannot be
evaluated. The study authors did not provide a NOAEL. However a NOAEL of 8 mg/kg-day
and a LOAEL of 40 mg/kg-day are determined from the data, based on the increase in relative
kidney weight.
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Bayer, 1993
Bayer (1993) provides another short-term study in rats. The original source (Bayer,
1993) was in German and is proprietary (not peer reviewed). EPA had the document translated
on December 30, 2010. The study was stated not to be subject to GLP guidelines but was stated
to generally be conducted in compliance with GLP guidelines with the exception that it was not
examined by the quality assurance department. The study was conducted as a dose-range study
for use in what the study authors refer to as a subacute study. Male Wistar rats (5/treatment
group) were administered 0, 1, 10, 100, or 1000 mg/kg-day of TCPP (purity reported to be
97.85%, but this includes all isomers) in peanut oil via gavage for seven consecutive days (see
Table 3B). Animals were 9 weeks old at the start of the experiment in order to study possible
treatment-related testicular effects. Animals were observed once or twice a day for mortality and
clinical signs of toxicity. Body weight was measured at the start and end of the experiment.
Food and water consumption were measured at the beginning and before the end of the
experiment, and consumption over the 7 days was calculated. On Day 8 all animals were
sacrificed with diethyl ether and necropsied. The testicles (paired) were the only organ weighed.
No histopathology was performed. There were no significant differences in mortality, clinical
signs of toxicity, body weight, or food consumption. Water consumption was significantly
increased by 32% in the 1000-mg/kg-day group. Although absolute and relative testes weights
were decreased by >10% in the 100-mg/kg-day group, this was due to small testes in one animal
and was not considered biologically significant by the study authors. No other significant effects
were noted. The NOAEL is considered to be 1000 mg/kg-day and no LOAEL can be
determined.
Stauffer Chemical Company, 1980a
Stauffer (Stauffer Chemical Company, 1980a) conducted another short-term study in rats.
The original source (Stauffer Chemical Company, 1980a) was unavailable for review at this
time. This study was considered proprietary and could not be obtained from the owner. An
OECD SIDS (OECD, 2000) provided a peer-reviewed summary of the data. CD rats
(10/sex/treatment group) were administered via the diet for two weeks 0-, 4200-, 6600-, 10,600-,
or 16,600-ppm Fyrol PCF, which was stated in the study description to contain 70 ± 5% TCPP
and 22 ± 5% 2-chloropropanol phosphate. Average daily intakes of Fyrol PCF are estimated to
be 0, 379, 595, 956, and 1498 mg/kg-day in males and 0, 423, 665, 1067, and 1672 mg/kg-day in
females (based on average body weight [U.S. EPA, 1994b], and average daily food consumption
[U.S. EPA, 1988]). Because the compound was stated to contain only 70% TCPP, this would be
equivalent to average daily intakes of TCPP of 0, 265, 417, 669, and 1048 mg/kg-day in males
and 0, 296, 465, 747, and 1170 mg/kg-day in females. The OECD SIDS document (OECD,
2000) states that the study was not conducted according to GLP. Animals were examined for
clinical signs of toxicity, food consumption, body weight, hematology, clinical chemistry,
cholinesterase, gross necropsy, and select organ weights and histopathology. However, specifics
(including statistical analyses performed) were not provided in the OECD SIDS document
(OECD, 2000) (see Table 3B).
There were no treatment-related clinical signs noted. There were no treatment-related
effects observed in hematology, clinical chemistry, or cholinesterase activity. High-dose
(1048 mg/kg-day) males had a significant decrease in body weight gain and food consumption at
Week 1 (magnitude of changes were not specified in the study summary). It was not indicated if
this only occurred at Week 1 or continued throughout the study. Increases in absolute and
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relative liver weight were reported but were stated not to be accompanied by histopathological
changes. OECD considered the NOAEL to be 10,600 ppm (i.e., 669 mg/kg-day) (OECD, 2000),
based on significant reduction in weight gain and reduced food consumption at the higher dose
(1048 mg/kg-day) in males. However, no data were provided, and there is no indication of the
magnitude of increase that was observed.
Metabolism/Toxicokinetic Studies
After a single oral dose of 50 |imol/kg, the majority of radio-labeled TCPP was recovered
in the urine (67.17%) followed by the feces (22.17%) and expired air (7.72%) (Minegishi et al.,
1988) (see Table 3B). Although there were high levels of TCPP found in the kidneys, liver, and
lung after 3 hours, the levels decreased rapidly and were associated with excretion of the
chemical as opposed to bioaccumulation. Measurements of biliary excretion indicated that
enterohepatic circulation occurs. Stauffer Chemical Company (1984) also found that TCPP was
rapidly eliminated (89% in 72 hours) with the majority excreted in the urine and feces.
Mode-of-Action/Mechanistic Studies
No mode-of-action or mechanistic studies on TCPP were identified.
Immunotoxicity
No immunotoxicity studies on TCPP were identified.
Neurotoxicity
Neurotoxicity was evaluated in 18 white Leghorn hens (Sprague et al., 1981) (see
Table 3B). Although the hens exhibited decreased body weight, ceased egg production, severe
feather loss, and one death, there was no behavioral or histological evidence of neurotoxicity. A
short-term study (Stauffer Chemical Company, 1980a) and a subchronic study (Freudenthal and
Henrich, 1999) examined cholinesterase levels (details provided above in the "Short-term
studies" and "Subchronic studies" sections) and found no effects after either 2 weeks (Stauffer
Chemical Company, 1980a) or 90 days (Stauffer Chemical Company, 1981) of treatment.
The potential of several phosphate ester flame retardants, including TCPP, to induce
developmental neurotoxicity was examined in vitro using PC12 cells (Dishaw et al., 2011).
TCPP reduced cell number but not cell growth. Additionally, TCPP promoted emergence of a
cholinergic phenotype—but not a dopaminergic phenotype—from undifferentiated cells. This
tendency to skew neural differentiation may elicit neurodevelopmental changes that would not be
observed in classic developmental assays.
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Table 3A. Summary of Tris(l-chloro-2-propyl)phosphate Genotoxicity Studies
Endpoint
Test system
Dose
Concentration"
Resultsb
Comments
References
Without
Activation
With
Activation
Genotoxicity studies in prokaryotic organisms
Reverse mutation
Ames preincubation or plate assay;
Salmonella typhimurium strains TA 97,
97a, 98, 100, 102, 104, 1535, 1537, and/or
1538 in the presence or absence of S9.
1 mM
10 |imo 1/piate
5.0 |iL/platc
333-2000 ng/plate
1.0 |iL/platc


Stauffer Chemical Company
specified the compound as
Fyrol PCF, which is a trade
name and is 70 ± 5% TCPP.
Follman and
Wober (2006);
Nakamura et al.
(1979);
Stauffer Chemical
Company
(1978a)°;
Zeiger et al.
(1992);
Mehlman et al.
(1980)°
SOS repair
induction
ND
ND
ND
ND
ND
NA
Genotoxicity studies in nonmammalian eukaryotic organisms
Mutation
A modified Ames assay with yeast
(Saccharomyces cereviseae) incubated at
30°C without S9 activation and 37°C with
activation for 3-5 d.
5.0 |iL/platc


No gene mutations were
observed. Compound was
specified to be Fyrol PCF
(trade name), which is
70 ±5% TCPP. DMSO was
used as the vehicle.
Stauffer Chemical
Company(1978a)°
Recombination
induction
ND
ND
ND
ND
ND
NA
Chromosomal
aberration
ND
ND
ND
ND
ND
NA
Chromosomal
malsegregation
ND
ND
ND
ND
ND
NA
Mitotic arrest
ND
ND
ND
ND
ND
NA
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Table 3A. Summary of Tris(l-chloro-2-propyl)phosphate Genotoxicity Studies
Endpoint
Test system
Dose
Concentration"
Resultsb
Comments
References
Without
Activation
With
Activation
Genotoxicity studies in mammalian cells—in vitro
Mutation
A mouse lymphoma mutation assay using a
Fisher mouse lymphoma cell line derived
fromthel5178Y thymidine kinase (TK) cell
line.
0.48 nL/mL


TCPP did not induce forward
mutations in this assay.
Compound was specified to be
Fyrol PCF (trade name),
which is 70 ± 5% TCPP.
DMSO was used as the
vehicle.
Stauffer Chemical
Company(1978b)°
Mutation
A murine lymphoma mutagenesis assay
with and without S9.
NR

+
Compound was stated to be
Antiblaze 80 (trade name),
which is 75 ± 10% TCPP. In
the first activation,
mutagenicity was evident at
highest dose with no dose
response. In the second
activation, mutagenic dose
response was observed at all
doses. At the highest dose,
mutation frequency was 18
times the negative controls.
Mobil Oil Corp.
(1981)°'d
Mutation
A BALB/3T3 cell (mouse embryonic
fibroblast cell line) transformation assay;
104 cells were cultured with TCPP for 72 h
and incubated for 3-4 wk, stained, and
scored.
0.039-0.312 nL/mL
±
NA
Compound was stated to be
Fyrol PCF (trade name),
which is 70 ± 5% TCPP.
Nondose-related increase in
cell transformation was
observed at
0.039-0.312 nL/mL (higher
doses demonstrated
cytotoxicity). Foci occurred at
equal frequency indicating a
possible solubility or kinetics
issue.
Stauffer Chemical
Company
(1978c)°
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Table 3A. Summary of Tris(l-chloro-2-propyl)phosphate Genotoxicity Studies
Endpoint
Test system
Dose
Concentration3
Resultsb
Comments
References
Without
Activation
With
Activation
Mutation
A BALB/3T3 cell (mouse embryonic
fibroblast cell line) transformation assay;
104 cells were cultured with TCPP for 72 h
and incubated for 3-4 wk, stained, and
scored.
0.02-3.00 nL/mL

NA
Compound was stated to be
Fyrol PCF (trade name),
which is 70 ± 5% TCPP.
There was no morphological
transformation of BALB/3T3
in this assay.
Stauffer Chemical
Company (1978d;
1980b)°
Chromosomal
aberrations
ND
ND
ND
ND
ND
NA
Sister chromatid
exchange (SCE)
ND
ND
ND
ND
ND
NA
DNA damage
In a comet assay, 300,000 V79 hamster
fibroblast cells were cultured for 2 d with
test compound. Culture medium was then
replaced by fresh medium and test
substance (1 jiM-1 mM). A final protein
concentration of 2-mg S9 protein/mL
incubation medium was obtained. Two
experiments were performed with a 24-h
incubation period.
1 mM


Induction of DNA strand
breaks could not be detected
neither in the presence nor in
the absence of S9 mix.
Follman and
Wober (2006)
DNA damage
In an initial unscheduled DNA synthesis
(UDS) assay, human WI-38 cells blocked in
G-phase were grown in medium containing
TCPP (referred to as Fyrol PCF, a trade
name) in DMSO at concentrations of 0.1,
0.5, 1, or 5 |iL/mL with and without S9-mix
from rat livers. Based on toxicity above
0.1 |iL/mL. the second assay was
performed using concentrations of 0.005,
0.01, 0.05, and 0.1 nL/mL.
0.01 nL/mL
±
±
Test substance (Fyrol PCF, a
trade name, 70 ± 5% TCPP)
demonstrated toxicity at all
concentrations in the first
study and was perhaps weakly
active at 0.01 |iL/mL with and
without activation, though no
associated dose response was
detected at higher
concentrations. Results were
ambiguous and equivocal with
and without activation.
Stauffer Report
(1978e)°
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Table 3A. Summary of Tris(l-chloro-2-propyl)phosphate Genotoxicity Studies
Endpoint
Test system
Dose
Concentration"
Resultsb
Comments
References
Without
Activation
With
Activation
DNA adducts
ND
ND
ND
ND
ND
NA
Genotoxicity studies in mammals—in vivo
Chromosomal
aberrations
In a rat bone marrow cytogenetics assay,
groups of 24 male Sprague-Dawley rats
were administered a single oral bolus dose
of 0.011-, 0.04-, or 0.11-mL/kg TCPP
(referred to as Fyrol PCF, a trade name).
Three equally sized groups also received
the same doses in subcutaneous injections
for 5 consecutive days. Animals were
sacrificed 6-48 h following the last dose,
and chromosome spreads were prepared
and analyzed for aberrations.
0.11 mL/kg

NA
Compound was stated to be
Fyrol PCF (trade name),
which is 70 ± 5% TCPP.
Mitotic index approximately
equaled that of the negative
control. Chromosome
aberration frequency was not
significantly different in
TCPP-treated animals;
therefore, TCPP is not
clastogenic.
Stauffer Chemical
Company
(1978f)°
Sister chromatid
exchange (SCE)
ND
ND
ND
ND
ND
NA
DNA damage
ND
ND
ND
ND
ND
NA
DNA adducts
ND
ND
ND
ND
ND
NA
Mouse biochemical
or visible specific
locus test
ND
ND
ND
ND
ND
NA
Dominant lethal
ND
ND
ND
ND
ND
NA
Genotoxicity studies in subcellular systems
DNA binding
ND
ND
ND
ND
ND
NA
aLowest effective dose for positive results, highest dose tested for negative results.
b+ = positive, ± = equivocal or weakly positive, - = negative, T = cytotoxicity, NA = not applicable, ND = no data, NDr = Not determined, NR = Not reported,
NR/Dr = Not reported by the study authors but determined from data.
Information was obtained from OECD SID (OECD, 2000). The original data were not available.
dAlthough the OECD SIDS document (OECD, 2000) did not specify an author for this study, a memo from Albright and Wilson (1989) stated that the study was from
Mobil but that the study was incomplete.
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Table 3B. Other Tris(l-chloro-2-propyl)phosphate Studies
Test
Materials and Methods
Results
Conclusions
References
Carcinogenicity other
than oral/inhalation
ND
ND
ND
NA
Other toxicity studies
(exposures other than
oral or inhalation)
In a neutral red uptake assay, cytotoxicity of TCPP
was evaluated in V79 hamster fibroblast cells.
15,000 cells per well were seeded in 200-|iL culture
medium and cultured for 24 h; cells were
withdrawn and incubated for 24 h with TCPP
(100 pM to 10 mM) in serum-free culture medium.
After 24 h, culture medium was withdrawn and
replaced with another containing 0.05-mg neutral
red/mL, incubated for 3 h, after which medium was
withdrawn again; cells were washed and fixed with
50% ethanol-1% acetic acid in aqua bidest. V79
cells were incubated in TCPP with and without
S9-mix activation. Uptake of neutral red was
determined photometrically.
Moderate toxicity >1 mM in the presence of
S9 (activation).
No cytotoxic effects detected up to
concentrations of 10 mM in the absence of S9
(no activation).
Cytotoxic effects only
occurred at relatively high
concentrations and were only
detected in this study in the
presence of S9. The protein
content was stated not to be
impacted either in the
presence or absence of S9
activation.
Follman and
Wober (2006)
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Table 3B. Other Tris(l-chloro-2-propyl)phosphate Studies
Test
Materials and Methods
Results
Conclusions
References
Other toxicity studies
(exposures other than
oral or inhalation)
In an Ishikawa cell assay, the activity of alkaline
phosphatase was measured as a parameter for an
estrogenic effect in estradiol sensitive human
endometrial adenocarcinoma Ishikawa cells by
TCPP. Ishikawa cells were cultured in medium
without phenol red with 5% fetal calf serum and
insulin-transferrin-selenium A-supplement. A total
of 125,000 cells were seeded per plate and
incubated with TCPP (10 nM-10 |iIVI. in ethanol).
After 72 h, cells were harvested, resuspended, and
analyzed. Alkaline phosphatase was assayed by
spectrometry of product formation by hydrolysis of
/j-nitrophenyl phosphate to /j-nitrophenol. Estrogen
receptor-mediated effects were confirmed with a
recombinant yeast assay with GLAXO ERa yeasts.
To test antiestrogenic TCPP potential, ERa yeasts
were induced by estradiol and then treated with the
test substances.
TCPP did not induce activity of alkaline
phosphatase in contrast to the positive control
(estradiol 1 |iIVI). In the yeast assay, activity
of (3-galactosidase secreted from GLAXO
ERa yeasts demonstrated an estrogenic
effect. TCPP did not reduce the induction
origination from estradiol.
TCPP does not show
estrogenic or antiestrogenic
potential.
Follman and
Wober (2006)
Short-term studies
Tris(chloropropyl)phosphate (a mixture that
includes TCPP) was administered to female Wistar
rats (5/group) at doses of 0, 8, 40, 200, or
1000 mg/kg-d in olive oil, presumably via gavage
for 7 d.
There were no changes in body weight.
Relative liver weight was increased at
1000 mg/kg-d by 9.7%. Relative kidney
weight was increased at >40 mg/kg-d by
9.8-20%, but level of increase was not dose
dependent. No histopathology was
performed.
NOAEL of 8 mg/kg-d and
LOAEL of 40 mg/kg-d based
on increased relative kidney
weight.
Kawasaki et al.
(1982)a
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Table 3B. Other Tris(l-chloro-2-propyl)phosphate Studies
Test
Materials and Methods
Results
Conclusions
References
Short-term studies
Male Wistar rats (5/group) were treated with TCPP
(97.85% purity; all isomers included) via gavage at
doses of 0, 1, 10, 100, or 1000 mg/kg-d for 7 d.
Animals were 9 wk old at the start of the study.
The only organ weighed was the testis.
There were no changes in mortality, clinical
signs of toxicity, body weight, or food
consumption. There was a decrease in
absolute and relative testes weights at
100 mg/kg-d; however, this was attributed to
small testes in one animal and is not
considered dose related. There was also an
increase in water consumption at
1000 mg/kg-d, but this change was not
considered adverse.
NOAEL of 1000 mg/kg-d; no
LOAEL available from the
data.
Bayer (1993)
Short-term studies
CD rats (10/sex/group) were treated with Fyrol
PCF via the diet. Average TCPP intakes from this
exposure were estimated to be 0, 265, 417, 669, and
1048 in males and 0, 296, 465, 747, and 1170 in
females. Animals were examined for clinical signs
of toxicity, food consumption, body weight,
hematology, clinical chemistry, cholinesterase,
gross necropsy, and select organs were weighed
and examined for histopathology.
Noted changes included decreased body
weight gain and food consumption at
1048 mg/kg-d in males. Increased absolute
and relative liver weights were also reported,
but no doses were given.
Compound was stated to be
Fyrol PCF (trade name),
which is 70 ± 5% TCPP.
NOAEL of 669 mg/kg-d and
LOAEL of 1048 mg/kg-d
based on decrease in weight
gain and food consumption.
Doses were adjusted for
TCPP content.
Stauffer
Chemical
Company
(1980a)b
Metabolism/
toxicokinetics
Test substance (TCPP) was labeled to produce
14C-TCPP (1.16 gyield), purified by column
chromatography (yield 227 mg), analyzed by TLC,
and purity ascertained by GC (>99%). Male Wistar
rats had their bile ducts cannulated. After recovery,
animals received a single oral dose (50 |imol/kg).
and then bile was collected and analyzed for
radioactivity. At 3, 6, 12, 24, 72, and 168 h after
administration, animals were sacrificed, and several
organs and tissues were removed to determine
radioactivity. Excretion half-life was computed.
Protein binding was determined using S-9 fraction
of rat liver and kidney.
Recovery in urine, feces, and expired air were
67.17 ±2.66, 22.17 ± 1.17, and
7.72 ± 0.84%, respectively. 44.9% of the
dose was excreted through the bile duct in
48 h. The biliary/fecal excretion ratio was
2.23 at 48 h. Tissue and blood distribution
results showed TCPP radioactivity most
present in the kidney, liver, and lung at 3 h
(27.26 ± 7.48, 28.64 ± 4.38, and
9.37 ± 1.51%, respectively). Distribution in
the kidney, liver, and lungs decreased by 12 h
and continued to decrease along with all
tissue types. Longest half-life observed was
in adipose tissue.
Biliary /fecal excretion ratio
suggests reabsorption of
biliary metabolites from the
GI tract suggesting
enterohepatic circulation.
High liver and kidney
distribution ratios reflect
excretion rather than
accumulation.
Minegishi et al.
(1988)
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Table 3B. Other Tris(l-chloro-2-propyl)phosphate Studies
Test
Materials and Methods
Results
Conclusions
References
Metabolism/
toxicokinetics
2-mL/kg-bw Fyrol PCF (stated to be 70 ± 5%
TCPP) containing 20 or 200 mg TCPP/kg-bw and
40 |iCi 14C-radiolabeled TCPP was administered to
CD rats. In recovery phase animals, at least 5
animals/sex received oral doses of 200 mg/kg, and
5 males received 20 mg/kg by single oral or i.v.
administration; urine, feces, and expired air were
collected over 8 d. In plasma phase animals, blood
samples, urine, and feces were collected from
dosed animals over 8 d. Collections were analyzed
for radioactivity and TCPP metabolites.
TCPP and metabolites were rapidly
eliminated (89% by 72 h). Terminal (plasma)
half-life was 48.7 ± 6.0 h. Biphasic
elimination followed first order kinetics.
Urine was the primary mode of excretion
dependent on dose and route of
administration. Total body burden (8 d)
<1%. Identifiable metabolites were
75-78.5% of urinary and fecal radiocarbon.
TCPP does not
bioaccumulate significantly
and is rapidly excreted.
Stauffer
Chemical
Company
(1984)b
Mode of action/
mechanistic
ND
ND
ND
NA
Immunotoxicity
ND
ND
ND
NA
Neurotoxicity
A group of 18 white Leghorn hens received an oral
dose of 13.2 g-TCPP/kg-bw initially and 3 wk later.
Animals were sacrificed 3 wk after second dose.
Decreased body weights and a death were
observed. Egg production ceased after the
first dose, and severe feather loss occurred.
No behavioral or histological evidence of
delayed neurotoxicity was observed.
Neurotoxicity was not
observed.
Sprague et al.
(1981)
Neurotoxicity
PC12 cells were treated with TCPP (50 |iIVI) and
murine nerve growth factor (to promote
differentiation). Media was renewed every 48 h.
Cell number and growth were assessed after a 4-
day exposure, and cell differentiation (measured by
enzyme activity) was assessed after a 6-day
exposure.
Decreased cell number—but not cell—
growth was observed. TCPP resulted in
increased cholinergic differentiation but had
no impact on dopaminergic differentiation.
Potential for developmental
neurotoxicity was observed.
Dishaw et al.
(2011)
aThis was published in a foreign journal, but a translation was provided by the National Institute of Health Science (NIHS, 1994).
information was obtained from an OECD SID document (OECD, 2000). The original data were not available.
NA = not applicable, ND = no data.
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DERIVATION OF PROVISIONAL VALUES
DERIVATION OF ORAL REFERENCE DOSES
Derivation of Subchronic Provisional RfD (Subchronic p-RfD)
Table 4 provides a summary of the relevant oral toxicity studies for TCPP. There are two
subchronic studies: one in mice and one in rats (Freudenthal and Henrich, 1999; NTP, 201 la,b),
and one developmental study in rats (Kawasaki et al., 1982) available that examine the effects of
oral exposure to TCPP. The study by Kawasaki et al. (1982) uses a tris(chloropropyl)phosphate
mixture; while TCPP is stated to be a component of the mixture, the relative abundance of TCPP
to the other species in the mixture and the contributions of those other species to any observed
toxicity are unknown, rendering the developmental studies by Kawasaki et al. (1982) unsuitable
for derivation of RfD values. The subchronic study by Freudenthal and Henrich (1999) utilized a
formulation that was only 70% TCPP. Information on the toxicological effects of the other
major chemical component noted by the study authors (2-chloropropanol phosphate) could not
be identified. It is unknown to what extent this chemical or others in the mixture may have
contributed to the observed toxicity. In this review, doses were corrected for the TCPP content;
however, this correction requires the assumption that the other chemicals in the mixture did not
contribute to the observed effects. This assumption may be overly conservative. This study is
not deemed suitable for derivation of quantitative toxicity values due to the uncertainties
associated with the low purity of TCPP used. The subchronic study by NTP (201 la,b), used
TCPP that was 95.7% pure and conducted a comprehensive evaluation of appropriate endpoints.
However, at the time that this review was prepared, the study was unpublished and only the
study abstract, summary tables, and complete data tables for mortality and body weight could be
obtained. For these reasons, a provisional subchronic RfD cannot be confidently derived here.
However a "screening level" value for subchronic oral exposure based on this study is provided
in Appendix A.
Table 4. Summary of Relevant Oral Systemic Toxicity Studies for
Tris(l-chloro-2-propyl)phosphate
References
Species,
#Sex (M/F)
Exposure
(ppm)
Frequency/
Duration
NOAEW
(mg/kg-d)
LOAELadj"
(mg/kg-d)
Critical endpoint
Freudenthal and
Henrich (1999)
Rat, 20/20
0, 800, 2500,
7500, or
20,000°
90 d
None
36
Increased absolute and
relative liver weight in
males
NTP (201 la,b)
Mouse,
10/10
0, 1250, 2500,
5000, 10,000,
20,000
14 wk
219
456
Increased relative liver
weight and decreased
terminal body weight in
males
Kawasaki et al.
(1982)
Rat, 0/11-14
0, 100, 1000,
or 10,000d
20 d
69
670
Missing 13th rib in
fetuses
"NOAELA|,[ = NOAEL (ppm or mg/kg food) x food consumption (kg/day) ^ body weight (kg).
''LOAEL Am = LOAEL (ppm or mg/kg food) x food consumption (kg/day) ^ body weight (kg).
°Compound used was only 70% TCPP; NOAEL and LOAEL values were adjusted to account for this.
dCompound used was tris(chloropropyl)phosphate, a mixture that contains TCPP. Doses are not adjusted for TCPP
content, as the exact make-up of the mixture is not known.
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Derivation of Chronic Provisional RfD (Chronic p-RfD)
There are no chronic studies available, so the best available study for deriving a chronic
provisional RfD is the subchronic study by NTP (201 la,b). However, as described above in the
"Derivation of Subchronic Provisional RfD (Subchronic p-RfD)" section, due to the
unavailability of the full study report at this time, a chronic provisional RfD cannot be
confidently derived here. However a "screening level" value for chronic oral exposure is
provided in Appendix A.
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS
No subchronic or chronic p-RfC can be derived because no inhalation studies with TCPP
were identified.
CANCER WEIGHT-OF-EVIDENCE DESCRIPTOR
Table 5 identifies the cancer WOE descriptor for TCPP.
Table 5. Cancer WOE Descriptor for TCPP
Possible WOE Descriptor
Designation
Route of Entry
(oral, inhalation, or both)
Comments
"Carcinogenic to
Humans "

NA

"Likely to Be
Carcinogenic to Humans "

NA

"Suggestive Evidence of
Carcinogenic Potential"

NA

"Inadequate Information
to Assess Carcinogenic
Potential"
Selected
Both
There is inadequate
human and animal
evidence of
carcinogenicity via
the oral or
inhalation route.
"Not Likely to Be
Carcinogenic to Humans "

NA

DERIVATION OF PROVISIONAL CANCER POTENCY VALUES
Table 5 identifies the cancer WOE descriptor for both oral and inhalation exposure to
TCPP as "Inadequate Information to Assess Carcinogenic Potential." Consequently, the lack of
data on the carcinogenicity of TCPP precludes the derivation of quantitative estimates for either
oral (p-OSF) or inhalation (p-IUR) exposure. However, at the time that this review was
prepared, a chronic carcinogenicity study using TCPP in the diet was planned by NTP (study
number C20712).
Tables 6 and 7 present a summary of noncancer and cancer values, respectively.
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Table 6. Summary of Noncancer Reference Values for TCPP (CASRN 13674-84-5)
Toxicity Type (units)
Species/Sex
Critical Effect
Provisional
Reference
Value
POD
Method
POD
UFc
Principal Study
Screening Subchronic
p-RfD
(mg/kg-d)
Mouse/M
Increase in incidence of
hepatocyte hypertrophy
1 x KT1
BMDLio
138
1000
NTP (2011a,b)
Screening Chronic p-RfD
(mg/kg-d)
Mouse/M
Increase in incidence of
hepatocyte hypertrophy
1 x i(T2
BMDLio
138
10,000
NTP (2011a,b)
Subchronic p-RfC
(mg/m3)
None
None
None
None
None
None
None
Chronic p-RfC
(mg/m3)
None
None
None
None
None
None
None

Table 7. Summary of Cancer Values for TCPP (CASRN 13674-84-5)
Toxicity Type
Species/Sex
Tumor Type
Cancer Value
Principal Study
p-OSF
None
None
None
None
p-IUR
None
None
None
None
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APPENDIX A. PROVISIONAL SCREENING VALUES
For reasons noted in the main PPRTV document, it is inappropriate to derive a
provisional chronic p-RfD for tris(l-chloro-2-propyl)phosphate (TCPP). However, information
is available for this chemical which, although insufficient to support derivation of a provisional
toxicity value, 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.
DERIVATION OF SCREENING PROVISIONAL ORAL REFERENCE DOSES
Derivation of Screening Subchronic Provisional RfD (Screening Subchronic p-RfD)
As discussed in the "Derivation of Subchronic Provisional RfD (Subchronic p-RfD)"
section, the subchronic study in mice by NTP (201 la,b) is chosen as the principal study. A
LOAEL of 456 mg/kg-day was identified based on increased relative liver weight and decreased
terminal body weight in male mice; a NOAEL of 219 was also identified in this study. Liver
histopathology was also observed, with a statistically significantly increased incidence of
hepatocyte hypertrophy in male mice at >2470 mg/kg-day and in female mice at >906 mg/kg-day
(NTP, 201 la). Benchmark dose (BMD) modeling was performed on the data to determine the
most appropriate POD. Details of the modeling results are provided in Appendix C. While the
lowest NOAELs from the NTP (201 la,b) study were for terminal body weight and relative liver
weight in male mice (219 mg/kg-day), the data for these endpoints could not be modeled, and a
lower BMDLio is available based on hepatocyte hypertrophy in male mice (see Table A. 1). The
most sensitive effect was hepatocyte hypertrophy in male mice with a BMDio of 310 mg/kg-day
and a BMDLio of 138 mg/kg-day. Further support for the induction of liver effects by TCPP is
provided by short-term studies (Kawasaki et al., 1982; Stauffer Chemical Company, 1980a) in
which increased liver weight was observed, and by the subchronic study using Fyrol PCF
(Freudenthal and Henrich, 1999) in which increased liver weight and increased incidence of
swelling around the periportal hepatocytes were observed.
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Table A.l. Potential Points of Departure (mg/kg-day) Available from NTP (2011a,b) Study
Endpoint
NOAEL
LOAEL
BMD10
BMDL10
Terminal body weight
M: 219
M: 456
M: N/A
M: N/A

F:1830
F:3590
F: N/A
F: N/A
Relative liver weight
M: 219
M: 456
M: N/A
M: N/A

F: 420
F: 906
F: N/A
F: N/A
Hepatocyte hypertrophy*
M: 737
M:2470
M: 310
M: 138

F: 420
F: 906
F: 802
F: 470
Hematology
M: 737
M: 2470
M: N/A
M: N/A

F:1830
F:3590
F: N/A
F: N/A
Mortality
M:4410
M: N/A
M: N/A
M: N/A

F:3590
F: N/A
F: N/A
F: N/A
*NOAEL and LOAEL values for hepatocyte hypertrophy are based on statistically significant (p < 0.05) changes in
incidence of hypertrophy according to a Fisher's Exact Test performed for this review.
The POD identified in this study is a BMDLio of 138 mg/kg-day.
This POD was derived using doses adjusted from ppm in the diet to mg/kg-day using
average food consumption and body-weight measurements provided in the study (see "Review of
Potentially Relevant Data" section for details).
The screening subchronic p-RfD for TCPP, based on the BMDLio of 138 mg/kg-day for
hepatocyte hypertrophy in male mice, is derived as follows:
Screening subchronic p-RfD = BMDLio UF
= 138 mg/kg-day 1000
= 1 x 10-1 mg/kg-day
Table A.2 summarizes the uncertainty factors for the screening subchronic p-RfD for
TCPP.
Table A.2. Uncertainty Factors for Screening Subchronic p-RfD of TCPP
UF
Value
Justification
ufa
10
A UFa of 10 is applied for interspecies extrapolation to account for potential toxicokinetic
and toxicodynamic differences between mice and humans.
ufd
10
A UFd of 10 is applied because the database includes only one unacceptable
developmental study in Wistar rats (Kawasaki et al., 1982b) and no two-generation
reproduction studies. Additionally, there is information suggesting the need for more
studies addressing the developmental neurotoxicity of TCPP (Dishaw et al., 2011).
UFh
10
A UFh of 10 is applied for intraspecies differences to account for potentially susceptible
individuals in the absence of information on the variability of response to humans.
ufl
1
A UFl of 1 is applied because the POD was developed using a BMDLi0.
UFS
1
A UFS of 1 is applied because a subchronic study was utilized.
UFC <3000
1000

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Derivation of Screening Chronic Provisional RfD (Screening Chronic p-RfD)
There are no available chronic studies using TCPP. The study by NTP (201 la,b) is
selected as the principal study for derivation of the screening chronic p-RfD. The critical
endpoint is increased incidence of hepatocyte hypertrophy in male mice. Details of the principal
study (NTP, 201 la,b) are provided in the "Review of Potentially Relevant Data" section.
Benchmark dose (BMD) analysis was performed with these data and is described in Appendix C.
The POD identified in this study is a BMDLio of 138 mg/kg-day.
This POD was derived using doses adjusted from ppm in the diet to mg/kg-day using
average food consumption and body weight measurements provided in the study (see "Review of
Potentially Relevant Data" section for details). No animal-to-human body weight adjustment is
used for oral noncancer assessments.
The screening chronic p-RfD for TCPP, based on the BMDLio of 138 mg/kg-day in male
mice, is derived as follows:
Screening Chronic p-RfD = BMDLio UFc
= 138 mg/kg-day ^ 10,000
= 1 x 10~2 mg/kg-day
Table A.3 summarizes the uncertainty factors for the screening chronic p-RfD for TCPP.
Table A.3. Uncertainty Factors for Screening Chronic p-RfD for TCPP
UF
Value
Justification
ufa
10
A UFa of 10 is applied for interspecies extrapolation to account for potential toxicokinetic
and toxicodynamic differences between mice and humans.
ufd
10
A UFd of 10 is applied because the database includes only one unacceptable
developmental study in Wistar rats (Kawasaki et al., 1982b) and no two-generation
reproduction studies. Additionally, there is information suggesting the need for more
studies addressing the developmental neurotoxicity of TCPP (Dishaw et al., 2011).
UFh
10
A UFh of 10 is applied for intraspecies differences to account for potentially susceptible
individuals in the absence of information on the variability of response to humans.
ufl
1
A UFl of 1 is applied because the POD was developed using a BMDLi0.
UFS
10
A UFS of 10 is applied because a subchronic-duration study was utilized.
UFC <3000
10,000

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APPENDIX B. DATA TABLES
Table B.l. Effect of 13-Week TCPP Exposure on Rat Body Weight"

ppm Fyrol PCF in diet (TCPP Adjusted Daily Dose to males, females in mg/kg-d)b
0
800 (36, 43)
2500 (112,120)
7500 (337, 399)
20,000 (944,1222)
Body weight
(g)c
Male
490 ± 35
491 ±39 (0.2)
477 ± 48 (2.7)
473 ±49 (3.5)
452 ± 40 (7.8)d
Female
263 ± 23
265 ± 25 (0.8)
264 ±31 (0.4)
250 ± 22 (4.9)
232 ± 16 (11.8)d
aSource: Freudenthal and Henrich (1999).
bAdjusted Daily Dose was calculated from the average daily Fyrol PCF consumption reported by the study authors
for each dose group and is adjusted to account for the 70% TCPP content of Fyrol PCF.
°Mean ± SD (% change from control).
dp < 0.05 compared to control.
Table B.2. Changes in Organ Weights Following 13-Week TCPP Treatment in CD Rats"

ppm Fyrol PCF in diet (TCPP Adjusted Daily Dose to males, females in mg/kg-d)b
0
800 (36,43)
2500 (112,120)
7500 (337, 399)
20,000 (944,1222)
Absolute liver
weight (g)c
Male
11.78 ± 1.04
13.65 ± 1.87 (16)d
13.99 ± 1.93 (19)d
13.56 ± 1.76 (15)d
15.47 ±2.34 (3 l)d
Female
6.63 ± 0.84
6.93 ±0.87 (4.5)
6.99 ±0.81 (5.4)
7.77 ± 1.21 (17)d
7.74 ±0.95 (17)d
Relative liver
weight (g)c
Male
24.06 ± 1.73
27.82 ± 3.42 (16)d
29.37 ± 3.38 (22)d
28.63 ± 1.72 (19)d
34.08 ± 2.99 (42)d
Female
25.15 ±2.25
26.1 ±2.08 (3.7)
26.57 ±1.65 (5.6)
31.04 ±4.09 (23)d
33.45 ± 5.00 (33)d
Relative
kidney weight
(g)c
Male
5.63 ±0.56
5.82 ±0.42 (3.4)
6.19 ±0.59 (9.9)
6.37 ± 0.49 (13)d
6.54 ±0.60 (16)d
Female
6.51 ±0.72
6.45 ±0.58 (0.9)
6.27 ±0.65 (3.7)
6.65 ±0.61 (2.2)
7.06 ± 1.18(8.4)
aSource: Freudenthal and Henrich (1999).
bAdjusted Daily Dose was calculated from the average daily Fyrol PCF consumption reported by the study authors for
each dose group and is adjusted to account for the 70% TCPP content of Fyrol PCF.
°Mean ± SD (% change from control).
dp < 0.05 compared to control.
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Table B.3. Histopathological Changes Following 13-Week TCPP Treatment in CD Rats"

ppm Fyrol PCF in diet (TCPP Adjusted Daily Dose to males, females in mg/kg-d)b
0
800 (36, 43)
2500 (112,120)
7500 (337, 399)
20,000 (944,1222)
Thyroid
follicular
hyperplasia
Male
5
5
3
10
8
Female
0
2
2
9
5
Liver
periportal
swelling
Male
0
0
0
0
9
Female
5
0
0
0
8
Renal cortical
tubular
degeneration
Male
0
0
0
13
7
Female
1
0
0
0
4
"Source: Freudenthal and Henrich (1999).
bAdjusted Daily Dose was calculated from the average daily Fyrol PCF consumption reported by the study authors
for each dose group and is adjusted to account for the 70% TCPP content of Fyrol PCF.
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Table B.4. Average Body Weight" in Male Mice Exposed to TCPP in the Diet for 14 Weeksb
TCPPC
Weeks on Study
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0
21.7 ±
1.1
23.3 ±
1.0
24.0 +
1.8
25.0 +
1.1
25.4 +
1.2
27.1 +
1.6
27.8 +
2.0
28.9 +
2.2
29.6 +
2.5
30.9 +
2.6
31.5 +
2.8
32.4 +
3.5
32.6 +
3.8
33.3 +
3.9
1250
(219)
21.9 +
0.9
(+0.9)
23.1 +
0.8
(-0.6)
24.0 +
0.9
(0)
24.9 +
1.1
(-0.4)
25.6 +
1.6
(+0.7)
26.6 +
1.7
(-1.8)
27.3 +
1.8
(-1.5)
28.5 +
2.0
(-1.5)
28.9 +
2.2
(-2.3)
29.4 +
1.6
(-4.8)
29.8 +
1.9
(-5.3)
30.9 +
2.1
(-4.6)
31.2 +
2.2
(-4.5)
32.0 +
2.1
(-3.9)
2500
(456)
21.8 ±
0.9
(+0.6)
22.9 +
0.9
(-1.5)
23.7 +
0.9
(-1.1)
24.6 +
0.8
(-1.6)
25.2 +
1.0
(-0.9)
25.7 +
1.2
(-5.3)
26.4 +
1.4
(-4.9)
27.5 +
1.3
(-5.0)
27.5 +
1.4
(-7.1)
27.5 +
3.0
(-11.1)*
28.4 +
2.0
(-9.7)
29.1 +
2.3
(-10.0)
29.1 +
2.1
(-10.9)
29.7 +
2.4
(-10.7)*
5000
(737)
21.9±
0.8
(+0.9)
22.3 +
1.0
(-4.2)
23.1 +
1.0
(-3.7)
23.6 +
0.9
(-5.4)*
24.0 +
1.1
(-5.6)*
24.7 +
1.0
(-8.9)*
25.4 +
1.0
(-8.5)*
25.9 +
0.9
(-10.4)
26.2 +
1.0
(-11.4)*
26.7 +
1.0
(-13.4)*
26.8 +
0.8
(-14.9)*
27.9 +
1.1
(-13.9)*
27.5 +
1.0
(-15.7)*
27.9 +
1.2
(-16.1)*
10,000
(2470)
21.2 ±
0.9
(-2.0)
21.7 +
0.6
(-6.9)*
22.3 +
0.5
(-7.0)*
22.8 +
0.5
(-8.9)*
22.9 +
0.5
(-9.7)*
23.9 +
0.9
(-11.9)*
24.2 +
0.6
(-12.8)*
24.8 +
0.7
(-14.3)*
25.0 +
0.7
(-15.6)*
24.0 +
2.7
(-22.2)*
25.1 +
1.0
(-20.2)*
25.9 +
1.3
(-20.1)*
25.6 +
1.1
(-21.6)*
25.3 +
2.8
(-24.2)*
20,000
(4410)
20.2 ±
0.7
(-6.6)*
20.1 +
1.7
(-13.5)*
21.0 +
0.8
(-12.3)*
21.5 +
0.6
(-14.1)*
21.8 +
0.9
(-14.1)*
22.1 +
0.7
(-18.2)*
22.7 +
0.8
(-18.1)*
23.4 +
0.8
(-19.2)*
23.3 +
0.9
(-21.2)*
23.9 +
0.9
(-22.6)*
24.0 +
0.8
(-23.7)*
25.0 +
0.9
(-22.8)*
24.4 +
1.0
(-25.2)
23.8 +
2.5
(-28.7)*
aAverage body weight expressed as mean ± SD in g (% change from control).
bSource: NTP (2011b).
°TCPP dose expressed as ppm in feed (mg/kg-day).
* Significantly different from control at p< 0.05 based on ANOVA and subsequent Dunnett's test performed for this review.
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Table B.5. Average Body Weight" in Female Mice Exposed to TCPP in the Diet for 14 Weeksb
TCPPC
Weeks on Study
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0
17.7 ±
1.1
18.8 ±
0.9
19.8 ±
1.1
20.4 ±
0.7
20.6 ±
0.8
21.8 ±
1.1
21.8 ±1.0
22.2 ±
0.8
23.3 +
0.9
24.4 +
0.7
23.4 +
1.5
24.0 +
1.2
24.6 +
(1.0)
24.5 +
1.0
1250
(198)
17.7 ±
0.8
(0)
18.8 ±
0.6
(0)
19.5 ±
0.7
(-1.9)
20.4 ±
0.9
(0)
20.6 ±
0.7
(0)
21.7 ±
0.5
(-0.5)
22.4 ±
0.7
(+2.6)
22.8 ±
0.6
(+3.0)
24.1 +
0.8
(+3.3)
24.7 +
0.8
(+1.1)
24.9 +
1.0
(+6.5)
24.7 +
0.9
(+2.6)
25.3 +
0.7
(+2.7)
21.6 +
0.5
(-12)*
2500
(420)
17.7 ±
0.6
(0)
14.6 ±
0.8
(-22.1)*
19.0 ±
0.9
(-4.4)
19.7 ±
0.8
(-3.2)
20.2 ±
0.5
(-1.6)
21.6 ±
0.8
(-1.0)
22.0 ±
0.8
(+0.9)
22.0 +
0.8
(-0.8)
23.2 +
0.8
(-0.7)
24.0 +
0.9
(-1.6)
24.5 +
0.8
(+4.7)
24.0 +
0.8
(0)
25.0 +
0.8
(+1.4)
22.7 +
3.0
(-7.5)
5000
(906)
17.4 ±
1.0
(-2.1)
16.6 ±
1.8
(-11.7)*
18.6 ±
1.0
(-6.3)*
19.5 ±
1.2
(-4.4)
19.9 ±
0.9
(-3.4)
20.8 ±
1.1
(-4.8)*
21.4 ±
1.3
(-1.9)
21.5 +
0.9
(-3.2)
22.2 +
0.8
(-5.0)*
23.1 +
1.0
(-5.3)*
23.1 +
0.9
(-1.2)
22.8 +
1.2
(-5.2)*
23.4 +
1.2
(-5.2)*
23.8 +
1.1
(-2.9)
10,000
(1930)
17.3 ±
0.7
(-2.6)
17.7 ±
0.6
(-5.7)
18.0 ±
0.7
(-9.1)*
18.6 ±
0.6
(-8.7)*
19.0 ±
0.8
(-7.8)*
19.9 ±
0.8
(-8.9)*
20.1 ±
0.9
(-7.8)*
20.5 +
0.9
(-7.5)*
21.1 +
0.7
(-9.6)*
22.1 +
1.0
(-9.4)*
22.2 +
1.0
(-5.1)*
21.7 +
0.9
(-9.5)*
22.2 +
1.3
(-9.9)*
22.2 +
1.4
(-9.5)*
20,000
(3590)
16.2 ±
1.0
(-8.6)*
17.3 ±
0.8
(-8.0)*
17.7 ±
0.8
(-10.9)*
17.8 ±
0.9
(-12.6)*
18.1 ±
0.8
(-11.8)*
18.8 ±
1.0
(-13.7)*
18.8 ±
0.8
(-13.8)*
18.8 +
1.1
(-15.2)*
19.8 +
0.8
(-15.3)*
20.4 +
0.9
(-16.5)*
20.5 +
1.0
(-12.3)*
20.5 +
1.0
(-14.7)
19.9 +
1.1
(-19.4)*
20.8 +
1.0
(-15.2)*
aAverage body weight expressed as mean ± SD in g (% change from control).
bSource: NTP (2011b).
°TCPP dose expressed as ppm in feed (mg/kg-day); dose adjusted using food consumption and body weight data reported in the study.
* Significantly different from control at p< 0.05 based on ANOVA and subsequent Dunnett's test performed for this review.
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Table B.6. Food Consumption, Liver Weight Change, and Hepatocyte Hypertrophy in Mice
Treated with TCPP in the Diet for 14 Weeks"
Males
TCPP dose (ppm in diet [mg/kg-d])b
0
1250
(219)
2500
(456)
5000
(737)
10,000
(2470)
20,000
(4410)
Mean daily food consumption (g [% change
from control])
4.6
4.8 (4)
4.8 (4)
5.2 (13)
5.9 (28)
5.0 (9)
Relative liver weight (% change from
control)
N/A
5°
llc
21°
40°
94°
Hepatocyte hypertrophy (# affected/total)
0/10
0/10
3/10
4/10
10/10d
10/10d
Females
TCPP dose (ppm in diet [mg/kg-d])b
0
1250
(198)
2500
(420)
5000
(906)
10,000
(1930)
20,000
(3590)
Mean daily food consumption (g [% change
from control])
3.3
3.5 (6)
3.6 (9)
3.8 (15)
3.7(12)
3.4(3)
Relative liver weight (% change from
control)
N/A
4°
6
llc
19°
47°
Hepatocyte hypertrophy (# affected/total)
0/10
0/10
0/10
5/10d
10/10d
10/10d
"Source: NTP (2011a).
bDose adjusted using food consumption and body weight data reported in the study.
Statistically different from control at p< 0.05 as reported by study authors.
Statistically different from control at p< 0.05 based on Fisher's Exact test performed for this review.
N/A: Not Applicable.
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APPENDIX C. BMD OUTPUTS
MODEL-FITTING PROCEDURE FOR QUANTAL NONCANCER DATA
The model-fitting procedure for dichotomous noncancer data is as follows. All available
dichotomous models in the EPA BMDS (version 2.1) are fit to the incidence data using the extra
risk option. The multistage model is run for all polynomial degrees up to n - 1 (where n is the
number of dose groups including control). Adequate model fit is judged by three criteria:
goodness-of-fit p-value (p > 0.1), visual inspection of the dose-response curve, and scaled
residual at the data point (except the control) closest to the predefined benchmark response
(BMR). Among all the models providing adequate fit to the data, the lowest BMDL is selected
as the POD when the difference between the BMDLs estimated from these models is more than
3-fold (unless it is an outlier); otherwise, the BMDL from the model with the lowest Akaike
Information Criterion (AIC) is chosen. In accordance with EPA (2000) guidance, benchmark
doses (BMDs) and lower bounds on the BMD (BMDLs) associated with a BMR of 10% extra
risk are calculated for all models.
MODEL-FITTING RESULTS FOR HEPATOCYTE HYPERTROPHY IN MALE MICE
(NTP, 2011a)
Applying the procedure outlined above to the data (see Table B.6) for hepatocyte
hypertrophy in male mice exposed subchronically to TCPP via diet for 14 weeks (NTP, 201 la),
all models provided adequate fit to the data (see Table C. 1). However, the first-degree
multistage model and the quantal-linear model provided poor fit in the low-dose region and were
excluded from consideration. Of the remaining models, the BMDLi0s differed by less than
3-fold, so the model with the lowest AIC (second-degree multistage) was selected. The BMDio
and BMDLio for hepatocyte hypertrophy in male mice were 310 and 138 mg/kg-day,
respectively. Figure C. 1 shows the fit of the second degree multistage model to the data.
33
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Table C.l. Model Predictions for the Incidence of Hepatocyte Hypertrophy
in Male Mice Treated with TCPP in the Diet for 14 Weeks
Model
Degrees of
Freedom
x2
X2 Goodness-of-Fit
/>-Valuc
AIC
BMD10
(mg/kg-d)
BMDL10
(mg/kg-d)
Gammab
4
1.31
0.8593
31.2323
345.328
177.454
Logistic
4
2.3
0.6813
32.4306
380.604
252.026
Log-Logistic0
4
1.84
0.7647
31.858
363.451
220.08
Log-Probitc
4
1.44
0.8367
31.3251
360.007
225.345
Multistage (degree = l)d
5
3.92
0.5611
34.6386
117.803
79.3911
Multistage (degree = 2)d
5
1.22
0.9425
29.3711
310.099
138.32
Multistage (degree = 3)d
4
1.25
0.8691
31.3627
315.472
123.483
Multistage (degree = 4)d
3
1.25
0.7419
33.3613
314.203
118.179
Multistage (degree = 5)d
4
1.23
0.8726
31.3542
312.626
116.479
Probit
4
1.99
0.738
32.0008
366.693
238.462
Weibullb
4
1.3
0.8612
31.3404
326.299
161.844
Quantal-Linear
5
3.92
0.5611
34.6386
117.803
79.3911
aValues <0.10 fail to meet conventional goodness-of-fit criteria.
bPower restricted to >1.
°Slope restricted to >1.
dBetas restricted to >0.
AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the dose/concentration associated
with the selected benchmark response; BMDL = 95% lower confidence limit on the BMD.
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Multistage Model with 0.95 Confidence Level
Multistage
0.8
0.6
0.4
0.2
BMDL
BMD
0
500
1000 1500 2000 2500 3000 3500 4000 4500
dose
16:34 03/24 2011
BMDs and BMDLs indicated are associated with an extra risk of 10% and are in units of
mg/kg-day (5 days/week).
Figure C.l. Fit of Multistage (degree = 2) Model to Data on Hepatocyte Hypertrophy in
Male Mice Treated with TCPP in the Diet for 14 Weeks
MODEL-FITTING RESULTS FOR HEPATOCYTE HYPERTROPHY IN FEMALE
MICE (NTP, 2011a)
Applying the procedure outlined above to the data (see Table B.6) for hepatocyte
hypertrophy in female mice exposed subchronically to TCPP via the diet for 14 weeks (NTP,
201 la), all models provided adequate fit to the data except for the first-degree multistage model,
the Weibull model, and the quantal-linear model (see Table C.2). Of the remaining models, the
BMDLios differed by less than 3-fold, so the model with the lowest AIC (log-logistic) was
selected. The BMDio and BMDLio for hepatocyte hypertrophy in female mice were 802 and
470 mg/kg-day, respectively. Figure C.2 shows the fit of the log-logistic model to the data.
35	Tris( 1 -chloro-2-propyl)phosphate

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Table C.2. Model Predictions for the Incidence of Hepatocyte Hypertrophy
in Female Mice Treated with TCPP in the Diet for 14 Weeks
Model
Degrees of
Freedom
x2
X2 Goodness-of-Fit
/>-Valuc
AIC
BMD10
(mg/kg-d)
BMDL10
(mg/kg-d)
Gammab
5
0.02
1
15.9118
658.262
432.104
Logistic
4
0
1
17.8629
849.083
473.396
Log-Logisticc
5
0
1
15.863
801.89
470.386
Log-Probitc
4
0
1
17.8629
773.617
451.846
Multistage (degree = l)d
5
9.34
0.0961
32.1341
124.7
85.3798
Multistage (degree = 2)d
5
2.57
0.7658
20.7235
353.942
243.55
Multistage (degree = 3)d
5
0.81
0.9764
17.4037
498.207
335.397
Multistage (degree = 4)d
5
0.34
0.9968
16.5128
575.256
375.808
Multistage (degree = 5)d
4
0.32
0.9888
18.4686
581.405
373.335
Probit
4
0
1
17.8629
795.498
440.581
Weibullbe



13.8644


Quantal-Linear
5
9.34
0.0961
32.1341
124.7
85.3798
aValues <0.10 fail to meet conventional goodness-of-fit criteria.
bPower restricted to >1.
°Slope restricted to >1.
dBetas restricted to >0.
eModel failed to reach convergence in the allowed number of iterations (250).
AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the dose/concentration associated
with the selected benchmark response; BMDL = 95% lower confidence limit on the BMD.
36
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Log-Logistic Model with 0.95 Confidence Level
0.8
0.6
0.4
0.2
Log-Logistic
BMDL
500 1000 1500 2000 2500 3000 3500
16:23 03/30 2011
BMDs and BMDLs indicated are associated with an extra risk of 10% and are in units of
mg/kg-day (5 days/week).
Figure C.2. Fit of Log-logistic Model to Data on Hepatocyte Hypertrophy in Female Mice
Treated with TCPP in the Diet for 14 Weeks
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MODEL-FITTING PROCEDURE FOR CONTINUOUS DATA
The model-fitting procedure for continuous data is as follows. The simplest model
(linear) in the EPA's BMD software (BMDS version 2.1.2) is first applied to the data while
assuming constant variance. If the data are consistent with the assumption of constant variance
(p> 0.1), then all of the available models are fit to the data while assuming constant variance.
Among the models providing adequate fit to the means (p> 0.1), the one with the lowest AIC for
the fitted model is selected for BMD derivation. If the test for constant variance is negative, the
models are run again while applying the power model integrated into the BMDS to account for
nonhomogenous variance. If the nonhomogenous variance model provides an adequate fit
(p> 0.1) to the variance data, then a model is chosen for BMD derivation based on adequate fit
to the means (p> 0.1) and lowest AIC. If the test for constant variance is negative and the
nonhomogenous variance model does not provide an adequate fit to the variance data, then the
data set is considered unsuitable for modeling.
MODEL-FITTING RESULTS FOR TERMINAL BODY WEIGHT IN MALE MICE
(NTP, 2011b)
Applying the procedure outlined above to the data (see Table B.4) for terminal body
weight in male mice exposed subchronically to TCPP via the diet for 14 weeks (NTP, 201 lb),
the variance was nonhomogenous and could not be modeled using the Power model in the BMD
software (see Table C.3). Therefore, these data are unsuitable for modeling. However, terminal
body weight and relative liver weight in male mice (which was also unsuitable for modeling due
to lack of means and standard deviations in data reporting) provided the lowest LOAEL and
NOAEL for the NTP (201 la,b) study. These values were 456 and 219 mg/kg-day, respectively.
BMD modeling of the incidence of hepatocyte hypertrophy was possible, and the BMDLio
(138 mg/kg-day) was lower than the NOAEL for liver and body weights. While the variance
models did not fit for terminal body weight in male mice, three models provide adequate fit to
the means (4th and 5th degree exponential models and the Hill model). Comparing the BMDios
from these models (389-419 mg/kg-day) to the BMDio for hepatocyte hypertrophy in males
(310 mg/kg-day) confirms that hepatocyte hypertrophy is a more sensitive effect than decreased
terminal body weight and, therefore, is an appropriate POD.
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Table C.3. Model Predictions for Terminal Body Weight in Male Mice Treated with TCPP in
the Diet for 14 Weeks"
Model
Variance
/;-Valueh
Means
/>-Valueb
AIC
BMDio
(mg/kg-d)
BMDL10
(mg/kg-d)
Constant variance
Exponential (degree = 2)
0.02296
0.004434
189.9877
1409.6
1164.08
Exponential (degree = 3)
0.02296
0.004434
189.9877
1409.6
1164.08
Exponential (degree = 4)
0.02296
0.6846
178.345
407.283
266.856
Exponential (degree = 5)
0.02296
0.6846
178.345
407.283
266.856
Hill0
0.02296
0.6892
179.599717
419.41
244.768
Linear1
0.02296
0.001763
192.06049
1603.47
1358.42
Polynomial0
0.02296
0.001763
192.06049
1603.47
1358.42
Power0
0.02296
0.001763
192.06049
1603.47
1358.42
Modeled variance
Exponential (degree = 2)
0.01867
0.003127
191.5604
1455.97
1177.79
Exponential (degree = 3)
0.01867
0.003127
191.5604
1455.97
1177.79
Exponential (degree = 4)
0.01867
0.6247
179.3946
389.155
245.682
Exponential (degree = 5)
0.01867
0.6247
179.3946
389.155
245.682
Hill0
0.01867
0.6216
180.590222
390.25
241.934
Linear1
0.01867
0.00126
193.593512
1651.91
1373.53
Polynomial0
0.01867
0.00126
193.593512
1651.91
1373.53
Power0
0.01867
0.00126
193.593512
1651.91
1373.53
aNTP (2011b).
bValues <0.10 fail to meet conventional goodness-of-fit criteria.
°Power restricted to >1.
Coefficients restricted to be positive.
MODEL-FITTING RESULTS FOR TERMINAL BODY WEIGHT IN FEMALE MICE
(NTP, 2011b)
The data for terminal body weight in female mice cannot be modeled due to a
nonmonotonic dose-response curve (see Table B.5).
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APPENDIX D. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2011) Threshold limit
values for chemical substances and physical agents and biological exposure indices. Cincinnati,
OH. As cited in HSDB (Hazardous Substances Data Bank). Available online at
http://toxnet.nlm.nih.eov/cei-bin/sis/htmleen7HSDB. Accessed on 9/12/2011. 783980
Albright and Wilson Americas. (1989) Eighteen health and safety studies on antiblaze 80 with
cover letter dated 021389. Albright & Wilson Americas, Inc. Glen Allen, VA; Report No.
TSCATS 311056 EPA/OTS Doc. #86-890000114. OTS# 0517715. 659039
ATSDR (Agency for Toxic Substances and Disease Registry). (2009) Draft toxicological
profile for phosphate ester flame retardants. U.S. Department of Health and Human Services,
Public Health Service, Atlanta, GA. Available online at
http://www.atsdr.cdc.eov/toxprofiles/tp202.pdf. Accessed on 9/12/2011. 1325317
Bayer, AG. (1993) Tris-chloroisopropylphosphate, vorversuch zur dosisfindung fur eine
subakute toxikologische studie an mannlichen wistar-ratten (in german) with cover letter dated
11/15/93. Germany, Report No. 86940000032. Available online at
http://www.ntis.eov/search/product.aspx?ABBR=OTS0556628. Translation provided on
December 30, 2010. 656603
CalEPA (California Environmental Protection Agency). (2008) All OEHHA acute, 8-hour and
chronic reference exposure levels (chRELs) as of December 18, 2008. Office of Environmental
Health Hazard Assessment, Sacramento, CA. Available online at
http://www.oehha.ca.eov/air/chronic rets/AllChrels.html. Accessed on 9/12/2011. 595416
CalEPA (California Environmental Protection Agency). (2009) OEHHA toxicity criteria
database. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available
online at http://www.oehha.ca.eov/risk//ChemicalDB/index.asp. Accessed on 9/12/2011.
595417
Dishaw, LV; Powers, CM; Ryde, IT; et al. (2011) Is the PentaBDE replacement, tris (1,3-
dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC 12 cells.
ToxicolApplPharmacol In press. Doi:10.1016/j.taap.2011.01.005. 781782
Follmann, W; Wober, J. (2006) Investigation of cytotoxic, genotoxic, mutagenic, and
estrogenic effects of the flame retardants tris-(2-chloroethyl)-phosphate (TCEP) and
tris-(2-chloropropyl)-phosphate (TCPP) in vitro. Toxicol Lett 161:124-134. Available online at
http://dx.doi.or6	.toxlet.2005.08.008. 656597
Freudenthal, RI; Henrich, RT. (1999) A subchronic toxicity study of Fyrol PCF in
Sprague-Dawley Rats. IntJ Toxicol 18(3):173—176. 679695
IARC (International Agency for Research on Cancer). (2011) Monographs on the evaluation of
carcinogenic risks to humans. Lyon, France: IARC. Available online at
http://monoeraphs.iarc.fr/ENG/Monoeraphs/PDFs/index.php. Accessed on 9/12/2011. 783869
40	Tris( 1 -chloro-2-propyl)phosphate

-------
FINAL
11-29-2012
IPCS (International Programme for Chemical Safety). (1998) Flame retardants:
Tris(chloropropyl) phosphate and tris(2-chloroethyl) phosphate. Environmental Health Criteria
209. Geneva: WHO. Available online at http://whqlibdoc.who.int/ehcAVHO EHC 209.pdf.
Accessed on 9/12/2011. 1325318
Kawasaki, H; et al. (1982) Studies on the toxicity of insecticides and food additives in pregnant
rats-(5) foetal toxicity of tris-(chloropropyl) phosphate. Chemical Manufacturers Association.
Submitted to the U.S. Environmental Protection Agency under TSCA Section 8D.
EPA86-950000008. OTS0557521. Translation provided in NMS (1994). 1325319
Mehlman, MA; Mackerer, CR; Schreiner, A. (1980) An Ames Salmonella/mammalian
microsome mutagenesis assay for determination of potential mutagenecity of
tris-(2-chloropropyl) phosphate. Mobil Environmental and Health Science Laboratory,
Princeton, NJ, Report No. 471-80. As cited in OECD (2000). 656588
Minegishi, KI; Kurebayashi, H; Nambaru, S; et al. (1988) Comparative studies on absorption,
distribution, and excretion of flame retardants halogenated alkyl phosphate in rats. Jap J Toxicol
Environ Health 34(2): 102-114. 656593
Mobil Oil Corporation. (1981) A murine lymphoma mutagenesis assay, heterozygous at the
thymidine kinase locus for the determination of the potential mutagenicity of Antiblaze 80
(unpublished). Environmental Affairs and Toxicology Department, Albright & Wilson
Americas. Inc., New York, Report No. 2422-80. As cited in OECD (2000) and Albright and
Wilson Americas (1989). 670280
Nakamura, A; Tateno, N; Kojima, S; et al. (1979) The mutagenicity of halogenated alkanols
and their phosphoric acid esters for Salmonella typhimurium. MutatRes 66(4):373-380.
Available online at http://dx.doi.org/10.1016/0165-1218(79)90048-X. 625040
NICNAS (National Industrial Chemicals Notification and Assessment Scheme). (2001)
Trisphosphates: Priority existing chemical assessment report. NICNAS, Sydney, Australia;
Report No. 17. Available online at
http://www.nicnas.gov.au/Publications/CAR/PEC/PEC17.asp. 656598
NIHS (National Institute of Health Science). (1994) Studies on the toxicity of insecticides and
food additives in pregnant rats - foetal toxicity of tris-(chloropropyl) phosphate, with cover letter
dated 10/12/94. National Institute of Health Sciences, Osaka, Report No. 86950000008.
Available online at http://www.ntis.gov/search/product.aspx?ABBR=OTSQ557521. 656604
NIOSH (National Institute for Occupational Safety and Health). (2011) NIOSH pocket guide to
chemical hazards. Index of chemical abstracts service registry numbers (CAS No.). Center for
Disease Control and Prevention, U.S. Department of Health, Education and Welfare,
Atlanta, GA. Available online at http://www.cdc.gov/niosh/npg/npgdcas.html. Accessed on
9/12/2011. 625692
NTP (National Toxicology Program). (201 la) 90 Days dosed-feed toxicity study of
tris(2-chloroisopropyl)phosphate (TCPP) (CAS No. 13674-84-5) in B6C3F1 Mice. NTP Study
Number C20712. Research Triangle Park, NC. 1325320
41	Tris( 1 -chloro-2-propyl)phosphate

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FINAL
11-29-2012
NTP (National Toxicology Program). (201 lb) Study data from study number C20712: "90
Days dosed-feed toxicity study of tris(2-chloroisopropyl)phosphate (TCPP) (CAS No.
13674-84-5) in B6C3F1. Mice". Available online at http://ntp-
apps.niehs.nih.gov/ntp tox/index.cfm?study no=C20712&study length=90%20Davs. Accessed
on 9/12/2011. 1325321
NTP (National Toxicology Program). (201 lc) 12th Report on carcinogens. U.S. Department of
Health and Human Services, Public Health Service, National Institutes of Health, Research
Triangle Park, NC. Available online at http://ntp-server.niehs.nih. gov/?obiectid=03C9AF75-
E - ' ' ' 40-D6A9EC0928DF8B15. Accessed on 9/12/2011. 737606
OSHA (Occupational Safety and Health Administration). (2006) Air contaminants:
occupational safety and health standards for shipyard employment, subpart Z, toxic and
hazardous substances. U.S. Department of Labor, Washington, DC; OSHA Standard 1915.1000.
Available online at http://www.osha.gov/pls/oshaweb/owadisp.show document?p table=
STANDARDS&p id=10286. Accessed on 9/12/2011. 625691
Sprague, GL; Sandvik, LL; Brookins-Hendricks, MJ; et al. (1981) Neurotoxicity of two
organophosphorus ester flame retardants in hens. J Toxicol Environ Health 8(3):507-518.
Available Online at http://dx.doi.org/10.1080/15287398109530Q87. 656590
Stauffer Chemical Company. (1978a) Mutagenicity evaluation of Fyrol PCF in the Ames
Salmonella/microsome plate test. Stauffer Chemical Company, Westport, CT; Report No.
T6361. As cited in OECD (2000). 656591
Stauffer Chemical Company. (1978b) Mutagenicity evaluation of Fyrol PCF in the mouse
lymphoma forward mutation assay. Stauffer Chemical Company, Westport, CT, Report No.
T6343A. As cited in OECD (2000). 656594
Stauffer Chemical Company. (1978c) Mutagenicity evaluation of Fyrol PCF in the in vitro
transformation of BALB/3T3 cells assay. Stauffer Chemical Company, Westport, CT; Report
No. T6357A. As cited in OECD (2000). 672972
Stauffer Chemical Company. (1978d) Evaluation of Fyrol PCF, Lot #8400-3-10 in the in vitro
transformation of BALB/3T3 cells assay. Stauffer Chemical Company; Westport, CT, Report
No. T-6359; Litton Project No. 20992. As cited in OECD (2000). 672973
Stauffer Chemical Company. (1978e) Evaluation of Fyrol PCF Lot 8400-3-10 in the
unscheduled DNA synthesis in human WI-38 cells assay. Stauffer Chemical Company,
Westport, CT; Report No. T6359; Litton Project No. 20991. As cited in OECD (2000). 656592
Stauffer Chemical Company (1978f) Mutagenicity evaluation of Fyrol PCF (Lot No. 4800-3-10)
in the rat bone marrow cytogenetic analysis. Stauffer Chemical Company, Westport, CT; Report
No. T-6539. As cited in OECD (2000). 672971
Stauffer Chemical Company. (1980a) Fyrol PCF: A two-week acute dietary range-finding study
in male and female Charles River Sprague-Dawley derived rats. Stauffer Chemical Company,
Westport, CT; Report No. T-10112. As cited in OECD (2000). 656596
42	Tris( 1 -chloro-2-propyl)phosphate

-------
FINAL
11-29-2012
Stauffer Chemical Company. (1980b) Fyrol PCF (Lot No. 4800-3-10) morphologic
transformation of BALB/3T3 cells. Stauffer Chemical Company, Westport, CT; Report No.
T-10182. As cited in OECD (2000). 672970
Stauffer Chemical Company. (1981) Fyrol PCF: 3-month dietary subchronic study in rats.
Stauffer Chemical Company, Westport, CT; Report No. T-10118. As cited in OECD (2000).
1325323
Stauffer Chemical Company. (1984) Fyrol PCF metabolism/pharmacokinetic study in rats,
stauffer chemical company, Westport, CT; Report No. T-10851. As cited in OECD (2000).
672969
OECD (Organisation for Economic Co-operation and Development). (2000) Tris(l-chloro-
2-propyl)phosphate. Screening Information Data Set (SIDS). Geneva, Switzerland: UNEP
Publications. Available online at http://www.chem.unep.ch/irptc/sids/oecdsids/13674845.pdf.
656600
U.S. EPA (Environmental Protection Agency). (1988) Recommendations for and
documentation of biological values for use in risk assessment. Environmental Criteria and
Assessment Office, Cincinnati, OH; EPA/600/6-87/008. Available online at
http://cfpub.epa.eov/ncea/cfm/recordisplav.cfm?deid=34855#Download. 064560
U.S. EPA (Environmental Protection Agency). (1994a) Chemical assessments and related
activities (CARA). Office of Health and Environmental Assessment, Washington, DC;
EPA/600/R-94/904. Available online at
http://nepis.epa.eov/Exe/ZyPURL.cgi?Dockev=6000lG8L.txt. 596444
U.S. EPA (Environmental Protection Agency). (1994b) Methods for derivation of inhalation
reference concentrations (RfCs) and application of inhalation dosimetry. Office of Research and
Development, Office of Health and Environmental Assessment, Washington, DC;
EPA/600/8-90/066F. Available online at http://cfpub.epa.eov/ncea/cfm/recordisplav.cfm?deid=
71993. 006488
U.S. EPA (Environmental Protection Agency). (2009) 2009 Edition of the drinking water
standards and health advisories. Office of Water, Washington, DC; EPA/822/R-09/011.
Available online at http://deq.state.wv.us/wqd/eroundwater/downloads/dwstandards
2009°o5Bl°o5D.pdf. Accessed on 9/12/2011. 086237
U.S. EPA (Environmental Protection Agency). (201 la) Integrated risk information system
(IRIS). Office of Research and Development, National Center for Environmental Assessment,
Washington, DC. Available online at http://www.epa.gov/iris/. Accessed on 9/12/2011. 003752
U.S. EPA (Environmental Protection Agency). (201 lb) Health effects assessment summary
tables (HEAST). 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. Available online at http://epa-heast.ornl.eov/. Accessed on 9/12/2011.
595422
43	Tris( 1 -chloro-2-propyl)phosphate

-------
FINAL
11-29-2012
Zeiger, E; Anderson, B; Haworth, S; et al. (1992) Salmonella mutagenicity tests: V. Results
from the testing of 311 chemicals. Environ MolMutagen 19(Suppl 21):2—141. Available online
at http://dx.doi.ore/10.1002/em.2850190603. 095748
44	Tris( 1 -chloro-2-propyl)phosphate

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