&EPA
United States
Environmental Protection
Aaencv
Office of Water
Regulations and Standards
Criteria and Standards Division
Washington DC 20460
EPA 440/5-80-043
October 1980
j
C . /
Ambient
Water Quality
Criteria for
Dichloropropane
and Dichloropropene
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AMBIENT WATER QUALITY CRITERIA FOR
DICHLOROPROPANES/DICHLOROPROPENES
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, D.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
-------
DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
ii
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FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (D.D.C. 1979).
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section 304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
111
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ACKNOWLEDGEMENTS
Aquatic Life Toxicology:
William A. Brungs, ERL-Narragansett
U.S. Environmental Protection Agency
David J. Hansen, ERL-Gulf Breeze
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
S. L. Schwartz (author)
Georgetown University School of
Medi ci ne
Christopher T. DeRosa (doc. mgr.)
ECAO-Cin
U. S. Environmental Protection Agency
Donna Sivulka (doc. mgr.)
ECAO-Cin
U. S. Environmental Protection Agency
Robert Donner, HERL
U. S. Environmental Protection Agency
Larry Fishbein
National Center for Toxicological
Research
Terri Laird
ECAO-Cin
U. S. Environmental Protection Agency
Chad Sandusky
U. S. Environmental Protection Agency
Benjamin L. Van Duuren
New York University Medical Center
Jerry F. Stara
ECAO-Cin
U. S. Environmental Protection Agency
Julian Andelman
University of Pittsburgh
Richard A. Carchman
Medical College of Virginia
Jaqueline V. Carr
U. S. Environmental Protection Agency
Patrick Durkin
Syracuse Research Corporation
Rolf Hartung
University of Michigan
Si Duk Lee
ECAO-Cin
U. S. Environmental Protection Agency
Joseph Santodonato
Syracuse Research Corporation
Yin-tak Woo
Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, T. Highland, R. Rubinstein.
IV
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TABLE OF CONTENTS
Page
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-l
Acute Toxicity B-l
Chronic Toxicity B-2
Plant Effects B-3
Miscellaneous B-4
Summary B-4
Criteria B-5
References B-ll
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure C-3
Ingestion from Water C-3
Ingestion from Food C-3
Inhalation C-4
Dermal C-7
Pharmacokinetics C-7
Effects (Dichloropropane) C-10
Acute, Subacute and Chronic Toxicity C-10
Mutagenicity C-l6
Carcinogenicity C-l 8
Effects (Dichloropropene) C-l8
Acute, Subacute and Chronic Toxicity C-18
Mutagenicity C-20
Carcinogenicity C-23
Effects (Dichloropropane/Dichloropropene Mixtures) C-23
Acute, Subacute and Chronic Toxicity C-23
Mutagenicity C-25
Carcinogenicity C-25
Criterion Formulation C-25
Dichloropropanes (PDC) C-26
Dichloropropenes (DCP) C-27
Summary C-28
References C-29
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CRITERIA DOCUMENT
DICHLOROPROPANES/DICHLOROPROPENES
CRITERIA
Aquatic Life
The available data for dichloropropanes indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low as 23,000
and 5,700 ug/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for dichloropropene indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low as 6,060
and 244 ug/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for dichloropropane indicate that acute and chronic
toxicity to saltwater aquatic life occur at concentrations as low as 10,300
and 3,040 yg/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for dichloropropene indicate that acute toxicity to
saltwater aquatic life occurs at concentrations as low as 790 vg/1 and would
occur at lower concentrations among species that are more sensitive than
those tested. No data are available concerning the chronic toxicity of
dichloropropene to sensitive saltwater aquatic life.
Human Health
Using the present guidelines, a satisfactory criterion cannot be derived
at this time due to the insufficiency in the available data for dichloropro-
panes.
VI
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For the protection of human health from the toxic properties of dichlo-
ropropenes ingested through water and contaminated aquatic organisms, the
ambient water criterion is determined to be 87 yg/1.
For the protection of human health from the toxic properties of dichlo-
ropropenes ingested through contaminated aquatic organisms alone, the ambi-
ent water criterion is determined to be 14.1 mg/1.
vii
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INTRODUCTION
Principal uses of dichloropropanes and dichloropropenes are as soil
fumigants for the control of nematodes, in oil and fat solvents, and in dry
cleaning and degreasing processes (Windholz, 1976). Dichloropropanes and
dichloropropenes can enter the aquatic environment as discharges from indus-
trial effluents, by runoff from agricultural land, and from municipal ef-
fluents. These compounds have been detected in New Orleans drinking water,
although they were not quantified (Dowty, et al. 1975). Most data on per-
sistence, degradation, and distribution of dichloropropanes and dichloropro-
penes deal with their presence in soils.
Dichloropropanes and dichloropropenes are liquids at environmental tem-
peratures and have molecular weights of 112.99 and 110.97, respectively
(Weast, 1977). Composition of specific compounds are shown in Table 1.
Lange (1952) reports a water solubility of 270 mg/100 ml at 20°C for
1,2-dichloropropane. The vapor pressure of 1,2-dichloropropane is 40 mm Hg
at 19.4°C (Sax, 1975). A review of various fumigants, fungicides, and ne-
matocides by Goring and Hamaker (1972) lists the water solubility at 20°C as
0.27 percent for cis-l,3-dichloropropene and 0.28 percent for trans-l,3-di-
chloropropene.
Mixtures of 1,2-dichloropropane and cis- and trans-l,3-dichloropropene
are used as soil fumigants. When heated to decomposition, 1,2-dichloropro-
pane emits highly toxic fumes of phosgene, while 1,3-dichloropropene gives
off toxic fumes of chlorides (Sax, 1975).
Dichloropropenes have been shown to undergo photochemical formation of
free radicals (Richerzhagen, et al. 1973). The cis- and trans-isomers of
A-l
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TABLE 1
Some Physical Properties of Dichloropropanes and Dichloropropenes*
Dichloropropanes
1,1-PDC
1,2-PDC
1,3-PDC
2,2-PDC
Boiling
point ( C)
88.1
96.4
120.4
69.3
Density
1.132
1.156
1,188
1.112
Dichloropropenes
1,1-DCP
l,2(cis)-DCP
l,3(trans)-DCP
l,3(cis)-DCP
l,3-(trans)-DCP
Boiling
point ( C)
76-77
77
104.3
112
Density
1.186
1.182
1.217
1.224
*Source: Weast, 1977
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1,3-dichloropropene have undergone biodehalogenation by a Pseudomonas spe-
cies isolated from the soil (Belser and Castro, 1971). 1,3-Dichloropropene
has been shown to react with biological materials (cow's milk, potatoes, hu-
mus-rich soil) to produce 3-chloroallyl methyl sulfide (Dekker, 1972).
In the nonaquatic environment, movement of dichloropropene and dichloro-
propane in the soil results from diffusion in the vapor phase, as these com-
pounds tend to establish an equilibrium between concentrations in vapor,
water, and absorbing phases (Leistra, 1970). Degradation of some of these
compounds can occur in the soil. Van Dijk (1974) reports that cis- and
trans-l,3-dichloropropene can be chemically hydrolyzed in moist soils to the
corresponding 3-chloroalkyl alcohols, which are capable of metabolizing to
carbon dioxide and water by a bacterium (Pseudomonas sp.). Although field
applications of 1,3-dichloropropene have shown between 15 and 80 percent
decomposition (Van Dijk, 1974), the large amount that can be absorbed (80 to
90 percent) can result in considerable residues existing months after appli-
cation is completed (Leistra, 1970). 1,2-Dichloropropane, however, appears
to undergo minimal degradation in the soil, with the major route of dissipa-
tion appearing to be volatilization (Roberts and Stoydin, 1976). The per-
sistence and degradation of dichloropropanes and dichloropropenes depends on
susceptibility to hydrolysis (Thomason and McKenry, 1973), soil types
(Leistra, 1970), and temperature (Van Dijk, 1974; Thomason and McKenry,
1973). For example, cis-DCP is chemically hydrolyzed in moist soils to the
corresponding cis-3-chloroallyl alcohol, which can be microbially degraded
to carbon dioxide and water by Pseudomonas sp. (Van Dijk, 1974).
The distribution of PDC and DCP within soils depends upon soil condi-
tions. These same conditions in turn influence their potential as persis-
tent health hazards as soil contaminants potentially toxic to developing
crop plants. When Telone^ is applied to a moist, warm soil at a rate of
A-3
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234 1/ha, cis-DCP can be expected to remain in the soil at concentrations
greater than 10 pg/1 for two to four months, depending on the soil type
(Thomason and McKenry, 1973). Under certain conditions, developing roots
and tubers of crop plants can absorb small quantities of the remaining com-
pounds (Williams, 1968). However, fumigation of sandy soils with relatively
low dosage of alkyl nematocides under proper conditions produced no residues
of nematocides and had no adverse effects on the flavor or nutritional value
of lima beans, carrots, or citrus fruits (Emerson, et al. 1969). These were
the only food crops tested. No information was found concerning the concen-
trations of the PDC and DCP in commercial foodstuffs. Thus, the amount of
these compounds ingested by humans through food is not known.
A-4
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REFERENCES
Belser, N.O. and C.E. Castro. 1971. Biodehalogenation: Metabolism of the
nematocides cis- and trans-3-chloroallyl alcohol by a bacterium isolated
from soil. Jour. Agric. Food Chem. 19: 23.
Dekker, W.H. 1972. 3-Chlorallyl methyl sulfide, a product from the reac-
tion of 1,3-dichloropropene and biological materials. Medea, Fac. Andbouwa-
wetensch., Ryksania. Geal. 37: 865.
Dowty, B., et al. 1975. Halogenated hydrocarbons in New Orleans drinking
water and blood plasma. Science. 87: 75.
Emerson, G.A., et al. 1969. Effects of soil fumigants on the quality and
nutritive value of selected fruits and vegetables. VIII. International
Nutritonal Congress Symposium. Sept. 2. Prague, Czechoslovakia.
Goring, C.A.I, and J.W. Hamaker. 1972. Organic chemicals in the soil envi-
ronment. Environment. Marcel Dekker, Inc., New York.
Lange, N.A. 1952. Lange's Handbook of Chemistry. 8th ed. Handbook Pub-
lishers, Inc., Sandusky, Ohio.
Leistra, M. 1970. Distribution of 1,3-dichloropropene over the phases in
soil. Jour. Agric. Food Chem. 18: 1124.
A-5
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Richerzhagen, T., et al. 1973. Photochemical formulation of free radicals
from chlorolefins as studied by electron spin resonance. Jour. Phys. Chem.
77: 1819.
Roberts, R.T. and 6. Stoydin. 1976. The degradation of (Z)- and (E)-l,3-
dichloropropenes and 1,2-dichloropropanes in soil. Pestic. Sci. 7: 325.
Sax, N.I. 1975. Dangerous Properties of Industrial Materials. Reinhold
Book Corp., New York.
Thomason, I.J. and M.V. McKenry. 1973. Part I. Movement and fate as af-
fected by various conditions in several soils. Halgardia. 42: 393.
Van Dijk, H. 1974. Degradation of 1,3-dichloropropenes in soil. Agro-Eco-
systems. 1: 193.
Weast, R.C. (ed.) 1977. Handbook of Chemistry and Physics. 58th ed. CRC
Press, Inc., Cleveland, Ohio.
Williams, I.H. 1968. Recovery of cis- and trans-l,3-dichloropropene resi-
dues from two types of soils and their detection and determination by elec-
tron capture gas chromotography. Jour. Econ. Bnt. 61: 1432.
Windholz, M. (ed.) 1976. The Merck Index. 9th ed. Merck and Co., Inc.,
Rahway, New Jersey.
A-6
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Aquatic Life Toxicology*
INTRODUCTION
The available freshwater aquatic life data for these two classes of com-
pounds with one exception are for dichloropropanes. Where data exist for
both 1,3-dichloropropene and 1,3-dichloropropane tested under similar con-
ditions, the propene is much more toxic than the propane.
The data base for dichloropropanes and dichloropropenes and saltwater
organisms is limited to studies with 1,2- and 1,3-dichloropropane, and 1,3-
dichloropropene. Toxicity tests with saltwater organisms have not been done
on other chemicals in these classes; and effects of salinity, temperature,
or other water quality factors on toxicity are unknown.
EFFECTS
Acute Toxicity
Daphnia magna is the only freshwater invertebrate species tested with
these classes of compounds (Table 1). Under static test conditions the 48-
hour EC^Q values for 1,1-, 1,2-, and 1,3-dichloropropane were 23,000,
52,500, and 282,000 ug/l, respectively (U.S. EPA, 1978). The 48-hour EC5Q
value for 1,3-dichloropropene under static test conditions is 6,150 ug/l
(U.S. EPA, 1978). This compound is 46 times more toxic than 1,3-dichloro-
propane.
The bluegill was also exposed to 1,1-, 1,2-, and 1,3-dichloropropane un-
der similar conditions and yielded 96-hour LC50 values of 97,900, 300,000,
and greater than 520,000 wg/l (Tables 1 and 4), respectively (U.S. EPA,
1978). The 96-hour LC values for fathead minnows tested under flow-
*The reader is referred to the Guidelines for Deriving Water Quality
Criteria for the Protection of Aquatic Life and Its Uses in order to better
understand the following discussion and recommendation. The following
tables contain the appropriate data that were found in the literature, and
at the bottom of each table are calculations for deriving various measures
of toxicity as described in the Guidelines.
B-l
-------
through conditions with measured concentrations are 139,300 and 131,100 wg/1
for 1,2-dichloropropane and 1,3-dichloropropane, respectively.
From these tests it appears that toxicity generally decreases as the
distance between the chlorine atoms increases with 1,2- being less toxic
than 1,1-dichloropropane. This was true for Daphnia magna also. Dawson, et
al. (1977) reported a 96-hour LC50 value of 320,000 yg/l for bluegill ex-
posed to 1,2-dichloropropane; this result is similar to that previously men-
tioned for that species.
The 96-hour LC5Q value for 1,3-dichloropropene is 6,060 yg/1 for blue-
gill (U.S. EPA, 1978). This LC5Q value is approximately two orders of
magnitude lower than that for 1,3-dichloropropane. ^
Mysidopsis bahia, the only saltwater invertebrate species acutely test-
ed, was more sensitive than the fishes (Table 1). For mysid shrimp, 1,3-di-
chloropropene (96-hour LC5Q . 790 vg/1) was 13 times more toxic than 1,3-
dichloropropane (96-hour LC5Q =» 10,300 ug/1); this is in agreement with
the conclusion drawn from the data (Table 1) for Daphnia magna.
The 96-hour LC5Q values (Table 1) were 240,000 tfg/l for the tidewater
silverside and 1,2-dichloropropane (Dawson, et al. 1977); for the sheepshead
minnow the values were 86,700 yg/1 for 1,3-dichloropropane and 1,770 yg/1
for 1,3-dichloropropene (U.S.EPA, 1978). The LC5Q value for 1,3-dichloro-
propane is 49 times greater than that for 1,3-dichloropropene. The LC5Q
value for 1,2-dichloropropane and the tidewater silverside is much greater
than those for 1,3-dichloropropane and 1,3-dichloropropene and the sheeps-
head minnow, but it is impossible to tell whether the difference is due to
different toxicities of the chemicals or responses of the species.
Chronic Toxicity
Embryo-larval tests have been conducted with the fathead minnow and 1,2-
and 1,3-dichloropropane and 1,3-dichloropropene (Table 2). As was true in
B-2
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the acute toxicity tests, the propene was much more toxic. Two tests were
conducted with 1,2-dichloropropane and the chronic values are 60,000 ug/l
(U.S. EPA, 1978) and 8,100 ug/l (U.S. EPA, 1980). No cause for this differ-
ence is known. The chronic values for 1,3-dichloropropane and 1,3-dichloro-
propene and the fathead minnow are 5,700 and 244 ug/l, respectively. As was
found with the acute toxicity data, 1,3-dichloropropene was much more toxic
than 1,3-dichloropropane.
Only one study on chronic toxicity of dichloropropanes and dichloropro-
penes to saltwater organisms using measured concentrations has been found
(Table 2). In a life-cycle study with the mysid shrimp, the chronic value
for 1,3-dichloropropane was 3,040 ug/l (U.S. EPA, 1978). Using this datum
and that in Table 1 from the same study, an acute-chronic ratio of 3.4 is
obtained.
An embryo-larval test with the sheepshead minnow and 1,2-dichloropropane
has been conducted (U.S. EPA, 1978); however, the test concentrations were
not measured. The highest no effect concentration was 82,000 ug/l and there
was a significant effect on growth at 164,000 ug/l (Table 4).
Plant Effects
For 1,3-dichloropropene, the 96-hour EC™ values, based on chlorophyll
a^ and cell numbers of the freshwater alga, Selenastrum capricornutum, were
4,950 and 4,960 ug/l, respectively (Table 3). The respective values for
1,3-dichloropropane were 48,000 and 72,200 u9/l- Thus the propene is much
more toxic than the propane, as was true with the fish and invertebrate spe-
cies.
The saltwater alga, Skeletonema costatum, was as sensitive to 1,3-di-
chloropropene (Table 3) as fishes and mysid shrimp. The 96-hour EC50
value for growth, based on concentrations of chlorophyll £ in culture, was
1,000 ug/l. The EC50 calculated from cell numbers was 1,040 ug/l.
B-3
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As with fishes and mysids, 1,3-dichloropropane was less toxic than 1,3-
dichloropropene to Skeletonema costatum. The 96-hour EC™ value from data
for chlorophyll a^was 65,800 yg/1; for cell number it was 93,600 yg/1.
There were no data reported in the literature on effects of dichloropro-
panes or dichloropropenes on freshwater or saltwater vascular plants.
Miscellaneous
In a test conducted on a mixed assemblage of emerald shiners and fathead
minnows exposed to 1,3-dichloropropene (Scott and Wolf, 1962), 100 percent
of the fish survived three days at 1,000 yg/1, and none survived at 10,000
yg/1 (Table 4). This is in general agreement with the value of 6,060 yg/1
for the 96-hour LCgo value for the bluegill (U.S. EPA, 1978).
Summary
There may be a general pattern of decreased acute toxicity as the dis-
tance between the chlorine atoms increases for the dichloropropanes and two
freshwater species. The 48-hour EC5Q values for Daphnia magna ranged from
23,000 to 282,000 ug/1 for 1,1-, 1,2-, and 1,3-dichloropropane. For the
same sequence of chemicals, the 96-hour LC5Q values for the bluegill range
from 97,900 to greater than 520,000 yg/1. Chronic values for the fathead
minnow were 60,000 and 8,100 yg/1 for 1,2-dichloropropane and 5,700 yg/1 for
1,3-dichloropropane. The lowest 96-hour ECgQ values for the alga, Sele-
nastrum capricornutum, were 4,950 and 48,000 yg/1 for 1,3-dichloropropene
and 1,3-dichloropropane, respectively. In both acute and chronic tests with
freshwater organisms, 1,3-dichloropropene was one to two orders of magnitude
more toxic than 1,3-dichloropropane.
Most of the saltwater data are for 1,3-dichloropropane and 1,3-dichloro-
propene. The propene was much more toxic to the mysid shrimp and sheepshead
minnow, with 96-hour LC5Q values of 790 and 1,770 yg/1, respectively, than
B-4
-------
the propane with 96-hour LC values of 10,300 yg/1 for the shrimp and
86,700 yg/1 for the minnow. The chronic value for 1,3-dichloropropane and
the mysid shrimp was 3,040 yg/1, which provides an acute-chronic ratio of
3.4. The saltwater alga, Skeletonema costatum, had 96-hour EC™ values of
1,000 and 1,040 yg/1 for 1,3-dichloropropene and 65,800 and 93,600 yg/1 for
1,3-dichloropropane.
CRITERIA
The available data for dichloropropanes indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low as 23,000
and 5,700 yg/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for dichloropropene indicate that acute and chronic
toxicity to freshwater aquatic life occur at concentrations as low as 6,060
and 244 yg/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for dichloropropane indicate that acute and chronic
toxicity to saltwater aquatic life occur at concentrations as low as 10,300
and 3,040 yg/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
The available data for dichloropropene indicate that acute toxicity to
saltwater aquatic life occurs at concentrations as low as 790 yg/1 and would
occur at lower concentrations among species that are more sensitive than
those tested. No data are available concerning the chronic toxicity of
dichloropropene to sensitive saltwater aquatic life.
B-5
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Table 1. Acute values for dlchloropropanes-dlchloropropones
DO
Species
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
C 1 adoceran.
Daphnla magna
Cladoceran,
Daphnla magna
Fathead minnow.
Plmep hales promelas
Fathead minnow.
PI map hales promelas
Blueglll,
Lepomls macrochirus
Blueglll,
Lepomls macrochirus
Blueglll,
Lepomls macrochirus
Blueglll,
Lepomls macrochirus
Mysld shrimp.
Mysldopsls bah la
Mysld shrimp,
Mysldopsls bah la
Method*
S, U
S, U
S, U
S, U
FT, M
FT, M
S, U
S, U
S, U
S, U
S, U
S, U
Chemical
FRESHWATER
1,1-dlchloro-
propane
1,2-dlchloro-
propane
1,3-dlchloro-
propane
1,3-dlchloro-
propene
1,2-dlchloro-
propane
1,3-dlchloro-
propane
1, l-dichloro-
propane
1,2-dlchloro-
propane
1,2-dlchloro-
propane
1,3-dlchloro-
propene
SALTWATER
1,3-dlchloro-
propene
1,3-dlchloro-
propane
LC50/EC50
-------
Table 1. (Continued)
Species Method*
Sheepshead minnow, S, U
Cyprlnodon varlegatus
Sheepshead minnow, S, U
Cyprlnodon varlegatus
Tidewater si Ivors I de, S, U
Menidia beryl Una
Chemical
SALTWATER
1,3-dlchloro-
propene
1,3-dlchloro-
propane
1,2-dlchloro-
propane
LC50/EC50 Species Acute
(ug/l) Value (ug/l) Reference
SPECIES
1,770 1,770 U.S. EPA, 1978
86,700 86,700 U.S. EPA, 1978
240,000 240,000 Dawson, et al. 1977
* S = static, FT = flow-through, U = unmeasured, M = measured
No Final Acute Values are calculable since the minimum data base requirements are not met.
W
1
-4
-------
Table 2. Chronic values for dlchloropropanes-dlchloropropenes
Cd
I
en
Species
Method*
Chemical
Chronic
LlHits Value
(tig/1) (ug/l)
Reference
Fathead minnow, E-L
Plmephales promelas
Fathead minnow, E-L
Plmephales promelas
Fathead minnow, E-L
Plmephales promelas
Fathead minnow, E-L
Plmephales promelas
Mysld shrimp, LC
Mysldopsls bah la
* E-L = embryo- larval, LC = partial
Species
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Mysld shrimp,
Mysldopsls bah la
FRESHWATER SPECIES
1,2-dlchloro- 40,000- 60,000
propane 91,000
1,2-dlchloro- 6,000- 8,100
propane It, 000
1,3-dlchloro- 4,000- 5,700
propane 8,000
1,3-dlchloro- 180- 244
propene 330
SALTWATER SPECIES
1,3-dlchloro- 2,200- 3,040
propane 4,200
life cycle or full life cycle
Acute-Chronic Ratio
Chronic Acute
Value Value
Chemical (ug/l) (ug/l)
1,2-dlchloro- 8,100 139,300
propane
1,2-dlchloro- 60,000 139,300*
propane
1,3-dlchloro- 5,700 131,100
propane
1,3-dlchloro- 3,040 10,300
propane
U.S. EPA, 1978
U.S. EPA, 1980
U.S. EPA, 1980
U.S. EPA, 1978
U.S. EPA, 1978
Ratio
17
2.3
23
3.4
* This acute value Is from a different study (ERL-D, 1980) but was used here because the study (U.S. EPA,
1978) that provided the chronic value of 60,000 ug/l did not Include an acute test with this species.
-------
Table 3. Plant values for dIchIoropropanes-dIchIoropropenes (U.S. EPA* 1978)
CXI
I
ID
Species
Alga,
Selenastrum capricornutum
Alga,
Selenastrum capricornutum
Alga,
Selenastrum capricornutum
Alga,
Selenastrum capricornutum
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Alga,
Skeletonema costatum
Chemical
FRESHWATER
1,3-dlchloro-
propene
1,3-dlch loro-
propene
1,3-dlchloro-
propane
1,3-dlch loro-
propane
SALTWATER
1,3-dlchloro-
propene
1,3-dlch loro-
propene
1,3-dlchloro-
propane
1,3-dlchloro-
propane
Effect
MMMBMHWK
SPECIES
Ch lorophy 1 1 a
96- hr EC50
Cel 1 numbers
96-hr EC50
Ch lorophy 1 1 a
96-hr EC50
Cel 1 numbers
96-hr EC50
SPECIES
Ch lorophy 1 1 a
96-hr EC50
Cel 1 number
96-hr EC50
Ch lorophy 1 1 a
96-hr EC50
Cel 1 number
96-hr EC50
Result
(pg/D
4,950
4,960
48,000
72,200
1,000
1,040
65,800
93,600
-------
Table 4. Other data for dlchloropropanes-dlchloropropenes
Species
Mixed group of
Emerald shiner,
Nltropls ather I noIdes
and
Fathead minnow,
Plmephales promelas
Blueglll,
Lepomls macrochIrus
Chemical
1,3-dlchloro-
propene
1,3-dlchloro-
propane
Duration Effect
FRESHWATER SPECIES
3 days
96 hrs
Mortality
LC50
Result
lyg/D Reference
100* survl- Scott & Wolf, 1962
val at 1,000
100* mortal-
ity at 10,000
>520,000 U.S. EPA, 1978
I
I-1
o
Sheepshead minnow,
Cyprlnodon varlegatus
1,2-dlchloro-
propane
SALTWATER SPECIES
33 days
Growth
Inhibition
164,000 U.S. EPA, 1978
-------
REFERENCES
Dawson, G.W., et al. 1977. The acute toxicity of 47 industrial chemicals
to fresh and saltwater fishes. Jour. Hazard. Mater. 1: 303.
Scott, C.R. and P.A. Wolf. 1962. The antibacterial activity of a series of
quaternaries prepared from hexamethylenetetramine and halohydrocarbons.
Appl. Microbiol. 10: 211.
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.
U.S. EPA. 1980. Unpublished laboratory data. Environmental Research Labo-
ratory - Duluth.
-------
Mammalian Toxicology and Human Health Effects
INTRODUCTION
For purposes of discussion in this document, "dichloropropane"
refers to 1,2-dichloropropane and will be abbreviated "PDC" (for
propylene dichloride); "dichloropropene" refers to 1,3-dichloro-
propene and will be abbreviated "DCP." In the case of the latter,
the cis- or trans- isomer will be designated when known. Lack of
such designation will indicate lack of further information on spe-
ciation or that a mixture of the two isomers is involved.
PDC and DCP are used primarily as soil fumigants, alone or in
combination. PDC is also used as a solvent and a chemical inter-
mediate, though comparative data concerning quantities utilized for
pesticide and nonpesticide purposes were not found. D-D^is the
Shell trademark for a combination preparation. The published anal-
wj. ui.^a t/i.=t/«i.»v.J.vy.. »-- .j , — — - ...... ---- -- ------- is the
Dow trademark for DCP. De Lorenzo, et al. (1977) described muta-
genicity studies with Telenet containing 30 percent of each isomer
of DCP and 20 percent DCP. Telone 2 described by Nater and
Gooskens (1976) contains about 92 percent DCP and 3 to 5 percent
PDC. PDC has also been marketed in combination with chlorpicrin;
DCP has been marketed in combination with ethylene dibromide and
carbon tetrachlor ide (Dowfume EB-5^0.
Both PDC and DCP are volatile. The extent of this volatility
is, as will be seen, an important consideration for interpretation
of toxicological data and establishment of water quality criteria.
C-l
-------
TABLE 1
Published Analytical Data on D-D
Soil Fumigant
O
to
1,2-Dichloropropane
Other Chlorinated
Hydrocarbons
Composition (%)
1,
3-Dichloropropene
cis-
trans-
Martin &
Worthing
(1974)
nit 50
Spencer
(1973)
60-66
30-33
30-33
De Lorenzo,
et al.
(1977)
40
Nater &
Gooskens
(1976)
53
30-35
a
27
20
+, present but quantity not indicated
JOther chlorinated hydrocarbons reported include one or more of: 3,3-dichloropropene;
2,3-dichloropropene; 1,2-dichloropropene; 2,2-dichloropropane; 1,2,3-trichloropropane;
epichlorohydrin; allyl chloride.
-------
Stanford Research Institute (1975), in a study for the National
Science Foundation, reported that 60 million pounds per year of a
mixture of DCP/PDC were produced for use as a soil fumigant. Thus,
there is a potential for contamination of water and food via the
soil.
EXPOSURE
Ingestion from Water
Dichloropropane and dichloropropene can enter the aquatic en-
vironment as discharges from industrial and manufacturing pro-
cesses, as runoff from agricultural land, and from municipal ef-
fluents. These compounds have been identified but not quantified
in New Orleans drinking water (Dowty, et al. 1975). The National
Academy of Sciences' Safe Drinking Water Committee (1977) lists
both PDC and DCP as organic contaminants found in finished drinking
water, with no available information on chronic toxicity and with
the highest concentration in finished water of 1.0 jug/1 for each
compound.
Ingestion from Food
A bioconcentration factor (BCF) relates the concentration of a
chemical in aquatic animals to the concentration in the water in
which they live. The steady-state BCFs for a lipid-soluble com-
pound in the tissues of various aquatic animals seem to be propor-
tional to the percent lipid in the tissue. Thus, the per capita in-
gestion of lipid-soluble chemical can be estimated from the per
capita consumption of fish and shellfish, the weighted average per-
cent lipids of consumed fish and shellfish, and a steady-state BCF
for the chemical.
C-3
-------
Data from a recent survey on fish and shellfish consumption in
the United States was analyzed by SRI International (U.S. EPA,
1980). These data were used to estimate that the per capita con-
sumption of freshwater and estuarine fish and shellfish in the
United States is 6.5 g/day (Stephan, 1980). In addition, these
data were used with data on the fat content of the edible portion of
the same species to estimate that the weighted average percent
lipids for consumed freshwater and estuarine fish and shellfish is
3.0 percent.
When no measured steady-state bioconcentration factor (BCF) is
available for any compound, the equation "Log BCF = (0.85 Log P) -
0.70" can be used (Veith, et al. 1979) to estimate the steady-state
BCF for aquatic organisms that contain about 7.6 percent lipids
(Veith, 1980) from the octanol/water partition coefficient (P). The
measured log P value was obtained from Hansch and Leo (1979). When
no measured value could be found, a calculated log P value was ob-
tained using the method described in Hansch and Leo (1979). The
adjustment factor of 3.0/7.6 = 0.395 is used to adjust the estimat-
ed BCF from the 7.6 percent lipids on which the equation is based to
the 3.0 percent lipids that is the weighted average for consumed
fish and shellfish in order to obtain the weighted average biocon-
centration factor for the edible portion of all freshwater and
estuarine aquatic organisms consumed by Americans (Table 2).
Inhalation
The atmospheric levels of PDC and DCP are not known. However,
the possible sources of entry of these compounds to the atmosphere
C-4
-------
TABLE 2
Estimated BCFs for Isomers of PDC and DCP
Compound
Log P
Meas. Calc.
Estimated
Steady State
BCF
Weighted
Average BCF
1,1-Dichloropropane
1,2-Dichloropropane
1,3-Dichloropropane
2,2-Dichloropropane
1,1-Dichloropropene
2,3-Dichloropropene
3,3-Dichloropropene
1,2-Dichloropropene
(cis- and trans-)
1,3-Dichloropropene
(cis- and trans-)
2.00
2.34
2.02
2.34
2.67
1.91
1.79
2.07
1.63
19.4
10.4
10
19.4
37.1
8.38
6.62
11.5
4.84
7.66
4.11
3.95
7.66
14.7
3.31
2.61
4.54
1.91
C-5
-------
a-re from the manufacture of commercial fumigants, the production of
oil and fat solvents, the agricultural use of fumigants, and from
the use of PDC and DCP in drycleaning and degreasing processes.
The exact amounts of PDC and DCP which each of the sources contrib-
ute to the atmosphere could not be ascertained.
Fumigant mixtures of PDC and DCP are applied to the soil in
liquid form, usually by means of a chisel applicator. Small
amounts of these mixtures escape into the atmosphere by natural
diffusion up through the soil profile, and some may leak into the
atmosphere from the soil surface through inadequately sealed chisel
shank holes. An estimate of the total amount of cis-DCP lost to the
atmosphere after a typical application of Telone^ to a 30.5 cm
depth in a warm, moist, sandy loam soil would amount to approxi-
mately 5 to 10 percent (Thomason and McKenry, 1973). The Cali-
fornia State Department of Agriculture reported that in 1971 ap-
proximately 1,285 metric tons of pesticide containing DCP were used
in that state. It can be estimated that approximately 72 tons, or 8
percent, of DCP were lost to the atmosphere (Calif. State Dep.
Agric. 1971).
Since levels of PDC and DCP have not been measured in the
atmosphere, it is impossible to determine the amounts of these com-
pounds that could be inhaled by the general public. There appears
to be an occupational risk to workers who handle these compounds,
although information on actual exposure levels is not available in
the published literature.
06
-------
dermal
Dermal exposure to PDC and DCP is of concern to people who
must work with these compounds. This is especially true for the
agricultural workers who must mix and apply these compounds to the
fields.
PHARMACOKINETCS
No data were available which deal with the absorption, distri-
bution, biotransformation, or elimination of PDC or DCP in humans.
Only one report was found which deals with the pharmacokinetics of
these compounds (Hutson, et al. 1971). This report deals primarily
with the retention potential of the compounds; the presentation of
data on which a pharmacokinetic model could be based is limited.
The investigators administered PDC and the cis- and trans-
isomers of DCP to rats. For each of the compounds, six rats (200 to
250 g, Carworth Farm E strain) of each sex were dosed via stomach
tube with 0.5 ml of arachis oil solution of 1,2-dichloro-
(1-14C)propane (0.88 mg, 8.5 uCi), cis-l,3-dichloro(2-14C)propene
(2.53 mg, 7.68uCi), or trans-l,3-dichloro(2-14C) propene (2.70
mg, 8.50 juCi). The excretion of radioactivity as percent of the
administered dose was determined in the urine, feces, and expired
air of these animals at 24-hour intervals over a 4-day period. The
animals were sacrificed after the fourth day following the admin-
istration of the compounds, and the radioactivity remaining in
their carcasses was measured.
Data resulting from the study are shown in Tables 3 and 4. The
authors claim that 80 to 90 percent of administered radioactivity
was eliminated within the first 24 hours. This would include the
C-7
-------
TABLE 3
Rates of Excretion of Radioactivity from Rats After the Oral
Administration of Three Components of D-D™*
O
I
CO
Excretion of radioactivity (% of administered dose)
in 24-hr periods (after administration)
Compounds
1, 2-Dichloropropane
cis-1, 3-Dichloropropene
trans-l,3-Dichloropropene
1, 2-Dichloropropane
cis-1, 3-Dichloropropene
trans-1, 3-Dichloropropene
Sex
M
F
M
F
M
F
M
F
M
F
M
F
0-24
48.5 + 5.23
51.9 + 1.59
81.3 + 2.76
80.3 + 5.34
54.6 + 1.92
58.7 ± 1.08
5.0 + 2.66
3.8 + 0.95
2.0 + 0.38
1.4 + 0.43
1.3 + 0.37
1.9 + 0.24
— „ . .
24-48
1.9 + 0.45
1.8 + 0.22
1.9 + 0.21
1.2 + 0.29
0.6 + 0.06
1.1 + 0.16
0.7 + 0.10
0.7 + 0.12
0.8 + 0.28
0.2 + 0.04
0.2 -f 0.11
0.2 + 0.10
i '
48-72
Urine
0.5 + 0.12
0.4 + 0.06
0.6 + 0.14
0.4 + 0.23
0.3 + 0.04
0.5 + 0.13
Faeces
0.9 + 0.56
0.2 + 0.02
0.3 + 0.14
0.1 + 0.03
0.4 + 0.15
0.2 + 0.15
72-96
0.2 + 0.03
0.3 + 0.05
0.3+ 0.06
0.4 + 0.23
0.1 + 0.02
0.2 + 0.09
0.2 + 0.08
0.2 + 0.02
0.2 + 0.08
0.1 + 0.05
0.1 + 0.05
0.1 + 0.02
Total
(0-96 hr)
51.1 + 5.27
54.4 + 1.48
84.1 + 2.94
82.3 + 5.18
55.6 + 1.90
60.5 + 1.00
6.8 + 2.61
4.9 + 1.07
3.3 + 0.53
1.8 + 0.42
2.0 + 0.28
2.4 + 0.26
*Source: Hutson, et al. 1971.
-------
TABLE 4
Recoveries of Radioactivity from Rats in the 4 Days Following Oral
Administration of Three Components of D-D
(percent of administered dose)
[RJ
o
i
Recovery of radioactivity
Compounds
Sex
Urine
Faeces
Exhaled Air
Carbon
Dioxide**
1 , 2-Dichloropropane
cis-1, 3-D ichloropropene
trans-l,3-Dichloropropene
M
F
M
F
M
F
51.
54.
84.
82.
55.
60.
1 +
4 +
1 +
3 +
6 +
5 +
5.27
1.48
2.94
5.18
1.90
1.00
6.8
4.9
3.3
1.8
2.0
2.4
+ 2.
+ 1.
+ 0.
+ 0.
+ 0.
+ 0.
61
07
53
42
28
26
___
19.3
5.3
2.4
22.7
24.4
_
(5)
(3)
(3)
(3)
(3)
Other volatile
radioactivity**
— — —
23.1
1.4
3.5
—
(5)
(2)
-
(2)
*Source: Hutson, et al. 1971.
**Values given are means for the numbers of animals indicated in parentheses.
indicated otherwise, values given are the means jfSEM for groups of six rats.
Except where
-------
radioactivity in the expired air, though the data for that fraction
for the first 24 hours were not given.
If 80 percent of the administered dose is eliminated in 24
hours, this would mean a total elimination constant of approxi-
mately 0.07 hr~ . Approximately 50 percent of the administered
dose of PDC and trans-DCP was eliminated by the urine in 24 hours.
This would represent an elimination constant for urine of approxi-
mately 0.03 hr . These compounds, on the basis of their physical
properties, should distribute in total body water, in a rat a com-
pound distributed in total body water with no accompanying storage
or biotransformation would have a urinary elimination constant of
approximately 0.50 hr"1. Thus, the decreased clearance seen is due
either to the renal tubular reabsorption (decreased clearance), in-
corporation into virtual volume of distribution (increased apparent
volume of distribution), or both. The latter is the most likely,
with compensation occurring by biotransformation. In the case of
cis-DCP, the participation of biotransformation is more evident.
EFFECTS
Dichloropropane
Acute, Subacute, and Chronic Toxicity
The acute LD5Q values which have been obtained for PDC and re-
lated compounds are shown in Table 5.
The earliest reference to the acute oral toxicity of the di-
chloropropanes in mammals was reported in a study of the anthel-
mintic action of orally administered dichloropropanes in dogs
(Wright and Schaffer, 1932). An oral dose of 5,700 mg PDC per kg
body weight caused loss of coordination and staggering 15 minutes
C-10
-------
TABLE 5
List of W>sos for Dichloropropane and Dichloropropene
Compound Route
1,2-Dichloropropane Inhalation
Oral
Permal
1,1-Dichloropropane Oral
Dermal
„ 1 ,3-Dichloropropene-l Inhalation
I
M
H- Oral
Dermal
2,3-Dichloro-l-propene Oral
Dermal
D-D® (Nematocide) Inhalation
Oral
Telone^ (Nematocide) Oral
Species
Rat
Rat
Rat
Guinea
Pig
Rabbit
Rat
Rabbit
Rat
Mice
Rat
Mice
Rabbit
Rat
Rabbit
Rat
Rat
Mice
Rat male
Rat female
LD5Q Value
9224 mg/m3
2200 rog/kg
2200 mg/kg
2000 to
4000 mg/kg
10,200 mg/kg
6500 mg/kg
16,400 mg/kg
4530 mg/m3
140 + 25 mg/kg
300 + 27 mg/kg
2100 + 260 mg/kg
320 mg/kg
1930 mg/kg
4530 mg/kg
140 + 25 mg/kg
300 + 27 mg/kg
713 mg/kg
470 mg/kg
Notes
8 hr exposure - 3/6
mortality
Carworth-Wistar strain*
Russian Paper
Lethal dose
Single dose skin
penetration
Carworth-Wistar strain*
Single dose skin
penetration
Cumulative high acute
toxiclty
Single dose skin
penetration
Carworth-Wistar strain*
Single dose skin
penetration
Long-Evans strain
Long-Evans strain
Long-Evans strain
Reference
Smyth, et al. 1969
Smyth, et al. 1969
Ekshtat, et al. 1975
Anon. 1967
Smyth, et al. 1969
Smyth, et al. 1954
Smyth, et al. 1954
Hine, et al. 1953
Mine, et al. 1953
liine, et al. 1953
Hine, et al. 1953
Hine, et al. 1953
Smyth, et al. 1962
Smyth, et al. 1962
Hine, et al. 1953
Hine, et al. 1953
Hine, et al. 1953
Torkelson & Oyen, 1977
Torkelson & Oyen, 1977
*Single dose oral toxicity after 14 days.
-------
after administration, complete lack of coordination after 90 min-
utes, followed by death 3% hours after administration. An oral
dose of 3,500 mg DCP per kg body weight caused staggering, partial
narcosis, and death within 24 hours. The dogs killed by the oral
administration of the dichloropropanes exhibited hypostatic con-
gestion of the lungs, congestion of the kidneys and bladder, and
hemorrhages in the stomach and respiratory tract. Pathologically
the liver showed passive congestion and severe cloudy swelling,
accumulation of large fat droplets in some lobules, and marked
deposition of bile pigments around the central veins. The kidneys
showed severe passive congestion and degeneration of the tubular
epithelium. Oral doses as low as 350 mg of dichloropropane per kg
body weight caused moderately severe lesions in the liver, gastro-
intestinal tract, and kidneys (Wright and Schaffer, 1932).
A series of inhalation toxicology studies by Heppel and his
coworkers provide some information as to the relative toxicity of
PDC. Initial studies (Heppel, et al. 1946) were done with rats,
mice, guinea pigs, and rabbits (and dogs at 1,000 ppm) utilizing
daily 7-hour exposure periods and a concentration range of 1,000 to
2,200 ppm. A concentration of 2,200 ppm was lethal to over 50 per-
cent of the animals of all four species after up to eight expo-
sures. Mice were the most sensitive, with 10 of 11 dying before the
completion of one exposure period. In addition, animals were ex-
posed to 1,600 ppm of PDC, but the data are no more revealing than
that already presented.
C-12
-------
Gross effects observed in the animals included weight loss,
CNS depression (cortical and medullary), rales, and neuromuscular
weakness. Prothrombin time, BSP excretion, total plasma protein,
A/G ratio, BUN, and serum phosphate were not altered in the dogs
which died after exposure to 1,000 ppm. Hematological studies in-
dicated no changes except for "somewhat lower" red cell counts and
hemoglobin in exposed rabbits.
Gross and histopathological examination revealed a range of
liver abnormalities from visceral congestion to fatty degeneration
to extensive multilobular areas of coagulation necrosis. Other
pathological effects observed among animals from all concentrations
included: renal tubular necrosis and fibrosis, splenic hemosidero-
sis, pulmonary congestion, bronchitis, pneumonia, and fatty degen-
eration in the heart. Subsequent studies utilizing 2,200 ppm were
performed (Highman and Heppel, 1946) to obtain further pathological
data. These studies served to further document the earlier obser-
vations.
In another inhalation study (Heppel, et al. 1948), rats,
guinea pigs, and dogs were exposed to 400 ppm of PDC for 128 to 140
daily 7-hour periods (given five days per week). The only effect
observed was a decreased weight gain by rats. However, considering
the pharmacokinetic data discussed earlier, it may be that, by
utilizing a five day per week schedule, the investigators were not
attaining the prolonged exposure they might have anticipated.
Mice were then exposed in the same fashion. As in the pre-
vious study, mice (C57) were more sensitive to PDC, and apparent
C-13
-------
treatment-related "slight fatty degeneration of the liver" was ob-
served.
Sidorenko, et al. (1976) studied the effects of the continuous
inhalation of 1 and 2 mg PDC/1 air in albino male rats (200 to
400 g). Blood acetylcholinesterase and blood catalase activities,
red and white blood cell counts, hemoglobin, and animal weight were
measured after 2, 4, 24, 48, 72, and 96 hours, and after 6 and 7
days of continuous exposure. Histopathological examination of the
liver and kidneys, determination of ribonocleic acid, glycogen,
lipids, oxidation process (succinate dehydrogenase activity), DPN-
diaphorase, acid and alkaline phosphatase, and quantitative evalua-
tion of the liver DNA were performed on the exposed animals. Sig-
nificant changes in catalase and cholinesterase activity and thres-
hold index were observed as early as four hours after the start of
the inhalation of 1.0 mg PDC/1. Significant changes occurred in
all of the above mentioned tests after 24 hours of continuous expo-
sure to 1.0 mg PDC/1 air.
The livers of rats that were continuously exposed to 1.0 mg
PDC/1 air for seven days were examined histologically and showed
protein and fat dystrophy, suppression of enzyme activity, and
decreased ribonucleoproteins centralized in the centrolobular sec-
tions. Cells of peripheral sections of lobules showed fewer chang-
es and underwent displacements of an adaptational nature in the
form of hyperplasia and hypertrophy of cellular and intracellular
structures. The number of unicellular polyploidal hepatocytes
increased significantly, whereas the number of binuclear cells was
reduced. In some instances the amount of ploidy equaled 16n.
C-14
-------
These adaptive changes were accompanied by increased ribonucleopro-
teins and increased enzyme activity on the periphery of the hepato-
cytes. In the kidney, as in the liver, regions of greater or lesser
sensitivity to PDC were found, and adaptational changes were found
in the distal segments of the nephron which showed increased activ-
ity (Sidorenko, et al. 1976).
The effect of PDC on the functional state of the rat was fur-
ther demonstrated by Kurysheva and Ekshtat (1975). Blood serum
cholesterol, beta-lipoproteins, and gamma-globulin levels in-
creased after the 10th day of daily oral doses of 14.4 and 360 mg
PDC per kg body weight. By day 20 of dosing, the serum cholin-
esterase was inhibited, whereas the fructose-1-monophosphate aldo-
lase, alanine transaminase, and asparagine transaminase were in-
creased. After 30 days of dosing the alanine transaminase was in-
hibited.
In the range-finding studies of Smyth, et al. (1954, 1962,
1969), acute inhalation toxicity studies of new chemical compounds
were performed to indicate the comparative hazards of handling
these compounds and the degree of care necessary to protect the ex-
posed workmen* The studies consisted of exposing groups of six
male Carworth-Wistar rats (90 to 100 g body weight) to either sat-
urated vapor or known vapor concentrations of compounds for a known
period of time and then observing the mortality of the exposed rats
during a 14-day observation period. It was recorded that a group
of six rats could survive a 10-minute exposure in a saturated vapor
atmosphere of PDC with no death during the 14-day observation per-
iod. In another exposure study, one 8-hour exposure to 2,000 ppm
C-15
-------
PDC in air killed 3 of 6 rats during the 14-day observation period
(Smyth, et al. 1969). It was found that a group of six rats could
survive an exposure of only two minutes in a saturated vapor atmos-
phere of 1,1-dichloropropane (7,630 mg 1,1-dichloropropane/l air).
One 4-hour exposure to 17.6 mg 1,1-dichloropropane/l air killed 4
of 6 rats within the 14-day observation period (Smyth, et al.
1954).
St. George (1937) described the effects of PDC poisoning in
humans. Symptoms included headache, vertigo, lacrimation, and ir-
ritation of the mucous membrane. Changes in the blood are similar
to those of "marked anemia."
Another case7 report described the acute oral toxicity of PDC
in a 46-year-old man who accidently ingested about 50 ml of a
cleaning solution containing PDC. Within two hours after inges-
tion, he went into a deep coma with mydriasis and hypertonia; after
24 hours he regained consciousness with treatment of artificial
ventilation and osmotic diuresis. However, after 36 hours he went
into irreversible shock and died of cardiac failure with lactic
acidosis and hepatic cytolysis. Necropsy examination showed
centre- and mediolobular acute hepatic necrosis (Larcan, et al.
1977).
Mutagenicity
De Lorenzo, et al. (1977) reported PDC to be mutagenic in j3.
typhimurium strains TA 1535 and TA 100 with or without metabolic
conversion. No such activity was found in TA 1978, TA 1537, or TA
98 (Table 6). This implies missense, but not frameshift mutations.
However, this is further discussed in the section dealing with mu-
tagenic ity of DCP.
C-16
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TABLE 6
Mutagenicity of D-D© , Telone © , PDC and DCP as Determined by the "Ames"
Test With (W) and Without (WO) Liver Microsomal Fraction*
Number of mutant colonies/plate with Salmonella strains
TA 1978
TA 1535
TA 100
O
H-
-4
Compound
/tjA
Telone \~s
D-D® soil
f umigant
cis-DCP
trans-DCP
PDC
Amount/plate
100
250
1
2.5
5
10
500
5
15
25
20
50
100
20
50
100
10
20
50
*jg
ug
mg
mg
mg
mg
jug
mg
mg
mg
ug
pg
W
ug
ug
wg
mg
mg
mg
WO
24
36
45
53
61
15
11
38
80
75
19
90
119
27
68
115
27
38
48
W
115
225
249
270
365
150
123
181
300
446
21
71
131
31
75
91
38
21
15
WO
12
48
75
115
150
78
35
45
151
145
243
680
1210
235
430
925
75
210
411
W
15
59
90
135
220
61
42
61
151
150
77
490
990
109
381
828
81
185
312
WO
178
225
263
425
282
192
125
198
350
470
594
1800
1750
362
1750
1820
220
480
850
W
151
191
242
385
500
212
112
250
450
512
731
2100
1551
650
2200
1500
185
450
920
*Source: De Lorenzo, et al. 1977.
-------
Bignami, et al. (1977) also reported the mutagenicity of PDC
in TA 1535 and TA 100. They studied the induction of point muta-
tions (8-azaguanine resistance) and somatic segregation (crossing
over and nondisjunction) in A. nidulans, using the spot test tech-
nique. PDC was shown to significantly raise the frequency of mu-
tants resistant to 9-azaguanine.
Dragusanu and Goldstein (1975) reported that PDC causes chro-
mosomal aberrations in rat bone marrow. Trace impurities of PDC
were tested and found to be inactive.
Carcinogenicity
In none of the studies described to this point was evidence of
Carcinogenicity observed. However, Heppel, et al. (1948) tried to
induce hepatomas in C3H strain of mice by repeated inhalation of
1.76 mg PDC/1 air. Only 3 of 80 C3H strain mice survived a total of
37 exposure periods and a subsequent observation period of seven
months, at which time the three remaining mice were 13 months of
age. These three mice showed multiple hepatomas histologically
similar to those induced by carbon tetrachloride. The livers of
these mice also showed many large mononuclear cells laden with
lipochrome resembling ceriod. Although inhalation of 1.76 mg PDC/1
air induced hepatomas, too few mice survived the exposures and
observation period to make a statistically valid evaluation. No
hepatomas were observed in control animals.
Dichloropropene
Acute, Subacute, and Chronic Toxicity
Acute LD5Qs for DCP and its isomers are given in Table 5. Most
of the information on the toxicity of DCP comes from a study by
Torkelson and Oyen (1977). Rats were exposed to 3 ppm (13.6 mg/m )
C-18
-------
for periods of 0.5, 1, 2, or 4 hours/day, 5 days/week for 6 months.
Only the rats exposed four hours per day showed an effect, and this
was manifested as cloudy swelling of the tubular epithelium. Fur-
ther studies were done on rats, guinea pigs, and rabbits exposed to
1 or 3 ppm of DCP, 7 hours per day for 125 to 130 days over a 180-
day period. Hematological studies were run midway and near the end
of the study. No changes which could be attributed to the treat-
ment were seen in hematocrit, WBC, hemoglobin, or differential
count. The only effects the authors described which could be
attributed to treatment were cloudy swelling of renal tubular
epithelium in male rats and an increase in liver weight/body weight
ratio in female rats. Some rats were also allowed a 3-month recov-
ery period. After this time no changes attributable to treatment
were observed. In experiments preliminary to these (complete data
not published), rats and guinea pigs were exposed to 50 ppm DCP, 7
hours per day for 19 out of 28 days and 27 out of 39 days. Changes
attributable to treatment for the shorter period were equivocal.
After the longer period, gross examination revealed some liver and
kidney changes (Torkelson and Oyen, 1977). These authors also
cited unpublished data of others indicating liver, kidney, and lung
injury in animals receiving oral doses of DCP in the LD range.
The studies of Torkelson and Oyen (1977) indicate 1 ppm DCP by in-
halation as a no observable adverse effect level (NOAEL). The au-
thors recommend this as a time-weighted threshold limit value (TLV).
Strusevich and Ekshtat (1974) investigated the effects of DCP
on the trypsin, trypsin inhibitor, amylase, and lipase activities
in the blood serum of albino rats. The animals were fed daily doses
C-19
-------
af 0.1, 0.5, and 2.5 mg of DCP per kg body weight for six months.
The results showed that the trypsin activity increased through the
six months of administration, and the activity of trypsin inhibitor
decreased after the second month of administration. The blood
lipase activity permanently increased, and amylase tended to be
reduced.
Kurysheva and Ekshtat (1975) studied the effects of daily oral
doses of DCP on the functional state of the rat liver. They fed
groups of albino rats daily oral doses of 2.2 and 55 mg of DCP per
kg for 30 days. The results showed that by day 30 of administration
the excretory liver function was altered, as evidenced by prolonged
pigment circulation in the blood, raised thymol test values, cho-
lesterol level, and stimulated increase of fructose 1-monophosphate
aldolase.
In human sensory tests, 13.6 mg DCP/m air was detected by 7
of 10 human volunteers who were exposed to 11.6 or 4.5 mg DCP/m
air for 1 to 3 minutes. Some of the volunteers reported fatiguing
of the sense of smell after a few minutes of exposure. Seven of the
ten volunteers were able to detect 4.5 mg DCP/m air, but it was
noticeably fainter (Torkelson and Oyen, 1977).
Mutagenicity
De Lorenzo, et al. (1977) reported that DCP was mutagenic to
S_. typhimurium TA 1535 and TA 100 but not the TA 1978, TA 1538, or
TA 98. Mutagenicity was the same with or without the addition of
liver microsomal fraction. The authors concluded that because the
results are similar to those seen with PDC, the same mechanistic
implications may exist.
C-20
-------
In another study, Neudecker, et al. (1977) found the cis- and
trans- isomers of DCP to give positive results in an assay system
with strains TA 1535, TA 1537, and TA 1538. Both isomers of DCP
were mutagenic to strain TA 1535 with and without microsomal acti-
vation. The cis- isomer was found to be two times more reactive
than the trans- isomer.
Neudecker, et al. (1977) also found a significant difference
in the survival rate of the bacteria exposed to varying concentra-
tion of both isomers. At all concentrations tested, survival rates
of cells exposed to cis-DCP were generally lower than those of bac-
teria exposed to the trans- isomer.
It can be seen from Table 6 that DCP may be about three orders
of magnitude more mutagenic than PDC. Also, it can be seen that
Telone^ and D-D^ (see Table 1 for composition of the products
used in this study) are mutagenic to TA 1535 and TA 100, as might be
expected. However, they are also mutagenic to TA 1978 (in the pre-
sence of the microsomal fraction), indicating a frameshift muta-
tion. In the Criterion Formulation section of this document it is
suggested that mixtures of PDC and DCP may result in a negative
deviation from Raoult's Law. That is, the vapor pressure of the
mixture is lower than the vapor pressure of either individual com-
ponent. The implication is that less evaporation of material may
occur when the mixture is used. Another possibility is that the
presence of one compound results in the forcing of the other
through an alternate, or normally minor, metabolic pathway, leading
to the formation of larger amounts of a normally minor mutagenic
metabolite.
C-21
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Care inogenicity
Van Duuren, et al. (1979) designed a study to evaluate the
carcinogenicity of 15 halogenated hydrocarbons by a multiple bio-
assay procedure. From their studies, the authors have suggested
certain structure/activity relationships concerning carcinogen-
icity and the bioassay procedure. Among the compounds studied was
cis-DCP. All studies utilized 30 male ICR/Ha Swiss mice per group.
The compound was studied by three procedures.
(1) Initiation-Promotion: 122 mg applied once in 0.2 ml
acetone followed 14 days later by 5 jug (in 0.2 ml
acetone) of the tumor promoter, phorbol myristate
acetate (PMA), three times weekly for 428 to 576
days.
(2) Repeated Skin Application: 41 or 122 mg in 0.2 ml
acetone to shaved skin three times weekly for 400 to
494 days.
(3) Subcutaneous Injection: 3 mg in 0.05 ml trioctanoin
injected subcutaneously in the left flank once week-
ly for 538 days.
In the initiator-promoter studies, six papillomas in four mice
were observed. This result was not significantly different from
promotor controls. Repeated skin application revealed three papil-
lomas in three mice for the 122 mg dose; this was not significantly
different from control animals which had no tumors. No tumors were
observed for the animals receiving the 41 mg dose.
In the case of subcutaneous administration, six mice developed
local sarcomas which represent a statistically significant differ-
ence relative to controls (0/100). In none of the studies were
treatment-related remote tumors observed.
C-22
-------
Dichloropropane/Dichloropropene
(mixtures containing at least 10 percent PDC)
Acute, Subacute, and Chronic Toxicity
Acute oral LD5Q values for D-D^ are shown in Table 5. Hine,
et al. (1953) reported gross behavioral responses to lethal and
near lethal doses similar to those seen for PDC and DCP alone.
Gross pathological examination of the rats that died showed dis-
tention of the stomach by fluids and gas and erosion of the gastro-
intestinal mucosa, with occasional hemorrhage. Hemorrhage of the
lungs and fatty degeneration of the liver were occasionally seen in
rats that died several days after administration. The mortality
curve was abrupt; all mice died at the highest dose level (432 mg D-
D^kg), about one-half at the next level (288 mg D-D^/kg), and
only one at the two lowest levels (192 and 132 mg D-D^/kg body
weight). Rats showed the same type of curve.
Hine, et al. (1953) also studied the acute inhalation toxicity
of the commercial product D-D^. They exposed 24 adult Long-Evans
rt>\
strain rats for four hours to concentrations of D-D^ ranging fr'om
@o T5
^,Uww vw «*,-«« ...3 /m . The exposure to D-D caused respira-
tory distress, dyspnea, hypernea, mucous nasal discharge, and lac-
rimation. Dilatation of the capillaries was evident in the ears.
Gross pathological examination of the rats that died from the expo-
sures showed severe edema of the lungs, with varying degrees of in-
terstitial and alveolar hemorrhage, and distention of the stomach
and upper small intestine. Congestion and fatty degeneration of
CR}
the liver also were noted occasionally in animals exposed to D-D^-X
Russian scientists have investigated the effects of low oral
and chronic doses of mixtures of dichloropropanes and dichloro-
C-23
-------
propenes and D-D& in the exocrine function of the rat pancreas,
the central nervous system, the kidney function in rabbits, and the
functional state of the liver (Strusevich and Ekshtat, 1974,
Fedyanina, et al. 1975; Kurysheva, 1974; Kurysheva and Ekshtat,
1975).
Strusevich and Ekshtat (1974) studied the effect of D-D® on
the exocrine function of the pancreas by orally administering doses
of 0.1, 0.6, and 3.0 mg D-D^kg body weight to young male albino
rats daily for six months. These doses of D-D®caused an increase
in trypsin and lipase activities and decreased the trypsin inhibi-
tor activity of the blood.
The percutaneous absorption of the product D-D® was studied
by Hine, et al. (1953). Nineteen rabbits were depilated over the
back and flanks in a cylindrical swath between the fore and hind
legs, immobilized, and a tight-fitting girdle was slipped over the
shaved area. Undiluted D-D®in doses of 1,200 and 4,800 mg/kg body
weight were introduced under the girdle and was allowed to remain
in contact with the skin for 24 hours. The rabbits exhibited de-
creased body movement and depressed respiration. One rabbit re-
ceiving 3,000 mg D-D^kg had developed mucous nasal discharge.
Seven of the ten rabbits receiving the three higher doses of D-D®
died in 8 to 48 hours, and the five rabbits receiving the lowest
dose (1200 mg D-DvS/kg) survived.
Three cases of adverse reactions to D-D^have been reported
in the Netherlands. Three patients had developed symptoms after
several years of repeated exposures to the soil fumigant D-D®
during its application to the fields. Most of the dermal contact
C-24
-------
(R)
was through the feet, caused by the D-D^ dripping inadvertantly
into the shoes of the farmers during the spraying operation. By
patch testing, the existence of a contact allergic sensitivity to
D-D® could be proven in one patient. Patch tests with compounds
related to D-D® suggest that the cause of contact allergy must be
sought in the propene(s) fraction of D-D^X All three patients ex-
hibited an itchy erythematous rash on the arms, face, and ears
following contact with D-D^ (Nater and Gooskens, 1976).
Mutagenicity
The mutagenicity of mixtures of PDC and DCP is discussed in
the previous section.
Carcinogenicit^y
Pertinent data could not be located in the available litera-
ture concerning the carcinogenicity of mixtures of PDC and DCP.
C-25
-------
CRITERION FORMULATION
Dichloropropane (PDC)
PDC has not been adequately tested for carcinogenicity, and
chronic or subchronic ( < 90 days) oral toxicity data are not
available. Based on either the TLV (ACGIH, 1977) or subchronic in-
halation toxicity data (Heppel, et al. 1948), a pharmacokinetic
model or the Stokinger and Woodward (1958) approach might be used
to estimate an oral allowable daily intake (ADI) from which a water
quality criterion could be derived; however, the subchronic inhala-
tion data of Heppel and coworkers (1948) is somewhat ambiguous.
Exposures to 400 ppm (1,867 mg/m3), 7 hours per day for 128 to 140
days were noted to cause slight fatty degeneration of the liver in
mice. However, under similar conditions, concentrations of 1,760
mg/m caused high mortality in mice after 37 exposures. Conse-
quently, the 1,867 mg/m exposure cannot be used as a reasonable
estimate of a lowest observable adverse effect level (LOAEL).
Since the TLV is based primarily on the results of Heppel and co-
workers (1948), the use of the TLV in deriving a criterion would
not be appropriate. In addition, the positive mutagenicity studies
on PDC have become available since the TLV was recommended.
The only other information that might be useful in assessing
potentially hazardous levels of PDC in water is the study by
Kurysheva and Ekshtat (1975), in which changes in serum enzyme
levels were noted in rats after oral doses of 14.4 mg/kg/day for 30
days. Because of the short duration of this study, it cannot be
used to derive a water quality criterion by the existing method-
ology. If a safety factor of 1,000 were applied to this lowest
observable effect level (LOEL), the use of the standard assumptions
C-26
-------
(70 kg human body weight, 0.0065 kg daily fish consumption, 2 1
daily water consumption) and a bioconcentration factor of 4.11
results in a water level of 483 jjg/1.
Dichloropropene (DCP)
DCP has not been adequately tested for carcinogenicity. When
given to rats at daily oral doses of up to 2.5 mg/kg, DCP induced
changes in blood serum enzymes after six months (Strusevich and
Ekshtat, 1974). Daily oral doses of 2.2 and 55 mg/kg/day for 30
days caused changes in the liver function of rats (Kurysheva and
Ekshtat, 1975). Taking the results of Strusevich and Ekshtat
(1974), 2.5 mg/kg/day may be considered a LOEL for rats. However,
the changes in liver function noted by Kurysheva and Ekshtat (1975)
suggest that this may be near or at the LOAEL. Because of this
uncertainty and because of the positive mutagenic activity of DCP
in the absence of a valid test for carcinogenicity, a safety factor
of 1,000 will be used to derive the ADI. Assuming a human body
weight of 70 kg, the ADI is 175 ug (2.5 mg/kg/day x 70 kg - 1000).
Given the bioconcentration factor of 1.91 and assuming a daily con-
sumption of 2 1 of water and 0.0065 kg of fish, the ambient water
quality criterion (C) is 87 wg/1:
_ 175 jug _ _
-
_
~ 2 + (0.0065 x 1.91)-
A major problem with this criterion is that the DCP isomer or
mixture of isomers used by Strusevich and Ekshtat (1974) was not
specified. Although the available acute toxicity data (Table 5) do
not suggest that the 1,3- and 2,3-isomers differ markedly, signifi-
cant differences are apparent in the elimination rates of the cis-
C-27
-------
and trans- forms of 1,3-dichloropropene. The inability to derive
isomer-spec ific criteria, along with the previously discussed lim-
itations of the general DCP criterion, should be considered in the
use of this criterion.
Summary
A valid ambient water quality criterion for PDC cannot be de-
rived. Based on the results of a 30-day oral study in rats, a water
concentration of 483 jug/1 can be calculated.
For DCP, an ambient water quality criterion of 87 jug/I can be
calculated based on a six month oral study in rats. The criterion
can be alternatively expressed as 14.1 mg/1 if exposure is assumed
to be from the consumption of fish and shellfish products alone.
C-28
-------
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