DICHLOROPROPANES/DICHLOROPROPENES
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
DICHLOROPROPANES/DICHLOROPROPENES
CRITERIA
Aquatic Life
1,1-d ichloropropane
The data base for freshwater aquatic life is insuffi-
cient to allow use of the Guidelines. The following recommen-
dation is inferred from toxicity data for saltwater organisms and
1,3-dichloropropane.
For lf1-dichloropropane the criterion to protect fresh-
water aquatic life as derived using procedures other than the
i
Guidelines is 410 u.g/1 as a 24-hour average and the concentration
should not exceed 930 ug/1 at any time.
For saltwater aquatic life, no criterion for 1,1-di-
chloropropane can be derived using the Guidelines, and there are
insufficient data to estimate a criterion using other procedures.
l.f 2-d ichloropropane
The data base for freshwater aquatic life is insuffi-
cient to allow use of the Guidelines. The following recommen-.
dation is inferred from toxicity data for saltwater organisms and
1,3-dichloropropane. r
For 1,2-dichloropropane the criterion to protect fresh-
water aquatic life as derived using procedures other than the
Guidelines is 920 ug/1 as a 24-hour average and the concentration
should not exceed 2,100 ug/1 at any time.
The data base for salt water aquatic life is insuffi-
cient to allow use of the Guidelines. The following recommenda-
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.felon is ^inferred 'from "toxicity data on related chemicals and ;from
data for saltwater and freshwater-organisms.
For 1, 2-dichloropropane the -criterion ,to -prote'ct salt-
water aquatic life as derived using procedures other .than the
.Guidelines is 400 ug/1 as a 24-hour average .and 'the concentration
.should not exceed 910 -ug/1 at any time.
1,3-d ichloropropane
The data base for freshwater aquatic -life-is linsuff i-
.cient to allow use of the-Guidelines. The follow.i'ng recommen-
-dation is inferred from toxicity data forosaltwater^organisms^and
1,3-dichloropropane.
For 1,3-dichloropropane the criterion ^to^protect fresh-
water arquatic life as derived using procedures Bother ..than the
Guidelines is 4,800 ug/1 as a 24-hour average ~and -the -:concentra-
• tion'should not exceed 11,000 ug/1 at .any time.
For 1,3-dichloropropane the -criterion -to ^protect salt-
•water aquatic life as derived .using the Guidelines -is~79 ug/1 as a
~24-r-hour average and the concentration "should :not •exceed ,180 .ug/1
,;at..any time.
1,3-d ichloropropene
For 1,3-dichloropropene the "Criterion -to-protect-fresh-
water aquatic life as derived using .the Guidelines .is 18 ug/1 ss a
24-hour average and the concentration:should notexceed 250 ug/1
.at any time.
The -data base for saltwater aquatic -life is insufficient
to allow use of the Guidelines. The following recommendation .is
inferred from toxicity data for freshwater -organisms.
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For 1,3-dichloropropene the criterion to protect salt-
water aquatic life as derived using procedures other than the
Guidelines is 5.5 ug/1 as a 24-hour average and the concentration
should not exceed 14 ug/1 at any time.
Human Health
For the protection of human health from the adverse effects
of dichloropropanes and dichloropropenes ingested through the con-
sumption of contaminated fish and water, the following criteria
are suggested: dichloropropanes - 203 ug/1; dichloropropenes -
0.63 ug/1.
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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 pro-
cesses (Windholz, 1976). Dichloropropanes and dichloropro-
penes can enter the aquatic environment as discharges from
industrial effluents, by runoff from agricultural land, and
from municipal effluents. These compounds have been detected
in New Orleans drinking water, although they were not quanti-
fied (Dowty, et al. 1975). Most data on persistence, degra-
dation and distribution of dichloropropanes and dichloropro-
penes deal with their presence in soils.
Dichloropropanes and dichloropropenes are liquids at
environmental temperatures that have molecular weights of
112.99 and 110.97, respectively (Weast, 1975). 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 nematocides by Goring
and Hamaker (1972) lists the water solubility at 20°C as 0.27
percent for cis-1,3-dichloropropene and 0.28 percent for
trans-1,3-d ichloropropene.
Mixtures of 1,2-dichloropropane and cis- and trans-1,3-
dichloropropene are used as soil fumigants. When heated to
decomposition, 1,2-dichloropropane emits highly toxic fumes
of phosgene, while 1,3-dichloropropene gives off toxic fumes
of chlorides (Sax, 1975).
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TABLE 1
Boiling Boiling
Dichloropropanes point (decj.C) Density Dichloropropenes point (deg.C) Density
1,1-PDC 88.1 1.132 1,1-DCP 76-77 1.186
1^2-PDC 96.4 1.156 l,2(cis)-DCP
1,3-PDC 120.4 1.188 1,3(trans)-DCP 77 1.182
2,2-PDC 69.3 1.1}2 l,3(cis)-DCP 104.3 1.217
l,3(trans)-DCP 112 1.224
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Dichloropropenes have been shown to undergo photochemi-
cal formation of free radicals (Richerzhagen, et al. 1973).
The cis and trans isomers of 1,3-dichloropropene have under-
gone biodehalogenation by a Pseudomonas species isolated -from
the soil (Belser and Castro, 1971). 1,3-Dichloropropene has
been shown to react with biological materials (cow's milk, •
potatoes, humus-rich soil) to produce 3-chloroallyl methyl
sulfide (Dekker, 1972).
It is determined that both dichloropropanes and di-
chloropropenes, like other pesticides, can be concentrated
from the water column by low trophic-level organisms such as
algae, which in turn can pass these compounds on to higher
animals through the food chain. Specific instances of bioap-
cumulation and bioconcentration of these compounds by members
of the aquatic environment are lacking.
In the non-aquatic environment, movement of dichloropro-
pene and dichloropropane in the soil results from diffusion
in the vapor phase, as these compounds tend to establish an
equilibrium between concentrations in vapor, water and ab- ;
sorbing phases (Leistra, 1970). Degradation of certain of
these compounds can occur in the soil. Van Dijk (1973) re-
ports that cis- and trans-1,3-dichloropropene can be chemi-
cally hydrolyzed in moist soils to the corresponding 3-
chloroalkyl alcohols, which are capable of metabolism to car-
bon dioxide and water by a bacterium (Pseudomonas sp.). Al-
though field applications of 1,3-dichloropropene have shown
between 15 and 80 percent decomposition (Van Dijk, 1973), the
large amount that can be absorbed (80 to 90 percent) can
A-3
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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 dissipation appearing to be volatili-
sation (Roberts and Stoydin, 1976). The persistence.and
.degradation of dichloropropanes and dichloropropenes depends
on.susceptibility to hydrolysis (.Thomason and':MeKen/ry, 1973),
soil types (Leistra, 1970), and temperature (Van Dijk, 1973;
. Thomason and McKenry, 1973).
The actions of dichloropropanes ,;and dichloropropenes on
., living,, organisms seems to depend.upon the .isomer (volatility,
.:sol.ubility, etc.) and the individual organisms. Addition-
;al^.y, judging by the rapid excretion.of dichloropropanes and
. diehloropropenes in rats, it is unlikely that these compounds
>• will., remain and accumulate in-mammals.
Dichloropropanes and dichloropropenes were;both shown to
be- mu.tagenic but differed in degree. However, .both were
shown to have a low tumor causing potential if any at.all.
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REFERENCES
Belser, N.O., and C.E. Castro, 197-1. Biodehalogenation:
metabolism of the nematocides cis-and trans-3-choroallyl
alcohol by a bacterium isolated from soil. Jour. Agric. Food
Chem. 19: 23.
i
Dekker, W.H. 1972. 3-Chorallyl methyl sulfide, a product
from the reaction of 1,3-dichloropropene and biological
materials. Medea, Fac. Andbouwawetensch., Ryksania. Geal.
37: 865.
Dowty, B., et al. 1975. Halogenated hydrocarbons in New
Orleans drinking water and blood plasma. Science 87: 75.
t
Goring, C.A.I., and J.W. Hamaker. 1972. Organic chemicals in
the soil environment. . Environment. Marcel Dekker, Inc., New
York.
i
Lange, N.A. 1952. Lange's handbook of chemistry. 8th ed.
Handbook Publishers, Inc., Sandusky, Ohio.
Leistra, M. 1970. Distribution of 1,3-dichloropropene over
the phases in soil. Jour. Agric. Food Chem. 18: 1124.
Richerzhagen, T., et al. 1973. Photochemical formulation of
free radicals from chlorolefins as studied by electron spin
resonance. Jour. Phys. Chem. 77: 1819.
A-5
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, RvT., and G. Stoydin. 1976\, The degradation of- (Z)-
and (E)-lj3-dichloropropenes and l,2;-dichloropropanes in
sol.l. Pestic. Scl. 7: 3.25.
Sax:, N.I. 1975. Dangerous properties of, industrial
materials. Reinhold Book Corp./ New York;.
TKomason, I.J., and M.V. McKenry. 1973.- Part. I. Movement
and- fate as affected by various conditions' in several, soils.
Ha?lg:ardia 42: 393.
Van: Dijk,, H. 1973. Degradation of 1,3-dichloropropenes? in
s;a±lU». Agror-Ecosys terns 1:. 193.
Wind:ho-l.zr.r M-. , ed. 1976. The Merck Index. 9th. ed-. Merck and
«f Inc.,( Rahway, N.J.
A-6
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
The available freshwater aquatic life data for these two
classes of compounds with one exception are for dichloropropanes.
Where data exist for both 1,3-dichloropropene and 1,3-dichloro-
propane tested under similar conditions, the propene is much more
toxic than the propane.
Acute Toxicity
The bluegill was exposed to 1,1-, 1,2-, and 1,3-dichloro-
propane under similar conditions (Table 1) and yielded unadjusted
96-hour LC50 values of 97,900, 280,000, and greater than 520,000
ug/1 (Table 5), respectively (U.S. EPA, 1978). From these tests
(Table 1) it appears that the toxicity decreases as the distance
between the chlorine atoms increases with 1,2- being less toxic
than 1,1-dichloropropane. Dawson, et al. 1977 reported a 96-hour
LC50 value of 320,000 ug/1 for bluegill exposed under similar
*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
following tables contain the appropriate data that were found in
the literature, and at the bottom of each table are the calcula-
tions for deriving various measures of toxicity as described in
the Guidelines. •
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conditions to 1,2-dichloropropane and this result is similar to
that previously mentioned.
The 96-hour LC50 value for 1,3-dichloropropene is 6,060 ug/1
for bluegill (U0So EPA, 1978). This LC50 value is approximately
two orders of magnitude lower than that for 1,3-dichloropropane,
The Final Fish Acute Values for 1,1- and lf2-dichloropropane
and 1,3-dichloropropene are 14,000, 42,000, and 850 ug/1, respec-
tively.
Daphnia magna is the only invertebrate species tested with
these classes of compounds (Table 2). Under static test condi-
tions the 48-hour EC50 values for 1,1-, 1,2-, and 1,3-dichloropro-
pane were 23,000, 52,500, and 282,000 ug/1, respectively (U.S.
EPA, 1978) o As with the fish, the toxicity decreases with in-
creasing distance between the chlorine atoms. The 48-hour EC50
value for 1,3-dichloropropene under static test conditions is
6,150 ug/1 (UoS. EPA, 1978)„ This compound is many times more
toxic than 1,3-dichloropropane.
Based on data for Daphnia magna, the Final Invertebrate Acute
Values for 1,1-, 1,2-, and 1,3-dichloropropane and 1,3-dichloro-
propene are 930, 2,100, 11,000, and 250 ug/1, respectively. Since
these concentrations are lower than the equivalent concentrations
for fish, they also become the Final Acute Values.
Chronic Toxicity
An embryo-larval test has been conducted (Table 3) with the
fathead minnow and 1,3-dichloropropene. The chronic value (122
ug/1) is obtained by dividing the geometric mean of the limits by
two. After division of this chronic value by the species sensi-
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tivity factor (6.7) a Final Fish Chronic Value of 18 ug/1 is ob-
tained for 1,3-dichloropropene.
No other chronic data are available for any dichloropropane
or other dichloropropene.
Plant Effects
For 1,3-dichloropropene, the 96-hour EC50 values, based on
chlorophyll a_ and cell numbers of the alga, Selenastrum capri-
cornutum, were 4,950 and 4,960 ug/1/ respectively (Table 4). The
respective values for 1,3-dichloropropane are 48,000 and 72,200
ug/1. Thus the propene is much more toxic than the propane, as is
true with the bluegill and Daphnia magna.
Residues
No measured steady-state bioconcentration factors (BCF) are
available for any dichloropropane or dichloropropene. Bioconcen-
tration factors can be estimated for the dichloropropanes using
the octanol-water partition coefficients of 220, 105, and 100 for
1,1-, 1,2-, and 1,3-dichloropropane, respectively. These coeffi-
cients are used to derive estimated BCF's of 35, 20, and 19 for
1,1-, 1,2-, and 1,3-dichloropropane, respectively. An octanol-
water partition coefficient was calculated for 1,3-dichloropropene
to be 43 and this value is used to derive an estimated BCF of 10.
These estimated BCFs for aquatic organisms assume approximately an
eight percent lipid content. If it is known that the diet of the
wildlife of concern contains a significantly different lipid con-
tent, appropriate adjustments in the estimated BCFs should be
made.
B-3
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Ml see 11 aoaeK&u s
Iji a test conducted on a mixe-d assemblage of emerald shiners
and fathead minnows exposed to -lf3-dichloroprop:ene, 100 'percent of
the fish survived three days at 1,000 v.g/1, and none survived at
.10,000 ug/1 (Scott and Wolf, 1962). This is in general agreement
with the value of 6,060 ug/1 for the 96-hour LC50 value for the
bluegill (U.S. EPA, 1978).
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures-
1,1-d ichloropropane
Final Fish Acute Value = 14,000 ug/1
Final Invertebrate Acute Value = 930 ug/1
Final Acute Value = 930 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = not available
0»44 x Final Acute Value = 410 ug/1
1-2-d ichloropropane
Final Fish Acute Value = 42,000 ug/1
Final Invertebrate Acute Value = 2,100 ug/1
Final Acute Value = 2,100 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = not available
0.44 x Final Acute Value = 920 ug/1
1,3-dichloropropane
Final Fish Acute Value = not available
Final Invertebrate Acute Value = 11,000 ug/1
B-5
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Final Acute Valua = 11,000 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = 48,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 48,000 ug/1
0»44 x Final Acute Value = 4,800 ug/1
1,3-d ichloropropene
Final Fish Acute Value = 850 ug/1
Final Invertebrate Acute Value = 250 ug/1
Final Acute Value = 250 ug/1
Final Fish Chronic Value = 18 ug/1
Final Invertebrate Chronic Value = not available
Final Plant Value = 5,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 18 ug/1
0.44-x Final Acute Value = 110 ug/1
No freshwater criterion can be derived for any dichlopropane
using the Guidelines because no Final Chronic Value for either
fish or invertebrate species or a good substitute for either value
is available.
However, data for 1,3-dichloropropane and saltwater organisms
can be used as the basis for estimating criteria.
For 1,3-dichloropropane and saltwater organisms, 0.44 times
the Final Acute Value is less than the Final Chronic Value derived
from a life cycle test with the mysid shrimp. Therefore, a rea-
sonable estimate of criteria for dichloropropanes and freshwater
organisms would be 0.44 times the Final Acute Value. The lack of
B-6
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a Final Fish Acute Value for 1,3-dichloropropane and freshwater
fish is probably not important since the Final Fish Acute Value is
greater than the Final Invertebrate Acute Value for all three
cases with freshwater and saltwater organisms in which both values
are available* ;
1,1-d ichloropropane
The maximum concentration of I,1-dichloropropane is the Final
Acute Value of 930 ug/1 and the estimated 24-hour average concen-
tration 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 estimated 24-hour average
concentration.
CRITERION: For 1,1-dichloropropane the criterion to protect
freshwater aquatic life as derived using procedures other than the
Guidelines is 410 ug/1 as a 24-hour average and the concentration
should not exceed 930 ug/1 at any time.
1,2-d ichloropropane
The maximum concentration of I,2-dichloropropane is the Final
Acute Value of 2,100 ug/1 and the estimated 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 estimated 24-hour
average concentration.
CRITERION: For 1,2-dichloropropane the criterion to protect
freshwater aquatic life as derived using procedures other than the
Guidelines is 920 ug/1 as a 24-hour average and the concentration
should not exceed 2,100 ug/1 at any time.
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1,3-d ichloropgopane
The maximum concentration of 1,3-dichloropropane is the Final
Acute Value of 11,000 ug/1 and the estimated 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 estimated 24-hour
average concentration.,
CRITERION? For -1,3-dichloropropane the criterion to protect
freshwater aquatic life as derived using procedures other than the
Guidelines is 4,800 ug/1 as a 24-hour average and the
concentration should not exceed 11,000 ug/1 at any time.
lyS-dichloropropene
The maximum concentration of 1,3-dichloropropene is the Final
Acute Value of 250 ug/1 and the 24-hour average concentration is
the Final Chronic Value of 18 ug/l° 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 1,3-dichloropropene the criterion to protect
freshwater aquatic life as derived using the Guidelines is 18 ug/1
as a 24-hour average and the concentration should not exceed 250
ug/1 at any time0
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Table l. Freshwater ftalt acuto values for dicliloropropanea •- dlchloropropenea
Adjusted
Tout Chemical Time . • LCbU LOU
DO
1
vo
Dlucglll, S U
Leponia mucrochirus
Bluegill. S U
I'.eponila macrochlrua
Blucglll, S U
I.epomls macrochlrua
Bluuglll, S U
l.epomls macrochirus
* S - utatlc
** U *• unmeasured
Geometric mean of adjusted values:
1,1-dlchloro-
propane
1,2-dichloro-
propano
1,2-dlchloro-
propane
1,3-dlchloro-
propene
1 ,'1-dichloropropana
96 97,900 53,500
96 320,000 174,900
96 280,000 153,000
96 6.060 3.310
53.500
- 53,500 Mg/1 ~3~!F~ "
163,600
U.S. EPA,
1978
Daws on, et al.
1977
U.S. EPA,
197B
U.S. EPA,
1978
14,000 Mg/1
•. • ah ^V/t/V 1 «
1.2-dlchloropropane - 163.600
3.9
3.310
1,3-dlchloropropena « 3.310 Mg/1 3.9 " 850 ug/1
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Table 2.Freshwater invertebrate acute valuea for dicliloropropanes - dlchloffonropeneo
(U.S. EPA, 1978)
Adjusted
Test . Chemical Time LC'jU ICio
Cladoceran,
Raphnta roagna
Cladocerun,
Riiphnia roagna
CSadoceran,
Oaplinia roagna
Cladoceran.
Dapjmla magna
* S - sfcatlc
tjj ** U - unmeasured
^ Geometric mean of
S U 1,1-dlchloro- 48 23,000 19,500
propane
S U 1,2-dlchloro- 48 52.500 44,500
propane
S U 1.3-dJclUoro- 48 282.000 239,000
propane
S U 1,3-dlchloro- 48 6,150 5,210
propene
•
adjusted valuesi i.l-dlchloiropropana « 19,500 t>g/l — il~~ B 9^° fg/l
1,2-dlchloropropano - 44,500
1,3-dlchloropropane - 239,000 i.g/1
1,3-dtchloropropehe • 5.210
>- - 2,100
- 11,000 ng/1
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Table 3. Freshwater fish chronic values for dlchloropropanea - dlchloropropenea
(U.S. EPA, 1978)
Chronic
Llnita Value
Organ! urn IS"! |uq/H fU'l/H
1,3-dlchloropropene
Fathead minnow E-l.* 180-330 122
Ptmephalea promclaa
* E-L - embryo-larval
.Geometric mean of c
Lowest chronic value - 122 pg/l
122
.Geometric mean of chronic values - 122 i»g/l 5-7 - 18
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Table 4. Freuhwater plant effects for cllchloropropanea - dichloropropenea (U.S. EPA, 1978)
Organ! tm
Alga.
Selenaatruie
capricornutum
Alga,
Sclcnautrunt
capricornutuni
Concentration
tuq/11
I.3-dichloropropena
Chlorophyll a 4,950
EC50 after
96 l.ir
Call numbers 4,960
EC50 afcer
96 hr
1.S^dlchloropropane
hM^
CD
to
Alga,
Sclenaatrun
caprtcprnutuiB
Alga,
Selenastrum
cnpFIcornutura
Chlorophyll a
EC50 after ~
96 hr
Cell numbers
EC50 after
96 hr
48,000
72,200
Lowest plant valuet l,3-<|ichloropropene - 4,950 Mg/&
1,3-dichloropropone = 48,000 pg/i
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Table 5. Other freshwater data for dlchloropropanes - dlcltloropropenea
Teat Result
Organism DiiliiiQQ £1L££1 (ug/^> . Reference
1.3-d.ichloropropena
Mixture of -
Emerald shiner.'
Ho tr op is athertnodlea
actinia
SJT3 3 daya Mortality 100% Scott and Wolf. 1962
Futhead minnow, survival
Ploicphalea promelaa at 1,000
100% mortality
at 10.000
1.3-dtchloropropane
Blucglll. 96 hra LCSO >520.000 U.S. EPA. 197B
CD I.c pom IB macrochlriia
I
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SALTWATER ORGANISMS
Introduction
The data base for dichloropropanes and dichloropropenes and
saltwater organisms is limited to studies with 1,2-dichloropro-
pane, 1, 3-dichloropropane, and 1,3-dichloropropene. Toxicity
tests with saltwater organisms have not been done on other chemi-
cals in this class and effects of salinity, temperature, or other
water quality factors on toxicity are unknown. Only one fish and
one invertebrate species have been tested with individual di-
chloropropanes and dichloropropenes.
Acute Toxicity
The unadjusted 96-hour LC50 values (Table 6) were 240,000
ug/1 for 1,2-dichloropropane and the tidewater silverside (Dawson
et ale 1977), 86,700 y,g/l for 1,3-dichloropropane, and 1,770 ug/1
for 1,3-dichloropropene and the sheepshead minnow (U.S. EPA,
1978). The adjusted LC50 value for 1,3-dichloropropane is 49
times greater than that for 1,3-dichloropropene. The LC50 value
for 1,2-dichloropropane and the tidewater silverside is much
greater than those for 1,3-dichloropropane and 1,3-dichloropropene
and the sheepshead minnow, but it is impossible to tell whether
the difference is due to different toxicities of the chemicals or
responses of the species. When the adjusted LC50 values are
divided by the Guidelines species sensitivity factor, the follow-
ing Final Fish Acute Values are obtained: 1,3-dichloropropene, .
260 ug/1; 1,3-dichloropropane, 13,000 ug/1; 1,2-dichloropropane,
35,000 ug/1.
Mysidopsis bahia, the only invertebrate species tested in
acute tests, was more sensitive than the-fishes (Table 7). For
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mysid shrimp, 1,3-dichloropropene (96-hour LC50 = 790 ug/1) was 13
times more toxic than 1,3-dichloropropane (96-hour LC50 = 10,300
ug/1). Comparable data for Daphnia magna (Table 2) show that 1,3-
dichloropropene was 46 times more toxic than 1,3-dichloropropane.
When the adjusted LC50 values for each compound are divided by the
species sensitivity factor (49), the Final Invertebrate Acute
Values are 14 ug/1 for 1,3-dichloropropene and 180 ug/1 for 1,3-
d ichloropropane.
Chronic Toxicity
Only one study on chronic toxicity of dichloropropanes and
dichloropropenes to saltwater organisms has been found (Table 8).
In a life-cycle study with the mysid shrimp, the chronic value for
1,3-dichloropropane was 3,040 ug/1 (U.S. EPA, 1978). When this
result is adjusted by the species sensitivity factor (5.1), the
Final Invertebrate Chronic Value is 600 ug/1 for 1,3-dichloro-
propane, a value higher than that for Invertebrate Acute Value
(180 ug/D- This is the result of a larger sensitivity factor for
the acute toxicity data and the .fact that the 96-hour LC50 value
(10,300 ug/1) for the mysid shrimp is close to the chronic value
(3,040 ug/D for the same species.
Plant Effects
The saltwater alga, Skeletonema costatum, was as sensitive to
1,3-dichloropropene as fishes and mysid shrimp (Table 9). The
96-hour EC50 value for growth, based on concentrations of
chlorophyll a_ in culture, was 1,000 ug/1. The EC50 calculated
from cell numbers was 1,040 ug/1.
As with fishes and mysids, 1,3-dichloropropane was less toxic
to Skeletonema costatum than 1,3-dichloropropene. The 96-hour
B-15
-------
EC50 value from data for chlorophyll a_ was 65,800 ug/1; for cell
number it was 93,600 ug/1.
There are no data reported in the literature on effects of
dichloropropanes or dichloropropenes on saltwater vascular
plants.
Residues
No measured steady-state bioconcentration factors (BCF) are
available for any dichloropropane or dichloropropene. Bioconcen-
tration factors can be estimated for the dichloropropanes using
the octanol-water partition coefficients of 220, 105, and 100 for
1,1-, 1,2-, and 1,3-dichloropropane, respectively. These coeffi-
cients are used to derive estimated BCF's of 35, 20, and 19 for
1,1-, 1,2-, and 1,3-dichloropropane, respectively. An octanol-
water partition coefficient was calculated for 1,3-dichloropropene
to be 43 and this value is used to derive an estimated BCF of 10.
These estimated BCFs for aquatic organisms assume approximately an
eight percent lipid content. If it is known that the diet of the
wildlife of concern contains a significantly different lipid con-
tent, appropriate adjustments in the estimated BCFs should be
made.
Miscellaneous
No other data for dichloropropanes or dichloropropenes have
been found for saltwater species.
B-16
-------
CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
1,2-d ichloropropane
Final Fish Acute Value = 35,000 ug/1
Final Invertebrate Acute Value = not available
Final Acute Value = 35,000 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
Final Plant Value = not available
Residue Limited Toxicant Concentration = not available
Final Chronic Value = not^available
0.44 x Final Acute Value = 15,000 ug/1
1,3-dichloropropane
Final Fish Acute Value = 13,000 ug/1
Final Invertebrate Acute Value = 180 ug/1
Final Acute Value = 180" ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = 600 ug/1
Final Plant Value = 66,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 600 ug/1
0.44 x Final Acute Value = 79 ug/1
B-17
-------
1; 3-d ichloropropene
Final Fish Acute Value = 260 ug/1
Final Invertebrate Acute Value = 14 ug/1
Final Acute Value = 14 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value - not available
Final Plant Value = 1,000 ug/1
Residue Limited Toxicant Concentration = not available
Final Chronic Value = 1,000 ug/1
Oo44 x Final Acute Value = 6.2 ug/1
1,3-d ichloropropane
The maximum concentration of 1,3-dichloropropane is the Final
Acute Value of 180 ug/1 and the 24-hour average concentration is
0.. 44 times the Final Acute Value. No important adverse effects on
saltwater aquatic organisms have been reported to be caused by
concentrations lower than the 24-hour average concentration.
CRITERION: For 1,3-dichloropropane the criterion to protect
sraltwater aquatic life as derived using .the Guidelines is 79 ug/1
as a 24-hour average and the concentration should not exceed 180
ug/1 at any time.,
1,2-d ichloropropane
No saltwater criterion can be derived for 1,2-dichloropropane
using the Guidelines because no Final Chronic Value for either
fish or invertebrate species or a good substitute for either value
is available.
However, data for 1,3-dichloropropane and saltwater organisms
and 1,2-dichloropropane and freshwater organisms can be used to
estimate a criterion for 1,2-dichloropropane.
B-18
-------
For 1,3-dichloropropane and saltwater organi'sms the Final
i
Invertebrate Acute Value divided by the Final Fish Acute Value is
180 ug/1/13,000 ug/1 = 0.014. The comparable quotient for
1,2-dichloropropane and freshwater organisms is 2,100 ug/1/57,000
ug/1 = 0.037. The average quotient is 0.026. Multiplying this
value times the Final Acute Value for 1,2-dichloropropane and
saltwater fish results in an estimated Final Invertebrate Acute
Value of 0.026 x 35,000 ug/1 = 910 u9/l» Thus the estimated Final
Acute Value for 1,2-dichloropropane is 910 ug/1. Multiplying this
Final Acute Value by 0.44 gives 400 U9/1«
For 1,3-dichloropropane and saltwater organisms, 0.44 times
the Final Acute Value is less than the Final Chronic Value derived
from a life cycle test with the mysid shrimp. Therefore, a
reasonable estimate of a criterion for 1,2-dichloropropane and
saltwater organisms would be 0.44 times the Final Acute Value.
The maximum estimated concentration of 1,2-dichloropropane is
the Final Acute Value of 910 ug/1 and the estimated 24-hour
average concentration is 0.44 times the Final Acute Value. No
important adverse effects on saltwater aquatic organisms have been
< i
reported to be caused by concentrations lower than the estimated
24-hour average concentration.
CRITERION: For 1,2-dichloropropane the criterion to protect
saltwater aquatic life as derived using procedures other than the
Guidelines is 400 ug/1 as a 24-hour average and the concentration
should not exceed 910 ug/1 at any time.
1,1-d ichloropropane
No saltwater criterion can be derived for 1,1-dichloropropane
using the Guidelines because no Final Chronic Value for either
B-19
-------
fish or invertebrate species or a good substitute for either value
is available, and there are insufficient data to estimate a cri-
terion using other procedures.
1,3-d ichloropropene
No saltwater criterion can be derived for 1,3-rdichloropropene
using the Guidelines because no Final Chronic Value for either
fish or invertebrate species or a good substitute for either value
is available. "^
However, data for 1,3-dichloropropene and freshwater fish can
be used to estimate a criterion 'for 1,3-dichloropropene.
For 1,3-dichloropropene and freshwater fish the Final Chronic
Value divided by the Final Acute Value is 18 ug/1/850 ug/1 - 0.021
Multiplying this value times the Final Acute Value for 1,3-di-
chloropropene and saltwater fish results in an estimated Final
Fish Chronic Value of 0.021 x 260 ug/1 = 5-5 ug/1. Thus the
estimated Final Chronic Value is 5.5 u5/l and is slightly lower
than 0.44 times the Final Acute Value.
The maximum concentration of l,3-dichl:oropropene is .the Final
Acute Value of 14 ug/1 and the estimated 24-hour average concen-
tration is the Final Chronic Value of .5.5 ug/1. No important
adverse effects on saltwater aquatic organisms have been reported
to be caused by concentrations lower than the estimated 24-hour
average concentrations.
CRITERION^ For 1,3-dichloropropene the criterion to protect
saltwater aquatic life as derived using procedures other than the
Guidelines is 5.5 ug/1 as a 24-hour average and the -concentration
should not exceed 14 ug/1 at any time.
B-20
-------
03
I
NJ
T Jib A a A, Marine fish acute vuluea for dicUloropropanes - dichloropropenes
Adjusted
£i uasuse
Test
Sliaepsheed ralr.noy,
Cyprlnodpn yarjlegatua
Sheepshead alimcu,
Cyjirinodon yarlegatnia
Tidcwfltsr gllveraido,
Hgjiidla beryltino
s
s
g
u
u
u
Time
lll£§)
1,3- 96
dichloiopropane
1.3- 96
dichlocopropsns
LCUU
lHil£iL
1,770
968 U.S. EPA, 1978
86,700 47,399 U.S. EPA, 1978
dlchloropsropans
96
246.000 131,
Oavreon. at al. 197?
* S = etatic
** U •» uniucaaured
Geometric me en of aiSJuatail valuaoi 1,3-dlchlaropr-cpeite » 963 t>g/l
i,3-dichtoropropane • A7.399
• 131,208
968
377 = 26Q jig/I
— - 13,000
131.208
35,000
-------
Table 7. Marine Invertebrate acute values for dichloropropanea - dichloropropenea
(U.S. EPA, 1978)
0^1..
My aid shrimp,
Uyeidojittia liulita
My a id shrimp,
Hyatdopaia bahja
Bioaeeay T
-------
03
r
Table 8, Marine Invertebrate chronic valuea for dlchloropropanea - dlchloropropanes
(U.S. EPA, 1978)
Chronic
Limit a Value
Tgst*
Hysld shrimp, UC 2,200-4,200 3,040**
Hystdopata pahta
* LC • life cycle or partial life cycle
** 1 , 3-dlchloropropane
Geometric aeon of chronic valuea • 3,040 ng/l " " 60°
Lowest chronic value -3,040 |ig/l
-------
Table 9. Marine plant effects for dtehloroptropunes - dlchloropropenes (U.S. EPA, 1978)
c>
i
ro
Organism
Alga,
Skfclctonema costatua
8!
-------
REFERENCES
Dawson, G.W., et al. 1977. The acute toxicity of 47 indus-
trial 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 hexamethylenetetra-
mine and halohydrocarbons. Appl. Microbiol. 10: 211.
U.S. EPA. 1978. In-depth studies on health and environmental
impacts of selected water pollutants. Contract No. 68-01-
4646.
B-25
-------
Mammalian Toxicology and Human Health Effects
EXPOSURE
Introduction
For purposes of discussion in this document, "dichloro-
propane"'refers to 1,2-dichloropropane and will be abbreviated
"PDC" (for propylene dichloride); "dichloropropene" refers
to 1,3-dichloropropene 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 speciation 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 intermediate, though comparative data concerning
quantities utilized for pesticide and non-pesticide purposes
were not found. 'D-D1 is the Shell trademark for a combina-
tion preparation. The published analyses of this preparation
vary, as seen in Table 1. 'Telone1 is the Dow trademark '
for DCP. De Lorenzo, et al. (1977) described mutagenicity '
TJ
studies with Telone 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
P
ethylene dibromide and carbon tetrachloride (Dowfume EB-5 ).
C-l
-------
TABLE .1
/t>\
Published Analytical Data on D-Dv ' Soil Fumigant
Composition (%)
1,3
dichloropropene
cis
trans
Martin &
Worthing
(1974)
nit 50
+a
Spencer
(1973)
60-66
30-33
30-33
De Lorenzo,
et al.
(1977)
40
Nater &
Gooskens
(1976)
53
1,2-dichloropropane
Other.Chlorinatedb
Hydrocarbons
30-35
27
20
a: +, present but quantity not indicated
b: Other 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.
.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. Stanford Research Institute
(1975) in a study for the National Science Foundation, report-
ed 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.
C-2
-------
Ingestion from Water
Dichloropropane and dichloropropene can enter the aquatic
environment as discharges from industrial and manufacturing
processes, as run-off'from agricultural land, and from munici-
pal effluents. These compounds have been identified but
not quantified in New Orleans drinking water (Dowty, et
al. 1975). The National Academy of Science's Safe Drinking
Water Committee (1977) lists both PDC and DCP as organic
contaminants found in finished drinking water, with no avail-
able information on chronic toxicity and with the highest
concentration in finished water of 1.0 ug/1 for each compound.
Ingestion from Food
Most data on the persistence, degradation, and distri-
bution PDC and DCP deal with their presence in soils. Follow-
ing field application, movement of these compounds in the
soil results from vapor phase diffusion (Leistra, 1970).
The rate of degradation of PDC and DCP in soil depends on
the susceptibility to hydrolysis, soil types, soil temperature,
and soil moisture (Thomason and McKenry, 1973; Leistra,
1970; Van Dijk, 1974). For example, cis-DCP is chemically
hydrolyzed in moist soils to the corresponding cis-3-chloroal-
lyl 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 conditions. These same conditions in turn influence
their potential as persistent health hazards as soil contami-
nants, potentially toxic to developing crop plants. When
applied at recommended rates, field applications of DCP
C-3
-------
have shown between 15 to 80 percent decomposition after
several weeks (Van Dijk, 1974) „ The remaining residues
V
may exist for several months following application (Williams,
1968; Leistra, 1970). When TeloneR is applied to a moist,
warm soil at a rate of 234 liters per hectare, cis-DCP can
be expected to remain in the soil at concentrations greater
tha 10 jug/1 of soil 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 compounds (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 concentrations of the PDC and DCP in commercial food
stuffs. Thus, the amount of these compounds ingested by
humans through food is not known.
A bioconcentration factor (BCF) relates the concentration
of a chemical in water to the concentration in aquatic organ-
isms, but BCF's are not available for the edible portions
of all four major groups of aquatic organisms consumed in
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 Ameri-
cans. A recent survey on fish and shellfish consumption
C-4
-------
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:
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.
No measured steady-state bioconcentration factors (BCF)
are available for either dichloropropenes or dichloropropanes;
however, the equation "Log BCF =0.76 Log P - 0.23" can
be used (Veith, et al. Manuscript) to estimate the BCF for
aquatic organisms that contain about eight percent lipids
from the octanol-water partition coefficient (P). An adjust-
ment factor of 2.3/8.0 = 0.2875 can be used to adjust the
estimated BCF from the 8.0 percent lipids that is the weighted
average for consumed fish and shellfish. Thus, the weighted
average bioconcentration factor for edible portions of all
aquatic organisms consumed by Americans can be calculated.
C-5
-------
Compound
1 / 1-dichloropropane
1 , 2-dichloropropane
1 , 3-dichloropropane
1,3-dichloropropane
P
220
105
100
43
BCF
35
20
19
10
Weighted BCF
10
5.8
5.5
2.9
Inhalation
The atmospheric levels of PDC and DCP are not known.
However, the possible sources of entry of these compounds
to the atmosphere are from the manufacture of commercial
fumigants, the production of oil and fat solvents, the agri-?
cultural 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 contribute
to the1 atmosphere could not be ascertained. -.. . >
F'umigant 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 approximately
five to ten percent (Thomason and McKenry, 1973). The Cali-
fornia State Department of Agriculture reported that in
1971 approximately 1,285 metric tons of pesticide containing
C-6
-------
DCP were used in that State. It can be estimated that approxi-
' > 9
mately 72 tons or eight percent of DCP were lost to the
atmosphere (Calif. State Dep. Agric. 1971).
Since levels of the PDC and DCP have not been measured
in the atmosphere it is impossible to determine the amounts
of these compounds that could be inhaled by the general
public. However, there is an occupational risk to the workers
that handle these compounds, though information on actual
exposure levels is not available in the published literature.
Dermal
Dermal exposure to the 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.
PHARMACQKINETCS
No data were revealed which deal with the absorption,
distribution, 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 poten-
tial 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 grams, Carworth Farm E strain) of each
sex were dosed via stomach tube with 0.5 ml of arachis oil
14
solution of 1,2-dichlororo (1- C) propane (0.88 mg, 8.5
14
uCi), cis-l,3-dichloro (2- C) propene (2.53 mg, 7.68 uCi),
14
or trans-l,3-dichloro (2- C) propene (2.70 mg, 8.50 uCi).
C-7
-------
The excretion of radioactivity as percent of the administered
dose was determined in the urine, feces and respired air
of these animals at 24-hour intervals over a four-day period.
The animals were sacrificed after the fourth day following
the- administration of the compounds and the radioactivity
remaining in their carcasses was measured.
Data resulting from the study are shown in Tables- 2a
and 2b., The authors claim that, 80 to 90 percent of administ-
ered radioactivity was eliminated within the first 24 hours.
This would include the radioactivity in the expired air
though the data for that fraction for the first 24 hours
w,ere not given.
If 80 percent; of the administered dose is eliminated
in 24 hours, this would mean a total elimination constant
of. approximately 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
_T
constant for urine of approximately 0.03 hr~ . The compounds,
on the basis: of their physical properties, should distribute
in total body water. In a rat a compound distributed in
total body water with no accompanying storage or biotransfor-
mation would have a urinary elimination constant of approxi-
mately 0.50 hr~ . Thus, the decreased clearance seen is
due either to the renal tubular reabsorption (decreased
clearance), incorporation into virtual volume of distribution
(increased apparent volume of distribution), or both. The
last is. the most likely, with compensation occurring by bio-
transformation. In the case of cis-DCP, the participation
of biotransformation is more evident.
C-8
-------
TABLE 2 a
Rates of Excretion of Radioactivity from Rats After the Oral
Administration of Three Components of D-D.
(Hutson, et al. 1971)
Excretion of radioactivity (% of administered dose)
in 24-hr periods (hr after administration)
Compounds Sex
1,2-Dichloropropane M
o F
i cis-l,3-Dichloropropene M
F
trans-l,2-Dichloroproprene M
F
1,2-Dichloropropane M
F
cis-l,3-Dichloropropene M
F
trans-l,3-Dichloropropene M
F
The values given are the means
0-24
48.5 +
51.9 +
81.3 +
80.3 +
54.6 +
58.7 +
5.0 +
3.8 +
2.0 +
1.4 +
1.3 T
1.9 +
+SEM for
24-48
5.23
1.59
2.76
5.34
1.92
1.08
2.66
0.95
0.38
0.43
0.37
0,24
groups
Urine
1.9 +
1.8 4-
1.9 +
1.2 +
0.6 +
1.1 +
Faeces
0.7 +
0.7 +
0.8 +
0.2 +
0.2 T
0.2 +
of six
0.45
0.22
0.21
0.29
0.06
0.16
0.10
0.12
0.28
0.04
0.11
0.10
rats.
48-72
0.5
0.4
0.6
0.4
0.3
0.5
0.9
0.2
0.3
0.1
0.4
0.2
+ 0.12
+ 0.06
+ 0.14
+ 0.23
+ 0.04
+ 0.13
+ 0.56
+ 0.02
+ 0.14
+ 0.03
+ 0.15
+ 0.15
72-96
0.2
0.3
0.3
0.4
0.1
0.2
0.2
0.2
0.2
0.1
0.1
0.1
+ 0.03
+ 0.05
+ 0.06
4- 0.23
+ 0.02
+ 0.09
-t- 0.08
-1- 0.02
+ 0.08
+ 0.05
+ 0.05
+ 0.02
Total
(0-96 hr)
51.1
54.4
84.1
82.3
55.6
60.5
6.8
4.9
3.3
1.8
2.0
2.4
+
+
+
T
T
±
+
7
+
+
T
+
5.27
1.48
2.94
5.18
1.90
1.00
2.61
1.07
0.53
0.42
0.28
0.26
-------
TABLE 2b
Recoveries of Radioactivity from Rats in the 4 Days Following Oral
Administration of Three Components of D-D.
(percent of administered dose)
(Hutson, et al. 1971)
Recovery of radioactivity
Compounds
Sex
Urine
Feces
Exhaled Air
Carbon
Dioxide*
o
i
0
1,2-Dichloropropane
cis-l,3-Dichloropropene
txans-l,3-Dichloropropene
M
F
M
F
M
F
51.1
54.4
84.4
82.3
55.6
60.4
+ 5.27
+ 1.48
+ 2.94
T 5.18
+ 1.90
T 1.00
6.9
4.9
3.3
1.8
2.1
2.3
+ 2.61
+ 1.07
+ 0.53
+ 0.42
+ 0.28
+ 0.26
19
5
2
22
24
___.— .
.3
.3
.4
.7
.4
_
(5)
(3)
(3)
(3)
(3)
Other volatile
radioactivity*
.__
23.1
1.4
3.5
_.
(5)
-
(2)
(2)
* Values given are means for the numbers of animals indicated in parentheses.
Except where indicated otherwise* values given are the means +SEM for groups of six rats.
-------
EFFECTS
Dichloropropane
Acute/ Sub-acute and Chronic Toxicity
Table 3 shows the acute LD5Q values which have been
obtained for PDC and related compounds.
The earliest reference to the acute oral toxicity of
the dichloropropanes in mammals was reported in a study
of the anthelmintic action of orally administered dichloro-
propanes in dogs (Wright and Schaffer, 1932). An oral dose
of 5,700 mg PDC per kilogram body weight caused loss of
coordination and staggering 15 minutes after administration,
complete lack of coordination after 90 minutes, followed
by death 3% hours later. An oral dose of 3,500 mg DCP per
kilogram body weight caused staggering, partial narcosis,
and death within 24 hours. The dogs killed by the oral
administration of the dichloropropanes exhibited hypostatic
congestion of the lungs, congestion of the kidneys and bladder,
and hemorrhages in the stomach and respiratory tract. Patho-
logically 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 dichloropropanes per kilogram body weight
caused moderately severe lesions in the liver, gastrointesti-
nal 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)
C-ll
-------
were done with rats, mice, guinea pigs, and rabbits (and
dogs at 1,000 ppm) utilizing daily seven-hour exposure periods
and a concentration range of 1,000 to 2,200 ppm. A concentra-
tion of 2,200 ppm was lethal to over 50 percent of the animals
of all four species after up to eight exposures. Mice were
the most sensitive, 10/11 dying before the completion of
one exposure period. In addition, animals were exposed
to 1,600 ppm of PDC but the data are no more revealing than
that already presented.
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 indicated no changes except
for "somewhat lower" red cell counts and hemoglobin in expos-
ed rabbits.
Gross and histopathological examination revealed a
range of liver abnormalities from visceral congestion to
fatty degeneration to extensive multilobular areas of -coagula-
tion necrosis. Other pathological effects observed among
animals from all concentrations included: renal tubular
necrosis and fibrosis, splenic hemosiderosis, pulmonary
congestion, bronchitis, and pneumonia and fatty degeneration
in the heart. Subsequent studies utilizing 2,200 ppm were
performed (Highman and Heppel, 1946) to obtain further patho-
logical data. These studies served to further document
the earlier observations. However, there might be a possi-
bility of the presence of what we now refer to as drug-induced
phospholipidoses.
C-13
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In another study (Heppel, et al- 19484 rats, guinea
pigs, and dogs were exposed to 400 ppm of PDC for 128 to
140 daily seven-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 getting the prolonged
exposure they might have expected.
Mice were then exposed in the same fashion. As in
the previous study, mice (C57) were more sensitive to PDC;
and apparent treatment-related "slight fatty degeneration
i
of the liver" was observed„
Sidprenko, et al. (1976) studied the effects of the
continuous inhalation of 1 and 2 mg PDC per liter air in
albino male rats (200 to 400 grams) . Blood acetylcholinester-
ase and blood catalase activities, red and white blood cell
counts, hemoglobin, ancl animal weight were measured after
2, 4, 24, 48, 72, 96 hours and after six and seven 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 evaluation of the liver DNA were performed
on the exposed animals. Significant changes in catalase
and cholinesterase activity and threshold index were observed
as early as four hours after the start of the inhalation:
of 1.0 mg PDC per liter air. Significant changes occurred'
in all of the above mentioned tests after 24 hours of contin-
uous exposure to 1.0 mg PDC per liter air.
C-14
-------
The livers for rats that were continuously exposed
to 1.0 mg PDC per liter air for seven days histologically
showed proteinfat dystrophy, suppression of enzymic activity,
and decreased ribonucleoproteins centralized in the centrolob-
ular sections. Cells of peripheral sections of lobules
i '' '
1 ( i
showed fewer changes and underwent displacements of an adapta-
tional 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 equalled 16n. These adaptive
changes were accompanied by increased ribonucleoproteins
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 activity (Sidorenko, et ai. 1976).
The effect of PDC on the functional state of the rat
was further demonstrated (Kurysheva and Ekshtat, 1975).
Blood serum chloesterol, beta-lipo proteins and gamma-globulin
levels increased after the 10th day of daily oral doses
of 14.4 and 360 mg PDC per kilogram body weight. By day
20 of dosing, the serum cholinesterase was inhibited whereas
the fructose-1-monophosphate aldolase, alanine transaminase,
and asparagine transaminase were increased and after 30
days of dosing the alanine transaminase was inhibited.
C-15
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I'tp the range-find ing studies: o^f Smyth, et alo (19S4,
.,, 19^69) , 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 exposed workmen. The studies, consisted of
exposing .g-roups of six male Garworth-wistar rats (9-0 to
100. grams body weight) to either saturated vapors or known
vapor concentrations of compounds for a known period of
time and then observing the mortality of; the exposed rats
during ai M-day observation per.iod. 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 period. In another exposure study,
one eight-hour exposure to 8.8 mg PDC per liter air killed
three: of" six 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
atmospnere of 1,1-dichloropropane (7,630. mg 1,1-dichloropro-
pane: per liter air). One four-hour exposure to 17.6 mg
1,1-dichloropropane per liter air killed four of six 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 irritation of the mucous membrane. Changes in the blood
are similar to those of "marked anemia."
Another case report described found 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 ingestion, he went into a deep coma with
C-16
-------
mydriasis and hypertonia; after 24 hours he regained conscious-
ness 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 §_._ 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 4)„ This implies missense,
but not frameshift mutations. However, this is further
discussed in the section dealing with mutagenicity of DCP.
Bignami, et al. (1977) also reported the mutagenicity
of PDC in TA 1535 and TA 100. They studied the induction
of point mutations (8-azaguanine resistance) and somatic
segregation (crossing over and non-disjunction) in A. nidulans,
using the spot test technique. PDC was shown to significantly
raise the frequency of mutants resistant to 9-azaguanine.
Dragusanu and Goldstein (1975) reported 'that PDC causes
chromasomal 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 per liter air.
Only three of 80 C3H strain mice survived a total of 3.7
exposure periods and a subsequent observation period of
C-17
-------
TABLE 4
Mutagenicity of D-D^5), Telenet, PDC and DCP as Determined by the "Ames"
Test With (W) and without (WO) Liver Microsomal Fraction.
(De Lorenzo, et al. 1977)
Number of mutant colonies/plate with Salmonella strains
TA 1978
TA 1535
TA 100
Compound
Telone ^
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
pg
pg
mg
mg
mg
mg
>g
mg
mg
mg
pg
jug
^g
jug
jug
/jg
mg
rag
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
c,±2
73V
2100
1551
650
2200
1500
185
450
920
C-18
-------
7 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 tetrachlor-
ide. The livers of these mice also-showed many large mononuc-
lear cells laden with lipochrome resembling ceriod. Although
inhalation of 1.76 mg PDC per liter 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, Sub-acute and Chronic Toxicity
Acute LD50 for DCP and isomers is given in Table 3.
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 ) for periods of 0.5, one, two, or four-
hours/day, five days a week for six months. Only the rats
exposed 4 hours per day showed an effect and this was mani-
fested as cloudy swelling of the tubular epithelium. Further
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 were 'seen in
hematocrit, WBC, hemoglobin, or differential count, which
could be attributed to the treatment. The only effect the
authors described which could be attributed to treatment
was 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 three-month
C-19
-------
recovery 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 LDen range. The studies of Torkelson and
Oyen (1977) cited indicate 1 ppm DCP by inhalation as a
NOAEL. The authors recommend this as a time-weighted 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 of 0.1, 0.5 and 2.5 mg of DCP per kilo-
gram 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
C-20
-------
function was altered as evidenced by prolonged pigment cir-
culation in the blood, raised thymol test values, cholesterol
level, and stimulated increase of fructose 1-monophosphate
aldolase.
In human sensory tests, 13.6 mg air was detected by
seven of ten human volunteers who were exposed to 11.6 or
4.5 mg DCP/mg air for one to three 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/m air, but it was noticeably
fainter (Torkelson and Oyen, 1977)„
Mutagenicity
De Lorenzo, et al. (19'77) 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.
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 activation. The cis-isomer
was found to be two times more reactive than the trans-isomer.
Neudecker, et al. (1977) also found a significant dif-
ference in the survival rate of the bacteria exposed to
varying concentration of both isomers. At all concentrations
tested, survival rates of cells exposed to cis- DCP were
generally lower than those of bacteria exposed to the trans-
isomer .
C-21
-------
It can be seen from Table 4 that DCP may be about three
orders of magnitude more mutagenic than PDC. Also, it can
be seen that TeloneR and D-DR (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 presence of microsomal
fraction) indicating a frame-shift mutation. 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 component.
The implication is that less evaporation of material may
occxxr 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.
Car c i nog en i c i ty
Van Duuren, et al. (In press) designed a study to evalu-
ate the carcinogenicity of 15 halogenated hydrocarbons by
a multiple bioassay procedure. From their studies, the
authors have suggested certain structure/activity relation-
ships concerning carcinogenicity and the bioassay procedure.
Among the compounds studied was cis-DCP. The compound was
studied by three procedures.
(1) Initiation-Promotion: 122 mg applied once in
0.2 ml actone followed 14 days later by 5 ug (in 0.2
ml acetone) of the tumor promoter, phorbol myristate
acetate (PMA), three times weekly for 428 to 576 days.
C-22
-------
(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 weekly
for 538 days.
All studies utilized 30 male ICR/Ha Swiss mice per group.
In the initiator-promoter studies, six papillomas in
four mice were observed. This result was not significantly
;
different from promoter controls. Repeated skin application
revealed three papillomas 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 was statistically significant
from controls (0/100). In none of the studies were treatment-
related remote tumors observed.
Dichloropropane/Dichloropropene
(mixtures containing at least 10 percent PDC)
Acute, Sub-acute and Chronic Toxicity
P
Acute oral LDnn values for D-D are shown in Table
3. 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 distention of the stomach by fluids
and gas and erosion of the gastrointestinal mucosa, with
occasional hemorrhage. Hemorrhage of the lungs and fatty
degeneration of the liver were occasionally seen in rats
C-23
-------
that died after several days after administration. The
mortality curve MC&S abrupt? £.11 mice died at the highest
dose level(432 mg D-D /kg), about one-half at the next level
(288 mg D-DR/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 strain rats for four hours to concentrations
R R 3
of D-D ranging from 2,000 to 81,500 mg D=D /m „ The exposure
t>
to D-D caused respiratory distress, dyspnea, hypernea,
mucous nasal discharge, and lacrimation., Dilatation of
the capillaries was evident in the ears. Gross pathological
examination of the rats that died from the exposures showed
severe edema of the lungs, with varying degrees of intersti-
tial and alveolar hemorrhagef and distention of the stomach
and upper small intestine. Congestion and fatty degeneration
of the liver also were noted occasionally in animals exposed
to D-DR.
Russian scientists have investigated the effects of
low oral and chronic doses of mixtures of dichloropropanes
R
and dichloropropenes 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
R
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
C-24
-------
w-eight to young male albino rats daily for six months.
p
These doses of D-D caused an increase in trypsin and lipase
activities and decreased the trypsin inhibitor activity
of the blood.
P
The precutaneous absorption of the product D-D was
studied by Hine, et al. (1953). Nineteen rabbits were depi-
lated over the back and flanks in a cylindrical swath between
the fore and hind legs, immobilized, and a tight-fitting
P
girdle was slipped over the shaved area. Undiluted D-D
in doses of 1200 and 4800 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 decreased :
body movement and depressed respiration. One rabbit receiving
P
3000 mg D-D /kg had developed mucous nasal discharge. Seven
of the ten rabbits receiving the three higher doses of D-
D
D died in 8 to 48 hours, and the five rabbits receiving
the lowest dose (1200 mg D-D /kg) survived.
P
Three cases of untoward reaction to D-D have been
reported in the Netherlands. Three patients had developed
symptoms after several years of repeated exposures to the
R
soil fumigant D-D during its application to the fields.
Most of the dermal contact 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 exist-
P
ence of a contact allergic sensitivity to D-D could be
proven in one patient. Patch tests with compounds related
P
to D-D suggest that the cause of contact allergy must be
P
sought in the propene(s) fraction of D-D . All three patients
C-25
-------
exhibited an itchy erythematojjs rash on the arras, face and
P
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.
Carcinogenicity
No data were retrived concerning the carcinogenicity
of mixtures of PDC and DCP.
C-26
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CRITERIA FORMULATION
Consideration of Mathematical Model
There are no carcinogenicity data on which water quality
criteria for PDC and DCP can be based. Similarly, no-observ-
able-adverse-effeet-level data following oral administration
of the compounds to man or experimental animals are not
available. Consequently, the water quality criteria must
be based on NOAEL's obtained from inhalation toxicology
data.
The conversion of inhalation toxicology data to water
quality standards is usually done by the procedure described
by Stokinger and Woodward (1958). This procedure essentially
involves an estimation of the daily intake of a substance
if man was exposed to that substance according to the time
and concentration limits of the MOAEL. This amount is then
multiplied by a relative absorption factor expressed as
"inhalation absorption factor/ingestion absorption factor"
to give the amount of material which would have to be ingested
daily to be equivalent to that amount of material absorbed
during daily exposure to NOAEL levels»
There are a number of pitfalls to this approach. Since
the final results of the calculations represent estimates,
at best, most of the pitfalls are of theoretical rather
than practical concern. However, there is one aspect of
the calculation which is practically inestimatable without
some biological data. This concerns estimation of relative
absorption by various routes of administration. From pharmaco-
kinetic concepts, much of which have become evident since
C-27
-------
Stokinger and Woodward published their method, it is unreason-
able to expect a justifiable estimate of relative absorption
factors without experimental data relating route of administra-
tion to blood level. Because such data are not available
for PDC and DCP, another approach was devised to extrapolate
inhalation data to ingestion data.
The approach was based on the following:
/\ X = X, where:
3, O
A = Ostwald coefficient for vapor phase at 37° C
X = alveolar gas concentration = inhalation NOAEL
3
Xb = arterial blood concentration at equilibrium on
exposure to X
Cl
Thus, if X, can validly be calculated in this way,
a
then the amount of material which would have to be ingested
to yield that blood level at equilibrium, i.e., ingestion
NOAEL can be expressed as follows:
i,
Ingestion NOAEL = out x X.x VQ where:
'xout = fraction of body burden eliminated every 24 hours
V = apparent volume of distribution of the body burden
in man (70 kg)
The allowable daily intake (ADI) can then be expressed in
the usual fashion:
ADI = Ingestion NOAEL
uncertainty factor
All of the factors described are estimatable at one
degree or another based on the data available for PDC and
DCP= The derivation of the ingestion NOAEL has been done
assuming that equilibrium is reached during conditions of
the inhalation NOAEL and that the ingestion NOAEL is taken
as a single dose. It is recognized that possibly the first
C-28
-------
a-nd certainly the second assumption does not represent the
actual situation. However, the experimental data are too
imprecise and the population habits too variable to make
the correction of these assumptions. It should be recognized,
however,.that by utilizing these two assumptions the error
is in the direction of underestimating the ingestion NOAEL.
Derivation of Ostwald Coefficient
The Ostwald coefficient (A) is defined as the ratio
of the concentration of a gas in a liquid to the concentration
of the gas in an equivalent volume of gas above that liquid.
By definition, the Ostwald coefficient of a gas and water
at any particular temperature could be expressed:
water solubility (g/1)
cone, or vapor(g/1)at a partial
pressure equal to vapor pressure
In the criteria formulation, j\ for water is used as
that for blood. A review of data on volatile anesthetic
agents indicated this approach was acceptable. The applica-
bility of this procedure to estimation of Xb can be seen
from the data of Heppel, et al. (1946). They determined
blood concentration of PDC in rabbits and dogs after a seven-
hour exposure period. From their exposure data, blood levels
were calculated based on the Ostwald coefficient determined
here (see below) and a hematocrit of 0.50. The data are
as follows:
Animal Exposure Blood cone. Blood Cone.
cone, (mg/1) Found (mg/1) Calculated (mg/1)
28.6
16.7
13.0
C-29
Rabbits
Rabbits
Dogs
10.3
6.0
4.7
15-29
6-11
13-16
-------
D i Gta&Qr opr opane
The data for the vapor pressure (P) were developed
by Nelson and Young (1933). From their data it was determined
that P (20°C) = 40 mm Hg and P (38°C) = 90 mm Hg. Unfortu-
nately the only solubility data available were that for
20°C. However, data available on trichloroethylene and
chloroform indicated that
P°
= 0.512
A similar relationship was found for ether. This factor
was. utilized for PDC:
Solubility in water =2.7 g/1
P 40
Concentration in air = n/v =
RT 62 x 293
0.0022 mole/1 =0.25 g/1
A38° = 10.8 x 0.512 = 5.5
Dichloropropene
A valid vapor pressure value for DCP could not be identi-
;
fied as such. However, the Fire Protection Guide on Hazardous
Materials (1975) cited the vapor air density of DCP (cis
and trans), as 1.4 at 37.8°C. Vapor air density (D) can
*
be expressed as:
where P = vapor pressure (at 37.8°)
P'= ambient pressure.(760 mm Hg)
d = vapor density (3.8 for DCP)
Therefore
. •
P = -P^P = 109 mm Hg.
C-30
-------
This is a feasible relationship to the vapor pressure
of 90 nun Hg at 38°C reported for PDC. An assumption of
parallelism for plots of log vapor pressure vs. 1/T for
PDC and DCP is reasonable. Thus the vapor pressure of DCP
at 20°C.can be assumed to be 59 mm Hg. This conversion
is necessary since the only available solubility data for
DCP is at 20°.
Thus
n/v - If - 62 x9293 = °'0032 moles/1
=0.36 g/1
solubility of DCP in water at 20° =1.0 g/1
_ _ 1.0 g/1 _ o a
20° - 0.36 g/1 - 2*8
38o = 2.8 x 0.512 = 1.4
D-D , as described by Martin and Worthing (1974) has a vapor
pressure of 35 mm Hg at 20°; as described by Spencer (1973),
it has a vapor pressure of 31.3 mm Hg at 20 C (see Table
1). If these values are accurate, then the mixture of PDC
and DCP can be assumed to be a negative deviation from Raoult's
law. Measurements of partial pressure of binary solutions
show that most of them can be classified as deviating from
Raoult's law, either positively or negatively. The implica-
tion of this behavior of mixtures of PDC and DCP has been
discussed in the criterion document regarding the interpreta-
tion of mutagenicity data.
C-31
-------
Derivation of Elimination Constant (k)
The derivation of k is the most speculative portion
of the model. From the data presented earlier, it can be
assumed that the rat excretes 80 percent of a dose in 24
hours. It is likely, however, that PDC and DCP fit a two
compartment pharmacokinetic model, at the least. Only the
first (water) compartment in the rat can be reasonably esti-
mated from the data available. Based on differences in
glomerular filtration rate/weight relationships between
rat and man, the k of a rat was reduced from 0.80 x 24 hr~
to 0.25 x 24 hr~ . This is .a moderate estimate which should
also allow for known higher rates of biotrans.formation in
the rat when compared to man.
Derivation of Volume of Distribution
The volume of- distribution (VD) of the compounds was
assumed to be in a total body water plus fat:
Thus
VD = VTBW+
-------
To account for this, it was recognized that the NOAEL
inhalation exposure were based on seven to eight hours of
exposure. Consequently, a safety factor was incorporated
in the V_. calculation such that the lipid space was corrected
to include only that apparent fat volume which would be
filled during 8 hours of exposure.
Thus
V
• VTBW + (VF X ^ O/W X F8h}
where
P. = fraction of final equilibrium level of substance
F fat after 8 hours.
In (1-F) = -kt
where
\f _ plasma flow rate per minute in fat (0.11)
v^ ^0/w
t = 480 minutes
Dichloropropane
* o/w - 10?
FQh = 0.05
VD = 36 + (10 x 105 x 0.05) = 89
Dichloropropene
A o/w - 43
F8h = °'11
VD = 36 + (10 x 43 x 0.11) = 83
Criteria
As stated above:
ADI = Ingestion NOAEL
Uncertainty factor
C-33
-------
The uncertainty factor for both PDC and DCP was taken as
100 based on the fact that the inhalation data utilized
appears highly reliable and conversions to ingestion NOAEL
had built in underestimation factors.
Finally;
PP — ALlJ.
*-* 2 + (BCF x 0.0187)
Where
CR = water quality criterion
2 = liters of water consumed p'er day
BCF = bioconcentration faction in edible portion
fish (obtained from USEPA Duluth Laboratory)
0.0187 = estimated consumption (kg) by an individual
daily
Dichloropropane
The inhalation NOAEL for PDC is 75 ppm (350 mg/m )
which is the ACGIH TLV (Am. Conf. Gov. Ind. Hyg.f 1977)
A = 5.5
Xa = 350 jug/1
Xb = 5.5 x 0.35 = 1925 jug/1
VD = 89 1
k = 0.25 x 24 hr"1
ADI . 0,25. 1925 f 89! . 428
BCF = 5.8
CR = 2 - 203
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Dichloropropene
The inhalation NOAEL for DCP is 1 ppm (4.5 mg/ra ) which
is that recommended by Torkelson and Oyen (1977) .
X3 = 4.5 jug/1
. d
Xb = 1.4 x 4.5 = 6.3 jug/1
k = 0.25 x 24 hr"1
BCF =2.9
CR =
(2.9 x 0.0187) w'w"
In summary, based upon the use of an inhalation no-
observed-adverse-effect-level in rats (DCP), the ACGIH recom-
mended TLV (PDC), and an uncertainty factor of 100, the
criterion level corresponding to the estimated acceptable
daily intake of 1.3 jug/day for DCP and 428 jug/day for PDC
is .63 ;ug/l and 203 jug/1, respectively. Drinking water accounts
for 95 percent of the assumed exposure for PDC and 98 percent
for DCP. The criterion level can alternatively be expressed
as 3.9 mg/1 for PDC and 24 jag/I for DCP if exposure is assumed
to be from the consumption of fish and shellfish products
alone.
C-35
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