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DISCLAIMER
This report Is 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
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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 1n "Appendix: Literature Searched."
Literature search material 1s 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 llfespan. 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 1s 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-|* (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-
genldty are derived. The RQ Is used to determine the quantity of a
hazardous substance for which notification 1s required In the event of a
release as specified under the Comprehensive Environmental Response, Compen-
sation and Liability Act (CERCLA). These two RQs (chronic toxldty and
cardnogenldty) represent two of six scores developed (the remaining four
reflect 1gn1tab1l1ty, reactivity, aquatic toxldty, and acute mammalian
toxldty). Chemfcal-spedflc RQs reflect the lowest of these six primary
criteria. The methodology for chronic toxldty and cancer based RQs are
defined In U.S. EPA, 1984 and 1986a, respectively.
111
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EXECUTIVE SUMMARY
Chloroacetaldehyde (107-20-0) 1s a colorless liquid with an acrid,
penetrating odor (Hawley, 1981; Wlndholz, 1983). This compound Is prepared
Industrially by carefully controlled chlorlnatlon of acetaldehyde (Wlndholz,
1983). Chloroacetaldehyde 1s no longer manufactured 1n the United States
(HSOB, 1987), although H Is probably Imported. Chloroacetaldehyde 1s used
as a fungicide, 1n the manufacture of 2-am1noth1azole, 1n facilitating the
removal of bark from trees and 1n dentistry (Lawrence and Autlan, 1972; U.S.
EPA/NIH, 1987; Wlndholz, 1983).
In the atmosphere, Chloroacetaldehyde Is expected to exist almost
entirely In the vapor phase. Reaction with photochemlcally generated
hydroxyl radicals (t,,- = 1«7 days) and physical removal by wet deposition
would probably be the dominant fate processes. Chloroacetaldehyde removed
from the atmosphere by wet deposition, however, may reenter the atmosphere
by volatilization. In water, volatilization Is expected to be a signifi-
cant, If not the dominant, removal mechanism. The volatilization half-life
from a river 1 m deep, flowing 1 m/sec with a wind velocity of 3 m/sec has
been estimated to be -2 days. Chloroacetaldehyde Is not expected to undergo
chemical oxidation, bloaccumulate significantly In aquatic organisms or
adsorb significantly to suspended solid or sediments In water. In moist
soil, Chloroacetaldehyde 1s expected to be highly mobile and susceptible to
significant leaching. The relatively high vapor pressure of chloroacetalde-
\
hyde suggests that H would volatilize fairly rapidly from dry soil surfaces.
No monitoring data are available to Indicate ambient air or water
levels, drinking water or food contamination or dermal exposure. Potential
sources of Chloroacetaldehyde entering the environment are losses at
1v
-------
processing sites, losses during transport, disposal processes and use as a
fungicide. Ando and Sayato (1984) suggested that VCM can migrate Into
drinking water from water pipes made of polyvlnyl chloride and subsequently
react with chlorine present In the drinking water, forming chloroacetalde-
hyde. The detection of chloroacetaldehyde as a result of chlorlnatlon of
VCM 1n drinking water, however, required the presence of much higher
concentrations of both VCM and chlorine than are expected to be present
under typical conditions. Therefore, the formation of chloroacetaldehyde 1n
potable water by this process Is questionable. Another possible source of
chloroacetaldehyde 1n the atmosphere 1s - formation from reaction of
1,3-d1chloropropene with ozone and OH radicals (Tuazon et al., 1984).
1,3-D1chloropropene 1s a highly volatile component of widely used
Insectlddal fumlgants (Tuazon et al., 1984).
Little Information 1s available regarding the toxlclty of chloroacet-
aldehyde to aquatic organisms. A 96-hour LC_n of 1.5 mg chloroacetalde-
hyde/B. was reported for the copepod, Nltocra splnlpes (Bengtsson and
Tarkpea, 1983). Sea lampreys, however, were unaffected by exposure to 5 mg
chloroacetaldehyde/a, for 24 hours (Applegate et al., 1957).
No pertinent data regarding the absorption and distribution of chloro-
acetaldehyde were located 1n the literature. Metabolism and excretion ^ata
were limited to one study (Green and Hathway, 1977), In which three urinary
metabolites [N-acetyl-S-(2-hydroxyethyl) cystelne, S-(carboxymethyl)
cystelne and th1;od1glycol1c add] were found following oral administration
of chloroacetaldehyde to rats.
Few studies regarding the systemic toxldty of chloroacetaldehyde
following administration of the compound by relevant routes (I.e., oral and
Inhalation) were located In the available literature. Exposure of rats,
-------
guinea pigs, rabbits and mice to chloroacetaldehyde (5.1 mg/m3) by Inhala-
tion 7 hours/day, 5 days/week for 6 months had no adverse health effects on
any of the animal species tested (Dow Chemical Company, 1962). Weekly oral
administration of chloroacetaldehyde to mice (0.25 mg chloroacetaldehyde/
mouse/week) over an entire lifetime was without effect on the mortality rate
(Van Duuren et al., 1979). The oral LD5Q of chloroacetaldehyde was
reported to be between -82 mg/kg 1n mice and 89-103 mg/kg In rats (Lawrence
et al., 1972).
Intraperltoneal doses of chloroacetaldehyde of 0.0016 and 0.0032 ml/kg
given to rats were associated with the production of a focal, chronic,
bronchopneumonla, Increases 1n segmented neutrophlls and decreases 1n both
erythrocytes and lymphocytes (Lawrence et al., 1972). No hematologlcal or
pulmonary effects were associated with a dose of 0.0008 mi chloroacetalde-
hyde/kg. Chloroacetaldehyde Injected IntraperHoneally In rats (0.0016 or
0.0032 ml/kg) 3 times/week for 12 weeks was reported to produce changes. 1n
the respiratory epithelium, suggestive of a premallgnant condition (Lawrence
et al., 1972).
Chloroacetaldehyde has been shown to Increase the pentobarb1tal-1nduced
sleeping time of mice (Lawrence et al., 1972) and to cause J_n vitro hemoly-
s1s 1n rabbit erythrocyte preparations and cytotoxldty 1n murlne L-cell
preparations.
Oral weekly administration of chloroacetaldehyde to mice (0.25 mg/mouse/
week) for the Hfespan did not Increase the Incidence of forestomach tumors
over that observed In untreated controls (Van Duuren et al., 1979).
Chloroacetaldehyde was negative as a whole carcinogen or as a tumor
Initiator when tested on the skin of mice (Van Duuren et al., 1979; Zajdela
et al., 1980).
vl
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Cardnogenldty data resulting from human occupational exposure were not
located 1n the available literature; also there were no ep1dem1olog1cal
studies regarding possible carcinogenic effects associated with exposure to
chloroacetaldehyde.
Chloroacetaldehyde has been demonstrated to be mutagenlc 1n a variety of
assays using both prokaryotes and eukaryotes with and without metabolic
activation (B1gnam1 et al., 1980; Rannug et al., 1976; McCann et al., 1975;
Malavellle et al., 1975; Phillips et al., 1980; Garro and Phillips, 1980;
Hussaln and Osterman-Golkar, 1984; Perrard, 1985; lorprleno et al., 1977;
Huberman et al., 1975; Rosenkranz, 1977).
Pertinent data regarding the teratogenldty or other reproductive
effects associated with exposure to chloroacetaldehyde were not located In
the available literature dted 1n Appendix A.
RfDs for chloroacetaldehyde are not presented as the available date were
regarded as Inadequate. Data are Insufficient for determining an RQ based
on chronic toxldty or on carc1nogen1dty. Since data regarding the
carcinogenic potential of chloroacetaldehyde are Inadequate, this chemical
Is placed 1n EPA Group D -- not classifiable as to human carclnogenldty.
-------
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 2
2. ENVIRONMENTAL FATE AND TRANSPORT 4
2.1. AIR 4
2.1.1. Reaction with Hydroxyl Radicals 4
2.1.2. Reaction with Ozone 4
2.1.3. Physical Removal Processes 4
2.2. WATER. . " ........ 4
2.2.1. Oxidation 4
2.2.2. Photolysis 5
2.2.3. Mlcroblal Degradation 5
2.2.4. Volatilization 5
2.2.5. Adsorption 5
2.2.6. B1oaccumulat1on . .... 5
2.3. SOIL . 6
2.3.1. Mlcroblal Degradation ...'.' 6
2.3.2. Adsorption 6
2.3.3. Volatilization 6
2.4. SUMMARY 6
3. EXPOSURE 8
4. AQUATIC TOXICITY 9
4.1. ACUTE TOXICITY 9
4.2. CHRONIC EFFECTS 9
4.3. PLANT EFFECTS . . 9
4.4. SUMMARY 9
5. PHARMACOKINETCS 10
5.1. ABSORPTION 10
5.2. DISTRIBUTION 10
5.3, METABOLISM . 10
5.4. EXCRETION 11
5.5. SUMMARY . 13
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TABLE OF CONTENTS (cont.)
Page
6. EFFECTS 14
6.1. SYSTEMIC TOXICITY 14
6.1.1. Inhalation Exposures 14
6.1.2. Oral Exposures 14
6.1.3. Other Relevant Information 14
6.2. CARCINOGENICITY. . . 16
6.2.1. Inhalation 4 • 16
6.2.2. Oral. 16
6.2.3. Other Relevant Information. ... 17
6.3. MUTAGENICITY 20
6.4. TERATOGENICITY . 23
6.5. OTHER REPRODUCTIVE EFFECTS 23
6.6. SUMMARY 23
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. Inhalation 26
8.1.2. Oral 26
8.1.3. Other Routes 26
8.1.4. Weight of Evidence 26
8.1.5. Quantitative Risk Estimates . . 27
8.2. SYSTEMIC TOXICITY 27
8.2.1. Inhalation Exposures 27
8.2.2. Oral Exposures 28
9. REPORTABLE QUANTITIES 29
9.1. BASER ON SYSTEMIC TOXICITY 29
9.2. BASED ON CARCINOGENICITY 29
10. REFERENCES 32
APPENDIX A: LITERATURE SEARCHED 40
APPENDIX B: SUMMARY TABLE FOR CHLOROACETALDEHYDE 43
1x
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LIST OF TABLES
No. Title Page
6-1 Weekly Intragastrlc Administration of an Aqueous Solution
of Chloroacetaldehyde to Ha:ICR Mice: Incidence of Fore-
stomach Tumors 18
6-2 Mutagenldty Testing of Chloroacetaldehyde 21
9-1 Chloroacetaldehyde: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 30
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LIST OF ABBREVIATIONS
BCF B1oconcentrat1on factor
CAS Chemical Abstract Service
DNA Oeoxyr1bonude1c acid
GC Gas chromatography
Koc Soil sorptlon coefficient
Kow Octanol/water partition coefficient
LCso Concentration lethal to 50% of recipients
1050 Dose lethal to 50% of recipients
MED Minimum effective dose
MS Mass spectrometry
NOEL No-observed-effect level
ppm Parts per million
ppth Parts per thousand
RfD Reference dose
RQ Reportable quantity
VCM Vinyl chloride monomer
x1
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1. INTRODUCTION
1.1. STRUCTURE AND CAS NUMBER
Chloroacetaldehyde Is also known as 2-chloro-l-ethanal and 2-chloro-
acetaldehyde (HSDB, 1987). The structure, CAS number, empirical formula and
molecular weight are as follows:
H 0
I //
Cl-C-C
I \
H H
Molecular weight: 78.50
Empirical formula: C.H.CIO
CAS Registry number: 107-20-0
1.2. PHYSICAL AND CHEMICAL PROPERTIES
At room temperature, Chloroacetaldehyde 1s a clear, colorless liquid
possessing an acrid, penetrating odor (Hawley, 1981; Wlndholz, 1983). It 1s
soluble 1n water at concentrations <50%, but It .forms Insoluble hemlhydrate
at concentrations >50% (U.S. EPA/NIH, 1987). Selected physical and chemical
properties are as follows:
Melting point
(40% aqueous d1l.):
Boiling point:
(40% aqueous d1l.):
Vapor pressure at 20°C:
Log Kow: ;
Water solubility at 20°C
Flashpoint:
Density
(40% aqueous d1l,):
Refractive. Index
(40% aqueous dll., 25°C)
-16.3°C
85°C
100 mm Hg
0.39
~5xl O5 mg/9.
87.7°C
1
'•
25
1.397
Hawley, 1981
Hawley, 1981
ACGIH, 1981
U.S. EPA, 1987a
U.S. EPA/NIH, 1987
Hawley, 1981
Hawley, 1981
Hawley, 1981
0086cl
-1-
01/21/88
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1.3. PRODUCTION DATA
Chloroacetaldehyde 1s prepared Industrially by carefully controlled
chlorlnatlon of acetaldehyde (Wlndholz, 1983). The following Information on
chlororoacetaldehyde was obtained from the U.S. EPA TSCA Production File
(U.S. EPA, 1977):
Company/Location Production/Import Volume
Texas Eastman Co. 1-10 million pounds
Longvlew, TX
International Flavors & Fragrances Inc. <1000 pounds
Union Beach, NO (Importer)
Henley and Co., Inc. confidential
New York, NY (Importer)
According to HSDB (1987), Chloroacetaldehyde 1s no longer produced commer-
cially In the United States; however, CMR (1986) lists five domestic
suppliers for this compound, which suggests that Chloroacetaldehyde 1s
probably Imported Into the United States. Import data for recent years were
not located 1n the available literature cited 1n Appendix A.
1.4. USE DATA
Chloroacetaldehyde 1s used as a fungicide, In the manufacture of
2-am1noth1azole, 1n facilitating the removal of bark from trees and 1n
dentistry (Lawrence and Autlan, 1972; U.S. EPA/NIH, 1987; Wlndholz, 1983).
1.5. SUMMARY
Chloroacetaldehyde (107-20-0) 1s a colorless liquid with an acrid,
penetrating odor\(Hawley, 1981; Wlndholz, 1983). This compound 1s prepared
Industrially by carefully controlled chlorlnatlon of acetaldehyde (Wlndholz,
1983). Chloroacetaldehyde 1s no longer manufactured 1n the United States
0086d -2- 01/21/88
-------
(HSDB, 1987), although It 1s probably Imported. Chloroacetaldehyde 1s used
as a fungicide, 1n the manufacture of 2-am1noth1azole, 1n facilitating the
removal of bark from trees and 1n dentistry (Lawrence and Autlan, 1972; U.S.
EPA/MIH, 1987; Wlndholz, 1983).
0086d -3- 01/21/88
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2. ENVIRONMENTAL FATE AND TRANSPORT
Limited data regarding the environmental fate and transport of chloro-
acetaldehyde were located In the available literature. When possible,
predictions regarding environmental fate and transport were derived from
physical properties or molecular structure. <:"
2.1. AIR >
Based on a vapor pressure of 100 mm Hg at 20°C, chloroacetaldehyde 1s
expected to exist almost entirely 1n the vapor phase 1n the atmosphere
(ACGIH, 1981; Elsenrelch et al., 1981). .
2.1.1. Reaction with Hydroxyl Radicals. Using the method of Atkinson
(1985), the rate constant for the reaction of chloroacetaldehyde with photo-
chemlcally generated hydroxyl radicals In the atmosphere has been estimated
to be 9.4xlO~12 cm3/molecule-sec at 25°C. Assuming an average hydroxyl
radical concentration of 5xl05 molecules/cm3 (Atkinson, 1985), the
hydroxyl reaction half-life was estimated to be 1.7 days.
2.1.2. Reaction with Ozone. Reaction of chloroacetaldehyde with ozone 1n
the atmosphere 1s not expected to be an Important fate process (U.S. EPA,
1987b).
2.1.3. Physical Removal Processes. Based on Its relatively high water
solubility 1t appears that chloroacetaldehyde would be highly susceptible to
removal from the atmosphere by wet deposition; however, any chloroacetalde-
hyde removed from the atmosphere by this mechanism has the potential to
reenter the atmosphere by volatilization.
2.2. WATER
2.2.1. Oxidation. Chloroacetaldehyde Is expected to be Inert to chemical
@» '
oxidation In aqueous solution (Jaber et al., 1984).
0086d -4- 01/21/88
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2.2.2. Photolysis.' Data regarding the photolysis of chloroacetaldehyde
1n water were not located 1n the available literature cited 1n Appendix A.
2.2.3. Mlcroblal Degradation. Stuckl and Le1s1nger et al. (1983) deter-
mined that Pseudomonas CElr degraded 2-chloroethanol to glycollc add
through chloroacetaldehyde and 2-chloroacetate (Intermediary compounds).
This Information Indicates that biological degradation of chloroacetaldehyde
Is likely to occur; however, the significance of this Information with
regard to the blodegradatlon of chloroacetaldehyde under environmental
conditions 1s uncertain.
2.2.4. Volatilization. Henry's Law constant for chloroacetaldehyde was
estimated to be 2xlO~s m3-atm/mol at 25°C using the bond contribution
method of H1ne and Mookerjee (1975). This value suggests that volatiliza-
tion of chloroacetaldehyde from all bodies of water would be a significant
fate process (Lyman et al., 1982). Based on this value of Henry's Law
constant, the volatilization half-life of chloroacetaldehyde from a river
1 m deep., flowing 1 m/sec with a wind speed of 3 m/sec was estimated to be
~2 days using the method of Lyman et al. (1982).
2.2.5. Adsorption. Experimental data regarding the adsorption of chloro-
acetaldehyde to suspended solids and sediments In water were not located In
the available literature cited 1n Appendix A; however, the relatively high
water solubility and low K suggest that adsorption to suspended solids
and sediments 1n water Is probably not a significant fate process.
2.2.6. B1oaccumalat1on. A BCF of 1 was estimated for chloroacetaldehyde
using a linear regression equation based on a log K of 0.39 (Lyman et
al., 1982; U.S. EPA, 1987a). This BCF value and the relatively high water
solubility of this compound suggest that chloroacetaldehyde would not
bloaccumulate significantly 1n aquatic organisms.
0086d -5- 01/21/88
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2.3. SOIL
2.3.1. Mlcroblal Degradation. As has been discussed In Section 2.2.3.,
blodegradatlon of chloroacetaldehyde 1s likely to occur, but no experimental
data are available that would allow estimations of blodegradatlon rates In
soil under environmental conditions.
2.3.2. Adsorption. A K of 39 was estimated for chloroacetaldehyde
using a linear regression equation based on a log K of 0.39 (U.S. EPA,
1987a; Lyman et al., 1982). This KQC value and the relatively high water
solubility of chloroacetaldehyde suggest that this compound would be very
highly mobile In soil and susceptible to significant leaching (Swann et al.,
1983). .
2.3.3. Volatilization. Based on a vapor pressure of 100 mm Hg at 20°C
(ACGIH, 1981) chloroacetaldehyde 1s expected to volatilize fairly rapidly
from dry soil surfaces.
2.4. SUMMARY
In the atmosphere, chloroacetaldehyde 1s expected to exist almost
entirely 1n the vapor phase. Reaction with photochemically generated
hydroxyl radicals (t,/? = 1.7 days) and physical removal by wet deposition
would probably be the dominant fate processes. Chloroacetaldehyde removed
from the atmosphere by wet deposition, however, may reenter the atmosphere
by volatilization. In water, volatilization Is-expected to be a signifi-
cant, 1f not the dominant, removal mechanism. The volatilization half-life
from a river 1 m'deep, flowing 1 m/sec with a wind velocity of 3 m/sec has
been estimated to be ~2 days. Chloroacetaldehyde 1s not expected to undergo
chemical oxidation, bloaccumulate significantly In aquatic organisms or
adsorb significantly to suspended solid or sediments 1n water. In moist
0086d -6- 01/21/88
-------
soil, chloroacetaldehyde 1s expected to be highly mobile and susceptible to
significant leaching. The relatively high vapor pressure of chloroacetalde-
hyde suggests that It would volatilize fairly rapidly from dry soil surfaces.
0086d _7_ 01/21/88
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3. EXPOSURE
No monitoring data are available to Indicate ambient air or water
levels, drinking water or food contamination or dermal exposure. Potential
sources of chloroacetaldehyde entering the environment are losses at
processing sites, losses .during transport, disposal processes and use as a
fungicide. Ando and Sayato (1984) suggested that VCH can migrate Into
drinking water from water pipes made of polyvlnyl chloride and subsequently.
react with chlorine present 1n the drinking water, forming chloroacetalde-
hyde:. The detection of chloroacetalde as a result of chlorlnatlon of VCM In
-drinking water, however, required the presence of much higher concentrations
of both VCM and chlorine than are expected to be present under typical
conditions. Therefore, the formation of chloroacetaldehyde 1n potable water
by this process 1s questionable. Another possible source of chloroacetalde-
hyde 1n the atmosphere 1s formation from reaction of 1,3-d1chloropropene
with ozone and OH radicals (Tuazon et al., 1984).. 1,3-D1chloropropene Is a
highly volatile component of widely used Insectlddal fumlgants (Tuazon et
al., 1984).
0086d -8- 01/21/88
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4. AQUATIC TOXICITY
4.1. ACUTE TOXICITY
Only two studies were found In the literature concerning the acute
aquatic toxlclty of chloroacetaldehyde. The 96-hour 1C for the
harpaetlcold copepod, NUocra splnlpes. was reported to be 1.5 mg/8.
(Bengtsson and Tarkpea, 1983). Exposure took place In brackish water with a
salinity of 7 ppth. No signs of distress were observed In the sea lamprey,
Petromyzon marlnus. exposed to 5 mg chloroacetaldehyde/a for 24 hours
(Applegate et al.f 1957).
4.2. CHRONIC EFFECTS
Pertinent data regarding the effects of chronic exposure of aquatic
biota to chloroacetaldehyde were not located 1n the available literature
cited 1n Appendix A.
4.3. PLANT EFFECTS
Pertinent' data regarding the effects resulting from exposure of plants
to chlorbacetaldehyde were not located 1n the available literature cited 1n
Appendix A.
4.4. SUMHARY
Little Information 1s available regarding the toxldty of chloroacet-
aldehyde to aquatic organisms. A 96-hour LC,Q of 1.5 mg chloroacetalde-
hyde/si was reported for the copepod, NUocra splnlpes (Bengtsson and
Tarkpea, 1983). Sea lampreys, however, were unaffected by exposure to 5 mg
chloroacetaldehyd«/l for 24 hours (Applegate et al., 1957).
0086d -9- 01/21/88
-------
5. PHARMACOKINETICS
5.1. ABSORPTION
Pertinent data regarding the absorption of chloroacetaldehyde following
either oral or Inhalation exposure were not located 1n the available litera-
ture cited 1n Appendix A.
5.2. DISTRIBUTION
Pertinent data regarding the distribution of chloroacetaldehyde were not
located 1n the available literature dted 1n Appendix A.
5.3. METABOLISM
The metabolism of chloroacetaldehyde has not been studied extensively.
Chloroacetaldehyde has been found to be a metabolite of a variety of halo-
genated organic compounds (GuengeMch et al., 1980; Gwlnner et al., 1983),
but only one study (Green and Hathway, 1977) was found regarding the metabo-
lism of chloroacetaldehyde Itself. An aqueous solution of chloroacetalde-
hyde was administered, by gavage to four adult AlderTy-Park male rats at a
dose level of 50 mg/kg (Green and Hathway, 1977). An unspecified number of
control animals was also used. Urine was collected and separated Into
fractions by anlon-exchange chromatography. The 3N acetic add fraction was
analyzed by GC-MS and mass fragmentography for N-acetyl-S-(2-hydroxyethyl)
cystelne. The 3N HC1 fraction was analyzed by GC-MS for thlodlglycoUc and
chloroacetlc acids. N-acetyl-S-(2-hydroxyethyl) cystelne and S-(carboxy-
methyl) cystelne were found 1n the urine of chloroacetaldehyde-treated rats
and presumably not 1n the urine of control animals. ThlodlglycoUc add, a
derivative of S-(carboxymethyl) cystelne, was the major urinary metabolite
and accounted for 9.2X of the administered chloroacetaldehyde dose.
A metabolic scheme proposed by Green and Hathaway (1977) Indicates that
the first step In the metabolism of chloroacetaldehyde 1s conjugation with
0086d -10- 01/21/88
-------
glutathlone to yield S-formylmethylglutath1one (Figure 5-1). Metabolism of
S-formylmethylglutath1one can then proceed along two alternate pathways.
One pathway Involving further degradation and cleavage of the glutamate and
glyclne residues from glutathlone results 1n the appearance'of N-acetyl-S-
(2-hydroxy-ethyl) cystelne. The other pathway Involving dehydrogenatlon of
S-formyl-methylglutath1one and further glutathlone cleavage results 1n the
formation of S-(carboxymethyl) cystelne. Transam1nat1on followed by oxlda-
tlve decarboxylatlon of S-(carboxymethyl) cystelne leads to formation of the
major urinary metabolite, thlodlglycoUc add.
Evidence for the existence of two separate pathways of S-formylmethyl-
glutathlone metabolism comes from an experiment In which S-(2-hydroxyethyl)
cystelne was administered orally to a separate group of rats (Green and
Hathway, 1977). In this group of rats, the urinary yield of thlodlglycoUc
acid was 0.5% of the administered dose, whereas the urinary yield of thlodl-
glycoUc acid was 9.2% of the administered dose 1n chloroacetaldehyde-
treated rats. This Indicates that, following chloroacetaldehyde
administration, the formation of S-(carboxymethyl) cystelne (and the
subsequent formation of th1od1glyco!1c acid) proceeds by a route that 1s
Independent of the formation of N-acetyl-S-(2-hydroxyethyl) cystelne.
5.4. EXCRETION
The only Information located regarding excretion of chloroacetaldehyde
and Its metabolites was that of Green and Hathway (1977). The three urinary
metabolites observed following oral administration of chloroacetaldehyde
were thlodlglycoUc add, S-(carboxymethyl) cystelne and N-acetyl-S-(2-
hydroxyethyl) cystelne. Information regarding other routes of elimination
was not located 1n the available literature.
0086d -11- 03/30/88
-------
C1CHZ - C - H
Ch1 oro*cetaldehyde
•» Glutathione
C = 0
I
CHCHjS
NH
C = 0
I
CH - CHpSCHpCHO
I
NH
I
S-foriy)«
OH
C = 0
I
CHCHZ S CH2 C02H
NH
COeH
CHCH, SCH,CH,
I I
NH(Qc) OH
C0H
C0H
S-Ccarbo>y«*thyl> cyctaiiw
COeH
- CH2SCH2C02H
C
II
0
S(CHeC02H)2
Thiodislycolic acid
FIGURE 5-1
Proposed Scheme for the Metabolism of Chloroacetaldehyde
Source: Green and Hathway, 1977
0086d
•-12-
01/21/88
-------
5.5. SUMMARY
No pertinent data regarding the absorption and distribution of chloro-
acetaldehyde were located In the literature. Metabolism and excretion data
were limited to one study (Green and Hathway, 1977), 1n which three urinary
metabolites (N-acetyl-S-(2-hydroxyethyl) cystelne, S-(carboxymethyl)
cystelne and th1od1glyco!1c add) were found following oral administration
of chloroacetaldehyde to rats.
0086d -13- 01/21/88
-------
6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposures.
6.1.1.1. SUBCHRONIC — Rats (20/sex), guinea pigs (8/sex), rabbits
(2/sex) and mice (10 females) were exposed to chloroacetaldehyde at 1.6 ppm
(5.1 mg/m3) 7 hours/day, 5 days/week for 6 months (Dow Chemical Company,
1962). There was a similar number of air-exposed and unexposed control
animals for each species. Gross and microscopic examination and observa-
tions of growth,- mortality, hematology and organ weights Indicated that
chloroacetaldehyde exposure produced no adverse effects on the health ,of any
of the species tested.
6.1.1.2. CHRONIC ~ Pertinent data regarding the toxldty of chloro-
acetaldehyde following chronic Inhalation exposure were not located 1n the
available literature cited In Appendix A.
6.1.2. Oral Exposures.
6.1.2.1, SUBCHRONIC — Pertinent data regarding the toxldty of
chloroacetaldehyde following subchronlc oral exposure were not located 1n
the available literature dted 1n Appendix A.
6.1.2.2. CHRONIC — One study of the toxldty of chloroacetaldehyde
following chronic oral administration was found 1n the available literature.
In this study (Van Duuren et al., 1979), HarlCR Swiss mice were given
chloroacetaldehyde In water by gavage at a dose of 0.25 mg chloroacetalde-
hyde/mouse/week. •" The study was conducted over the lifetime of the mice
'.
(<636 days). The mortality rate of the chloroacetaldehyde-treated mice did
not differ from that of untreated controls. No other details were provided.
6.1.3. Other Relevant Information. Rats (5/sex), guinea pigs (5/sex), 5
female mice and 1 female rabbit were exposed by Inhalation to 5 ppm of
0086d -14- 01/21/88
-------
chloroacetaldehyde 7 hours/day, 5 days/week, for a total of 8 exposures 1n
10 days (Dow Chemical Company, 1962). There were similar numbers of
unexposed controls. Exposed animals exhibited slight eye and nasal Irrita-
tion. The growth of the male rats was slightly depressed and the female
rabbit exhibited central lobular fatty degeneration of the liver. No other
adverse effects related to chloroacetaldehyde exposure were observed. The
growth of the other exposed animal groups was the same as controls, organ
weight and gross pathology data were negative, and there was no microscopic
evidence of adverse effects In tissues.
A subchronlc toxldty study of chloroacetaldehyde was conducted In male
Sprague-Dawley rats by administering a 0.5% aqueous solution of the compound
Intraperltoneally 3 times/week for 12 weeks (Lawrence et a!., 1972). The
dose levels used (calculated as pure chloroacetaldehyde) were 0, 0.00032,
0.0008, 0.0016 and 0.0032 mi chloroacetaldehyde/kg. There were 12 rats In
all groups except for the highest dose group, which had 8. Liver function
tests (I.e., sulfobromophthaleln excretion), organ weight determinations,
and hlstologlcal and hematologlcal examinations were performed. .The highest
dose level (0.0032 ml/kg) caused death In 5/8 rats during the course of
the study. The two highest dose levels (0.0016 and 0.0032 ml chloroacet-
aldehyde/kg) were associated with the production of a focal, chronic
bronchopneumonla, Increases In segmented neutrophlls and decreases 1n both
erythrocytes and lymphocytes. There was also a significant decrease 1n
hemoglobin at the 0.0032 ml/kg dose level. No hematologlcal or pulmonary
'.
effects were associated with a dose of 0.0008 ml chloroacetaldehyde/kg.
The results of liver function tests were unremarkable.
The acute toxldty of chloroacetaldehyde was also Investigated following
oral administration of the compound to rats and mice (Lawrence et al.,
0086d -15- 01/21/88
-------
1972). The oral LD50 value 1n mice was 0.0692 mi chloroacetaldehyde/kg
(or 82.3 mg/kg, assuming a specific gravity of 1.19 for chloroacetaldehyde)
and 1n rats, the oral L05Q was 0.0751 ml/kg (or 89.3 mg/kg).
Chloroacetaldehyde administration, either by Intraperlto'neal Injection
or by Inhalation exposure, Increased the pentobarbltal sleeping time In mice
(Lawrence et al., 1972). Inhalation of chloroacetaldehyde at a concentra-
tion of 0.042 mg/m3 for 31 seconds on 3 consecutive days before pento-
.barbUal administration resulted 1n a significant Increase 1n sleeping time
as measured by the duration of loss of the righting reflex. Similarly, an
Increase In pentobarbltal-lnduced sleeping time was noted 1n mlee Injected
IntrapeMtoneally with 0.00061 ml chloroacetaldehyde/kg for 3 days before
pentobarbltal administration. These results were subsequently shown not to
be an artifact of chloroacetaldehyde-lnduced hepatic necrosis.
In in vitro experimentation, chloroacetaldehyde was found to cause
hemolysls 1n rabbit erythrocyte preparations and cytotoxldty In murlne
L-cell preparations (Lawrence et al., 1972).
6.2. CARCINOGENICITY
6.2.1. Inhalation. Pertinent data regarding the cardnogenlcHy of
chloroacetaldehyde following Inhalation exposure were not located 1n it he
available literature cited 1n Appendix A.
6.2.2. Oral. One study was located 1n the literature regarding the
carclnogenlclty of chloroacetaldehyde following oral administration of the
compound with ml.ce. Ha:ICR Swiss mice (30 males and 30 females) received
weekly oral doses of chloroacetaldehyde (0.25 mg chloroacetaldehyde/mouse/
week) in water (Van Duuren et al., 1979). The mice were treated with
chloroacetaldehyde until they were moribund or found dead. The time of
0086d -16- 03/30/88
-------
death of the last mouse was 636 days. Control animals (100 females and 60
males) received no chloroacetaldehyde. In addition, a positive control
group received B-prop1olactone.
Following treatment, the stomach, liver and kidneys were analyzed for
tumors. The results Indicated that the Incidence of forestomach tumors 1n
chloroacetaldehyde-treated mice were not significantly different from
untreated controls (Table 6-1). In addition, none of the tumors found In
the chloroacetaldehyde-treated mice were squamous carcinomas. Mice treated
with 3-prop1olactone, however, had significantly (p<0.0005) Increased
Incidences of both total forestomach tumors and squamous carcinomas.
B-Prop1olactone-treated mice also experienced decreased longevity, whereas
the rate of mortality was not adversely affected by chloroacetaldehyde
treatment.
6.2.3. Other Relevant Information. Several studies have been performed
to determine whether chloroacetaldehyde produces tumors 1n the skin follow-
ing topical or subcutaneous application; Chloroacetaldehyde (T.O mg/mouse)
dissolved 1n 0.1 ma acetone was applied to the shaved dorsal surface of 30
female Ha:ICR Swiss mice 3 times/week for 83 weeks (Van Duuren et al.,
1979). Control groups consisted of untreated and acetone-treated mice.
Following treatment, skin, liver, stomach and kidney tissue were observed
for pathology. No skin paplllomas were observed 1n the chloroacetaldehyde-
treated mice and the Incidence of remote tumors was not significantly
different from controls.
Van Duuren et al. (1979) also studied the possible skin tumor1gen1dty
of chloroacetaldehyde by administering the compound 1n water subcutaneously
and subchronlcally to 30 female Ha:ICR Swiss mice (0.25 mg chloroacetalde-
hyde/mouse/week for 90 weeks). As a positive control, 30 mice received 0.30
0086d -17- 01/21/88
-------
TABLE 6-1
Weekly Intragastrlc Administration of an Aqueous Solution
of Chloroacetaldehyde to Ha:ICR Swiss Mice:
Incidence of Forestomach Tumors3
Sex
M
F
M
F
H
F
M
F
Ooseb
(mg/mouse)
0
0
0.25
0.25
0
0
0.25
0.25
Duration of
Treatment0**1
(days)
636
649
636
630
636
649
636
630
Tumor Type
all
all
all
all
squamous cell
carcinoma
squamous cell
carcinoma
squamous cell
carcinoma
. squamous cell •
Tumor
Incidence
8/60
5/100
1/30,
3/30
1/60
0/100
0/30
0/30
Strengths of Study:
Weakness of Study:
carcinoma
QUALITY OF EVIDENCE
Lifetime exposure by relevant route; large numbers of
control animals; positive controls used.
Only one, nontoxlc dose given; weekly administration;
limited number of endpolnts explored.
Overall Adequacy: Inadequate
aSource: Van Duuren et al., 1979
^Compound administered once a week
cM1ce treated until moribund or found dead
^Duration of study equal to duration of treatment
0086d
-18-
01/21/88
-------
mg B-proplolactone on the same treatment schedule. Other (negative) control
groups received nothing (100 mice), water (30 mice) or trloctanoln (30
mice). There were no observed differences between chloroacetaldehyde-
treated mice and negative control groups with respect to local sarcoma
Incidence. The positive control, B-proplolactone-treated mice, had a
statistically significant (p<0.0005) Increase In tumor Incidence.
Several studies also Indicate that chloroacetaldehyde 1s unable to
function as an Initiator of skin paplllomas 1n Initiation-promotion tumorl-
genesls experiments. Chloroacetaldehyde (1.0 ml/mouse) was applied 1n 0.1
ml acetone to the shaved backs of 30 female Swiss mice (Van Duuren et al.,
1979). Chloroacetaldehyde Initiation was followed 14 days later by applica-
tion of 2.5 yg of the tumor promoter PMA In 0.1 ml acetone. Promotion
with PMA was continued 3 times/week for ~60 weeks. Positive controls were
given 0.020 mg DMBA as an Initiator, whereas negative controls received
repeated exposure to the promoter at dose levels of 0.0025 (120 mice) or
0.0050 (90 mice) mg PMA/mouse. Paplllomas were found .1n 3/30 chloroacet-
aldehyde-lnltlated mice, which was not significantly different from the
papHloma Incidence observed In the PMA-treated controls (9/120 and 6/90 for
the respective PMA doses). The papllloma Incidence 1n DMBA-1n1t1ated mice
(29/30) was significantly higher (p<0.0005) than the tumor Incidence In PMA
controls.
Initiation of skin tumoMgenesIs 1n mice using chloroacetaldehyde was
also studied by Zajdela et al. (1980). Male XVIInc/Z mice (groups of 20-28)
received single applications of chloroacetaldehyde dissolved In 80 yl
acetone on their shaved backs at dose levels of 0.05, 0.1, 1.0 or 2.5 mg
chloroacetaldehyde/mouse. Chloroacetaldehyde Initiation was followed by
promotion with TPA 3 times/week for 42 weeks. The occurrence of paplllomas
0086d -19- 03/30/88
-------
and carcinomas was observed 1n the mice for ~84 weeks. The positive control
group consisted of 45 mice Initiated with 50 yg DMBA, followed by promo-
tion with croton oil 3 times/week for 12 weeks. Negative controls consisted
of 28 mice receiving TPA (3 times/week for 42 weeks) without chloroacetalde-
hyde Initiation. Survival was not affected by chloroacetaldehyde treatment
and was similar to the survival rate of TPA-treated negative controls (22/28
TPA controls lived for 84 weeks). In contrast, only 7/45 positive control
(DMBA-treated) mice survived the average observation period of 50 weeks.
The Incidence of paplllomas 1n the chloroacetaldehyde-1n1t1ated mice was
neither dose-related nor statistically different from the negative controls,
and none of the chloroacetaldehyde-1n1t1ated mice had skin carcinomas.
Persistent paplllomas and skin carcinomas were observed, however, 1n 37/45
mice treated with DHBA-croton oil.
Lawrence et al. (1972) Injected chloroacetaldehyde IntraperUoneally In
Sprague-Dawley rats (0.0016 or 0.0032 ma chloroacetaldehyde/kg) 3 times/
week for 12 weeks. The authors reported "These changes Included focal
chronic bronchopneumonla and certain changes of respiratory epithelium
suggesslve of a premallgnant condition", but this 1s not supported by any
data.
No carclnogenldty data from human occupational exposure were located 1n
the available literature nor were ep1dem1olog1cal studies located regarding
possible carcinogenic effects related to chloroacetaldehyde exposure.
6.3. MUTAGENICJTY
Chloroacetaldehyde has been tested for mutagenlclty In both prokaryotes
and eukaryotes using a variety of assays (Table 6-2). Forward and reverse
mutation assays 1n prokaryotes have been positive both with and without
metabolic activation of chloroacetaldehyde (B1gnam1 et al., 1980; Rannug et
al.. 1976; McCann et al., 1975; Malavellle et al., 1975; Phillips et al.,
0086d -20- 07/05/88
-------
Hutagentclty Testing of Chloracetaldehyde
o
CO
IV
I
o
C*
Assay
Reverse
nutation
Reverse
nutation
Reverse
nutation
Reverse
•utatton
Reverse
mutation
Reverse
nutation
Forward
mutation
DMA repair
Indicator/
Organism
Salmonella
typhlmurlum
TA98. TA100
TA1535. TA1537. .
TA1S38
S. typhlimirlum
TA98. TA100
TA1S3S. TA1S37,
TA1538
S. tvphlmurlum
TA100. TA1535
S. typhlnurlum
TA1S35
S. typhlnurlum
TA1530
Bacillus
subtllts
llv 82.
lev A169
markers
B. subtllls
$105
strains G68
Gb7075
Escherlchla
coll pol A*
pol A*
Compound
and/or
Purity
NR
45X aqueous
solution
45X aqueous
solution
aqueous
solution
SOX aqueous
solution
SOX aqueous
solution
SOX aqueous
solution
NR
Application Concentration Activating
or Dose System
plate -2-28 yg/plate -S-9
Incorporation
plate 3-60xlO~» ±S-9
Incorporation pi/plate
spot test 3-30 rag/plate »S-9
plate 0.1-1. 5, nN -S-9
Incorporation
plate 0.4-40 *S-9
Incorporation iinol/njt
plate Incorpo- 0.2S-S oH NR
ration (DNA
transformation
mixture)
plate 1-4 a* NR
Incorporation
NR 10 »t NR
Response Comment
<• Highly mutagenlc to
TA100, weakly muta-
genlc to TA1S3S
»A Positive In TA100;
addition of S-9
decreased response.
*/» Positive In TA100;
addition of S-9
decreased response.
*• Dose-dependent In-
creases In revertants
at doses which were
originally cytotoxlc
f/f Highly cytotoxlc at
the highest concen-
tration
* Dose -dependent In-
crease In mutation
activity with base
pair, but not with
frameshlft, mutation
strain
t Mutagenlc to both
normal and repair-
deficient host cell
reactivation strains
t Preferential Inhibi-
tion of pol A*
growth
Reference
HcCann et al. .
1975
Blgnaml
et al.. 1980
Blgnaml
et al.. 1980
Rannug et al..
1976
Nalavetlle
et al.. 197S
Phillips
et al.. 1980
Garro and
Phillips. 1980
Rosenkranz.
1977
CO
00
-------
o
0
CO
c*
a.
Assay
Forward
mutation
Reverse
mutation
Reverse
mutation
£J Forward
i mutation
Forward
mutation
Gene
conversion
Polycls-
tronlc
mutation
Single
point
mutation
ON Forward
J^ mutation
Indicator/
Organism
E. coll
Sd-4
E. coll
K12 All
K12 A23
K12 A46
Streptomyces
coellcolor
A3(2) strain
his Al
S. coellcolor
A3(2) strain
his Al
Schlzosac-
charomyccs
pombe PI
Saccharomyces
cerevlslae D4
Asperqlllus
nldulans 35
A. nldulans 35
CHO V79 cells
Compound
and/or
Purity
dissolved
" In '0.2 M
EtOH
aqueous
solution
45X aqueous
solution
45X aqueous
solution
SOX aqueous
solution
SOX aqueous
solution
45X aqueous
solution
45X aqueous
solution
SOX aqueous
solution
TABLE 6-2 (cont
Application Concentration
or Dose
liquid -0.1-4 mM
suspension
liquid 10-200 mM
suspension
plate Incorpo- 0.25-1.0 wt
ration and
spot test
plate Incorpo- 0.25-10 ut
ration and
spot test
liquid 0.78-6.25 mM
suspension
liquid 3.1-12.5 mM
suspension
plate 20-40 pt
Incorporation
spot test 5-20 pt
liquid 1.6-12.8 pM
cultures
''
Activating Response Comment
System
NR * Dose-dependent muta-
tion to streptomycin
nondependence
none * Dose-response;
Reversion frequency
greatest near 100X
cytotoxlclty
none «• Strongly mutagenlc
only In spot test
none * Mutagenlc only In
spot test
^S-9 *A Dose-response
±S-9 i Weak Increase In
mutation frequency
at cytolethal con-
centrations
none <• Nutagenlclty not
replicated In spot
test
none «• ' Stronger Induction of
8-azoguanlne resis-
tance In liquid test
NR *
Reference
Hussaln and
Osterraan-
Golkar. 1984
Perrard. 1985
Blgnaml
et al.. 1980
Blgnaml
et al.. 1980
Lorprleno
et al.. 1977
Lorprleno
et al.. 1977
Blgnaml
et al.. 1980
Blgnaml
et al.. 1980
Huberman
et al.. 1975
GO
00
NR = Not reported
-------
1980; Garro and Phillips, 1980; Hussaln and Osterman-Golkar, 1984; Perrard,
1985). In eukaryotes (yeast), chloroacetaldehyde has been demonstrated
overall to be mutagenlc 1n a number of mutation assays (LorpMeno et al.,
1977; B1gnam1 et al., 1980). Chloroacetaldehyde has also proven to be
mutagenlc In mammalian cells (Huberman et al., 1975).
6.4. TERATOGENICITY
Pertinent data regarding the teratogenldty of chloroacetaldehyde were
not located 1n the available literature dted 1n Appendix A.
6.5. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding other reproductive effects of chloroacetalde-
hyde were not located 1n the available literature dted 1n Appendix A.
6.6. SUMMARY
Few studies regarding the systemic toxldty of chloroacetaldehyde
following administration of the compound by relevant routes (I.e., oral and
Inhalation) were located In the available literature. Exposure of rats,
guinea pigs, rabbits and mice to chloroacetaldehyde (5.1 mg/m3) by Inhala-
tion 7 hours/day, 5 days/week for 6 months had no adverse health effects on
any of the animal species tested (Dow Chemical Company, 1962). Weekly oral
administration of chloroacetaldehyde to mice (0.25 mg chloroacetaldehyde/
mouse/week) over an entire lifetime was without effect on the mortality rate
(Van Duuren et al., 1979). The oral LD5Q of chloroacetaldehyde was
reported to be -82 mg/kg In mice and 89-103 mg/kg 1n rats (Lawrence et al.,
1972). f
Intraperltoneal doses of chloroacetaldehyde of 0.0016 and 0.0032 ma/kg
given to rats were associated with the production of a focal, chronic,
bronchopneumonla, Increases In segmented neutrophlls and decreases 1n both
erythrocytes and lymphocytes (Lawrence et al., 1972). No hematologlcal or
0086d -23- 06/24/88
-------
pulmonary effects were associated with a dose of 0.0008 ml chloroacetalde-
hyde/kg. Chloroacetaldehyde Injected IntraperHoneally 1n rats (0.0016 or
0.0032 ml/kg) 3 times/week for 12 weeks was reported to produce changes In
the respiratory epithelium, suggestive of a premallgnant condition (Lawrence
et al.. 1972).
Chloroacetaldehyde has been shown to Increase the pentobarbHal-lnduced
sleeping time of mice (Lawrence et al., 1972) and to cause In vitro hemoly-
s1s In rabbit erythrocyte preparations and cytotoxlclty 1n murlne L-cell
preparations.
Oral weekly administration of Chloroacetaldehyde to mice (0.25 mg/mouse/
week) for the llfespan did not Increase the Incidence of forestomach tumors
over that observed In untreated controls (Van Duuren et al., 1979).
Chloroacetaldehyde was negative as a whole carcinogen or as a tumor
Initiator when tested on the skin of mice (Van Duuren et al., 1979; Zajdela
et al., 1980).
Cardnogenldty data resulting from human occupational exposure were not
located 1n the available literature; also there were no ep1dem1olog1cal
studies regarding possible carcinogenic effects associated with exposure to
Chloroacetaldehyde.
Chloroacetaldehyde has been demonstrated to be mutagenlc 1n a variety of
assays using both prokaryotes and eukaryotes with and without metabolic
activation (B1gnam1 et al., 1980; Rannug et al., 1976; McCann et al., 1975;
Malavellle et al.., 1975; Phillips et al., 1980; Garro and Phillips, 1980;
Hussaln and Osterman-Golkar, 1984; Perrard, 1985; LorpMeno et al., 1977;
Huberman et al., 1975; Rosenkranz, 1977).
Pertinent data regarding the teratogenlcHy or other reproductive
effects associated with exposure to Chloroacetaldehyde were not located 1n
the available literature dted In Appendix A.
0086d -24- 06/24/88
-------
7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
Because of chloroacetaldehyde's severely Irritating nature, a celling
limit of 1 ppm (~3 mg/m3) has been recommended for human occupational
exposure (ACGIH, 1986). Continuous exposure to this level of chloroacet-
aldehyde was discouraged, however, because of the compound's demonstrated
mutagenlc activity (ACGIH, 1986). The celling limit of 1 ppm was adopted by
the ACGIH (1987). The OSHA (1985) permissible exposure limit 1s also 1 ppm
for chloroacetaldehyde.
7.2. AQUATIC
Guidelines and standards for the protection of aquatic biota from
chloroacetaldehyde were not located 1n the available literature cited 1n
Appendix A.
0086d -25- 06/24/88
-------
8. RISK ASSESSMENT
8.1. CARCINOGENICITY
8.1.1. Inhalation. Pertinent data regarding the cardnogenldty of
chloroacetaldehyde following Inhalation exposure were not located 1n the
available literature cited 1n Appendix A.
8.1.2. Oral.. The only study found In the available literature concerning
the carclnogenldty of chloroacetaldehyde following oral administration was
that of Van Duuren et al. (1979), 1n which 30 male and 30 female Ha:ICR
Swiss mice receiving 0.25 mg chloroacetaldehyde/mouse once a week for up to
636 days did not exhibit an Increased Incidence of forestomach total tumors
or squamous carcinomas compared with that of negative controls. Thirty mice
of each sex receiving a positive control substance, B-prop1olactone, on a
weekly basis had statistically significant (p<0.0005) Increases In both
total forestomach tumors and squamous carcinomas. Because of an Inadequate
number of mice 1n each group and the use of only one dose level, this study
was judged Inadequate for assessment of the carcinogenic potential of
chloroacetaldehyde. ;
8.1.3. Other Routes. Several studies (Van Duuren et al., 1979; Zajdela
et al., 1980) have demonstrated that chloroacetaldehyde 1s not tumorlgenlc
to the skin following repeated exposure either by the topical or subcuta-
neous routes. These same studies also demonstrated that chloroacetaldehyde
does not function as an Initiator when used 1n Initiation-promotion skin
tumor1genes1s experiments.
8.1.4. Weight of Evidence. Because there are no data regarding the
carclnogenldty of chloroacetaldehyde 1n humans and because the only study
on the carclnogenldty of chloroacetaldehyde 1n mice following oral exposure
0086d -26- 06/24/88
-------
(Van Duuren et al., 1979) was judged Inadequate for assessment of chloro-
acetaldehyde carcinogenic potential, this compound 1s placed 1n EPA Group 0
(U.S. EPA, 1986b) - not classifiable as to human carclnogenlcHy.
8.1.5. Quantitative Risk Estimates. The lack of adequate studies on the
carclnogenlcHy of chloroacetaldehyde following exposure either by the oral
or Inhalation route precludes the derivation of quantitative risk estimates.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposures.
8.2.1.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) -- Rats, rabbits,
guinea pigs and mice were .exposed to 1.6 ppm chloroacetaldehyde (5.1
mg/m3) by Inhalation 7 hours/day, 5 days/week for 6 months (Dow Chemical
Company, 1962). There were no adverse effects on growth, mortality,
hematology or organ weights. H1stolog1cal analyses were also unremarkable.
The study by Dow Chemical Company (1962) was the only Inhalation
toxldty study of chloroacetaldehyde that was of sufficient duration to be
classified as either subchronlc or chronic. A number of animal species were
used 1n this study but the numbers of animals In each group were low. In
addition, there was only one exposure level In this study of
chloroacetaldehyde toxldty and this exposure level proved to be a NOEL
(I.e., no dose response data are available). Even though RfDs were derived
using this study (U.S. EPA, 1986c, 1987c), revaluation of the data base
under the present RfD guidelines has determined 1t to be Inadequate for
derivation of RfQs.
8.2.1.2. CHRONIC EXPOSURES — Data regarding the toxldty of chloro-
acetaldehyde following chronic Inhalation exposure were not located 1n the
available literature.
0086d -27- 07/05/88
-------
8.2.2. Oral Exposures.
8.2.2.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) — There were no
data located 1n the literature regarding the toxldty of chloroacetaldehyde
following subchronlc oral exposure.
8.2.2.2. CHRONIC EXPOSURES — A chronic oral study of chloroacetalde-
hyde toxldty Indicated that the longevity of 30 male and 30 female Ha:ICR
Swiss mice was unaffected by exposure to 0.25 mg chloroacetaldehyde/mouse/
week over an entire lifetime (Van Duuren et al., 1979). This dosing
schedule (I.e., one dose/week) was suggestive of repeated acute rather than
chronic exposure and-thls study was therefore deemed Inadequate for chronic
toxldty risk assessment.
0086d -28- 07/05/88
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The systemic toxldty of chloroacetaldehyde was discussed In Section 6.1.
Because the chloroacetaldehyde exposure level used In the subchronlc
Inhalation toxldty study by Dow Chemical Company (1962) did not produce
observable toxldty, the data are Insufficient for derivation of an RQ
(Table 9-1).
9.2. BASED ON CARCINOGENICITY
Studies regarding the carclnogenldty of chloroacetaldehyde were
reviewed 1n Section 6.2. and summarized In Table 6-1. The only study of the
carcinogenic effects of chloroacetaldehyde following exposure by a relevant
route (I.e., oral or Inhalation) was that by Van Duuren et al. (1979), 1n
which 30 male and 30 female mice given an oral dose of chloroacetaldehyde
(0.25 mg chloroacetaldehyde/mouse/week) over the course of a lifetime had an
Incidence of forestomach tumors and squamous carcinomas that did not exceed
that of negative controls. Because of the small number of mice used and the
use of only one chloroacetaldehyde dose level, this study was not considered
adequate to assess the carclnogenldty of chloroacetaldehyde.
Van Duuren et al. (1979) and Zajdela et al. (1980) also reported that
chloroacetaldehyde was unable to function as a skin tumoMgen either follow-
ing repeated exposure to the compound Itself or by using chloroacetaldehyde
as an Initiator followed by treatment with several promoting agents.
Lawrence et al. (1972), however, reported changes suggestive of a premallg-
nant condition 1n the respiratory epithelium of rats Injected 1ntraper1to-
neally with chloroacetaldehyde (0.0016 or 0.0032 mi/kg) 3 times/week for
12 weeks.
0086d -29- 07/05/88
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TABLE 9-1
Chloroacetaldehyde
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Dose:
Effect:
Reference:
RVd:
RVe: : ^
Composite Score:
RQ: Data are not sufficient for deriving an RQ.
0086d -30- 07/05/88
-------
Structurally related compounds, such as formaldehyde and acetaldehyde,
are known to be carcinogenic. Unlike these related compounds, there are no
data available to show carcinogenic activity of chloroacetaldehyde. Chloro-
acetaldehyde 1s mutagenlc and a presumed Intermediate In* the metabolic
pathway of ethylenedlchlorlde. Because Information on the potential
cardnogen1c1ty of chloroacetaldehyde 1s Inadequate, there being only
positive short term data Indicating potential the overall evidence Indicates
that chloroacetaldehyde should be classified 1n we1ght-of-ev1dence Group D
because of Inadequate data (U.S. EPA, 1986b). Accordingly, Group D
compounds cannot be ranked on the CERCLA hazard ranking scheme.
0086d -31- 07/05/88
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10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1981.
Documentation of the Threshold Limit Values, 4th ed. Supplemental Documen-
tation. Cincinnati, OH. p. 82.
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1986.
Documentation of the Threshold Limit Values and Biological Exposure Indices,
5th ed. Cincinnati, OH. p. 120.
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1987.
TLVs - Threshold limit values and biological exposure Indices for 1987-1988.
Cincinnati, OH. p. 14.
Ando, M. and Y. Sayato. 1984. Studies on vinyl chloride migrating Into
drinking water from pbly(v1nyl chloride) pipe and reaction between vinyl
chloride and chlorine. Water Res. 18(3): 315-318.
Applegate, V.C., J.H. Howell, A.E. Hall, Jr. and M.A. Smith. 1957.
Toxldty of 4346 Chemicals to Larval Lampreys and Fishes. Spec. Sd. Rep.
F1sh. No. 207, F1sh and Wildlife Service, USDI, Washington, DC. p. 157.
(Cited 1n U.S. EPA, 1986c)
;
Atkinson, R. 1985. Kinetics and mechanisms of the gas phase reactions of
the hydroxyl radical with organic compounds under atmospheric conditions.
Chem. Rev. 85: 69-201.
0086d -32- 07/05/88
-------
Bengstsson, B.E. and M. Tarkpea. 1983. The acute aquatic toxlclty of some
substances carried by ships. Mar. Pollut. Bull. 14(6): 213-214.
B1gnam1, M., G. Contl, L. Contl, et al. 1980. MutagenlcHy of halogenated
aliphatic hydrocarbons In Salmonella typhlmuMum. Streptomyces coellcolor
and Asper1q1l1us nldulans. Chem. B1ol. Interact. 30: 9-23.
CMR (Chemical Marketing Reporter). 1986. OPD Chemical Buyers Directory,
74th annual ed., H. Van, Ed. Schnell Publishing Co., New York, NY.
Dow Chemical Company. 1962. Toxldty of chloroacetaldehyde determined on
experimental animals (unpublished report). Biochemical Research Laboratory,
The Dow Chemical Company, Midland, MI.
E1senre1ch, S.J., B.B. Looney and J.D. Thornton. 1981. Airborne organic
contaminants of the Gireat; Lakes ecosystem. Environ. Sd. Techno!. 15(1):
30-38.
Garro, A.J. and R.A. Phillips. 1980. Detection of mutagen-lnduced lesions
1n Isolated DNA by marker rescue of Bacillus subtnils phase 105. Mutat.
Res. 73(1): 1-13. (CUed In U.S. EPA, 1986c)
Green, T. and U.E. Hathway. 1977. The chemistry and biogenesis of the
S-conta1n1ng metabolites of vinyl chloride In rats. Chem. B1ol. Interact.
17(2): 137-150.
0086d -33- 07/05/88
-------
Guengerlch, P.P., W.M. Crawford, J.Y. Domoradzkl, T.L. MacDonald and P.G.
Watanabe. 1980. Iri vitro activation of 1,2-d1chloroethane by mlcrosomal
and cytosollc enzymes. Toxlcol. Appl. Pharmacol. 55: 303-317. (CHed In
U.S. EPA, 1986c)
Gwlnner, L.M., R.J. La1b, J.G. Fllser and H.M. Bolt. 1983. Evidence of
chloroethylene oxide being the reactive metabolite of vinyl chloride toward
DNA: Comparative studies with 2,2-d1chlorod1ethyl ether. Cardnogen1s1s.
4(11): 1483-1486. (CHed 1n U.S. EPA, 1986c)
Hawley, G.G. 1981. The Condensed Chemical Dictionary. Van Nostrand
Relnhold Co., New York. p. 232.
Mine, J. and P.K. Mookerjee. 1975. The Intrinsic hydrophlllc character of
organic compounds. Correlations 1n terms of structural contributions. J.
Org. Chem. 40(3);: 292-298.
HSDB (Hazardous Substance Data). 1987. Report No. 2521. On-Llne October
19, 1987. CAS No. 302-17-0.
Huberman, E., H. Bartsch and L. Sachs. 1975. Mutation Induction In Chinese
hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide
and 2-chloroacetaldehyde. Int. 0. Cancer. 16: 639-644. (CHed 1n U.S.
EPA, 1986c)
0086d -34- 07/05/88
-------
Hussaln, S. and S. Osterman-Golkar. 1984. Dose-response relationships for
mutations Induced 1n E_. coll by some model compounds. WHh an addendum:
Reaction kinetics 1n water of chloroethylene oxide, chloroacetaldehyde, and
chloroacetone. HeredHas. 101(1): 57-68.
Jaber, H.M., W.R. Mabey, A.T. Lu1, et al. 1984. Data Acquisition for
Environmental Transport and Fate Screening. SRI Intl., Menlo Park, CA. EPA
600/6-84/009. NTIS PB84-243906. p. 46.
Lawrence, W.H. and J. Autlan. 1972. Possible toxic effects from Inhalation
of dental Ingredients by alteration of drug biologic half-life. J. Dent.
Res. 51: 878.
Lawrence, W.H., E.O. DllUngham, J.E. Turner and J. Autlan. 1972. Toxldty
profile of chloroacetaldehyde. J. Pharm. Sd. 61: 19-25.
LorpMeno, N., R. Barale, S. BaroncelH, et al. 1977. Induction of gene
mutations and gene conversions by vinyl chloride metabolites In yeast.
Cancer Res. 3(1): 253-257.
Lyman, W.J., W.F. Reehl and D.H. Rosenblatt. 1982. Handbook of Chemical
Property Estimation Methods. McGraw-Hill Book Co., New York. p. 4-9, 5-5,
15-13 to 15-34. f
Malavellle, C., H. Bartsch, A. Barbln et al. 1975. Mutagenldty of vinyl
chloride, chloroethyleneoxlde, chloroacetaldehyde, and chloroethanol.
Blochem. Blophys. Res. Commun. 63: 363-370. (CHed In U.S. EPA, 1986c)
0086d -35- 07/05/88
-------
McCann, J., V. Simmon, D. Stre1tw1eser and B.N. Ames. 1975. MutagenlcHy
of chloroacetaldehyde, a possible metabolic product of 1,2-d1chloroethane
(ethylene dlchlorlde), chloroethanol (ethylene chlorohydrln), vinyl chloride
and cyclophosphamlde. Proc. Natl. Acad. Sc1. USA 72(8): 3190-3193. (CHed
1n U.S. EPA, 1986c)
OSHA (Occupational Safety and Health Administration). 1985. OSHA Safety
and Health Standards. Code of Federal Regulations. 29: 1910-1000. (Cited
In U.S. EPA, 1986c)
Perrard, M.H. 1985. MutagenlcHy and toxlclty of chloroethylene oxide and
chloroacetaldehyde. Exper1ent1a. 41: 676-677.
Phillips, R.A., S.A. Zahler and A.J. Garro. 1980. Detection of mutagen-
Induced lesions 1n Isolated ONA using a new Bacillus subtnis transforma-
tion-based assay. Mutat. Res. 74(4): 267-281. (CHed 1n U.S. EPA, 1986c)
Rannug, U., R. Goethe and C.A. Wachtmelster. 1976. The mutagenlclty of
chloroethylene oxide, chloroacetaldehyde, 2-chloroethanol and chloroacetlc
add, conceivable metabolites of vinyl chloride. Chem. Blol. Interact. 12:
251-263. (CHed 1n U.S. EPA, 1986c)
Rosenkranz, H.S. 1977. MutagenlcHy of halogenated alkanes and their
derivatives. Environ. Health Perspect. 21: 79-84.
Stuckl, G. and T. Le1s1nger. 1983. Bacterial degradation of 2-chloro-
ethanol proceeds via 2-chloroacet1c add. FEMS M1crob1ol. Lett. 16:
123-126. (Taken from CA98:120827v)
0086d -36- 07/05/88
-------
Swann, R.L., D.A. laskowskl, P.J. HeCall, K. Vander Kuy and H.J. Dlshburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorptlon constant, water to air
ratio and water solubility. Res. Rev. 85: 17-28.
Tuazon, E.G., R. Atkinson, A.M. Winer and J.N. Pitts, Jr. 1984. A study of
the atmospheric reaction of l,3-d1chloropropene and other selected organo-
chlorlne compounds. Arch. Environ. Contain. Toxlcol. 13: 691-700.
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 Toxlclty 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 Carclnogenldty 1n Support of
Reportable Quantity Adjustments Pursuant to CERCLA Section 102. Prepared by
the Office of Health and Environmental Assessment, Carcinogen Assessment
Group, Washington DC for the Office of Solid Waste and Emergency Response,
Washington, DC.
0086d -37- 07/18/88
-------
U.S. EPA. 19865. Guidelines for Carcinogen Risk Assessment. Federal
Register. 51(185): 33992-34003.
U.S. EPA. 1986c. Health and Environmental Effects Profile for Chloroacet-
aldehyde. 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, Washington, DC.
U.S. EPA. 1987a. Graphical Exposure Modeling System (GEMS). CLOGP3
computer program. PC version. Office of Toxic Substances, Washington, DC.
U.S. EPA. 1987b. Graphical Exposure Modeling System (GEMS). Fate of
Atmospheric Pollutants (FAP). PC version. Office of Toxic Substances,
Washington. DC.
U.S. EPA. 1987c. Interim Methods for Development of Inhalation Reference
Doses. Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for the Office
of A1r Quality Planning and Standards, Research Triangle Park, NC.
U.S. EPA/NIH (National Institute of Health). 1987. OHM-TADS (Oil and
Hazardous Materials Technical Assistance Data System). On-Hne computer
data base.
Van Duuren, B.L., B.M. Goldschmldt, G. Loewengart, et al. 1979. Cardno-
genldty of halogenated oleflnlc and aliphatic hydrocarbons 1n mice. J.
Natl. Cancer Inst. 63(6): 1433-1439.
0086d -38- 07/18/88
-------
Hlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co., Inc.,
Rahway. NO. p. 296.
Zajdela, P., A. Crolsy. A. Barbln, C. Malavellle, L. Tomatlc and H. Bartsch.
1980. Carclnogenlclty of chloroethylene oxide, an ultimate reactive metabo-
lite of vinyl chloride, and b1s(chloromethyl)ether after subcutaneous admin-
istration and 1n Initiation-promotion experiments 1n mice. Cancer Res.
40(2): 352-356.
0086d -39- 07/18/88
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APPENDIX A
LITERATURE SEARCHED
This HEED 1s 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 In October 1987, and the following secondary
sources were reviewed:
ACGIH (American Conference of Governmental Industrial Hyg1en1sts).
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 1n 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. 2ff78 p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed.. Vol. 2B. John WHey and
Sons, NY. p. 2879-3816.
Clayton, G.O. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
0086d -40- 07/05/88
-------
Grayson, M. and D. Eckroth, Ed. 1978-1984. K1rk-0thmer Encyclo-
pedia of Chemical Technology, 3rd ed. John Wiley 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 Relrihold 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.
1392, 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.
0086d -41- 07/05/88
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In addition, approximately 30 compendia of aquatic toxlclty 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 M.T. Flnley. 1980. Handbook of Acute Toxldty
of Chemicals to F1sh and Aquatic Invertebrates. Summaries of
Toxlclty Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965-1978. U.S. Dept. Interior, F1sh 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.
0086d -42- 07/05/88
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o
o
CD
APPENDIX B
Sunnary Table for Chloroacetaldehyde
Inhalation Exposure
Subchronlc
Chronic
9
Species
!
guinea pig
guinea pig
Exposure
5.1 mg/m*. 7 hours/day,
5 days/week (0.51 mg/kg/day)
5.1 mg/m*. 7 hours/day.
5 days/week (0.51 mg/kg/day)
Effect RfD or qj*
NOEL 0.4 rag/day or
0.02 rag/m»
NOEL 0.04 rag/day or
0.002 mg/raa
Reference
Dow Chemical
Company. 1962
Dow Chemical
Company. 1962
Carclnogenlclty
NO
Oral Exposure.
Subchronlc
Chrpnlc
CarclnogenlcHy
guinea pig 5.1 og/m*. 7 hours/day.
5 days/week (0.51 mg/kg/day)
guinea pig 5.1 aq/m*. 7 hours/day.
5 days/week (0.51 mg/kg/day)
NOEL 0.003 mg/kg/day '
or 0.2 rog/day .V
NOEL 0.0003 mg/kg/day
or 0.02 rag/day
NO
Dow Chemical
Company. 1962
Dow Chemical
Company. 1962
REPORTABLE QUANTITIES
Based on Chronic Toxlclty: NO
Based on Carclnogenlclty: NO
ND = Not determined
O
Ifl
oo
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