HALOETHERS
Ambient Water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
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CRITERION DOCUMENT
HALOETHERS
CRITERIA
Aquatic Life
4-bromophenylphenyl ether
For 4-bromophenylphenyl ether the criterion to protect fresh-
water aquatic life as derived using the Guidelines is 6.2 ug/1 as
a 24-hour average and the concentration should not exceed 14 ug/1
at any time.
For saltwater aquatic life, no criterion for 4-bromophenyl-
phenyl ether can be derived using the Guidelines, and there are
insufficient data to estimate a criterion using other procedures.
Human Health
There are insufficient toxicological data to calculate
exposure criteria for the haloethers covered in this document.
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Introduction
Haloethers are compounds which contain an ether moiety
(R-O-R) and halogen atoms attached to the aryl or alkyl
groups. Chloroethers appear to be the most important halo-
ethers used commercially and can be divided into two cate-
gories, alpha- and non-alpha-chloroethers (EPA, 1975).
Chloromethyl methyl ether (CMME) is the only alpha haloether
of commercial significance and is used primarily in the
»
synthesis of strong base ion exchange resins used in water
conditioning and for chemical separation processes. However,
CMME preparations are usually contaminated with 1 to 8 per-
cent bix(chloromethyl) ether (BCME) which has been demonstrat-
ed to be a potent carcinogen.
The beta-chloroethers are widespread environmental
contaminants. It has been suggested that they are: produced
or may be formed as by-products in sizable quantities, releas-
ed to and appear to persist in the environment, can pass
through drinking water treatment plants, and may be carcino-
genic. Bis(2-chloroethyl) ether (BCE) is used as a dewaxing
agent for lubricating oils and is a useful solvent for naph-
thenic components (Fairhall, 1949; Jacobs and Scheflan,
1953; Pollard and Lawson, 1955; Mervart, et al. 1960).
BCE has also been used to separate butadiene from butylene
(Lurie, 1965). The second major use of bis(2-chloroethyl)-
ether is in the textile industry as a cleaning agent, a
wetting agent and penetrant in combination with diethylene
glycol, sulphonated oils, etc. (Browning, 1953; Jacobs and
Scheflan, 1953; Allen, 1956). The compound generally is
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a good solvent for tars, fats, waxes, oils, resins and pec-
tins, and will dissolve cellulose esters when used with
10 to 30 percent ethanol (Fife and Reid, 1930).
Bis(2-chloroisopropyl) ether is an excellent solvent
and extractant for fats, waxes, and greases. It also finds
use as a cleaning and spotting agent as well as an additive
to paint and varnish removers (Hake and Rowe, 1963; Lurie,
1965).
The alpha-haloethers are more reactive than beta-halo-
ethers due to the two electronegative atoms (oxygen and
halogen) which are bonded to the same carbon (Summers, 1955).
This difference in reactivity is evident by the different
rates of hydrolysis. The most commercially significant
haloethers are the chloroethers. Chlorine substitution
on ethers tends to increase their density, boiling point,
and odor while decreasing their flammability and altering
their solubility properties. The fluorine substituted com-
pounds are much more volatile than their chlorinated ana-
logues (EPA, 1975).
The haloethers exist within a wide range of physical
properties. For example, boiling points may range from
43.2°C (2,2,2-trifluroethyl vinly ether) to 310°C (4-bromo-
phenylphenyl ether) (Lurie, 1965). Melting points can range
from 103.5°C (chloromethyl methyl ether) to -3°C (chloro-
methyl phenyl ether) (Hawley, 1971). The haloethers are
very soluble in benzene, carbon tetrachloride, and acetone
(Scheflan and Jacob, 1953) and miscible in all oils (Lurie,
1965).
Table 1 lists the physical properties of some haloethers.
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TABLE 1
Physical Properties of Haloethecs
Ether
bis (chloromethyl)
bis (2-chloroethyl)
(Chlorex)
bis (2-chlorisopropyl)
bis (2-chloroethoxy)
methane
Chloromethyl methyl
2- (2-chloroethoxy) ethyl
•f 2-chloroethyl
co
dichloromethyl methyl
dichloromethyl chloro-
methyl
bis (dichloromethyl)
tr ichloromethyl methyl
trichloromethyl
dichloromethyl
1-chloroethyl ethyl
2-chloroethyl ethyl
bis (1-chloroethyl)
Structure
(C1CH2)20
(C1CH2CH2)20
CH3
(C1CH2CH) 2O
(C1CH2CH20)2CH2
C1CH2OCH3
C12CHOCH3
C12CHOCH2C1
C12CHOCHC12
C13COCH3
C13COCHC12
CH3CHC10C2H5
(CH,CHC1),O
-3 ^
Boiling Melting
Point Point
(deg.C) (deg.C)
105 -41.5
178 -46.7
187.3 -96.8 to 99.8
218.1 -32.8
61 -103.5
84.5
129
143
106-110.5
159
2857mm
106
113
d20/4
1.315
1.2199
1.1127
1.234
1.0605
1.270
1.46430°C
1.558 30°C
1.4391
0.9495
0.9945
1.10625°C
Vapor Solubility
Pressure in water
(mm Hg) (g/iO)
0.7320°C 1.07
0.71-0.8520 C 0.17
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TABLE 1 (continued)
Ether
bis (2-bromoethyl)
bis (2-chloropropyl)
bis (3-chloropropyl)
bis (4-chlorobutyl)
2-chloroethyl vinyl
•f chloromethyl ethyl
chloromethyl phenyl
2,2-dichloro-l,l-
difluoroethyl methyl
(raethoxyflurane)
2,2,2-tnfloroethyl
vinyl
(fluoroxene or
fluoromar)
Structure
(BrCH2CH2)20
(CH3CHC1CH2)20
(C1CH2CH2CH2)2O
(C1CH2CH2CH2CH2)20
C1CH2CH2OCH=CHH2
C1CH2OCH2CH3
C1CH2OC6H5
CHC12CF2OCH3
CP3CH2OCH=CH2
Boiling Melting
Point Point
{deg.C) (deg.C)
11532mm
188
215745nun
84-865.5°C
109 -70
84
88-90 - 3
104 -35
43.2
Vapor
Pressure
d20/4 (nun Hg)
27°c
1.8227// (-
1.109
1.14020/20
25°C
1.0691" C
1.0493
1.0322°4
1.4262
1.13 286
Solubility
in water
(g/iO)
0.6
0.4
Lune, 1965; Allen, 1956; Tschamler, 1950; Krentz, 1963; Hake and Roe, 1963
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REFERENCES
Allen, H. 1956. Safety hazards on some newer fine chemicals.
Chem. Prod. Chem. News. 19: 482.
Browning, E. 1953. Beta, beta-dichloroethyl ether. In Toxi-
city of Industria Organic Solvents. Chemical Publishing
Co., Inc., N.Y. p. 266.
Fairhall, L.T. 1949. Dichloroethyl ether. In Industrial
Toxicology. Willis and Wilkins Co., Baltimore.
Fife, H.R., and E.W. Reid. 1930. New industrial solvents:
ethylene dichlor dichloroethyl ether, and disopropyl ether.
Industr. Engr. Chem. 22: 513.
Hake, C.L., and U.K. Rowe. 1963. Ethers. In Industrial Hygiene
and Toxicol. 2nd ed., ed. F.A. Patty. Interscience Publishers,
N.Y. 2: 1655.
Hawley, G.G. 1971. The Condensed Chemical Dictionary, 8th
ed. Van Nostrand, Reinhold-Co., New York.
Jacobs, M.B., and L. Scheflan. 1953. Oil- and water-repelling
substances. Ger. Offen. 2,247,111 24 pp.
Krantz, J.C., Jr. 1963. Anesthetics. Kirk-Othmer Encyclopedia
ot Chemical Technology, Vol. 2, 2nd ed., John Wiley and
Sons, Inc., N.Y. 2: 393.
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Lurie, A.P. 1965. Ethers. Kirk-Othmer Encyclopedia of Chemical
Technology Vol. 8, 2nd ed. John Wiley and Sons, Inc., N.Y.
Mervart, Z., et al. 1960. Economic analysis of the effect
of solvent characteristics on the isolation of 1,3-butadiene
by extractive distillate. Chem. Prumysl. 10j 132.
Pollard, W.R., and J.V. Lawson. 1955. Corrosion rates. Ind.
Eng. Chem. 47.
Scheflan, L., and H.B. Jacobs. 1953. The Handbook of Solvents.
Van Nostra Co., Inc., New York and London.
Summers, L. 1955. The alpha-haloalkyl ethers. Chem. Rev.
55: 301.
Tschmaler, H. 1950. Chlorex (Bis(2-chloroethyl)ether). Osterr.
Chem. Atg. 51: 145.
U.S. EPA. 1975. Investigation of selected potential environ-
mental contaminants: haloethers. NTIS, Off. Tox. Subst.,
Springfield, Virginia^
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
The only toxicity data for haloethers, other than for those
compounds discussed in the criterion document for chloroalkyl
ethers, are for 4-bromophenylphenyl ether and the bluegill, fat-
head minnow/ and Daphnia magna.
Acute Toxicity
The bluegill has been exposed to 4-bromophenylphenyl ether
and the unadjusted 96-hour LC50 is 4,940 ug/1 (Table 1). When
this result is adjusted for test conditions and species sensi-
tivity, a Final Fish Acute Value of 690 ug/1 is obtained.
Daphnia magna is more sensitive than the bluegill with an
unadjusted 48-hour EC50 of 360 ug/1 (Table 2). The Final Inver-
tebrate Acute Value for 4-bromophenylphenyl ether is 14 ug/1 and
this also is the Final Acute Value.
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life [43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The fol-
lowing tables contain the appropriate data that were found in the
literature, and at the bottom of each table for the calculations
for deriving various measures of toxicity as described in the
Guidelines.
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Chronic TOxicity
A chronic value for 4-brcmophenylphenyl ether, 61 ug/1, is
derived from an embryo-larval test with the fathead minnow in which
adverse effects on survival and growth were observed (Table 3) (U.S.
EPA, 1978). After division by the species sensitivity factor (6.7),
a Final Fish Chronic Value of 9.1 ug/1 is derived. Since no other
chronic value for an invertebrate or plant species or a Residue
Limited Toxicant Concentration is available, 9.1 ug/1 is also the Final
Chronic Value.
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
i
4-bromophenylphenyl ether
Final Fish Acute Value = 690 ug/1
Final Invertebrate Acute Value = 14 ug/1
Final Acute Value = 14 ug/1
Final Fish Chronic Value = 9.1 ug/1
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 9.1 ug/1
0.44 x Final Acute Value = 6.2 ug/1
The maximum concentration of 4-bromophenylphenyl ether is the
Final Acute Value of 14 ug/1 and the 24-hour average concentration
is 0.44 times the Final Acute Value. No important adverse effects
on freshwater aquatic organisms have been reported to be caused by
concentrations lower than the 24-hour average concentration.
CRITERION: For 4-bromophenylphenyl ether the criterion to
protect freshwater aquatic life as derived using the Guidelines is
6.2 ug/1 as a 24-hour average and the concentration should not
exceed 14 ug/1 at any time.
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0)
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Table 1. Freshwater fish acute values for haloethers (U.S. EPA, 1978)
Adjusted
Bioaseay Test Chemical Time LCbu Lcbo
Organism M^t-nod* Conct** Description tfera)
Blueglll. S U 4-Bromophenyl- 96 4,940 2,700
Lepomts macrochirua phenyl ether
* S • static
** U - unmeasured
Geometric mean of adjusted values: A-Bromophenylphenyl ether *• 2,700 Mg/1 ^ S • 690 pg/1
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CD
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Table 2 Freshwater invertebrate acute values for haloethers (U.S. EPA, 1978)
Organism
Cladoceran,
Daphnia magna
Bioassay Test Chemical
Method* Cone,** Description
S U 4-Bromophenyl-
phenyl ether
Time
itllB)
48
LCbU
(uq/1)
360
Adjusted
LC50
(uq/1)
300
* S = static
** U = unmeasured
Geometric mean of adjusted values: 4-Bromophenylphenyl ether = 300 ug/1
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Tafcle 3 Freshwater fish chronic values for haloethers (U.S. EPA. 1978)
Chronic
Limits Value
Organism Test* (ug/il (ug/il
4-BromophenylphenyI ether
Fathead minnow. E-L 89-167 61
Pimephales promelas
* E-L = embryo-larva
Geometric mean of chronic values - 61 pg/1 g—j =9.1 pg/1
Lowest chronic value - 61 Mg/1
CTv
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CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Available Data
No appropriate data are available for saltwater organisms and
any haloether other than those discussed in the criterion document
for chloroalkyl ethers.
CRITERION: No saltwater criterion can be derived for any
haloether using the Guidelines because no Final Chronic Value for
either fish or invertebrate species or a good substitute for
either value is available, and £here are insufficient data to
estimate a criterion using other procedures.
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HALOETHERS
REFERENCES
U.S. EPA. 1978. In-depth studies on health and environmental
impacts of selected water pollutants. U.S. Environ. Prot.
Agency, Contract No. 68-01-4646.
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Mammalian Toxicology and Human Health Effects
I. Introduction
The EPA is currently charged with establishing water quality criteria
for halogenated ethers. This document covers chlorinated aromatic ethers
including:
chlorophenyl phenyl ethers
bromophenyl phenyl ethers
polychlorinated diphenyl ethers
A separate document in this series, entitled "Chloroalkyl ethers," covers
the following compounds:
bis(chloromethyl)ether
bis(2-chloroethyl)ether
2-chloroethyl vinyl ether
bis(2-chloroisopropyl)ether
bis(2-chloroethoxy)methane
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II. Exposure
A. Ingestion
1. Water
Qualitative identifications of several haloethers in raw and
finished water have been reported. This information is summarized in Table 1.
The nomenclature used in specifying some haloethers creates a certain amount
of confusion in evaluating these monitoring data. For instance, in Table 1,
pentachlorophenoxy methyl ether is probably the same as pentachlorophenyl
methyl ether. The names used in Table 1 are those given in the various
references cited.
Shackelford and Keith (1976) have compiled information on the
frequency of organic compounds identified in water. This information was
taken from both the published literature and unpublished results of survey
analyses from EPA Regional Laboratories and Research Laboratories. Although
actual levels of the haloethers in waters are not specified, a breakdown is
given of the various types of waters found to be contaminated. This infor-
mation is presented in Table 2.
The study by Ewing and coworkers (1977) is based on the anal-
ysis of 204 water samples collected from fourteen heavily industrialized river
basins. As indicated in Table 1, pentachlorophenyl methyl ether was found in
12 samples (5.88%), with other chlorophenyl ethers found less frequently. As
Indicated above, the reports of "pentachlorophenoxy methyl ether" probably
refer to pentachlorophenyl methyl ether. The studies by Friloux (1971) and
the U.S. Environmental Protection Agency (1972) both summarized in Table 1,
were conducted in the New Orleans area.
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Table 1. Haloethers Qualitatively Identified in Water
(see text for details)
Reference
Haloether
*
vO
a\
1
•a
o
Jl
CJ
5
en
ff
o
l-l
•H
£
CO
•
S3
Bromophenyl phenyl ether
Bis(4-chlorophenyl)ether
Dichlorophenyl chlorophenyl ether
2,4,4'-Trichloro-2'-hydroxy-
dlphenyl ether
Dichlorophenyl methyl ether
Trichlorophenyl methyl ether
Tetrachlorophenyl methyl ether
Fentachlorophenyl methyl ether
Pentachlorophenoxy methyl ether
5
2
2
10
1
5
1
12
2
Frequency of occurrence.
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Table 2. Frequency Haloethers Identified in Various
Types of Water (Shackelford and Keith, 1976)
Water Type Contaminated
FDW River Raw Water
Bromophenyl phenyl ether 3 2
Bis (4-chlorophenyl) ether
Dichlorophenyl chlorophenyl ether
2,4,4' -Tr ichloro-2 ' -hydroxy-
diphenyl ether
Pentachlorophenyl methyl ether 331
Effluent
CHEM RS
2
2
1
1
from:
STP
2
Key
FDW - Finished drinking water
G8SK m Chemical plant
RS » Raw sewage
STP - Sewage treatment plant
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In the 1975 National Organics Reconnaissance
Survey by the U.S. Environmental Protection Agency, no halo-
ethers were found in the waters of Miami, Florida; Seattle,
Washington; Ottumwa, Iowa; or Cincinnati, Ohio (U.S. EPA,
1975).
2. Food
No monitoring data have been found on the
levels of haloethers in food.
A bioconcentration factor (BCF) relates the concentra-
tion of a chemical in water to the concentration in aquatic
organisms, but BCF's are not available for the edible portions
of all four major groups of aquatic organisms consumed in
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the United States. Since data indicate that the BCF for
lipid-soluble compounds is proportional to percent lipids,
BCF's can be adjusted to edible portions using data on percent
lipids and the amounts of various species consumed by Americans,
A recent survey on fish and shellfish consumption in the
United States (Cordle et al., 1978) found that the per capita
consumption is 18.7 g/day. From the data on the nineteen
major species identified in the survey and data on the fat
content of the edible portion of these species (Sidwell,
et al., 1974), the relative consumption of the four major
groups and the weighted average percent lipids for each
group can be calculated:
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Consumption Weighted Average
Group (Percent) Percent Lipids
Freshwater fishes 12 4.8
Saltwater fishes 61 2.3
Saltwater molluscs 9 1.2
Saltwater decapods 18 1.2
Using the percentages for consumption and lipids for each
of these groups, the weighted average percent lipids is
2.3 for consumed fish and shellfish.
Neither measured steady-state bioconcentration factors
{BCF) nor laboratory data (octanol-water partition coefficient)
are available for estimation of BCF at this time.
B. Inhalation
No monitoring information is available on the
levels of any chloroethers in ambient air.
C. Dermal
Because of the lack of monitoring data, no evalua-
tion of the importance of dermal exposures can be made for
the haloethers.
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III. Pharmacokinetics
No information has been encountered in the pharnacokinetics of the
haloethers under review.
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IV. Effects
1. Acute, Subacute, and Chronic
The acute and subacute oral toxlcity of various chlorinated phenyl
ethers is summarized in Tables 3 and 4. Because of the lack of experimental
detail presented in this summary of unpublished data by Hake and Rove (1963)
these results are difficult to interpret. However, the reported results on
"highly purified" pentachlorophenyl ether compared to the other pentachloro-
phenyl ether suggest that Impurities may be major toxic constituents.
Hake and Rowe (1963) report that "small amounts" of hexachloro-
diphenyl ether may cause acneform dermatitis in man.
2. Joint Action with Other Toxicants
No Information is available.
3. Teratogenicity
Ho information is available.
4. Mutagenicity
No information is available.
5. Carcinogenicity
No Information is available.
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Table 3. Chlorinated Phenyl Ethers Summary of Single-Dose
Oral Feeding Studies on Guinea Pigs (Hake and
Rowe, 1963)
Total Number
of Chlorines
1 x Cl
2 x Cl
3 x Cl
4 x Cl
5 x Cl
6 x Cl
After 4
Lethal dose
(mg/kg)
700
1,300
2,200
3,000
3,400
3,600
days
Survival
dose (mg/kg)
200
400
400
400
1,800
400
After
Lethal dose
(mg/kg)
600
1,000
1,200
50
100
50
30 days
Survival
dose (mg/kg)
100
50
200
0.5
5
5
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Table A. Chlorinated Phenyl Ethers: Results of Repeated Oral
Feeding of Rabbits (Hake and Rove, 1963)
Total
Number of
Chlorines
1
2
3
4
5
6
Dose
(mg/kg)
100
100
100
50
10
50
5
50
100**
10**
1**
5
1
0.1
Number of
doses
19
19
5
20
20
4
20
8
20
20
20
8
20
20
Number
days
29
29
12
29
29
10
29
21
29
29
29
10
28
28
of Effect
None
Mild liver injury
Death
Slight liver injury
No effect
Death
Severe liver injury
Death
Moderate liver injury
No growth
Slight liver injury
No effect
Death
Severe liver injury
No effect
Animals dosed 5 days/week x 4 weeks unless death intervened. Vehicles not
specified.
**
Highly purified pentachlorophenyl ether.
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V. Criterion Rationale
A. Existing Standards
The Occupational Safety and Health Administration (38 FR 23540) has
2 '
set a time-weighted average value of 500 yg/m for the following aromatic
chloroethers in the air of the working environment: monochlorophenyl phenyl
ether, dichlorophenyl phenyl ether, tricolorophenyl phenyl ether, tetrachloro-
phenyl phenyl ether, and pentachlorophenyl phenyl ether. This value has also
been adopted by the American Conference of Governmental and Industrial
Hygienistd (ACGIH, 1974). The standard is designed to prevent the formation
of chloracne in exposed workers.
B. Current Levels of Exposure
As detailed in Section II, only limited information is available on
the extent of human exposure to haloethers in water and no information is
available on ambient levels of haloethers in air or food. Quantitative
estimates of human exposure cannot be made.
C. Special Groups at Risk
Individuals working with haloethers or living in areas where these
haloethers are produced are probably at greater risk than the general popu-
lation.
D. Basis for the Standard
As indicated in Section V.A., the TLV for chlorophenyl phenyl ethers
2
is 500 jjg/m . By a process analogous to that used by Stokinger and Woodard
(1958), this standard could be used to calculate a water criterion. However,
since the TLV for these compounds is based on preventing chloracne, rather
than chronic toxicity, such a calculation would not be appropriate.
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There are not sufficient toxicologic data to calcu-
late exposure criteria for other haloethers covered in this
document.
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REFERENCES
AC6IH (American Conference of Governmental Industrial Hygienlsts) (1974),
Documentation of the Threshold Limit Values, 3rd Edition, 2nd Printing.
Eving, B.B., E.S.K. Chian, J.C. Cook, C.A. Evans, P.K. Hopke, and
E.G. Perkins (1977), Monitoring to Detect Previously Unrecognized
Pollutants in Surface Waters, EPA 560/6-77-015, 75 pp.
Friloux, J. (1971), "Petrochemical Wastes as a Pollution Problem in the Lower
Mississippi River," Paper submitted to the Senate Subcommittee on Air
and Water Pollution, April 5.
Hake, C.L. and V.K. Rowe (1963), "Ethers," in Industrial Hygiene and Toxicology,
2nd Edition, Patty, F.A. (ed.), Interscience Publishers, New York, ,2:1655-
1718.
Rosen, A.A., R.T. Skeel, and M.B. Ettinger (1963), "Relationship of River
Water Odor to Specific Organic Contaminants," J. Water Pollut. Contr.
Fedr., .35:777-782.
Shackelford, W.M. and L.H. Keith (1976), Frequency of Organic Compounds
Identified in Water, EPA-600/4-76-062, U.S. Environmental Protection
Agency, Athens, GA., 626 pp.
Stoklnger, H.E. and R.L. Woodward (1958), "Toxlcologlc Methods for Establishing
Drinking Water Standards," J. Amer. Water Works Assn., 50;515.
U.S. Environmental Protection Agency (1972), "Industrial Pollution of the
Lower Mississippi River in Louisiana," Region VI, Dallas, Texas,
Surveillance and Analysis Division.
U.S. Environmental Protection Agency (1975), Preliminary Assessmei £ of Sus-
pected Carcinogens in Drinking Water; Interim Report to Coiu cess,
Washington, D.C.
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