United States
Environmental Protection
1=1 m m Agency
EPA/690/R-13/005F
Final
8-27-2013
Provisional Peer-Reviewed Toxicity Values for
3,4-Dichlorobenzotrifluoride
(CASRN 328-84-7)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268
-------
AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Jeff Swartout
National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY
ICF International
9300 Lee Highway
Fairfax, VA 22031
PRIMARY INTERNAL REVIEWERS
Audrey Galizia, DrPH
National Center for Environmental Assessment, Washington, DC
Q. Jay Zhao, PhD, MPH, DABT
National Center for Environmental Assessment, Cincinnati, OH
This document was externally peer reviewed under contract to
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the contents of this document may be directed to the U.S. EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center (513-569-7300).
-------
TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS ii
BACKGROUND 1
DISCLAIMERS 1
QUESTIONS REGARDING PPRTVs 1
INTRODUCTION 2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER) 4
HUMAN STUDIES 7
ANIMAL STUDIES 7
Oral Exposure 7
Inhalation Exposure 10
OTHER DAT A 10
DERIVATION 01 PROVISIONAL VALUES 12
DERIVATION OF ORAL REFERENCE DOSES 13
Derivation of Subchronic Provisional RfD (Subchronic p-RfD) 13
Derivation of Chronic Provisional RfD (Chronic p-RfD) 13
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS 13
Derivation of Subchronic Provisional RfC (Subchronic p-RfC) 13
Derivation of Chronic Provisional RfC (Chronic p-RfC) 13
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR 13
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES 14
Derivation of Provisional Oral Slope Factor (p-OSF) 14
Derivation of Provisional Inhalation Unit Risk (p-IUR) 14
APPENDIX A. PROVISIONAL SCREENING VALUES 15
APPENDIX B. DATA TABLES 18
APPENDIX C. BMD MODELING OUTPUTS 19
APPENDIX D. REFERENCES 20
l
3,4-Di chl orob enzotrifluori de
-------
COMMONLY USED ABBREVIATIONS
BMC
benchmark concentration
BMCL
benchmark concentration lower confidence limit
BMD
benchmark dose
BMDL
benchmark dose lower confidence limit
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 inhalation reference concentration
p-RfD
provisional oral reference dose
RfC
inhalation reference concentration
RfD
oral reference dose
UF
uncertainty factor
UFa
interspecies uncertainty factor
UFC
composite uncertainty factor
UFd
database uncertainty factor
UFh
intraspecies uncertainty factor
UFl
LOAEL-to-NOAEL uncertainty factor
UFS
subchronic-to-chronic uncertainty factor
WOE
weight of evidence
11
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
3,4-DICHLOROBENZOTRIFLUORIDE (CASRN 328-84-7)
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 (www.epa.eov/iris). the respective PPRTVs are removed
from the database.
DISCLAIMERS
The PPRTV document provides toxicity values and information about the adverse effects
of the chemical and the evidence on which the value is based, including the strengths and
limitations of the data. All users are advised to review the information provided in this
document to ensure that the PPRTV used is appropriate for the types of exposures and
circumstances at the site in question and the risk management decision that would be supported
by the risk assessment.
Other U.S. Environmental Protection Agency (EPA) programs or external parties who
may choose to use PPRTVs are advised that Superfund resources will not generally be used to
respond to challenges, if any, of PPRTVs used in a context outside of the Superfund program.
QUESTIONS REGARDING PPRTVs
Questions regarding the contents and appropriate use of this PPRTV assessment should
be directed to the U.S. EPA Office of Research and Development's National Center for
Environmental Assessment, Superfund Health Risk Technical Support Center (513-569-7300).
1
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
INTRODUCTION
3,4-Dichlorobenzotrifluoride (3,4-DCBTF; CASRN 328-84-7; also known as
l,2-dichloro-4-[trifluoromethyl]-benzene) is a clear liquid solvent used as an intermediate in the
preparation of diphenyl ether herbicides such as acifluorfen and oxyfluorfen (U.S. EPA, 1987;
Yih and Swithenbank. 1975). It may also be used as a single-phase fluid in industrial cleaning
applications (Chen and Lindrose. 2000). The empirical formula for 3,4-DCBTF is C7H3CI2F3,
and its structure is shown in Figure 1, and the physicochemical properties of 3,4-DCBTF are
provided below in Table 1.
F
CI
CI
Figure 1. Structure of 3,4-Dichlorobenzotrifluoride
Table 1. Physicochemical Properties of 3,4-Dichlorobenzotrifluoride
(l,2-dichloro-4-[trifluoromethyl]-benzene); CASRN 328-84-7a
Property (unit)
Value
Boiling point (°C)
173.5°C
Melting point (°C)
-12
Density (g/cm3)
1.478
Vapor pressure (mm Hg at 20°C)
1.6 rninHg
pH (unitless)
ND
Solubility in water (ml/L at 23 °C)
11.6
Relative vapor density (air = 1)
ND
Molecular weight (g/mol)
214.9993
Flash point (°C)
77
Octanol/water partition coefficient (unitless)
ND
aValues from U.S. EPA (2005) and (ChemBlink).
ND = no data.
2
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
A summary of available toxicity values for 3,4-DCBTF from U.S. EPA and other
agencies/organizations is provided in Table 2.
Table 2. Summary of Available Toxicity Values for 3,4-Dichlorobenzotrifluoride
Source/Parameter"
Value
(Applicability)
Notes
Reference
Date Accessed
Noncancer
ACGIH
NV
NA
fACGIH. 2013s)
NA
ATSDR
NV
NA
(ATSDR. 2013)
NA
Cal/EPA
NV
NA
(Cal/EPA. 2012b 1
NA
NIOSH
NV
NA
(NIOSH. 2010)
NA
OSHA
NV
NA
(OSHA. 2011. 2006)
NA
IRIS
NV
NA
U.S. EPA
8-1-2013
Drinking water
NV
NA
OJ.S. EPA. 2011a)
NA
HEAST
NV
NA
(U.S. EPA. 2011b)
NA
CARA HEEP
NV
NA
(TJ.S. EPA. 1994)
NA
WHO
NV
NA
WHO
8-1-2013
Cancer
IRIS
NV
NA
U.S. EPA
8-1-2013
HEAST
NV
NA
(U.S. EPA. 2011b)
NA
IARC
NV
NA
IARC
8-1-2013
NTP
NV
NA
(NTP. 2011)
NA
Cal/EPA
NV
NA
(Cal/EPA. 2012a. b.
2009)
NA
"Sources: American Conference of Governmental Industrial Hygienists (ACGIH); Agency for Toxic Substances
and Disease Registry (ATSDR); California Environmental Protection Agency (Cal/EPA); National Institute for
Occupational Safety and Health (NIOSH); Occupational Safety and Health Administration (OSHA); Chemical
Assessments and Related Activities (CARA); Health and Environmental Effects Profile (HEEP); World Health
Organization (WHO); Integrated Risk Information System (IRIS); Health Effects Assessment Summary Tables
(HEAST); International Agency for Research on Cancer (IARC); National Toxicology Program (NTP).
NA = not applicable; NV = not available.
Literature searches were conducted on sources published from 1900 through
August 2013, for studies relevant to the derivation of provisional toxicity values for
3,4-DCBTF, CAS No. 328-84-7. Searches were conducted using U.S. 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
3
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
& Statistics and Life Sciences; NSCEP/NEPIS (U.S. 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 Content database among others); World Health Organization; and
Worldwide Science. The following databases outside of HERO were searched for relevant
health information: ACGM, AT SDR, CalEPA, U.S. EPA IRIS, U.S. EPAHEAST, U.S. EPA
HEEP, U.S. EPA OW, U.S. EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS.
REVIEW OF POTENTIALLY RELEVANT DATA
(CANCER AND NONCANCER)
Table 3 provides an overview of the relevant database for 3,4-DCBTF 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.
4
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
Table 3. Summary of Potentially Relevant Data for 3,4-Dichlorobenzotrifluoride (CASRN 328-84-7)
Category
Number of
Male/Female
Strain, Species,
Study Type, and
Study Duration
Dosimetry
Critical effects
NOAEL
BMDL/
BMCL
LOAEL
Reference
(Comments)
Notes
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
Short-Term
5/5, S-D, rat, diet,
28 d
0; 2; 20; 200;
2,000 ppm in
feed (nominal)
Reduced feed consumption (12-16%) at highest
dose. No other treatment-related effects. Study
considered invalid by the study authors because of
compound volatility in feed stock; also two
unidentified contaminants present in blood and urine
samples at high levels and in stock preparation at
lower levels.
NDr
DU
NDr
Raltech Scientific
Services, Inc.
(1978; as cited in
U.S. EPA. 2005)
NPR
5
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
Table 3. Summary of Potentially Relevant Data for 3,4-Dichlorobenzotrifluoride (CASRN 328-84-7)
Category
Number of
Male/Female
Strain, Species,
Study Type, and
Study Duration
Dosimetry
Critical effects
NOAEL
BMDL/
BMCL
LOAEL
Reference
(Comments)
Notes
Short-Term
15/15, S-D, rat, diet,
5 wk
0;125; 500;
2,000 ppm in
feed (nominal)
No treatment-related effects at any dose. Study
suspended early; considered invalid by the study
authors because of compound volatility in feed.
Impurities likely in test compound preparation.
NDr
DU
NDr
Raltech Scientific
Services, Inc.
(1979)
NPR
3/3, S-D rat, gavage,
7 d/wk, 14 d
0,7.5, 15, 30,
60, 120 mg/kg-d
Effects in mean liver weights and liver/body-weight
ratio (dose groups not specified, magnitude not
specified but not statistically significant); no other
treatment-related effects observed.
NDr
DU
NDr
Elars Bioresearch
Laboratories, Inc.
(1980; as cited in
U.S. EPA. 2005s)
NPR
5/5, albino CD rat,
gavage, 7 d/wk,
14 d
0, 7.5,15, 30,
60,
120 mg/kg-d
Hyaline droplet degeneration of tubular
epithelium within the renal cortex of kidneys in
3 male rats at the highest dose; no other kidney
effects observed; increased liver weight of
unspecified magnitude at highest dose. Possible
impurities in test compound preparation.
60
DU
120
Raltech Scientific
Services, Inc.
(1980; as cited in
U.S. EPA, 2005)
PS,
NPR
Chronic
ND
Developmental
ND
Reproductive
ND
Carcinogenicity
ND
2. Inhalation
Subchronic
NA
Chronic
ND
Developmental
ND
Reproductive
ND
Carcinogenicity
ND
DU = data unsuitable; NA = not applicable; ND = no data; NDr = not determined; NPR = not peer reviewed; PS = principal study; S-D = Sprague-Dawley.
6 3,4-Dichlorobenzotrifluoride
-------
FINAL
8-27-2013
HUMAN STUDIES
No data on the effects of 3,4-DCBTF in humans following inhalation or oral exposure
were identified. It was speculated by one source (ITC. 1983) that overexposure to vapors may
cause irritation of the nose and throat (HSDB, 201 1).
ANIMAL STUDIES
Oral Exposure
Short-Term Studies
Four unpublished (non-peer-reviewed) short-term oral studies in rats were identified in
the literature.
Raltech Scientific Services, Inc. (1978; as cited in U.S. EPA, 2005); 28-day rat feeding
study
In a 28-day, Good Laboratory Practice (GLP), range-finding study in Sprague-Dawley
rats, five animals per sex per dose group were fed 0; 2; 20; 200; or 2,000 ppm 3,4-DCBTF
(unknown purity) in the diet. The actual measured exposures were reported to be 2; 20; 211; or
2,440 ppm in the diet (timing of measurements not specified). However, the study authors
subsequently amended the report with a note stating that the study was considered to be invalid
because of the compound stability issue in feed as reported in Raltech Scientific Services, Inc.
(1979). In addition, in the original report (Raltech Scientific Services. 1978). the study authors
reported the presence of two unknown compounds in blood and urine from the treated animals at
levels approximately equal to 3,4-DCBTF itself. These same two compounds were found in the
stock 3,4-DCBTF preparation at levels up to 15% of the total mixture; it was unclear whether the
15% was representative of the total amount of impurities or each impurity. Although the study
authors stated that the two impurities could have contributed to the toxicity of the mixture
(Raltech Scientific Services. 1978). they concluded that the impurities were probably isomers of
3,4-DCBTF, perhaps of lower chlorination, but did not attempt to further identify or quantify
these components.
Individual body weights and total weekly feed consumption were measured weekly on
Days 7, 14, 21, and 28. Blood and urine samples were collected prior to the complete necropsy
conducted on each animal. No treatment-related deaths were reported. Gross pathology
demonstrated normal organ and tissue appearance in all rats, and the study authors stated that
lesions were found in the lung and lymph nodes but were not considered to be treatment-related.
There were no treatment-related effects on feed consumption, body weights, or body-weight
gains for females. However, there was a slight dose- and duration-dependent reduction of body
weights for males, although not statistically significant. Average male rat body weights at
4 weeks were reduced by 3-9%, with the largest reductions in the two highest dose groups.
Average male body weights in the highest dose group for the previous 3 weeks were consistently
lower than controls by about 5%. Body weights in previous weeks for all other treatment groups
were the same as controls. Also, body-weight gains for males were reduced by 11-20% from
control levels in all treatment groups in Week 4, with a 16% reduction at the lowest dose. A
slight dose- and duration-dependent reduction in total weekly feed consumption for males was
observed, culminating in reductions of 12 and 16% at 4 weeks in the two highest dose groups,
respectively. Also, relative feed consumption (as a fraction of body weight) at 4 weeks was
reduced by 5.6 and 7.4% for the two highest dose groups, respectively.
7
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
Although not statistically significant at the tested level (p < 0.05), reductions in feed
consumption, body-weight gain, and body weight for treated males at 4 weeks are apparent and
may have been treatment related. Actual exposures are difficult to quantify. Average daily oral
exposures would have been lower but perhaps as high as 70% of nominal doses, given
approximately a 10% average daily loss of 3,4-DCBTF from feed (based on the two reported
weekly recovery measures of 9 and 52%). Inhalation exposures could also have been present. In
addition, exposures to the two unidentified impurities, which might have been
structurally-similar isomers, could have contributed to the outcomes. No effects on feed
consumption or body weight were observed for 3,4-DCBTF after 4 weeks in the Raltech
Scientific Services, Inc. (1979) study at higher exposure levels (see following). The combined
uncertainties preclude the identification of a NOAEL or LOAEL for 3,4-DCBTF.
Raltech Scientific Services, Inc. (1979); 5-week rat feeding study
In a study originally designed to be 90 days in length, 15 male and 15 female
Sprague-Dawley rats were dosed with 0; 125; 500; or 2,000 ppm (unknown purity) in an oil
suspension in their feed, although dosages were not considered reliable as the compound was
subsequently found to be unstable in feed by the study authors (see following). The study was
conducted under GLP. The study was suspended after 5 weeks because 7-day stability studies
indicated that the compound was rapidly lost from the feed within 24 hours after the initial assay,
with only 9-52% remaining after 1 week from repeat studies. By this time, the animals had
progressed through the first week of mating in the reproduction part of the study but apparently
had been receiving a much lower dose than the protocol indicated (Raltech Scientific Services.
1979). Group mean weekly body weights and total feed consumption for the first 4 weeks were
given in the report. For this assessment, U.S. EPA calculated average daily feed consumptions
as fractions of body weight of 0.06 for males and 0.07 for females, with little variation across
treatment groups. Nominal adjusted average intakes over the first 4 weeks were 0, 7.5, 30, and
120 mg/kg-day for males and 0, 8.8, 35, and 140 mg/kg-day for females.
The animals were observed twice a day, and individual body weights and feed
consumption were measured on Days 7, 14, 21, and 28 of the test. Blood and urine samples were
collected prior to terminal sacrifice, and all animals sacrificed were subjected to gross
postmortem examinations. Body-weight gains were normal for all groups of animals and at
necropsy, and all animals were "essentially normal." Five animals had congested lungs or lungs
with pinpoint red foci, and four animals had uteri that were distended with fluid; the treatment
groups in which these effects were observed were not specified. One animal had an enlarged
thyroid, and another had an enlarged area in the mesenteric lymph nodes. The study authors
considered none of these lesions to be treatment related.
The study authors (Raltech Scientific Services. 1979) stated that the study was considered
invalid because of uncertainties regarding feed stability. In addition, U.S. EPA considers that the
purity of the test compound was likely compromised considering the presence of two
unidentified contaminants in the stock 3,4-DCBTF preparation for the previous 28-day
range-finding study (Raltech Scientific Services. 1978); the study authors did not comment on
this issue. As for the 28-day study (Raltech Scientific Services. 1979). significant inhalation
exposure may have occurred. Because of the considerable uncertainties, a NOAEL or LOAEL
cannot be identified for this study.
8
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
Elars Bioresearch Laboratories (1980; as cited in U.S. EPA, 2005); 14-day rat gavage
study
In a 14-day range-finding study in Sprague-Dawley rats, three animals per sex per dose
group were given 0, 7.5, 15, 30, 60, or 120 mg/kg-day of 3,4-DCBTF (95% purity) via daily
gavage (Elars Bioresearch Laboratories. 1980; as cited in U.S. EPA. 2005). This study was
conducted under GLP but was not peer reviewed. Corn oil was used as the diluent and vehicle
control. Clinical pathology was performed on one animal per sex per dose group prior to
terminal sacrifice. U.S. EPA (2005) stated that no treatment-related gross pathology or any other
abnormalities were observed. Mean liver weights and liver-to-body-weight ratios were increased
in treated groups and controls, but these were not statistically significant; the magnitude of the
liver-weight changes and the dose groups in which they occurred were not reported in the
secondary source (U.S. EPA, 2005). Original study results and statistical analyses are not
available for review, so the magnitude of the liver-weight changes cannot be evaluated for
establishing a LOAEL. Because of the lack of detail on liver weight, neither a NOAEL or
LOAEL can be identified from this study.
Raltech Scientific Services, Inc. (1980; as cited in U.S. EPA. 2005); 14-day rat gavage
study
Raltech Scientific Services, Inc. (1980; as cited in U.S. EPA, 2005)1 is selected as the
principal study for the derivation of screening provisional subchronic RfD. In a 14-day
range-finding study in albino CD rats, 5 animals per sex per dose group were given 0, 7.5, 15,
30, 60, or 120 mg/kg-day of 3,4-DCBTF (unknown purity) via gavage (Raltech Scientific
Services. Inc.. 1980; as cited in U.S. EPA. 2005). Corn oil was used as the diluent and vehicle
control. Compound stability is not an issue for this study because of gavage administration.
Individual body weights were measured daily, and feed consumption was measured each week.
Necropsy was performed on lungs, liver, and kidneys. In addition, erythrocyte count, total and
differential leukocyte count, hemoglobin, and hematocrit were determined. Terminal absolute
and relative liver weights in males at the highest dose, and "mean weight" at 30 mg/kg-day, were
significantly increased compared to the control group; no details on the magnitude of the
increases were provided. It is unclear from the study summary whether the "mean weight"
increase at 30 mg/kg-day refers to body weight or organ weight increase, and in which sex this
was observed. Gross pathology revealed a higher frequency of lung lesions in treated male rats
overall, and increased treatment-related incidence of liver and kidney lesions. Histopathologic
examination of the liver and kidney was performed. There was no dose-related pattern for
observed liver lesions, and no correlation could be made between increase in liver weight and the
number of liver lesions. According to the secondary source, U.S. EPA (2005). the changes in the
liver were of low incidence and were not toxicologically significant. In the kidney, hyaline
droplet degeneration of the tubular epithelium within the renal cortex occurred in five male rats,
three of whom were in the high-dose group. According to U.S. EPA (2005), this lesion occurs
spontaneously in the glomerulonephritis syndrome in rats but is infrequent in animals of this age.
Therefore, U.S. EPA (2005) concluded that the degenerative changes found in the kidney may be
test related.
Hyaline droplet accumulation in the renal proximal tubule epithelium in male rats could
be an indicator of alpha-2 urinary globulin accumulation, which does not occur in humans. For a
diagnosis of alpha-2 urinary globulin accumulation, a sequence of tubule epithelial cell necrosis,
'The original study report is not available.
9
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
granular cast formation, and medullary mineralization would need to be observed in the dose
response (U.S. EPA. 1991). Because the primary source is no longer available for this study and
U.S. EPA (2005) does not provide sufficient detail on the hyaline droplet accumulation, it is not
known whether the kidney changes are indicative of alpha-2 urinary globulin accumulation, and,
therefore, this possibility cannot be excluded from consideration. There was no evidence of
other kidney pathology. Other kidney effects such as varying degrees of congestion were
observed, but these were noted to be of low incidence and judged to be "not clearly dose-related"
by U.S. EPA (2005). No data are available from the original study, which was neither
peer-reviewed nor conducted under GLP. In addition, this study was conducted in the same
laboratory as the Raltech Scientific Services, Inc. (1979. 1978). so there is a probability that
impurities were present in the test compound stock preparation (at levels up to 15% of the total
mixture). However, because compound stability in feed and inhalation coexposure are not
concerns for this study, U.S. EPA has defined a NOAEL of 60 mg/kg-day and a LOAEL of
120 mg/kg-day based on the kidney effects observed in male rats in this study.
hilars Bioresearch Laboratories (1981)
This study was summarized in the Toxic Substances Control Act Test Submissions (SRC.
2010) database as a modified 90-day reproduction study in rats exposed to
para-chlorobenzotrifluoride (PCBTF). However, the original report stated that both 3,4-DCBTF
and PCBTF were tested but gave results only for PCBTF. The study was a 90-day reproduction
study, in which 20 male and 20 female Sprague-Dawley rats per group were treated daily with
either 0, 5, 15, or 45 mg/kg-day PCBTF (95% purity) via gavage for 4 weeks prior to mating.
Parental rats were dosed until the F1 litters were born and weaned at 21 days of age (for a total of
76 to 83 days of dosing), and weanling rats were dosed daily for at least 90 days. Weekly body
weight and feed consumption, clinical pathology, urinalysis, and gross necropsy were performed.
This study was conducted under GLP but does not appear to be peer-reviewed. Increased
absolute and relative liver weights were reported at the two highest doses, and increased absolute
kidney weights were reported at the highest dose. No gross or microscopic lesions were
observed in either organ. This study is only of interest with respect to the finding of increased
kidney weights following exposure to a structurally-similar compound, and it supports the
kidney effects reported in the principal study chosen for the screening subchronic p-RfD
(Raltech Scientific Services. Inc.. 1980; as cited inU.S. EPA. 2005). Otherwise, this study is not
informative as to 3,4-DCBTF toxicity.
Inhalation Exposure
No studies were identified.
OTHER DATA
The genotoxicity and mutagenicity of 3,4-DCBTF has been tested in several in vitro
studies (see Table 4) and one in vivo test system (see Table 5) with generally negative results.
All of the genotoxicity/mutagenicity study results were obtained from secondary sources (listed
in Table 5), and no original sources were available for review.
10
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
Table 4. Genotoxicity and Mutagenicity Studies of 3,4-Dichlorobenzotrifluoride In Vitro
Test System
Endpoint
Test
Conditions
Results"
Dosec
Reference
Without
Activation
With
Activationb
Salmonella
typhimurium
TA98, TA100,
TA1535,
TA1537,
TA1538
Reverse
mutation
Plate
incorporation
assay
10 |iL/platc
Litton Bionetics, Inc.
(1978; as cited in U.S.
EPA. 2005)
Saccharomyces
cerevisiae D4
Reverse
mutation
Plate
incorporation
assay
~
~
10 |iL/platc
Litton Bionetics, Inc
CI978a; as cited in
U.S. EPA. 2005)
Escherichia coli
W3110/polA+,
P3478/polA"
DNA Repair
test
Plate
incorporation
assay
~
~
10 |iL/platc
Litton Bionetics, Inc.
(1978a; as cited in
U.S. EPA. 2005)
Mouse
lymphoma
L5178Y cell
lines
Forward
mutation
assay
4-hr
exposure,
total test 24
hr
31,300 nL/mL
(nonactivation);
62,500 nL/mL
(activation)
Litton Bionetics, Inc.
CI978b; as cited in
SRC. 2010)
Mouse
lymphoma
L5178Y cell
lines
Sister
chromatid
exchange
(SCE)
4-hr exposure
+
20 |iL/mL
Stetka and Brusick
0.979; as cited in U.S.
EPA. 2005)
Human
heteroploid EUE
fibroblast cells
Induction of
unscheduled
DNA
synthesis
Unknown
+?
+?
Unknown
ITC 0.983; as cited in
HSDB. 2011)
Mouse fibroblast
BALB/3T3 cells
Cell
transformation
Unknown
-?
-?
Unknown
ITC 0.983; as cited in
HSDB. 2011)
a+ = positive, - = negative, ± = equivocal, ND = no data, ? = positive or negative results identified, but activation
status unknown.
bExogenous metabolic activation used.
°Lowest effective dose for positive results, highest dose tested for negative or equivocal results.
Table 5. Mutagenicity Studies of 3,4-Dichlorobenzotrifluoride In Vivo
Test System
Endpoint
Test Conditions
Results"
Dose"
Reference
Mouse (CD-I
males)
Mouse Urine
Assay
Mice given 50, 167, and
500 mg/kg by gavage once/d for
2 d. Urine samples collected
and tested for mutagenicity. No
details provided.
500 mg/kg
Litton Bionetics,
Inc. (1979; as
cited in U.S. EPA.
2005)
"+ = positive, - = negative.
bLowest effective dose for positive results, highest dose tested for negative or equivocal results.
11
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
DERIVATION OF PROVISIONAL VALUES
Tables 6 and 7 present a summary of noncancer and cancer reference values, respectively. IRIS data are indicated in the table, if
available.
Table 6. Summary of Noncancer Reference Values for 3,4-Dichlorobenzotrifluoride (CASRN 328-84-7)
Toxicity Type (units)
Species/Sex
Critical
Effect
p-Reference
Value
POD
Method
PODhed
UFC
Principal Study
Screening subchronic p-RfD
(mg/kg-d)
Rat/M
Kidney
lesions
5 x 10"2
NOAEL
14.4
300
Raltech Scientific Services. Inc. (1980; as
cited in U.S. EPA, 2005)
Screening chronic p-RfD (mg/kg-d)
NDr
Subchronic p-RfC (mg/m3)
NDr
Chronic p-RfC (mg/m3)
NDr
NDr = Not determined.
Table 7. Summary of Cancer Values for 3,4-Dichlorobenzotrifluoride (CASRN 328-84-7)
Toxicity Type
Species/Sex
Tumor Type
Cancer Value
Principal Study
p-OSF
NDr
p-IUR
NDr
NDr = Not determined.
12
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
DERIVATION OF ORAL REFERENCE DOSES
Derivation of Subchronic Provisional RfD (Subchronic p-RfD)
Four studies were evaluated for deriving a screening subchronic p-RfD for 3,4-DCBTF.
Two short-term feeding studies (Raltech Scientific Services. 1979. 1978) were excluded because
of test compound volatility in feed, resulting in highly uncertain oral exposures and potential
secondary inhalation exposures of unknown magnitude. In addition, two unidentified
contaminants at relatively high levels in blood and urine samples in the treated animals further
complicated the interpretation of the results. A 14-day rat gavage study (Raltech Scientific
Services. 1980; as cited in U.S. EPA. 2005) was also discounted because details on reported
increases in liver weight were lacking. The original study report for the remaining 14-day
gavage study in rats (Raltech Scientific Services. Inc.. 1980; as cited in U.S. EPA. 2005) was not
available, so this study was also deemed inadequate for the derivation of a subchronic p-RfD.
However, the (Raltech Scientific Services. Inc.. 1980; as cited in U.S. EPA. 2005) 14-day gavage
study in rats is used as the principal study to derive a screening subchronic p-RfD provided in
Appendix A of this document.
Derivation of Chronic Provisional RfD (Chronic p-RfD)
There were no chronic studies located regarding the toxicity of oral exposure to
3,4-DCBTF and, as stated above, the existing data are similarly insufficient for derivation of a
chronic p-RfD. Therefore, no chronic p-RfD is derived. In addition, no screening chronic p-RfD
is derived because the two unpublished 14-day studies (Elars Bioresearch Laboratories, 1980; as
cited in U.S. EPA, 2005; Raltech Scientific Services, Inc., 1980; as cited in U.S. EPA. 2005) are
deemed to be of inadequate duration for extrapolation to chronic exposure duration.
DERIVATION OF INHALATION REFERENCE CONCENTRATIONS
There are no relevant inhalation studies for evaluating subchronic or chronic toxicity
from 3,4-DCBTF exposure. The only inhalation study found was an acute lethality study in rats
(Duckworth. 1979; as cited in U.S. EPA. 2005) and is not suitable for consideration as the basis
for any provisional value from inhalation exposure to 3,4-DCBTF.
Derivation of Subchronic Provisional RfC (Subchronic p-RfC)
A subchronic p-RfC cannot be derived for 3,4-DCBTF because no subchronic inhalation
data are available.
Derivation of Chronic Provisional RfC (Chronic p-RfC)
A chronic p-RfC cannot be derived for 3,4-DCBTF because no chronic inhalation data
are available.
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR
There are no human or animal data available on the carcinogenicity of 3,4-DCBTF.
U.S. EPA has not classified 3,4-DCBTF for carcinogenicity, and no other agencies have
reviewed or classified the carcinogenic potential of the chemical (I ARC. 2010; Cal/EPA. 2008;
N I P. 2005). The cancer WOE descriptor for 3,4-DCBTF is "Inadequate Information to Assess
Carcinogenic Potential" (see Table 8).
13
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
Table 8. Cancer WOE Descriptor for 3,4-Dichlorobenzotrifluoride
Possible WOE Descriptor
Designation
Route of
Entry
Comments
"Carcinogenic to Humans "
NA
NA
No human carcinogenicity studies were identified.
"Likely to Be Carcinogenic to
Humans "
NA
NA
No animal carcinogenicity studies were identified.
"Suggestive Evidence of
Carcinogenic Potential"
NA
NA
No animal carcinogenicity studies were identified.
"Inadequate Information to
Assess Carcinogenic
Potential"
Selected
Both
Selected due to the lack of any data on
carcinogenicity.
"Not Likely to Be Carcinogenic
to Humans "
NA
NA
There are no data to indicate that
3,4-dichlorobenzotrifluoride is not likely to be
carcinogenic to humans.
Mutagenicity studies for 3,4-DCBTF have demonstrated generally negative results.
Results of the Ames test in Salmonella typhimurium, yeast, and E. coli were negative, as were
the fibroblast cell transformation assay, the forward mutation assay, and an in vivo urine
mutagenicity assay (ITC. 1983; as cited in HSDB. 2011; Litton Bionetics- Inc.. 1978b; as cited in
SRC. 2010; Litton Bionetics. Inc.. 1978a. 1979. as cited in U.S. EPA. 2005). Positive results
were noted in a sister chromatid exchange assay ("Stetka and Brusick. 1979; as cited in U.S. EPA.
2005). and 3,4-DCBTF induced unscheduled DNA synthesis in EUE cells (ITC. 1983; as cited in
HSDB, 2011). In the absence of epidemiological or rodent carcinogenicity studies, there is
inadequate information to assess the carcinogenic potential of 3,4-DCBTF.
DERIVATION OF PROVISIONAL CANCER POTENCY VALUES
Derivation of Provisional Oral Slope Factor (p-OSF)
No p-OSF can be derived for 3,4-DCBTF because no carcinogenicity data are available
by the oral route of exposure.
Derivation of Provisional Inhalation Unit Risk (p-IUR)
No p-IUR can be derived for 3,4-DCBTF because no carcinogenicity data are available
by the inhalation route of exposure.
14
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
APPENDIX A. PROVISIONAL SCREENING VALUES
For reasons noted in the main PPRTV document, it is inappropriate to derive provisional
subchronic or chronic p-RfDs for 3,4-DCBTF. 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 REFERENCES DOSES
Derivation of Screening Subchronic Provisional RfD (Screening Subchronic p-RfD)
Four studies were evaluated for deriving a screening subchronic p-RfD for 3,4-DCBTF.
Two short-term feeding studies (Raltech Scientific Services. 1979. 1978) were excluded because
of test compound volatility in feed, resulting in highly uncertain oral exposures and potential
secondary inhalation exposures of unknown magnitude. In addition, two unidentified
contaminants at relatively high levels in blood and urine samples in the treated animals further
complicated the interpretation of the results. A 14-day rat gavage study (Raltech Scientific
Services. 1980) was also discounted because details on reported increases in liver weight were
lacking. A single 14-day study was deemed adequate for the determination of a screening
subchronic p-RfD (Raltech Scientific Services. Inc.. 1980; as cited in U.S. EPA. 2005). The
original study report is not available for review; the results were summarized in U.S. EPA's High
Production Volume Information System (2005). This secondary source (U.S. EPA. 2005) is not
considered a peer-reviewed document. For this reason, use of this study as a principal study is
restricted to derivation of a screening value.
The selected principal study (Raltech Scientific Services. Inc.. 1980; as cited in U.S.
EPA. 2005) was a 14-day range-finding study using albino CD rats given 0, 7.5, 15, 30, 60, or
120 mg/kg-day of 3,4-DCBTF (unknown purity) via gavage. This study was not conducted
according to GLP (U.S. EPA. 2005). The study used five animals of each sex per dose group,
and only liver and kidney effects were examined. Hyaline droplet degeneration of tubular
epithelium in the renal cortex of the kidneys in male rats was observed. Because the primary
study was not available, it is not possible to determine whether the hyaline droplet degeneration
of tubular epithelium in the renal cortex of the kidneys in male rats was indicative of alpha
2u-globulin accumulation. Consequently, the observed kidney lesions are considered relevant to
humans (U.S. EPA. 1991). No other kidney effects were reported. The Elars Bioresearch
Laboratories (1981) study of the structurally related PCBTF isomer in rats reported increased
kidney weights at the highest dose (although no kidney lesions were observed), supporting the
kidney as a target for 3,4-DCBTF toxicity . Liver lesions were also reported in the (Raltech
Scientific Services. Inc.. 1980; as cited in U.S. EPA. 2005). but no correlation could be made
between increase in liver weight and the number of liver lesions. According to U.S. EPA (2005).
the changes in the liver were of low incidence and were not toxicologically significant. A
15
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
NOAEL of 60 mg/kg-day and a LOAEL of 120 mg/kg-day based on the kidney effects were
identified for Raltech Scientific Services, Inc. (1980; as cited in U.S. EPA. 2005). Although the
increase in absolute and relative liver weights in males at 120 mg/kg-day could be considered a
possible co-critical effect, the incidence and magnitude of these increases were not reported in
the secondary source (U.S. EPA. 2005). Therefore, the kidney lesions are considered as the
primary critical effect, and the NOAEL of 60 mg/kg-day was selected as the point of departure
(POD) for derivation of the screening subchronic p-RfD.
In U.S. EPA's Recommended Use of Body Weight314 as the Default Method in Derivation
of the Oral Reference Dose (U.S. EPA. 2011c). the Agency endorses a hierarchy of approaches
to derive human equivalent oral exposures from data from laboratory animal species, with the
preferred approach being physiologically based toxicokinetic (PBTK) modeling. Other
approaches may include using some chemical-specific information, without a complete PBTK
model. In lieu of chemical-specific models or data to inform the derivation of human equivalent
oral exposures, U.S. EPA endorses body weight (BW) scaling to the 3/4 power (i.e., BW3 4) as a
default to extrapolate toxicologically equivalent doses of orally administered agents from all
laboratory animals to humans for the purpose of deriving an RfD under certain exposure
conditions. More specifically, the use of BW3 4 scaling for deriving a RfD is recommended
when the observed effects are associated with the parent compound or a stable metabolite but not
for portal-of-entry effects or developmental endpoints.
A PBTK model for 3,4-DCBTF is not available for use in extrapolating doses from
animals to humans. The critical effect (kidney lesions) is not a portal-of-entry or developmental
effect and is presumed to be associated with the parent compound or a stable metabolite.
Therefore, scaling by BW3 4 is relevant for deriving human equivalent doses (HEDs) for these
effects.
Following U.S. EPA (2011c) guidance, the POD for kidney effects in adult animals is
converted to an HED through application of a dosimetric adjustment factor (DAF)2 derived as
follows:
DAF = (BWa1/4 - BWh1/4)
Where:
DAF = dosimetric adjustment factor
BWa = animal body weight
BWh = human body weight
Using a BWa of 0.25 kg for rats and a BWh of 70 kg for humans (U.S. EPA, 1988), the
resulting DAF is 0.24. Applying this DAF to the NOAEL, identified for the critical effect in
mature rats yields a NOAELhed as follows:
2As described in detail in Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral
Reference Dose (U.S. EPA. 2011c'). rate-related processes scale across species in a manner related to both the direct
(BW1'1) and allometric scaling (BW3'4) aspects such that BW3 4 BW11 = BW converted to a
DAF = BWa1/4 - BWhI/4.
16
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
NOAELhed = NOAEL (mg/kg-day) x DAF
= 60 mg/kg-day x 0.24
= 14.4 mg/kg-day
The screening subchronic p-RfD for 3,4-DCBTF is derived as follows:
Screening Subchronic p-RfD = NOAELhed ^ UF
= 14.4 mg/kg-day -^300
= 5 x 10"2 mg/kg-day
The composite UF of 300 is estimated, as presented in Table A.l.
Table A.l. Uncertainty Factors for Screening Subchronic p-RfD of
3,4-Dichlorobenzotrifluoride
UF
Value
Justification
ufa
3
A UFa of 3 (10°5) has been applied to account for uncertainty in characterizing the toxicodynamic
differences between rats and humans following oral 3,4-DCBTF exposure. The toxicokinetic
uncertainty has been accounted for by calculation of a human equivalent dose (HED) through
application of a dosimetric adjustment factor (DAF) as outlined in the U.S. EPA's Recommended Use
of Body Weight3/4 as the Default Method in Derivation of the Oral Reference DosefU.S. EPA. 201 lc).
ufd
10
A UFd of 10 has been applied because there are no acceptable two-generation reproductive toxicity
or developmental toxicity studies.
UFh
10
A UFh of 10 has been applied for inter-individual variability to account for human-to-human
variability in susceptibility in the absence of quantitative information to assess the toxicokinetics and
toxicodynamics of 3,4-DCBTF in humans.
ufl
1
A UFl of 1 has been applied for LOAEL-to-NOAEL extrapolation because the POD is a NOAEL.
UFS
1
Althoueh the duration of the principal studv (Raltech Scientific Sendees. Inc.. 1980; as cited in U.S.
EPA. 2005) is less than subchronic at 14 da vs. a UFS of 1 has been applied.
UFC
300
Derivation of Screening Chronic Provisional RfD (Screening Chronic p-RfD)
The 14-day study used is deemed to be of inadequate duration for extrapolation to
chronic exposure durations. Therefore, no screening chronic p-RfD is derived.
17
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
APPENDIX B. DATA TABLES
No data tables are presented.
18
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
APPENDIX C. BMD MODELING OUTPUTS
No BMD modeling was performed.
19
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
APPENDIX D. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2013). 2013 TLVs and
BEIs. Based on documentation of the threshold limit values for chemical substances and
physical agents and biological exposure indices. Cincinnati, OH.
AT SDR (Agency for Toxic Substances and Disease Registry). (2013). Minimal risk levels
(MRLs) for hazardous substances. Atlanta, GA. Retrieved from
http://www.atsdr.cdc.gov/mrls/mrllist.aspID - 2
Cal/EPA (California Environmental Protection Agency). (2008). Cal/EPA - OEHHA toxicity
criteria database. Sacramento, CA: Office of Environmental Health Hazard Assessment.
http://www.oehha.ca.gov/risk/Chem.icalDB/index.asp
Cal/EPA (California Environmental Protection Agency). (2009). Appendix A: Hot spots unit risk
and cancer potency values. Sacramento, CA: Office of Environmental Health Hazard
Assessment, http://www.oehha.ca.gov/air/hot spots/2009/AppendixA.pdf
Cal/EPA (California Environmental Protection Agency). (2012a). All OEHHA acute, 8-hour and
chronic reference exposure levels (chRELs) as on February 2012. Sacramento, CA:
Office of Environmental Health Hazard Assessment.
http://www.oehha.ca.gov/air/allrels.html
Cal/EPA (California Environmental Protection Agency). (2012b). OEHHA toxicity criteria
database. Sacramento, CA: Office of Environmental Health Hazard Assessment.
http ://www. oehha.ca. gov/tcdb/
ChemBlink. 3,4 Dichlorobenzotrifluoride [Database], Retrieved from
http://www.chem.blink.com/products/328-84-7.htm
Chen. HCB; Lindrose. M. Single phase cleaning fluid. (Occidental Chemical Corporation2000).
http://patents.iustia.eom/2000/06020299.html
Elars Bioresearch Labs (Elars Bioresearch Laboratories Inc.). (1981). Modified 90 day gavage
and reproduction study in rats: 3,4-DCBTF. (408188012). Niagara Falls, NY: Hooker
Chemical Company.
HSDB (Hazardous Substances Data Bank). (201 1). 3,4-Di chl orobenzotri tl uori de (CASRN: 328-
84-7). Washington, DC: National Library of Medicine, http://toxnet.nlm.nih.gov/cgi-
bin/sis/search/r?dbs+hsdb:@term+@ro+@rei+328-84-7
I ARC (International Agency for Research on Cancer). I ARC Monographs on the evaluation of
carcinogenic risk to humans. Available online at
http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php. Accessed 8-1-2013.
I ARC (International Agency for Research on Cancer). (2010). Ingested nitrate and nitrite and
cyanobacterial peptide toxins. Lyon, France.
http://monographs.iarc.fr/ENG/Monographs/vol94/mono94.pdf
ITC (TSCA Interagency Testing Committee). (1983). 3,4-di chl orobenzotri fl uori de: Information
review #346 (draft) [EPA Report], (EPA 560/ITC/83-0264). Washington, DC: U.S.
Environmental Protection Agency.
NIOSH (National Institute for Occupational Safety and Health). (2010). NIOSH pocket guide to
chemical hazards. Index of chemical abstracts service registry numbers (CAS No.).
Atlanta, GA: Center for Disease Control and Prevention, U.S. Department of Health,
Education and Welfare, http://www.cdc.gov/niosh/npg/npgdcas.html
N I P (National Toxicology Program). (2005). Report on carcinogens, eleventh edition. Research
Triangle Park, NC. http://ntp.niehs.nih.gov/index.cfm?obiectid=32BA9724-FlF6-975E-
7FCE50709CB4C932
20
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
NTP (National Toxicology Program). (201 1). Report on carcinogens: Twelfth edition (12th ed.).
Research Triangle Park, NC. http://ntp.niehs.nih.eov/ntp/roc/twelfth/rocl2.pdf
OSHA (Occupational Safety & Health Administration). (2006). Table Z-l limits for air
contaminants. Occupational Safety and Health Administration.
http://www.osha.gov/pls/oshaweb/owadisp.show document?p table=STANDARDS&p
id=9992
OSHA (Occupational Safety & Health Administration). (201 1). Air contaminants: occupational
safety and health standards for shipyard employment, subpart Z, toxic and hazardous
substances. (OSHA Standard 1915.1000). Washington, DC: U.S. Department of Labor.
http://www.osha.gov/pls/oshaweb/owadisp.show document?p table=STANDARDS&p
id=l0286
Raltech Scientific Services (Raltech Scientific Services Inc.). (1978). 3,4-
Dichlorobenzotrifluoride 28-day Feeding Study in Rats. (OTS0526723; EPA Doc # 40-
7888046). Madison, WI: Raltech Scientific Services, Inc.
http://www.ntis.gov/search/product.aspx7ABBR OTSQ526723
Raltech Scientific Services (Raltech Scientific Services Inc.). (1979). Analytical data on 3,4-
DCBTF in feed and animal data through termination of 90-day feeding and reproduction
study. (40-7988050; OTS0526731). Niagra Falls, NY: Hooker Chemical and Plastics
Company. http://www.ntis.gov/search/product.aspx7ABBR OTSQ52673 1
Raltech Scientific Services (Raltech Scientific Services Inc.). (1980). 3,4-DCBTF 14-day range
feeding and reproduction study in rats. (Study No. 79508-B). Raltech Scientific Services,
Madison WI for Hooker Chemicals and Plastics Corporation, Niagara Falls, NY. (As
cited in U.S. EPA 2005).
SRC (Syracuse Research Corporation). (2010). 3,4 dichlorobenzotrifluoride [Database],
Syracuse, NY: TSCATS; SRC. Retrieved from http://www.svrres.com/esc/tscats.htm
U.S. EPA (U.S. Environmental Protection Agency). Integrated risk information system (IRIS).
Available online at http://dx.doi.org/10.1177/1091581812466418. Accessed on 8-1-2013.
U.S. EPA (U.S. Environmental Protection Agency). (1987). Testing consent order on 3,4-
dichlorobenzotrifluoride and response to the Interagency Testing Committee: Final rule.
Fed Reg 52: 23547-23548.
U.S. EPA (U.S. Environmental Protection Agency). (1988). Recommendations for and
documentation of biological values for use in risk assessment [EPA Report], (EPA/600/6-
87/008). Cincinnati, OH. http://cfpub.epa.gov/ncea/cfm/recordisplav.cfm7deid 34855
U.S. EPA (U.S. Environmental Protection Agency). (1991). Alpha-2u-globulin: Association with
chemically induced renal toxicity and neoplasia in the male rat [EPA Report],
(EPA/625/3-91/019F). Washington, DC.
http://www.ntis. gov/ search/product, aspx? ABBR=PB92143 668
U.S. EPA (U.S. Environmental Protection Agency). (1994). Chemical assessments and related
activities (CARA) [EPA Report], (600R94904; OHEA-I-127). Washington, DC.
http://nepis.epa.gov/Exe/ZvlH'RL.cgi7Dockev 6Q0QlG8L.txt
U.S. EPA (U.S. Environmental Protection Agency). (2005). High Production Volume
Information System (HPVIS) - Chemical name: Benzene, 1,2 dichloro 4-
(trifluoromethyl)- CAS Number: 328-84-7 [EPA Report],
http://iaspub.epa. gov/oppthpv/quicksearch.displav?pChem=l 01941
U.S. EPA (U.S. Environmental Protection Agency). (201 la). 201 1 Edition of the drinking water
standards and health advisories [EPA Report], (EPA 820-R-11-002). Washington, DC.
http://water.epa.gov/action/advisories/drinking/upload/dwstandards2011.pdf
21
3,4-Di chl orob enzotrifluori de
-------
FINAL
8-27-2013
U.S. EPA (U.S. Environmental Protection Agency). (201 lb). Health Effects Assessment
Summary Tables (HEAST). Available online at http://epa-heast.ornl.gov/
U.S. EPA (U.S. Environmental Protection Agency). (201 lc). Recommended use of body weight
3/4 as the default method in derivation of the oral reference dose [EPA Report],
(EPA/100/R11/0001). Washington, DC.
http://www.epa.gov/raf/publications/interspecies-extrapolation.htm
WHO (World Health Organization). Online catalog for the Environmental Health Criteria Series.
Available online at http://www.who.int/ipcs/publications/ehc/en/. Accessed on 8-1-2013.
Yih. RY; Swithenbank. C. (1975). New potent diphenyl ether herbicides. J Agric Food Chem 23:
592-593.
22
3,4-Di chl orob enzotrifluori de
------- |