-------
DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
-------
PREFACE
Health and Environmental Effects Documents (HEEDs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
1s Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained for Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for 1n this document
and the dates searched are Included In "Appendix: Literature Searched."
Literature search material Is current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document 1s sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, 1s an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval I.e., for an Interval that
does not constitute a significant portion of the Hfespan. This type of
exposure estimate has not been extensively used, or rigorously defined as
previous risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used, for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs Is the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, RfDs are not estimated. Instead,
a carcinogenic potency factor, or q-j* (U.S. EPA, 1980), 1s provided.
These potency estimates are derived for both oral and Inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxldty and cardno-
genlclty are derived. The RQ Is used to determine the quantity of a hazard-
ous substance for which notification Is required 1n the event of a release
as specified under the Comprehensive Environmental Response, Compensation
and Liability Act . (CERCLA). These two RQs (chronic toxldty and carclno-
genldty) represent two of six scores developed (the remaining four reflect
1gn1tab1l1ty, reactivity, aquatic toxldty, and acute mammalian toxldty).
Chemlcal-spedf 1c RQs reflect the lowest of these six primary criteria. The
methodology for chronic toxldty and cancer based RQs are defined 1n U.S.
EPA, 1984 and 1986a, respectively.
111
-------
EXECUTIVE SUMMARY
4-Chlorobenzotr1fluor1de Is a colorless liquid at ambient temperatures,
with an aromatic odor .(Hawley, 1981; Boudaklan, 1980). It 1s practically
Insoluble In water (Elanco Products Company, 1984). This compound undergoes
easy nitration and nucleophHlc substitution reactions (Boudaklan, 1980).
Currently, Occidental Petroleum Corp. of Niagara Falls, NY, 1s the only
major manufacturer of this chemical 1n the United States (SRI, 1987; USITC,
1987). Data regarding the current U.S. production volume are not available,
although -10-50 million pounds was produced In 1977 (U.S. EPA, 1977). It 1s
produced from the reaction of 4-chlorobenzotr1chlor1de and anhydrous
hydrogen fluoride. This chemical 1s used primarily as an Intermediate In
the manufacture of certain dyes, drugs and herbicides (Boudaklan, 1980).
Of the three likely chemical processes that may lead to the loss of
4-chlorobenzotr1fluor1de in the atmosphere, neither direct -photolysis nor
Us reaction with atmospheric 0_ 1s significant (Atkinson et al., 1985).
0
Its reaction with photochemlcally produced HO radical has a rate constant of
2.3xlO~13 cm3/molecule-sec (Atkinson et al., 1985). Assuming the atmo-
spheric concentration of HO radical as 10* radicals/cm3, the lifetime
of this compound In the air has been estimated to be -50 days (Atkinson et
al., 1985). Therefore, the compound 1s expected to persist 1n the
atmosphere. In water, photolysis of the chemical 1s not Important (Elanco
Products Co., 1983a). Although the rates of aerobic and anaerobic
blodegradatlon of the compound 1n water could not be determined, these rates
are slower than the volatilization rate (Elanco Products Co., 1983b,c,d).
From the value of the ratio of the volatilization rate of the compound to
the oxygen reaeratlon rate determined experimentally (Elanco Products Co.,
1v
-------
1983d) and the values of oxygen reaeratlon rates 1n a few natural waters
(Thomas, 1982), the half-life for volatilization of the compound from water
has been estimated to be 1-6 days. The K value of 420-490 In sediments
oc
(Elanco Products Co.i 1983e) Indicates that the compound will sorb
moderately to suspended solids and sediments In natural waters. Based on
the experimentally determined BCF of 122-202 1n blueglll sunflsh, Lepomls
macrochlrus (Elanco Products Co., 1984), the compound Is not expected to
bloconcentrate significantly 1n aquatic organisms. From the data available
In aquatic studies, 1t can be predicted that photolysis In soil will be
unimportant, and some loss of the compound will occur from the soil surface
because of volatilization, although the volatilization process will become
less Important as the soil depth Increases. The K value of 510-530 1n
soil (Elanco Products Co., 1983e) Indicates that the compound may leach
through some soils, particularly soil from Improper disposal sites. No data
regarding the blodegradabllHy of ;the compound In soil are available.
There 1s a paucity of data on the levels of 4-chlorobenzotrlfluorlde 1n
environmental media. This compound was qualitatively detected 1n water from
Lake Ontario at Niagara River (Great Lakes Water Quality Board, 1983). The
source of the compound 1n the water was possibly the nearby manufacturer of
the chemical. Mauser and Bromberg (1982) reported the qualitative detection
of this compound In the sedlment/son/water samples collected from contami-
nated areas of Love Canal, Niagara Falls. Bass and yellow perch collected
from Niagara River and analyzed 1n 1978 contained 4-chlorobenzotr1fluor1de
1n the concentration range 0.17-2.0 ppm. The compound was not detected at a
later date (1980), however, at a detection limit of 0.01 ppm In various
samples of fish (walleye, brown trout and sucker) from Lake Erie and Lake
Ontario near the suspected contaminated areas (Occidental Chem. Corp.,
-------
1980b). Cacco and Ferrari (1982) reported the detection of this compound at
a level of 1 ppm In groundwater near an Improper disposal site near Vlcenza,
Italy.
Exposure of rainbow trout and blueglll sunflsh to 4-chlorobenzotrlfluo-
rlde generated 96-hour LC5Q values of 13.5 and 12.0 (10.3-13.9) mg/l,
respectively (Union Carbide Environmental Services, 1979b). Exposure of D.
magna to 4-chlorobenzotr1f1uor1de generated a 48-hour LC^n of 12.4
(10.7-14.5) mg/l (Union Carbide Environmental Services, 1979c).
The concentration of 4-chlorobenzotr1fluor1de that produced chronic
effects 1n aquatic organisms was ~l-2 orders of magnitude lower than that
produced for acute effects. The MATC for fathead minnow eggs was >0.54 but
<1.4 mg/l 4-chlorobenzotr1fluor1de. The MATC for |). magna was >0.03 and
<0.05 mg/l 4-chlorobenzotrlfluorlde (Union Carbide Environmental Services,
1979d).
The single study of [l*C]-4-chlorobenzotr1fluor1de metabolism using
rats (Qulstad and Mulholland* 1983) Indicated that the compound 1s absorbed
and excreted readily, predominantly as the parent compound. The major route
of excretion was through expired air, which accounted for 62-82% of the
dose. Urinary metabolites Identified were the glucuronldes of
d1hyclroxybenzotr1fluor1de and 4-chloro-3-hydroxybenzotr1fluor1de, which
accounted for <2.7 and 4.'4% of the dose, respectively. A minor urinary
metabolite, the mercaptuMc add conjugate of 4-chlorobenzotr1fluor1de
accounted for 0.1-0.2% of the dose.
Minimal to moderate renal tubular degeneration was observed In male rats
treated by gavage with 4-chlorobenzotr1fluorlde at doses >40 mg/kg/day for 3
months (Arthur and Probst, 1983). CentMlobular hypertrophy of the liver
was observed In male rats at 4-chlorobenzotr1fluor1de doses >150 mg/kg/day
v1
-------
and 1n female rats at 500 mg/kg/day. No significant effects were observed
1n rats treated for 3 months by gavage with 4-ch1orobenzotr1f1uor1de at 10
mg/kg/day.
In contrast to the- Arthur and Probst (1983) study, hlstologlcal kidney
and liver effects were not observed 1n a 2-generat1on study 1n which
Sprague-Dawley rats were treated by gavage with 4-chlorobenzotr1fluor1de at
doses <45 mg/kg/day for >90 days (Hooker Chemical Corp., 1981). 4-Chloro-
benzotrlfluoMde . treatment did not have any effect on reproductive
parameters.
A Russian study (Rapoport et al., 1986} reported that Inhalation
exposure of rats to 4-chlorobenzotr1fluor1de at concentrations >20.5 mg/m3
for 120 hours resulted 1n changes 1n blood analyses, motor activity and
muscle strength. Significant changes were not observed In rats exposed at
5.5 mg/m3 for 120 hours.
Hooker Chemical Corp. (1979a) reported a 4-hour LC™ for 4-chloro-
benzotrlfluorlde 1n Sprague-Dawley rats of 33 mg/m3. The oral LD5Q for
4-chlorobenzotr1fluorlde 1n Sprague-Dawley rats was reported as >5.0 ml/kg
(6.7 g/kg) (Hooker Chemical Corp., 1985a), while the dermal LD5Q In
rabbits was reported to be >2.0 mil/kg (2.7 g/kg) (Hooker Chemical Corp.,
1985b).
Except for positive results 1n assays of unscheduled DMA synthesis
(Benlgnl and Dogl1ott1, 1980) and sister chromatld exchange (Hooker Chemical
Corp., 1979c), results of mutagenldty assays of 4-chlorobenzotr1flubr1de
have been negative.
4-Chlorobenzotrlfluorlde has not been tested for cardnogenldty or
teratogenldty.
-------
Pertinent guidelines and standards, Including EPA ambient water and air
quality criteria, drinking water standards, FAO/WHO ADIs, EPA or FDA
tolerances for raw agricultural commodities or foods, and ACGIH, NIOSH or
OSHA occupational exposure limits were not located In the available
literature cited 1n Appendix A.
Because of the lack of data concerning carc1nogen1c1ty In humans and
animals, 4-chlorobenzotr1fluor1de can be classified as an EPA Group D
chemical. The derivation of carcinogenic potency factors and a cancer-based
RQ 1s precluded by the lack of cardnogen1c1ty data. Based on the Hooker
Chemical Corp. (1981) 2-generatlon study using rats, subchronlc and chronic
oral RfDs for 4-chlorobenzotr1fluor1de of 0.2 mg/kg/day (11 mg/day) and 0.02
mg/kg/day (1 mg/kg) were calculated. Because of the lack of supporting
studies, confidence 1n the oral RfDs 1s low. A chronic toxlclty RQ for
4-chlorobenzotrlfluorlde of 1000 was calculated from the Arthur and Probst
(1983) 90-day rat study.
vlll
-------
TABLE OF CONTENTS
Page
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES . . 1
1.3. PRODUCTION DATA 2
1.4. USE DATA 2
1.5. SUMMARY 3
2. ENVIRONMENTAL FATE AND TRANSPORT 4
2.1. AIR 4
2.2. WATER 5
2.3. SOIL 6
2.4. SUMMARY . 7
3. EXPOSURE. . 9
4. AQUATIC TOXICITY 10
4.1. ACUTE TOXICITY 10
4.2. CHRONIC EFFECTS 11
4.3. PLANT EFFECTS 11
4.4. SUMMARY. 11
5. PHARMACOKINETCS 13
5.1. ABSORPTION ................... 13
5.2. DISTRIBUTION 13
5.3. METABOLISM 14
5.4. EXCRETION 14
5.5. SUMMARY 15
6. EFFECTS 16
6.1. SYSTEMIC TOXICITY 16
6.1.1. Inhalation Exposure 16
6.1.2. Oral Exposure 16
6.1.3. Other Relevant Information 17
6.2. CARCINOGENICITY 19
6.2.1. Inhalation 19
6.2.2. Oral 19
6.2.3. Other Relevant Information 19
6.3. MUTAGENICITY 19
6.4. TERATOGENICITY 22
6.5. OTHER REPRODUCTIVE EFFECTS 22
6.6. SUMMARY 23
1x
-------
TABLE OF CONTENTS (cont.)
Page
7. EXISTING GUIDELINES AND STANDARDS 25
7.1. HUMAN 25
7.2. AQUATIC. . : 25
8. RISK ASSESSMENT 26
8.1. CARCINOGENICITY 26
8.1.1. Weight of Evidence. . 26
8.1.2. Quantitative Risk Assessment 26
8.2. SYSTEMIC TOXICITY 26
8.2.1. Inhalation Exposure 26
8.2.2. Oral Exposure ......" 26
9. REPORTABLE QUANTITIES 29
9.1. BASED ON SYSTEMIC TOXICITY 29
9.2. BASED ON CARCINOGENICITY 29
10. REFERENCES 32
APPENDIX A: LITERATURE SEARCHED. .... 40
APPENDIX B: SUMMARY TABLE FOR 4-CHLOROBENZOTRIFLUORIDE 43
-------
LIST OF TABLES
No. Title Page
6-1 Mutagenldty Testing of 4-Ch1orobenzotr1fluor1de 20
9-1 Composite Scores for the Oral ToxUHy of
4-Chlorobenzotr1fluor1de (97% Pure) 1n Corn 011 Using
Male F344 Rats. 30
9-2 4-Chlorobenzotr1fluor1de: Minimum Effective Dose (MED)
and Reportable Quantity (RQ) 31
x1
-------
LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
BCF B1oconcentrat1on factor
CAS -Chemical Abstract Service
CS Composite score
DNA DeoxyMbonuclelc acid
Koc Soil sorptlon coefficient standardized
with respect to organic carbon
Kow Octanol/water partition coefficient
Concentration lethal to 50% of recipients
Dose lethal to 50% of recipients
LOAEL Lowest-observed-adverse-effect level
MATC. Maximum allowable toxicant concentration
MED Minimum effective dose
NOAEL - No-observed-adverse-effect level
ppm Parts per million
RBC Red blood cell
RfD Reference dose
RQ Reportable quantity
RV(j Dose-rated value
RVP Effect-rated value
-------
1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
4-Chlorobenzotr1fluor1de Is also known as l-chloro-4-{tr1fluoromethyl)
benzene; (p-chlorophenyl )tr1fluoromethane; 4-chloro-a-a-a-tMf luoro-
toluene; p-chlorobenzotMfluoMde; and p-chlorotr1fluoromethylbenzene (HSDB,
1988).. The structure, molecular formula, molecular weight and CAS Registry
number for this compound are as follows:
C\
Molecular formula: C^H.CIF-
74 3
Molecular weight: 180.56
CAS Registry number: 98-56-6
1.2. PHYSICAL AND CHEMICAL PROPERTIES
4-Chlorobenzotr1fluor1de 1s a colorless liquid at ambient temperatures
(Boudaklan, 1980), with an aromatic odor (Hawley, 1981). It 1s not soluble
1n water but Is soluble 1n n-hexane (Elanco Products Company, 1984).
Selected physical properties of this compound are as follows:
Melting point: -36.0°C Hawley, 1981
Boiling point: 138.6°C Hooker Chems. and
^ Plastics Corp., 1980
Density: 1.338 g/cm3 at 25°C Boudaklan, 1980
Vapor pressure: 7.86 mm Hg at 25°C Hooker Chems. and
Plastics Corp., 1980
Water solubility: 29.1 mg/l at 23°C Hooker Chems. and
Plastics Corp., 1980
Odor threshold: 50% panel members at 0.63 Occidental Chems.
mg/m3 and 100% at 0.8 mg/m3 Corp., 1980a
Oil Id -1- 04/19/88
-------
•Log Kow: 3.52 Elanco Products
Company, 1984
Conversion 1 ppm = 7.51 mg/m3 at 20°C
factor 1n air: and 760 mm Hg
4-Chlorobenzotr1fluor1de undergoes several chemical reactions. Nitration
of this compound yields n1tro-subst1tuted products that are used as Inter-
mediates 1n the production of dyes, germicides and herbicides. Because of
the strong electron-withdrawing effect, this compound also undergoes nucleo-
ph1!1c substitution reactions (Boudaklan, 1980).
1.3. PRODUCTION DATA
According to EPA's TSCA production file (U.S. EPA, 1977), the major
producer of 4-chlorobenzotr1fluor1de 1n the United States In 1977 was Hooker
Chems. and Plastics Corp. of Niagara Falls, NY. This company produced
between 10 and 50 million pounds of the compound In 1977. At least three
companies Imported this chemical 1n the United States during the same year
.(U.S. EPA, 1977). More recent data (USITC, 1987; SRI, 1987) Indicate that
Occidental Petroleum Corp. at Niagara Falls, NY, the parent company of
Hooker Chems. and Plastics Corp., Is the only current major manufacturer of
the chemical 1n the United States. It 1s produced from the reaction of
4-chlorobenzotr1chlor1de and anhydrous hydrogen flourlde under high or
atmospheric pressure conditions (Boudaklan, 1980) or the reaction of
4-chlorotoluene with hydrogen fluoride (HSDB, 1988).
1.4. USE DATA
4-Chlorobenzotr1fluor1de Is used as an Intermediate In the manufacture
of certain dyes, drugs, herbicides and germicides (Boudaklan, 1980). It 1s
also used as a solvent and a dielectric fluid (Hawley, 1981).
Ollld -2- 04/19/88
-------
1.5. SUMMARY
4~Chlorobenzotr1fluor1de 1s a colorless liquid at ambient temperatures,
with an aromatic odor (Hawley, 1981; Boudaklan, 1980). It Is practically
Insoluble 1n water (Elanco Products Company, 1984). This compound undergoes
easy nitration and nucleophlUc substitution reactions (Boudaklan, 1980).
Currently, Occidental Petroleum Corp. of Niagara Falls, NY, Is the only
major manufacturer of this chemical 1n the United States (SRI, 1987; USITC,
1987). Data regarding the current U.S. production volume are not available,
although -10-50 million pounds was produced In 1977 (U.S. EPA, 1977). It Is
produced from the reaction of 4-chlorobenzotr1chlor1de and anhydrous
hydrogen fluoride. This chemical 1s used primarily as an Intermediate 1n
*the manufacture of certain dyes, drugs and herbicides (Boudaklan, 1980).
01 lid -3- 05/10/88
-------
2. ENVIRONMENTAL FATE AND TRANSPORT
2.1. AIR
The fate of 4-chlorobenzotr1fluor1de In the gas phase was studied by
Atkinson et al. (1985) and the results were applied to assess Us fate under
atmospheric conditions (Occidental Chem. Corp., 1984). Later, the same
study was published In the open literature (Atkinson et al., 1985).
Although the study did not directly determine the photolytlc fate of the
compound, the upper limit for photolytlc rate was Indirectly determined to
be 2.7xlO~6/ sec at a light Intensity -1.5 times higher than solar
radiation. Therefore, the lower limit for photolytlc lifetime (lifetime =
1/R,) under atmospheric conditions was estimated to be 6.5 days. Since
the compound exhibits Its first absorption band 1n the wavelength region*
230-280 nm and shows no detectable absorption at wavelengths >280 nm,
Atkinson et al. (1985) concluded that atmospheric photolysis 1s probably
unimportant compared with other loss processes. The same conclusion
regarding the significance of photolysis can be reached from the aquatic
photolysis study (Section 2.2.).
The rate constants for the vapor phase reaction of HO radical and 0_
with 4-chlorobenzotr1fluor1de at 23°C are 2.3xlO~i3 cm3/molecule-sec
and <5xlO~21 cm3/molecule-sec, respectively (Atkinson et al., 1985). If
the dally average atmospheric concentrations of HO radical and 0« are
assumed to be 10* radicals/cm3 and 7.2X1011 molecules/cm3, respec-
tively, the corresponding lifetimes will be 50 days and >8.8 years (Atkinson
et al., 1985). Therefore, 1n the absence of any other faster loss process,
the lifetime of this compound 1n the atmosphere will be close to 50 days and
1t will be very persistent 1n the ambient atmosphere.
Ollld -4- 05/10/88
-------
2.2. WATER
There 1s a paucity of data In the open literature regarding the fate and
transport of 4-chlorobenzotr1fluor1de 1n water. The data reported here were
obtained from the public files section of the reports of the major manu-
facturer as submitted to EPA's Office of Toxic Substances (OTS) under 8D
submission rules.
The photolytlc fate of this chemical 1n water was reported by Elanco
Products Co. (1983a). When a 10 ppm aqueous solution of the chemical In
sealed and sterilized glass tubes was exposed to natural light for <28 days,
no degradation was observed and almost 100% of the compound remained un-
altered. Therefore, 1t was concluded that the compound Is not photolablle.
The aerobic and anaerobic blodegradatlon of 4-chlorobenzotr1fluor1de 1n
water was also reported by Elanco Products Co. (1983b,c). When microorgan-
isms from soil and raw domestic sewage acclimatized to 4-chlorobenzotrl-
fluorlde were used as mlcroblal Inoculum for aerobic blodegradatlon study In
flasks with attached CO ' traps, only 13% of the Initial theoretical
compound could be accounted for on day 0, presumably because of
volatilization. By the fifth day, only 2% of the compound remained. The
report concluded that the high volatility of the compound precluded the
determination of Us aerobic blodegradatlve fate. Similarly, when the
compound was Inoculated with anaerobic dlgestor sludge under anaerobic
conditions for >59 days, 1t was determined that the compound might be
Inhibitory to anaerobic microorganisms for a period of 17 days at an Initial
concentration of 50 mg C/l. No conclusion regarding anaerobic
blodegradatlon of 4-chlorobenzotr1fluor1de could be drawn from these
experiments, however, because the control experiments showed unexplained
high losses of the compound (77%), possibly resulting from undefined abiotic
reactions.
01 lid -5- 05/10/88
-------
The loss of 4-ch1orobenzotr1fluor1de from water because of volatiliza-
tion was reported by Elanco Products Co. (1983d). With a 10 ppm aqueous
solution of the compound, the average ratio of compound volatilization rate
to oxygen reaeratlon rate was determined to be 0.64 at ambient temperature.
If 1t Is assumed that the oxygen reaeratlon rates from a pond, a river and a
lake are 0.19/day, 0.96/day and 0.24/day, respectively (Thomas, 1982), the
estimated volatilization half-lives from these water bodies would be -1-6
days. Therefore, H can be concluded that volatilization of the compound
from water 1s an Important process. The sorptlon of the compound by soil
and sediment was also reported by Elanco Products Co. (1983e). WHh sandy
loam soil of 1.2% organic matter content and clay loam soil of 3.1% organic
matter content, the authors of this report estimated the soil K value to
range between 510 and 530. The K value 1n sediments of 3.0-3.2% organic
matter content was -420-490. Therefore, the compound Is expected to remain
moderately sorbed to most soils and sediments.
Bloconcentratlon by Blueglll sunflsh, Lepomls macrochlrus. was tested In
a static nonaerated system 1n the presence of 0.025-0.25 ppm 4-chlorobenzo-
trlfluorlde for <48 hours (Elanco Products Co., 1984). A steady-state BCF
of 122-202 was estimated, Indicating that the compound will not bloconcen-
trate significantly 1n aquatic organisms.
2.3. SOIL
Data regarding the fate of 4-chlorobenzotr1flour1de In soil are
extremely limited. As discussed 1n Section 2.2., the K value for this
compound In soil has been experimentally determined to be 510-530 (Elanco
Products Co., 1983e). From this moderate K value, It can be predicted
that 4-chlorobenzotr1fluor1de may leach significantly from some soils 1f the
blodegradatlon rate 1n the soil 1s slower than the Infiltration rate. Since
Ollld -6- 04/19/88
-------
the compound was detected In a groundwater 1n Italy near an Improper
disposal site (Cacco and Ferrari, 1982), It Is likely that blodegradatlon,
at least 1n soils that contain high concentrations of the compound, will not
be fast. Based on data provided In Section 2.2., photolysis on soil
surfaces will probably be unimportant, and some loss of the compound will
occur from soil surfaces as a result of volatilization. Volatilization loss
from soil will become Increasingly less Important, however, as the soil
depth Increases. Based on the data available regarding Us fate In water,
It 1s likely that the compound will be persistent 1n most soils. The
absorption of the compound from soil and the subsequent possibility of
translocatlon to upper parts of plants were studied by Cacco and Ferrari
(1982), who demonstrated that the translocatlon of the compound from root to
leaves of grass and legumes 1s rapid; however, the compound 1s metabolized
rapidly 1n legumes but not 1n grass.
2.4. SUMMARY
Of the three likely chemical processes that may lead to the loss of
4-chlorobenzotrlfluoMde 1n the atmosphere, neither direct photolysis nor
Us reaction with atmospheric ()„ Is significant (Atkinson et al., 1985).
Its reaction with photochemlcally produced HO radical has a rate constant of
2.3xlO~13 cm3/molecule-sec (Atkinson et al., 1985). Assuming the atmo-
spheric concentration of HO radical as 106 radicals/cm3, the lifetime
of this compound 1n the air has been estimated to be -50 days (Atkinson et
al., 1985). Therefore, the compound Is expected to persist In the atmo-
sphere. In water, photolysis of the chemical 1s not Important (Elanco
Products Co., 1983a). Although the rates of aerobic and anaerobic blodegra-
datlon of the compound In water could not be determined, these rates are
slower than the volatilization rate (Elanco Products Co., 1983b,c,d). From
Ollld -7- 04/19/88
-------
the value of the ratio of the volatilization rate of the compound to the
oxygen reaeratlon rate determined experimentally (Elanco Products Co.,
1983d) and the values of oxygen reaeratlon rates 1n a few natural waters
(Thomas, 1982), the half-life for volatilization of the compound from water
has been estimated to be 1-6 days. The K value of 420-490 1n sediments
oc
(Elanco Products Co., 1983e) Indicates that the compound will sorb
moderately to suspended solids and sediments In natural waters. Based on
the experimentally determined BCF of 122-202 In Blueglll sunflsh, Lepomls
macrochlrus. (Elanco Products Co., 1984), the compound 1s not expected to
bloconcentrate significantly 1n aquatic organisms. From the data available
1n aquatic studies, 1t can be predicted that photolysis 1n soil will be
unimportant, and some loss of the compound will occur from the soil surface
because of volatilization, although the volatilization process will become
less Important as the soil depth Increases. The K value of 510-530 1n
soil (Elanco Products Co., 1983e) Indicates that the compound may leach
through some soils, particularly soil from Improper disposal sites. No data
regarding the b1odegradab1!1ty of the compound 1n soil are available.
Ollld -8- 05/10/88
-------
3. EXPOSURE
There Is a paucity of data on the levels of 4-chlorobenzotMfluor1de 1n
environmental media. This compound was qualitatively detected 1n water from
Lake Ontario at Niagara River (Great Lakes Water Quality Board, 1983). The
source of the compound 1n the water was possibly the nearby manufacturer of
the chemical. Hauser and Bromberg (1982) reported the qualitative detection
of this compound 1n the sediment/sol I/water samples collected from contami-
nated areas of Love Canal, Niagara Falls. Bass and yellow perch collected
from Niagara River and analyzed 1n 1978 contained 4-chlorobenzotr1fluor1de
1n the concentration range 0.17-2.0 ppm. The compound was not detected at a
later date (1980), however, at a detection limit of 0.01 ppm 1n various
samples of fish (walleye, brown trout and sucker) from Lake Erie and Lake
Ontario near the suspected contaminated areas (Occidental Chem. Corp.,
1980b).- Cacco and Ferrari (1982) reported the detection of. this compound at
a level of 1 ppm 1n groundwater near an Improper disposal site near Vlcenza,
Italy.
Ollld -9- 04/19/88
-------
4. AQUATIC TOXICITY
4.1. ACUTE TOXICITY
The acute toxldty of 4-chlorobenzotr1fluor1de to aquatic organisms was
assessed for two species of fish (rainbow trout, Salmo galrdnerl. and blue-
gill sunflsh, Lepomls macrochlrus) and a macrolnvertebrate (the crustacean,
Daphnla maqna). Exposure of rainbow trout to 4-chlorobenzotr1fluor1de In
static acute toxldty tests produced nominal 24-, 48-, 72- and 96-hour
LCrQ estimates of 13.5 mg/l (Union Carbide Environmental Services,
1979a). Confidence limits were not generated because of a lack of Inter-
mediate levels of mortality. No deaths were observed at 10 mg/8, 4-chloro-
benzotMfluorlde, and 100% mortality was observed at 18 mg/i for each
observation period. The test was conducted 1n reconstituted water at 12°C.
Exposure of blueglll sunflsh to 4-chlorobenzotr1fluor1de 1n static acute
toxldty tests produced nominal 24-, 48-, 72- and 96-hour LC5Q values with
95% confidence limits of 19.1 (15.9-22.9), 13.5 (11.5-15,8), 12.7
(11.4-14.1) and 12.0 (10.3-13.9) mg/S., respectively (Union Carbide
Environmental Services, 1979b). No deaths were observed at 5.6 mg/8.
4-chlorobenzotr1fluor1de after 96 hours. The test was conducted 1n
reconstituted water at 22°C.
Exposure of 0_. maqna to 4-chlorobenzotr1fluor1de In static acute
toxldty tests produced nominal 24- and 48-hour LCSQ estimates with 95%
confidence limits of 13.2 (11.4-15.2) and 12.4 (10.7-14.5) rag/i. respec-
tively (Union Carbide Environmental Services, 1979c). No deaths were
observed at 5.6 mg/l 4-chlorobenzotr1fluor1de after either 24 or 48 hours
of exposure. The test was conducted In well water at 21°C.
Ollld -10- 04/19/88
-------
4.2. CHRONIC EFFECTS
The chronic toxlclty of 4-chlorobenzotr1fluor1de to aquatic organisms
was assessed for a single species of fish (fathead minnow, Plmephales
promelas) and the macrolnvertebrate, D. maqna. Percentage hatch and
survival of fathead minnow embryos exposed to 4-chlorobenzotrlfluorlde were
used to estimate a 31-day MATC of >0.54 but <1.4 mg/l (EG&G Bionomics,
1981). Fathead minnow eggs were exposed to 4-chlorobenzotr1fluor1de 1n a
flowthrough system using well water at a temperature of 25°C. Measured
concentrations of 4-chlorobenzotr1fluor1de were used to calculate the MATC
value.
The chronic effects of exposure of D_. maqna to 4-chlorobenzotr1fluorlde
were assessed by generating 4-, 7-, 14- and 21-day LC5Q estimates with 95%
confidence limits of 0.163 (0.120-0.222), 0.150 (0.105-0.214), 0.073
(0.05-0.107) and 0.071 (0.047-0.107) mg/l, respectively (Union Carbide
Environmental Services, 1979d). In addition, brood size of -actively
reproducing D. maqna adults exposed to 4-chlorobenzotr1fluor1de was used to
estimate a 21-day MATC of >0.03 but <0.05 mg/l 4-chlorobenzotr1fluor1de.
The test was conducted 1n well water under flowthrough conditions at a mean
temperature of 20.8°C. Measured concentrations of 4-chlorobenzotr1fluor1de
were used to calculate the MATC and LC5Q values.
4.3. PLANT EFFECTS
There were no studies Identified that addressed the effects of exposure
of aquatic plants to 4-chlorobenzotr1fluor1de.
4.4. SUMMARY
Exposure of rainbow trout and blueglll sunflsh to 4-chlorobenzotrlfluo-
rlde generated 96-hour LC5Q values of 13.5 and 12.0 (10.3-13.9) mg/l,
respectively (Union Carbide Environmental Services, 1979b). Exposure of J).
Ollld -11- 05/10/88
-------
magna to 4-chlorobenzotr1fluor1de generated a 48-hour LCc0 of 12.4
(10.7-14.5) mg/8, (Union Carbide Environmental Services, 1979c).
The concentration of 4-chlorobenzotr1fluor1de that produced chronic
effects In aquatic organisms was ~l-2 orders of magnitude lower than that
produced for acute effects. The MATC for fathead minnow eggs was >0.54 but
<1.4 mg/l 4-chlorobenzotr1fluor1de. The MATC for D. maqna was >0.03 and
<0.05 mg/l 4-chlorobenzotr1fluor1de (Union Carbide Environmental Services,
1979d).
Ollld -12- 05/10/88
-------
5. PHARMACOKINETICS
5.1. ABSORPTION
A metabolism study of [CF3-l4C]-4-chlorobenzotr1fluor1de, which
found radioactivity In the expired air and urine of male and female
Sprague-Oawley rats treated at doses of 1 or 104 mg/kg (In corn oil),
Indicated that the compound 1s absorbed from the gastrointestinal tract
(Qulstad and Mulholland, 1983). Within 4 days of dosing, radioactivity In
the expired air and urine of treated rats accounted for 68-82% and 6-15% of
the dose, respectively, with the total by both routes ranging from 76-88%.
Only 2-4% of the dose was found In the feces. Analysis of blood for
radioactivity Identified a peak concentration of ~0.05 ppm, 1 hour after
dosing, suggest- 1ng that absorption from the gastrointestinal tract was
rapid.
5.2. DISTRIBUTION
Four days after' rats of both s.exes were given a gavage dose of
[CF,-lAC]-4-chlorobehzotr1fluor1de 1n corn oil (1 or 104 mg/kg), -1% of
0
the radioactivity remained In the carcass, except for selected tissues (see
below) (Qulstad and Mulholland, 1983). Analysis of organs and tissues,
Including the spleen, fallopian tubes and ovaries, testes, pancreas, lungs,
kidney, brain, heart, muscles, fat, liver, hide, stomach and Intestines,
revealed slightly higher levels of radioactivity 1n tissues from female rats
compared with male rats. The radioactivity 1n the tissues was Identified as
4-chlorobenzotr1fluor1de, and tissue concentrations ranged from <1-16
yg/kg following a 1 mg/kg dose, and <40-371 yg/kg following a 104 mg/kg
dose. The only exception was abdominal fat from female, but not male, rats,
which contained higher levels of radioactivity: 104 yg/kg following a 1
Ollld -13- 05/10/88
-------
mg/kg dose and 1420 yg/kg following a 104 mg/kg dose. Approximately 90%
of the radioactivity 1n the abdominal fat was Identified as 4-chlorobenzo-
trlfluoMde.
5.3. METABOLISM
In a metabolism study of [CF3-14C] 4-chlorobenzotr1fluor1de where
rats were treated orally, Qulstad and Mulholland (1983) found that the
compound was not metabolized extensively. At a dose of 1 mg/kg, -15% of the
dose was metabolized. Analysis of radioactivity 1n the expired air revealed
that unmetabollzed [l4C]-4-chlorobenzotr1fluor1de accounted for a majority
of the 62-82% of the dose recovered, with negligible amounts recovered as
"CO-. At least 56% of the radioactivity found 1n the feces was
unmetabollzed 4-chlorobenzotr1fluor1de; the remaining radioactivity was not
Identified. The major urinary metabolites Identified were the glucuronldes
of dlhydroxybenzotrlfluorlde and 4-chloro-3-hydroxybenzotr1fluor1de, which
accounted .for <2.7 and 4.4% of the total dose, respectively. A minor
metabolite, the mercaptuMc add conjugate of 4-chlorobenzotr1fluor1de,
accounted for 0.1-0.2% of the total dose, respectively. Because 4-chloro-
benzolc add and Us conjugates were not detected In the urine, the Inves-
tigators concluded that the CF- moiety was stable to hydrolysis. Little
o
difference In qualitative or quantitative metabolism between male and female
rats was observed.
5.4. EXCRETION
Four days after rats were given a single oral dose of [CF3-14C]-4-
chlorobenzotrlfluorlde 1n corn oil at 1 (four females, two males) or 104
mg/kg (two females), 62-82% of the dose was recovered In the expired air
(Qulstad and Mulholland, 1983). Analysis of air resulted In recovery of 35%
of the radioactivity before the rats defecated; this suggested that
pulmonary excretion was rapid, and confirmed that the radioactivity had been
Ollld -14- 05/10/88
-------
expired and had not volatilized from the feces. Radioactivity recovered 1n
the feces accounted for 2.6-3.5% of the dose, while urinary radioactivity
accounted for 13.6-14.9% of the dose following treatment at 1 mg/kg, and
5.9% of the dose at 104 mg/kg. Total recoveries ranged from 79-90%. The
Investigators stated that the relatively low recoveries were a reflection of
r-
difficulties In the radloassay of volatile [l4C]-4-chlorobenzotr1fluor1de.
5.5. SUMMARY
The single study of [l4C]-4-chlorobenzotr1fluor1de metabolism using
rats (Qulstad and Mulholland, 1983) Indicated that the compound 1s absorbed
and excreted readily,, predominantly as Ihe parent compound. The major route
of excretion was through expired air, which accounted for 62-8254 of the
dose. Urinary metabolites Identified were the glucuronldes of
d1hydroxybenzotr1fluor1de and 4-chloro-3-hydroxybenzotr1fluor1de, which
accounted for <2.7 and 4.4% of the dose, respectively. A minor urinary
metabolite, the mercaptuMc acid conjugate of 4-chlorobenzotr1fluor1de,
accounted for 0.1-0.2% of the dose.
Oil Id -15- 05/10/88
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposure. Pertinent data regarding the toxldty of
4-chlorobenzotrifluoride following subchronlc and chronic Inhalation
exposure were not located 1n the available literature dted 1n Appendix A.
6.1.2. Oral Exposure.
6.1.2.1. SUBCHRONIC — In a 3-month study, groups of 15 F344 rats/sex
(5-6 weeks old) were treated dally by gavage with 4-chlorobenzotr1fluor1de
(97.7% pure) 1n corn oil at doses of 0, 10, 40, 150 or 500 mg/kg/day (Arthur
and Probst, 1983). One male.rat at 10 mg/kg/day and two male rats at 500
mg/kg/day died. No significant dose-related physical or behavioral signs or
ophthalmic changes were noted. Transiently significant reductions 1n body
weight gain were observed 1n all dose groups, with body weight gain 1n males
at 500 mg/kg/day consistently below controls. Food Intake of all 4-chloro-
benzotrlfluorlde-treated rats was depressed throughout the study, . the
largest decrease being observed 1n males at 500 mg/kg/day. The only
significant hematology changes noted were 1n high-dose male rats, which had
a statistically significant (p<0.05) decrease In total erythrocytes and a
shift toward an Increase In neutrophlls and a decrease In lymphocytes.
Results of clinical chemistry analyses revealed slightly elevated levels of
serum urea nitrogen 1n male rats treated at 150 and 500 mg/kg. Total
blllrubin was Increased In both male and female rats at 500 mg/kg.
UMnalysIs Indicated mild prbtelnurla In both sexes at 150 and 500 mg/kg.
Determinations of hepatic p-nltroanlsole 0-demethylase activity showed
significantly (p<0.05) greater levels In males at 40, 150 and 500 mg/kg/day,
and 1n females at 500 mg/kg/day. At necropsy, relative liver and kidney
weights were significantly (p<0.05) Increased "at the higher doses"
Ollld -16- 05/10/88
-------
(presumably 150 and 500 mg/kgj. Thyroid weights were slightly Increased In
treated rats, with significant Increases (p<0.05) 1n females at 40 and 500
mg/kg. Slightly Increased adrenal weights were observed 1n males at 150 and
500 mg/kg/day and 1n females at 500 mg/kg/day. Hlstologlcal examinations
revealed renal tubular degeneration In one low-dose male rat (10 mg/kg/day)
and In all male rats treated at doses >40 mg/kg/day. The severity of the
renal lesions was dose-related, ranging from minimal (decreased cellular
height, Increased cytoplasmlc basophlUa, Increased hyaline droplet
formation) to moderate (Increased number of necrotlc cortical epithelial
cells, and prominent hyaline casts 1n tubules of the outer zone medulla and
occasionally In the cortex). Tubular degeneration was not observed In
female rats or 1n any male controls. Centrllobular hypertrophy was observed
In the livers of all males and one female rat treated at 150 mg/kg/day and
1n all rats treated at 500 mg/kg/day. CentMlobular hypertrophy was not
observed 1n control rats. Among high-dose rats, the effect-on the liver" was
slightly more prominent 1n males than 1n females. The Investigators
concluded that rats tolerated the 10 mg/kg dose for 90 days without
significant toxlclty.
6.1.2.2. CHRONIC -- Pertinent data regarding the toxlctty of
4-chlorobenzotr1fluor1de following chronic oral exposure were not located In
the available literature cited In Appendix A.
6.1.3. Other Relevant Information. Hooker Chemical Corp. (1979a)
reported a 4-hour LC5Q of 33.0 mg/m3 for 4-chlorobenzotMfluorlde 1n
Sprague-Dawley rats (male and female). No mortality occurred at 6.03 or
20.8 mg/m3. According to the Investigators, signs of Irritation during
the exposure (redness around the eyes, excessive lacrlmatlon, nasal
discharge) occurred at concentrations >20.8 mg/m3, and lung discoloration
on necropsy was observed In all exposure groups. These results suggest that
Ollld -17- 05/10/88
-------
pulmonary Irritation may be an Important component 1n the toxlclty of
4-chlorobenzotr1fluor1de following Inhalation exposure.
In a Russian study (Rapoport et al., 1986), male nonpurebred albino male
rats (numbers unspecified) were exposed to 4-chlorobenzotr1fluor1de at 5.5,
20.5, 71.6 or 440 mg/m3, continuously for 120 hours. The rats were
observed for at least 115 days following exposure. Examinations Included
body weight, muscular strength (grasping reflex), blood analyses (RBC and
leukocyte counts, hematocrlt, content of hemoglobin In one erythrocyte,
liver function, chollnesterase and lactate dehydrogenase) and studies of the
nervous system ("summation-threshold Index," motor activity). Exposure at
440 and 71.6 mg/m3 resulted 1n a change In "practically all of the
parameters studied." The 20.5 mg/m3 concentration was considered the
"minimally effective" concentration, while 5.5 mg/m3 was considered the
"subthreshold." The results, which are difficult to Interpret, are pre-
sented as time of onset of significant changes 1n parameters. In general,
time of onset of significant effects Increased with decreasing exposure
concentration. The study does not relate exposure concentration to
Incidence or severity of effects.
The oral LD5Q for 4-chlorobenzotr1fluor1de In Sprague-Dawley rats
(male and female) was reported as >5.0 ml/kg (6.7 g/kg) (Hooker Chemical
Corp., 1985a). At a dose of 5 ml/kg (6.7 g/kg), 2/8 male and 0/8 female
rats died during the 14-day observation period.
The dermal LD5Q 1n New Zealand White rabbits was reported to be >2.0
ml/kg (2.7 g/kg) (Hooker Chemical Corp., 1985b). 4-Chlorobenzotr1fluor1de
was applied to shaved abraded skin (back) and the test area was occluded.
Only one dose was studied; at 2 ml/kg (2.7 g/kg), 0/5 male and 1/5 female
rabbits died during the 14-day observation period.
Ollld -18- 05/10/88
-------
6.2. CARCINOGENICITY
6.2.1. Inhalation. Pertinent data regarding the carclnogenldty of
4-chlorobenzotr1fluor1de following Inhalation exposure were not located In
the available literature cited 1n Appendix A.
6.2.2. Oral. Pertinent data regarding the carclnogenldty of 4-chloro-
benzotr1fluor1de following oral exposure were not located In the available
literature cited 1n Appendix A.
6.2.3. Other Relevant Data. Hooker Chemical Corp. (1980) reported that
4-chlorobenzotr1fluor1de tested negative for cell transformation In
Balb/C3T3 cells. The compound (purity unspecified) was added to the culture
medium at concentrations of 0.1-40 nl/mi, which allowed 80 to 50% of the
cells to survive. The study did not report whether an activating system was
used. Lilly Research Laboratories (1983a) also found that 4-chlorobenzotr1-
fluoride (97% pure) tested negative for cell transformation In Balb/C3T3
cells." ' This-study was conducted 1n the presence of S-9, with-the compound
added to the .culture medium at concentrations of 10-300 pg/l. Reduced
survival was observed at 300 jig/mi, a concentration at which the
compound was not completely mlsdble with the culture medium.
6.3. MUTAGENICITY
Data regarding the mutagenldty of 4-chlorobenzotr1fluor1de are
presented In Table 6-1. 4-Chlorobenzotr1fluor1de tested negative 1n assays
for reverse mutation In Salmonella typhlmurlum (Haworth et a!., 1983; Hooker
Chemical Corp., 1978a). Urine from mice treated with 4-chlorobenzotrl-
fluoMde also tested negative 1n assays for reverse mutation 1n S.
typhlmurlum (Hooker Chemical Corp., 1979b). Negative results have been
reported for 4-chlorobenzotr1fluoMde 1n assays for reverse mutation In
Saccharomvces cerevlslae. DNA repair 1n Escher1ch1a coll (Hooker Chemical
01 lid -19- 05/10/88
-------
TABLE 6-1
Nutagenlclty Testing of 4-Chlorobenzotrtfluoride
Assay
Reverse
nutation
Reverse
nutation
Reverse
nutation
(urine assay)
Reverse
mutation
DMA repair
test
Forward
nutation
Unscheduled
DNA synthesis
Chromosome
aberrations
Indicator Purity
Organlsn
Salmonella 96X
typhlmurlum
TA1535. TA1537.
TA9B. TA100
S. typhlmurluro NR
TA1535. TA1537.
TA98, TA100
S. typhlmurlun NR
TA1535. TA1537.
TA98. TA100
Saccharoroyces NR
cerevlslae D4
Escherlchla NR
coll U3HO/po1A+.
P3478/polA-
L5178Y mouse NR
1 ymphoma
EUE cells NR
Chinese hamster NR
ovary cells
Application Concentration
or Dose
pre Incubation 10-1000 pg/plate
plate 0.01-10 pi/plate
Incorporation
male CO-1 nice 0.1, 0.2 or 0.3
treated by gavage nt urine/plate
for 2 days at 50,
167 or 500 rag/kg/
day; urine tested
for nutagenlclty
by plate Incor-
poration
plate 0.1-10 vft/plate
Incorporation
spot test 0.01-10 |ii/plate
(check) (check)
added to 3.13-50 nl/rot
culture medium
NR NR
added to 29.99-130 nt/mt .
cultures
Activating
System
»S-9
»S-9
i deconjuga-
tlng enzyme.
B-glucuront-
dase, before
urine was
added to
plate
± S-9
»S-9
±S-9
NR
±S-9
Response Comment
NC
NC
= Urine was collected
overnight (16 hours);
the tine between dosing
and urine collection
was not stated.
NC
NC
= Concentrations of >78
nfc/nl were highly
toxic to mouse lymphoma
cells.
» Study was available only
as an abstract, which
did not further describe
the cells used or the
study protocol.
Cells treated for 12
hours collected at 14 or
24 hours, cytotoxlclty
at 90 nft/mt.
Reference
Haworth et al.,
1983
Hooker Chemical
Corp.. 1978a
Hooker Chemical
Corp.. 1979b
Hooker Chemical
Corp., 1978a
Hooker Chemical
Corp.. 1978a
Hooker Chemical
Corp.. 1978b
Benign) and
Dogllottl. 1980
Lilly Research
Laboratories.
19B3b
-------
TABLE!
(cont.)
Assay
Sister
chromatld
exchange
Indicator Purity Application
Organism
LS178 mouse NR added to
lymphoma cells culture medium
Concentration
or Dose
0.0025. O.OOSO,
0.0100, 0.0200,
0.0400 |il/ml
Activating
System
iS-9
Response Comment
t Without activation, re-
sults were significant
at all concentrations.
Ulth activation, results
were significant at 0.0025
0.0100 and 0.0200 vl/ml
(not dose-related)
Reference
Hooker Chemical
Corp.. 1979c
t
Chromosome
aberrations
bone marrow
cells of rats
NR
gavage dose
0.5. 1.7 or 5.0
ml/kg
NA
Analyses were completed
6, 24 and 48 hours after
a single gavage dose.
Lilly Research
Laboratories,
1983c
NA - Not applicable; NC = no comment; NR = not reported
a
CO
-------
Corp., 1978a), forward mutation In mouse lymphoma cells (Hooker Chemical
Corp., 1978b), and chromosome aberrations In Chinese hamster ovary cells
(Lilly Research Laboratories, 1983b) and rat bone marrow cells (Lilly
Research Laboratories, 1983c). The only positive results for
4-chlorobenzotr1fluor1de were 1n an assay for unscheduled DNA synthesis 1n
EUE cells (cells were not further described) (Benlgnl and Dogl1ott1, 1980),
and In an assay for sister chromatld exchange 1n mouse lymphoma cells
(Hooker Chemical Corp., 1979c).
6.4. TERATOGENICITY
Pertinent data regarding the teratogenlcity of 4-chlorobenzotr1fluor1de
were not located 1n the available literature cited 1n Appendix A.
6.5. OTHER REPRODUCTIVE EFFECTS
Hooker Chemical Corp. (1981) reported results of a 2-generatlon repro-
ductive study 1n which groups of 20 Sprague-Dawley rats/sex were treated by
gavage with 4-chlorobenzotr1fluor1de (97% pure) 1n corn oil at doses of 0,
5, 15 or 45 mg/kg/day. The parental generation was treated for 4 weeks
before mating, throughout reproduction, and through the weaning of the F.
generation. The F, generation was culled to 10 pups/Utter on day 14, and
was treated for 90 days postweanlng. Offspring were not examined for
malformations. No treatment-related mortalities, behavior changes or
consistent treatment-related changes 1n weight gain and food consumption
were observed 1n the F_ or F, rats. No significant treatment-related
changes In hematology and clinical chemistry were noted in F_ or F,
rats. Treatment of rats with 4-chlorobenzotr1fluor1de had no effect on the
number of pups/Utter, pup surv1vabH1ty or length of gestation period.
Body weight of female pups from rats treated at 45 mg/kg/day was signifi-
cantly (p<0.05) decreased compared with controls on day 1 after birth. On
day 4, body weights of offspring (males and females) were significantly
Ollld -22- 05/10/88
-------
(p<0.05) Increased compared with controls 1n all treatment groups. At
necropsy, no dose-related gross lesions were observed 1n the FQ rats.
Hlstologlcal examinations were not completed. In the F. generation,
determination of organ weights revealed a nonsignificant dose-related
Increase In mean liver weights and mean I1ver-to-body weight ratios 1n both
sexes. Hlstologlcal examinations of major tissues and organs completed on
F, controls and on rats treated at 45 mg/kg/day did not reveal any
treatment-related effects.
6.6. SUMMARY
Minimal to moderate renal tubular degeneration was observed 1n male rats
treated by gavage with 4-chlorobenzotr1fluor1de at doses >40 mg/kg/day for 3
months (Arthur and Probst, 1983). CentMlobular hypertrophy of the Hver
was observed 1n male rats treated with 4-chlorobenzotr1fluor1de doses at
>150 mg/kg/day and In female rats at 500 mg/kg/day. No significant effects
were observed In rats treated for 3 months by gavage with
4-chlorobenzotr1fluor1de at 10 mg/kg/day.
In contrast to the Arthur and Probst (1983) study, hlstologlcal kidney
and liver effects were not observed 1n a 2-generat1on study In which
Sprague-Dawley rats were treated by gavage with 4-chlorobenzotr1fluor1de at
doses <45 mg/kg/day for >90 days (Hooker Chemical Corp., 1981). 4-Chloro-
benzotr1fluor1de treatment did not have any effect on reproductive
parameters.
A Russian study (Rapoport et al., 1986) reported that Inhalation
exposure of rats to 4-chlorobenzotr1fluoMde at concentrations >20.5 mg/m3
for 120 hours resulted 1n changes 1n blood analyses, motor activity and
muscle strength. Significant changes were not observed 1n rats exposed at
5.5 mg/m3 for 120 hours.
Ollld -23- 05/10/88
-------
Hooker Chemical Corp. (1979a) reported a 4-hour LC5Q for 4-chloro-
benzotMfluoride 1n Sprague-Dawley rats of 33 mg/m3. The oral LD5Q for
4-chlorobenzotr1fluor1de 1n Sprague-Dawley rats was reported as >5.0 mi/kg
(6.7 g/kg) (Hooker Chemical Corp., 1985a), while the dermal LD™ 1n
rabbits was reported to be >2.0 ml/kg (2.7 g/kg) (Hooker Chemical Corp.,
1985b).
Except for positive results 1n assays of unscheduled DNA synthesis
(Benlgnl and Dogllottl, 1980) and sister chromatld exchange (Hooker Chemical
Corp., 1979c), results of mutagenlclty assays of 4-chlorobenzotr1fluor1de
have been negative.
4-Chlorobenzotr1fluor1de has not been tested for carclnogenlclty or
teratogenldty.
Ollld -24- 04/19/88
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
Pertinent guidelines and standards, Including EPA ambient water and air
quality criteria, drinking water standards, FAO/WHO ADIs, EPA or FDA toler-
ances for raw agricultural commodities or foods, and ACGIH, NIOSH or OSHA
occupational exposure limits were not located In the available literature
dted 1n Appendix A.
*2. AQUATIC
Pertinent guidelines and standards for the protection of aquatic life
from exposure to 4-chlorobenzotr1fluor1de were not located 1n the available
literature cited 1n Appendix A.
Ollld -25- 04/19/88
-------
8. RISK ASSESSMENT
8.1. CARCINOGENICITY
Pertinent data regarding the cardnogenlcHy of 4-chlorobenzotr1fluor1de
were not located In the available literature cited 1n Appendix A.
8.1.1. Weight of Evidence. As a result of a lack of data concerning
cardnogenlclty In humans and animals, 4-chlorobenzotrlf luorlde can be
classified as an EPA Group D chemical (U.S. EPA, 1986b), not classifiable as
to human cardnogenlclty.
8.1.2. Quantitative Risk Estimates. The derivation of carcinogenic
potency factors for 4-chlorobenzotr1fluor1de 1s precluded by the lack of
cardnogenlclty data.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure. The derivation of Inhalation risk assessment
values for 4-chlorobenzotrlfluorlde Is precluded by the lack of subchronlc
and chronic Inhalation studies.
An LCgg study using rats (Hooker Chemical Corp., 1979a) suggested that
pulmonary Irritation may be an Important component 1n the toxlcity of
4-chlorobenzotr1fluor1de following Inhalation exposure. The only other
Inhalation study, a Russian study (Rapoport et al., 1986), reported changes
1n blood analyses, motor activity and muscular strength In rats exposed to
4-chlorobenzotr1fluor1de continuously at >20.5 mg/m3 for 120 hours.
Significant effects were not observed In rats exposed to 4-chlorobenzotrl-
fluorlde at 5.5 mg/m3 for 120 hours.
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME EXPOSURES -- In the 90-day study by
Arthur and Probst (1983), F344 rats were treated by gavage with 4-chloro-
benzotrlfluorlde In corn oil at 0, 10, 40, 150 or 400 mg/kg/day. No
Oil Id -26- 05/10/88
-------
significant treatment-related effects were observed at 10 mg/kg/day. In
male rats treated at >40 mg/kg/day, renal tubular degeneration was observed,
with severity Increasing from minimal effects at 40 mg/kg/day to moderate
effects at 150 mg/kg/day. CentMlobular hypertrophy In the liver was
observed 1n all male rats and 1n one female rat at 150 mg/kg/day, and 1n all
rats at 400 mg/kg/day.
The only other study of sufficient duration for risk assessment 1s the
»
2-generat1on study using Sprague-Dawley rats (Hooker Chemical Corp., 1981).
In this study, no significant treatment-related effects on reproduction or
h1stolog1cal changes were noted 1n rats treated by gavage with 4-chloro-
benzotrlfluorlde In corn oil at 0, 5, 15 or 45 mg/kg/day. The FQ rats
were treated for 4 weeks before mating, through mating and weaning, and the
F, were treated for 90 days after weaning. A nonsignificant dose-related
Increase In liver weights was noted In F, rats.
A 3-month rat study (Arthur and Probst, -1983) Indicated that the kidney
and liver are the target organs of 4-chlorobenzotr1fluor1de toxldty. The
LOAEL found 1n this study was 40 mg/kg/day, a dose at which minimal renal
tubular degeneration 1n male rats was observed. The highest NOAEL below the
40 mg/kg/day LOAEL Is the 15 mg/kg/day dose from the 2-generat1on rat study
(Hooker Chemical Corp., 1981). A subchronlc oral RfD of 0.2 mg/kg/day, or
11 mg/day for a 70 kg human, 1s calculated from the NOAEL of 15 mg/kg/day by
dividing the NOAEL by an uncertainty factor of 100, 10 to extrapolate from
animals to humans, and 10 to protect sensitive Individuals.
Confidence In this RfD 1s low. The studies useful for risk assessment
are limited to two rat studies. These studies Indicate a possible strain
difference; one study reported renal tubular degeneration In male F344 rats
treated with 4-chlorobenzotr1fluor1de at 40 mg/kg/day (Arthur and Probst,
Ollld -27- 05/10/88
-------
1983), but no treatment-related effects were observed In Sprague-Dawley rats
In a 2-generat1on study at 45 mg/kg/day (Hooker Chemical Corp., 1981). Low
confidence 1n the subchronlc RfD 1s also Indicated because of the lack of
teratogenlclty studies.
8.2.2.2. CHRONIC EXPOSURES -- Chronic oral studies of 4-chlorobenzo-
trlfluorlde were not available. A chronic oral RfD of 0.02 mg/kg/day or 1
mg/day for a 70 kg human can be derived by dividing the subchronlc oral RfD
by an additional uncertainty factor of 10 to extrapolate from subchronlc
exposure.
Confidence 1n this RfD Is low. There are only two rat studies available
concerning the toxldty of 4-chlorobenzotr1fluor1de, and they Indicate a
possible strain difference In the development of renal tubular degeneration.
Ollld -28- 05/10/88
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The only study reporting effects following subchronlc exposure to
4-chlorobenzotr1fluor1de 1s the 3-month study by Arthur and Probst (1983).
As discussed 1n Section 6.1.2.1. and summarized In Table 9-1, male rats
treated by gavage with 4-chlorobenzotr1fluor1de 1n corn oil at a dose of 40
mg/kg/day developed minimal renal tubular degeneration, while rats treated
at 150 mg/kg/day developed protelnurla, mild to moderate renal tubular
degeneration and centrllobular hypertrophy of the liver. As Indicated In
Table 9-1, the animal doses of 40 and 150 mg/kg/day correspond to human MEDs
of 43 and 149 mg/day, and RV.s of 3.0 and 2.2, respectively. The most
appropriate RV for minimal renal tubular degeneration observed at the
lower dose Is 3, and the RV for renal tubular degeneration associated
with mild protelnurla 1s 7. Multiplication of the RV.s by the RV s
yields CSs of 9.0 and 15.4 for minimal renal tubular degeneration and
tubular degeneration associated with protelnurla, respectively. Th-e highest
CS, 15.4, 1s the most appropriate basis for the RQ of 1000 (Table 9-2).
9.2. BASED ON CARCINOGENICITY
Pertinent data concerning the carclnogenldty of 4-chlorobenzotMfluo-
rlde were not located. Except for an assay for sister chromatld exchange
(Hooker Chemical Corp., 1979c) and an assay for unscheduled DMA synthesis
(Benlgnl and Dogl1ott1, 1980), mutagenlcHy assays have reported negative
results (see Section 6.3.). The lack of data concerning the carclnogenldty
of 4-chlorobenzotr1fluor1de In either humans or animals Indicates that the
compound should be classified as an EPA Group D chemical (U.S. EPA, 1986b),
not classifiable as to human carclnogenldty. Hazard ranking based on
carclnogenldty 1s not possible.
Oil Id -29- 05/10/88
-------
o
I
TABLE 9-1
Composite Scores for the Oral Toxlclty of 4-Chlorobenzotrlfluorlde (97X Pure) In Corn Oil Using Hale F344 Rats*
No. at
Start
15
15
Average
Body Ue1ghtb
(kg)
0.25
0.2
Dose/Exposure
40 rog/kg/day
by gavage for
3 months
150 mg/kg/day
by gavage for
3 months
Animal Dose
(rog/kg/day)
40
150
Equivalent
Human NEDC
(rog/day)
43
149
RVd Effect RVe
3.0 Minimal renal tubular 3
degeneration
2.2 Mild protelnurla. renal 7
tubular degeneration
and centrllobular hyper-
trophy of the liver
CS RQ
9 1000
15.4 1000
aSource: Arthur and Probst. 1903
Estimated from graphs
cAnimal dose multiplied by the cube root of the ratio of animal to reference human body weight (70 kg) and by 70 kg to express human NED In
tng/day, and divided by an uncertainty factor of 10 to expand from subchronlc to chronic exposure.
ca
CD
-------
TABLE 9-2
4-ChlorobenzotMfluoride
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: oral
Dose*: 149
Effect: mild protelnurla, renal tubular degeneration,
centrllobular hypertrophy of the liver
Reference: Arthur and Probst, 1983
RVd: - 2.2
RVe:. 7
Composite Score: 15.4
RQ: 1000
*Equ1valent human dose
Ollld -31- 05/10/88
-------
10. REFERENCES
Arthur, B.H. and K.S. Probst. 1983. A subchronlc study 1n Fischer 344 rats
given dally gavage doses of 4-chlorobenzotrlfluorlde (PCBTF). Toxicology
Division, Lilly Research Laboratories, Division of E11 Lilly and Company,
Greenfield, IN. U.S. EPA/OPTS Public Files. Microfiche #OTS0507306.
Atkinson, R., S. Aschmann, A. Winer and J. Pitts, Jr. 1985. Atmospheric
gas phase loss processes for chlorobenzene, benzotrlfluorlde, and 4-chloro-
benzotrlfluorlde, and generalization of predictive techniques for atmo-
spheric lifetimes of aromatic compounds. Arch. Environ. Contam. Toxlcol.
H(4): 417-425.
Benlgnl, 4. and E. Dogllottl. 1980. UDS studies on selected environmental
chemicals. Mutat. Res. 74: 217.
Boudaklan, M.M. 1980. Fluorlnated aromatic compounds. In.: Kirk-Othmer
Encyclopedia of Chemical Technology, 3rd ed., Vol. 10, M. Grayson, Ed. John
WHey and Sons, New York, NY. p. 901, 912, 921-925, 936.
Cacco, G. and G. Ferrari. 1982. Absorption and translocatlon of 4-{tr1-
fluoromethyljchlorobenzene 1n soil and crops. J. Agrlc. Food Chem. 30:
196-197.
EG&G Bionomics. 1981. The toxlclty of parachlorobenzotrlgluorlde (PCBTF)
to fathead minnow (Plmephales promelas) embryos and larvae. Report
#BW-81-3-838 (OTS0508145).
Ollld -32- 04/19/88
-------
Elanco Products Company. 1983a. Photolysis of p-chlorobenzotr1fluoMde In
water. Prepared by Lilly Res. Labs., Greenfield, IN. USEPA/OPTS Public
Files, 80 Submission. Microfiche #OTS 0507306.
Elanco Products Company. 1983b. Aerobic aquatic blodegradatlon of
4-chlorobenzotr1fluor1de. Prepared by Lilly Res. Labs., Greenfield, IN.
USEPA/OPTS Public Files, 80 Submission. Microfiche #OTS 0507306.
Elanco Products Company. 1983c. Anaerobic blodegradatlon of 4-chlorobenzo-
tr1fluor1de. Prepared by Lilly Res. Labs., Greenfield, IN. USEPA/OPTS
Public Files, 80 Submission. Microfiche #OTS: 0507306.
Elanco Products Company. 1983d. Volatilization rate of p-chlorobenzotr1-
fluorlde from water. Prepared by Lilly Res. Labs., Greenfield, IN. USEPA/
OPTS Public Files, 80 Submission. Microfiche #OTS 0507306.
Elanco Products Company. 1983e. Absorption of p-chlorobenzotr1fluor1de on
soil and sediment. Prepared by Lilly Res. Labs., Greenfield, IN. USEPA/
OPTS Public Files, 80 Submission. Microfiche #OTS 0507306.
Elanco Products Company. 1984. Bloconcentratlon of 14C-p-chlorobenzotM-
fluorlde by blueglll 1n a static test system. Prepared by Lilly Res. Labs.,
Greenfield, IN. USEPA/OPTS Public Files, 80 Submission. Microfiche #OTS
0507307.
Great Lakes Water Quality Board. 1983. An Inventory of chemical substances
Identified 1n the Great Lakes ecosystem. Vol. 1 - Summary. Report to the
Great Lakes Water Quality Board. Windsor Ontario. Canada, p. 12, 59, 90.
Ollld -33- 04/19/88
-------
Mauser, T.R. and S.M. Bromberg. 1982. EPA's monitoring program at Love
Canal 1980+. Environ. MonH. Assess. 2: 249-271.
Hawley, G.G., Ed. 1981. The Condensed Chemical Dictionary, 10th ed. Van
Nostrand Relnhold Co., New York, NY. p. 235.
Haworth, S., T. Lawlor, K. Mortlemans, W. Speck and E. Zelger. 1983.
Salmonella mutagenldty test results for 250 chemicals. Environ. Mutagen.
Suppl. 1: 3-5, 8-9, 16-21, 41, 51, 78.
Hooker Chemical Corp. 1978a. Mutagenldty evaluation of parachlorober.zo-
trlfluorlde (PCBTF) 1n the Ames Salmonella/mlcrosome plate test. Final
Report. Submitted by Litton Blonetlcs, Inc., Kensington, MD. U.S. EPA/OPTS
Public Files. Microfiche #OTS0508133.
Hooker Chemical Corp". 1978b. Mutagenldty evaluation of parachlorobenzo-
trlfluorlde In the mouse lymphoma forward mutation assay. Final report.
Submitted by Litton Blonetlcs, Inc., Kensington, MD. U.S. EPA/OPTS Public
Files. Microfiche #OTS0508135.
Hooker Chemical Corp. 1979a. An acute Inhalation toxldty study of
parachlorobenzotMfluorlde In the rat. Prepared by B1o/dynam1c Inc. U.S.
EPA/OPTS Public Files. Microfiche #OTS0508137.
Hooker Chemical Corp. 1979b. Mutagenldty evaluation of parachlorobenzo-
trlfluorlde 1n a In v1vo/Ui vitro urine assay. Final Report. Submitted by
LHton Blonetlcs, Inc., Kensington, MD. U.S. EPA/OPTS Public Files.
Microfiche #OTS0508139.
01 lid -34- 04/19/88
-------
Hooker Chemical Corp. 1979c. MutagenlcHy evaluation of parachlorobenzo-
trlfluorlde (PCBTF) In the sister chromatld exchange assay 1n L5178Y mouse
lymphoma cells. Final report. Submitted by LHton B1onet1cs, Inc.,
Kensington, MO. U.S. EPA/OPTS Public Files. Microfiche #OTS0508136.
Hooker Chemical Corp. 1980. Evaluation of p-chlorobenzotr1fluor1de In the
In vitro transformation of BALB/3T3 cells assay. Submitted by LHton
Blonetlcs, Inc., Kensington, MD. U.S. EPA/OPTS Public Files. Microfiche
#0150508144.
Hooker Chemical Corp. 1981. Modified 90-day gavage and reproduction study
1n rats PCBTF. Conducted by Elars Bioresearch Laboratories, Inc., Fort
Collins, CO. U.S. EPA/OPTS Public Files. Microfiche #OTS0508148.
Hooker Chemical Corp. 1985a. Acute oral toxicity (LD5Q) 1n albino rats.
Prepared by Raltech .Scientific .Services, Inc., Madison, HI. U.S. EPA/OPTS
Public Files. Microfiche #OTS508138.
Hooker Chemical Corp. 1985b. Acute dermal toxldty (LDro) In albino
rabbits. Prepared by Raltech Scientific Services, Inc., Madison, HI. U.S.
EPA/OPTS Public Files. Microfiche #OTS508134.
Hooker Chej^s. and Plastics Corp. 1980. Solubility of p-chlorobenzotrifluo-
rlde 1n water. USEPA/OPTS Public Files, 80 Submission. Microfiche #OTS
0508143.
Ollld -35- 04/19/88
-------
•HSDB (Hazardous Substances Data Bank). 1988. Office of Toxic Substances,
U.S. EPA, Washington, DC. Online retrieval January 21, 1988.
Lilly Research Laboratories. 1983a. Evaluation of compound #38502 1n the
BALB/C-3T3 Neoplastlc transformation assay with an Aroclor-lnduced rat liver
mlcrosomal (S9) metabolic activating system. Submitted by Arthur D. Little,
Incorporated, Cambridge, MA. U.S. EPA/OPTS Public Files. Microfiche
#OTS0507306.
Lilly Research Laboratories. 1983b. Chromosome aberrations 1n Chinese
hamster ovary cells: Test article compound 38502, Lot No. 633F02. Prepared
by Microbiological Associates, Bethesda., MD. U.S. EPA/OPTS Public Files.
Microfiche #OTS0507306.
Lilly Research Laboratories. 1983c. Activity of compound 38502 (T2025) 1n
the acute Vn vivo cytoqenetlc assay In male and female rats. Prepared by
Microbiological Associates, Bethesda, MD. U.S. EPA/OPTS Public Files.
Microfiche #OTS0507306.
Occidental Chem. Corp. 1980a. Odor threshold studies on eleven chemicals.
Prepared by Arthur D. Little, Inc., Cambridge, MA. USEPA/OPTS Public Files,
8D Submission. Microfiche #OTS 0205957.
Occidental Chem. Corp. 1980b. Analysis of fish samples from Lakes Erie and
Ontario for chlorinated benzotrlfluorldes as contaminants. Analyzed by FDA,
Washington, DC. USEPA/OPTS Public Files, 80 Submission. Microfiche #OTS
0507284.
Ollld -36- 04/19/88
-------
Occidental Chem. Corp. 1984. Loss processes for 4-chlorobenzotr1fluor1de
under atmospheric conditions. Prepared by R. Atkinson et al., Univ. of
Calif., Riverside, CA. USEPA/OPTS Public Files, 80 Submission. Microfiche
#OTS 0507309.
Qulstad, G.B. and K.M. Mulholland. 1983. Metabolism of p-chlorobenzotr1-
fluorlde by rats. J. Agrlc. Food Chem. 31(3): 585-589.
Rapoport, K.A., L.A. Teplklna, Y.G. Fel'dman, et al. 1986. Setting the
limits for parachlorobenzotrlfluorlde In atmospheric air. Gig. Sanlt. 10:
82-83. -(Russian translation) ;
SRI (Stanford Research Institute). 1987. 1987 Directory of Chemical
Producers. United States of America. SRI International, Menlo Park, CA.
p. 533. . • .
Thomas, R.G. 1982. Volatilization from water. In: Handbook of Chemical
Property Estimation Methods. Environmental Behavior of Organic Compounds,
W.J. Lyman et al., Ed. McGraw H111 Publishers, New York, NY. p. 15-20.
Union Carbide Environmental Services. 1979a. The acute toxldty of para-
chlorobenzotrlfluorlde to the rainbow trout, Salmo galrdnerl Richardson.
UCES Project No. 11506-81-08 (OTS 0508140).
Union Carbide Environmental Services. 1979b. The acute toxldty of
parachlorobe/izotrlfluoMde to the blueglll sunflsh, Lepomls macrochlrus
Raflnesque. UCES Project No. 11506-81-07 (OTS 0508149).
Ollld -37- 04/19/88
-------
Union Carbide Environmental Services. 1979c. The acute toxlclty of
parachlorobenzotrlfluoMde to the water flea. Daphnla maqna Straus. UCES
Project No. 11506-81-06 (OTS 0508141).
Union Carbide Environmental Services. 1979d. Daphnla maqna chronic study
testing parachlorotrlfluorlde (97% active Ingredient). UCES Project No.
11507-18 (OTS 0508142).
U.S. EPA. 1977. Computer print-out of non-confidential production data
from TSCA Inventory. OPTS, CID, U.S. EPA, Washington, DC.
U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of
Health Effect Assessment Chapter of the Consent Decree Water Criteria
Documents. Federal Register. 45(31): 49347-49357.
U.S. EPA 1984. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxldty Data. Prepared by the Office of Health
and Environmental Assessment, Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste and Emergency Response, Wash-
ington, DC.
U.S. EPA. 1986a. Methodology for Evaluating CardnogenlcHy 1n Support of
Reportable Quantity Adjustment Pursuant to CERCLA Section 102. Prepared by
the Office of Health and Environmental Assessment, Carcinogen Assessment
Group, Washington, DC for the Office of Solid and Emergency Response,
Washington, DC.
01 lid -38- 05/10/88
-------
U.S. EPA. 1986b. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
USITC (U.S. International Trade Commission). 1987. Synthetic Organic
Chemicals. United States Production and Sales, 1986. USITC Publ. 1892,
Washington, DC. p. 31, 41.
Ollld -39- 05/10/88
-------
APPENDIX A
LITERATURE SEARCHED
This HEED Is based on data Identified by computerized literature
searches of the following:
CHEMLINE
TSCATS
CASR online (U.S. EPA Chemical Activities Status Report)
TOXLINE
TOXLIT
TOXLIT 65
RTECS
OHM TADS
STORET
SRC Environmental Fate Data Bases .
SANSS
AQUIRE
TSCAPP
NTIS
Federal Register
CAS ONLINE (Chemistry and Aquatic)
HSDB
These searches were conducted 1n October 1987, and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1987. TLVs: Threshold Limit Values for Chemical Substances In the
Work Environment adopted by ACGIH with Intended Changes for
1987-1988. Cincinnati, OH. 114 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John Wiley and
Sons, NY. p. 2879-3816.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John WHey and
Sons, NY. p. 3817-5112.
01 lid -40- 04/19/88
-------
Grayson, H. and 0. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo-
pedia of Chemical Technology, 3rd ed. John WHey and Sons, NY. 23
Volumes.
Hamilton, A. and H.L. Hardy. 1974. Industrial Toxicology, 3rd ed.
Publishing Sciences Group, Inc., Littleton, MA. 575 p.
IARC (International Agency for Research on Cancer). IARC Mono-
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. IARC, WHO, Lyons, France.
Jaber, H.M., W.R. Mabey, A.T. L1eu, T.W. Chou and H.L. Johnson.
1984. Data acquisition for environmental transport and fate
screening for compounds of Interest to the Office of Solid Waste.
EPA 600/6-84-010. NTIS PB84-243906. SRI International, Menlo
Park, CA.
NTP (National Toxicology Program). 1987. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1984. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Relnhold Co., NY.
SRI (Stanford Research Institute). 1987. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1986. Report on Status Report 1n the Special Review
Program, Registration Standards Program and the Data Call 1n
Programs. Registration Standards and the Data Call 1n Programs.
Office of Pesticide Programs, Washington, DC.
USITC (U.S. International Trade Commission). 1986. Synthetic
Organic Chemicals. U.S. Production and Sales, 1985, USITC Publ.
1892, Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Relnhold Co., NY.
Worthing, C.R. and S.B. Walker, Ed. 1983. .The Pesticide Manual.
British Crop Protection Council. 695 p.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Ollld -41- 04/19/88
-------
In addition, approximately 30 compendia of aquatic toxldty data were
reviewed. Including the following:
Battelle's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data from- the Literature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and H.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxldty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, Fish and Wildlife
Serv. Res. Publ. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Plmental, D. 1971. Ecological Effects of Pesticides on Non-Target
Species. Prepared for the U.S. EPA, Washington, DC. PB-269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
EPA, Washington, DC. EPA 540/9-79-003. NTIS PB 80-196876.
Ollld -42- 04/19/88
-------
A90 days
15 mg/kg for
>90 days
NOAEL
NOAEL
ID
ID
ID
0.2 mg/kg/day or
11 mg/day for a
70 kg human
0.02 mg/kg/day or
1 mg/day for a 70
kg human
ID
Hooker Chemical
Corp., 1981
Hooker Chemical
Corp., 1981
REPORTABLE QUANTITIES
Based on chronic toxlcity:
Based on Carclnogenlclty:
1000
ID
Arthur and
Probst, 1983
CO
00 ID = Insufficient data
------- |