297 923
DDT
Ambient water Quality Criteria
Criteria and Standards Division
Office of Water Planning and Standards
U.S. Environmental Protection Agency
Washington, D.C.
-------
CRITERION DOCUMENT
DDT AND METABOLITES
CRITERIA
Aquatic Life
For DDT and metabolites the criterion to protect freshwater
aquatic life as derived using the Guidelines is 0.00023 ug/1 as a
24-hour average and the concentration should not exceed 0.41 ug/1
at any time.
The data base for saltwater aquatic life is insufficient to
allow use of the Guidelines. The following recommendation is in-
ferred from toxicity data for freshwater organisms.
For DDT and metabolites the criterion to protect saltwater
/
aquatic life as derived using procedures other than the Guidelines
is 0.0067 ugl as a 24-hour average and the concentration should
not exceed 0.021 ug/1 at any time.
Human Health
For the maximum protection of human health from the potential
carcinogenic effects of exposure to DDT through ingestion of water
and contaminated aquatic organisms, the ambient water concentra-
tion is zero. Concentrations of DDT estimated to result in addi-
tional lifetime cancer risks ranging from no additional risk to an
additional risk of 1 in 100,000 are presented in the Criterion
Formulation section of this document. The Agency is considering
setting criteria at an interim targe risk level in the range of
10~5, 10~6, or 10~7 with corresponding criteria of 0.98 ng/1,
0.098 ng/1, and .0098 ng/1, respectively. If water alone is con-
sumed, the water concentration should be less than 0.36 ug/1 to
keep the lifetime cancer risk below 10~~5.
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Introduction
DDT, first synthesized in Germany in 1874, has been ,
used extensively world-wide for public health and 'agricultural
programs. Its efficacy as a broad spectrum insecticide
and its low cost continue to make it the insecticide of
choice for those measures for most of the world.
;
Following an extensive review of health and environmental
hazards of the use of DDT, U.S. EPA decided to ban further
use of DDT. This decision was based on several properties
of DDT that had been well evidenced; (1) DDT and its metabolites
are toxicants with long-term persistence in soil and water,
(2) it is widely dispersed by erosion, runoff and volatiliza-
tion, (3) the low-water solubility and high lipophilicity
of DDT result in concentrated accumulation of DDT in the
fat of wildlife and humans which may be hazardous. Agri-
cultural use of DDT was canceled by the U.S. EPA in December,
1972. Prior to this, DDT had been widely used in the U.S.
with a peak usage in 1959 of 80 million pounds. This amount
decreased steadily to less than 12 million pounds by 1972.
Since the 1972 ban, the use of DDT in the U.S. has been
effectively discontinued.
DDT is acutely toxic to freshwater fishes at concentra-
tions as low as 0.8 jug/1 (Marking, 1966) and to invertebrates
at 0.18;ug/l (Sanders, 1972). It is chronically toxic to
the fathead minnow in the range of 0.37 to 1.48 jug/1 (Jarvinen,
et al. 1977). An average bioconcentration factor of 640,000
was calculated using data on 26 species of fish. For saltwater
fishes concentrations of DDT as low as 0.2 jag/1 have been
A-l
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reported to be acutely toxic (Eisler, 1970). For invertebrates
the figure is 0.14 jug/1 (Schimmel and Patrick, 1975). Chronic
toxicity data for saltwater organisms were not available.
The average marine fish bioconcentration factor was found
to be 22,467. Criteria for both freshwater and marine organisms
are based on bioconcentration.
A-2
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REFERENCES'
Eisler, R. 1970. Acute toxicities of organochlorine and
organophosphorus insecticides to estuarine fishes. Tech
Paper. Bur. Sport Fish. Wildl. U.S. Dept. Interior No. 46.
Innes, J.R.M., et al. 1969. Bioassay of pesticides and
industrial chemical for tumorigenicity in mice: a preliminary
note. Jour. Nat. Cancer Inst. 42: 1101.
Jarvinen, A.W., et al. 1977. Long-term toxic effects of
DDT food and water exposure on fathead minnows, Pimephales
promelas). Jour. Fish. Res. Board Can. 34: 2089.
Marking, L.L. 1966. Evaluation of p,p'-DDT as a reference
toxicant in bioassays. In Investigations in fish control.
U.S. Fish Wildl. Serv. Resour. Publ. 14: 10. U.S. Dep. Inter,
/
Sanders, H.O. 1972. Toxicity of some insecticides to four
species of malacostracan crustaceans. Bur. Sport Fish.
Wildl. Tech. Paper 66: 19.
Schimmel, S.C., and J.M. Patrick. 1975. Acute Bioassays.
Semi-Annual Report, U.S. Environmental Protection Agency,
Environmental Research Laboratory, Gulf Breeze, Florida.
pp. J.
A-3
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Terracini, B., et al. 1973. The effects of long-term feeding
of DDT to BALB/C mice. Int. Jour. Cancer 11: 747.
Tomatis, L., et al. 1974. Effect of long-term exposure
to l,l-dichloro-2,2-bis(p-chlorophenyl) ethylene, to 1,1-
dichloro-2>2-bis(p-chlorophenyl) ethane, and to the two
chemicals combined on CF-1 mice. Jour. Natl. Cancer Inst.
52: 883.
Turusov, V.Si, et al. 1973. Tumors in CF-1 mice exposed
for six consecutive generations to DDT. Jour. Natl. Cancer
Inst. 51: 983.
A-4
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AQUATIC LIFE TOXICOLOGY*
FRESHWATER ORGANISMS
Introduction
DDT is an insecticide that has been in use for many years and
,has probably been subject to more investigations than the other
chlorinated hydrocarbon pesticides such as aldrin, dieldrin, en-
drin, chlordane, and toxaphene.
In regard to fish toxicity, DDT has an intermediate toxicity
when compared with other chlorinated hydrocarbon pesticides. It
is less toxic than aldrin, dieldrin, endrin, and toxaphene but
more toxic than chlordane, heptachlor, lindane, and methoxychlor
(Henderson, et al. 1959; Katz, 1961).
Most acute data are from static tests; few flow-through
studies have been conducted. Chronic test data are available for
only one species of fish and none are available for aquatic in-
vertebrates.
*The reader is referred to the Guidelines for Deriving Water
Quality Criteria for the Protection of Aquatic Life [43 FR 21506
(May 18, 1978) and 43 FR 29028 (July 5, 1978)] in order to better
understand the following discussion and recommendation. The fol-
lowing tables contain the appropriate data that were found in the
literature, and at the bottom of each table are the calculations
for deriving various measures of toxicity as described in the
Guidelines.
B-l
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Few data are available on freshwater plant effects and those
that are indicate a wide range in concentrations where effects oc-
cur.
Many references on bioconcentration data are available, how-
eve'r, a number of these were not usable, either because the or-
ganisms did not appear to reach an equilibrium with the water con-
centration in laboratory experiments, or in the case of field
monitoring, there was not adequate documentation of the water con-
centration.
Acute Toxicity
Acute toxicity data are available for 25 species of fish for
a tiotal of 111 values (Table 1); of these, only four values are
not 96-hours in duration. Three of the 111 LC50 values are from
\
flow-through tests, and the rest are from static tests. Only one
of the three flow-through tests has a measured water concentra-
tion. The flow-through LC50 value for rainbow trout fry (Tooby,
et al. 1975) is equal to or less than 85 percent of the 13 static
values for the same species. The flow-through LC50 value for
brown trout (Alabaster, 1969) is less than 50 percent of the other
three values for the same species. The only flow-through test
with a measured water concentration (Jarvinen, et al. 1977) is for
the fathead minnow, and the LC50 value is greater than 87 percent
of all static LC50 values for the same species. Since the water
solubility of DDT is not high, it could be assumed that static
tests would underestimate toxicity as indicated by the rainbow
trout and brown trout data. The fathead minnow data, however, are
in contrast with these, perhaps because of species variability.
Lincer, et al. (1970) demonstrated that the fathead minnow was
B-2
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more sensitive to DDT in the static than in the flow-through test
(48-hour static = 7.4 ug/1; 48-hour flow-through = > 40 ug/D and
Macek and Sanders (1970) determined that among the five fish
species tested, variation in susceptibility to DDT was greatest in
the fathead minnow. Interspecific variability, shown by the LC50
values in Table 1, indicates that the^ fathead minnow is more vari-
able than 87 percent of the 25 species for which there-are data
available. Only three species are more variable, the goldfish,
guppy, and the brook trout; of these, the goldfish is the most
variable. The yellow perch is the most sensitive fish species to
DDT (96-hour LC50 of 0.6 ug/1; Marking, 1966) whereas the least
sensitive species is the goldfish (96-hour LC50 of 180 ug/1;
Marking, 1966). Therefore, the range of species sensitivity is
300 times.
Sixty percent of the species in Table 1 have at least one
LC50 value below the geometric mean for all species, but if based
upon the total number of data points, only 32 percent of all in-
dividual LC50 values fall below this mean. When the geometric
mean of all species in Table 1 is divided by the sensitivity fac-
tor (3.9), the LC50 value calculated to be equal to or less than
the LC50 value for 95 percent of all species is 1.3 ug/l« This
value is higher than only five values in the table, which are less
than five percent of the total number of values given, suggesting
a qood fiit of the data to the procedures in the Guidelines. The
Final Fish Acute Value is 1.3 ug/1.
Data are available for 19 invertebrate species for a total of
50 data points (Table 2). Invertebrate species for the most part
are more sensitive than fish, but the range in species sensitivity
B-3
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is greater (10,000 times as compared to 300 times for fish). The
least sensitive invertebrate species is the stonefly, Pteronarcys
californica for which a 96-hour LC50 value of 1,800 ug/1 was
demonstrated by Gaufin, et al. (1965). T,his LC50 value is almost
five times greater than the arithmetic mean of the other three
LC50 values for the same species (Table 2). The most sensitive
aquatic invertebrate species is the one week-old crayfish,
Orconectes nais (LC50 = 0.18 ug/1; Sanders, 1972).
Only two of the data for invertebrate species (Table 2) were
derived from flow-through tests. None of the data have measured
water concentrations. Seventy percent of all data points are from
96-hour tests, 28 percent from 48-hour tests, and only two percent
or one data point from a 26-hour test that was used as a 24-hour
value. The result of one flow-through test in Table 2 is one-
fourth of the static test result for the same species of scud,
Gammarus fasciatus (Sanders, 1972) whereas in another comparison
the result of a static test is lower than the result from a flow-
through test with the glass shrimp, Palaemonetes kadiakensis,
(Sanders, 1972). Therefore, as with the fish acute data, species
variability is demonstrated in toxicity differences between static
and flow-through tests. In Table 2, TDE is more toxic than DDT to
three invertebrate species (a glass shrimp, Palaemonetes kadia-
kensis and two species of scud, Gammarus fasciatus and Gammarus
lacustris but less toxic than DDT to the cladocerans, Daphnia
pulex and Simocephalus serrulatus and the sowbug, Asellus
brevicaudus.
When the geometric mean of all the data points in Table 2 is
divided by the species sensitivity factor (21), the estimated
B-4
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value at or below the LC50 value for 95 percent of all species is
0.41 ug/1- This value is lower than 90 percent of all the LC50
values and lower than the LC50 values for 89.5 percent of all of
the species in Table 2. When compared to the geometric mean of
the adjusted LC50 value for each species, it is lower than that of
all of the 19 species in the table. Because of the variability in
the invertebrate data base, the use of the sensitivity factor
seems to be appropriate. Since the Final Invertebrate Acute Value
(0.41; Table 2) is lower than the Final Fish Acute Value (1.3
ug/1; Table 1), the Final Acute Value for freshwater aquatic life
is 0.41 ug/1.
Chronic Toxicity
One chronic test with fathead minnows was found (Table 3).
The comparable 96-hour LC50 value (Jarvinen, et al. 1977) indi-
cates that the acute toxicity value is 65 times higher than the
chronic toxicity value. When the chronic value is divided by the
species sensitivity factor (6.7), a value (0.11 ug/1) is obtained
which should protect 95 percent of all species. Another method of
estimating the same value is obtained by multiplying the Final
Fish Acute Value by the application factor calculated from the
fathead minnow data; this estimate is 0.12 ug/lr only 10 percent
higher. There is no indication of the range of species sensitiv-
ity for chronic toxicity since only one chronic value is avail-
able. Since fathead minnows are among the least sensitive of the
species tested (Table 1; 79 percent of all species are more sensi-
tive), reduction of the chronic fathead minnow data by the sensi-
tivity factor is reasonable to protect more sensitive species
B-5
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from chronic toxicity. The Final Fish Chronic Value is the lowest
of the three estimates in Table 3, or 0.11 ug/1.
No invertebrate chronic toxicity data were found.
Plant Effects
Four species of algae have a wide range of sensitivity (2,700
tinies) with the highest about equally sensitive to DDT as fish and
invertebrate species (Table 4). The lowest and Final Plant Value
isL0.30 ug/1, determined from the growth and morphology data for
Chlorella sp. (Sodergren, 1968).
Residues
An average bioconcentration factor of 640,000 was calculated
for the 31 data points on the 26 species of fish in Table 5. Be-
cause of the persistence of DDT and its ability to bioaccumulate,
field' data were included if adequate water concentration measure-
ments were provided. Twenty-two field generated data points for
20 species of fish are available (Table 5) with an arithmetic mean
bioconcentration of 842,822, whereas only nine laboratory data
points for nine species of fish are available with an arithmetric
mean bioconcentration of 125,976. This indicates an almost seven
times greater bioconcentration in the field than in laboratory
tes.ts, which may be due to the many additional trophic levels in-
volved in field exposures or a difference in lipid content.
Data points in Table 5 pertaining to maximum permissible tis-
sue concentrations indicate that long-term dietary dosage at 2.8
to 3 mg/kg DDE (wet weight) can have adverse effects on reproduc-
tion of mallards (Heath, et al. 1969; Haseltine, et al. 1974),
black ducks (Longcore, et al. 1971; Longcore and Stendell, 1977),
B-6
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and screech owls (McLane and Hall, 1972). DDE has 'been found to
constitute 50 to 90 percent of the DDT analogs present in fish
(Jarvinen, et al. 1977). The DDE no-effect concentration for
shell thinning was estimated to be 0.5 mg/kg. or less in eggs of
brown pelicans (Blus, et al. 1972). Manx/times higher concentra-
tions in the eggs than concentrations that were fed for several
months have been found for other species. Ten times higher con-
centrations were observed in black duck eggs (Longcore, et al.
1971; Longcore and Stendell, 1977) and almos.t eight times higher
in sparrow hawk eggs (Lincer, 1975). Therefore, a dietary dosage
as low as 0.1 mg/kg in brown pelicans, which might be accumulated
to over 0.5 mg/kg in the eggs, might not protect them from shell
thinning. Anderson, et al. (1975) found that although the major
food source of brown pelicans contains a residue concentration of
only 0.15 mg/kg the pelican numbers were still below that neces-
sary for population stability. Therefore, the residue concentra-
tion of 0.15 mg/kg divided by the bioconcentration factor of
I
640,000 gives a Residue Limited Toxicant Concentration (RLTC) of
0.00023 ug/1.
Of the three available values, the Final Fish Chronic Value
(0.11 ug/D, the Final Plant Value (0.30 ug/D, and the RLTC
(0.00023 ug/D, the RLTC is the lowest and thus 0.00023 ug/1 be-
comes the Final Chronic Value.
Miscellaneous
Table 6 contains additional data points concerning the effect
of DDT on 23 species of freshwater aquatic life. None of these
data values however, is lower than the selected Final Chronic
B-7
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Value (0.00023 ug/D• The values range from extended time LC50
values to physiological and behavioral effects. The lowest value
in Table 6 is a hyperactive locomotor response observed by
Ellgaard, et al. (1977) for the bluegill, exposed at 0.008 ug/1•
This value is almost 35 times higher than the Final Chronic
Value.
B-8
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CRITERION FORMULATION
Freshwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value =1.3 ug/1
Final Invertebrate Acute Value = 0.41 ug/1
Final Acute Value = 0.41 ug/1
Final Fish Chronic Value =0.11 ug/1
Final Invertebrate Chronic Value = not available
Final Plant Value = 0.30 ug/1
Residue Limited Toxicant Concentration = 0.00023 ug/1
Final Chronic Value = 0.00023 ug/1
0.44 x Final Acute Value = 0.18 ug/1
The maximum concentration of DDT and metabolites is the Final
Acute Value of 0.41 ug/1 and the 24-hour average concentration is
the Final Chronic Value of 0.00023 ug/l« No importnt adverse
effects on freshwater aquatic organisms have been reported to be
caused by concentrations lower than the 24-hour average concentra-
tion.
CRITERION: For DDT and metabolites the criterion to protect
freshwater aquatic life as derived using the Guidelines is 0.00023
ug/1 as a 24-hour average and the concentration should not exceed
0.41 ug/1 at any time.
B-9
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1 Freshwater fish acute values for DDT and metabolites
Organism
Bioassay Test
Met-nod* Cone.**
DO
I
Coho salmon. S U
Oncorhynchus klsutch
Coho salmon, S U
Oncorhynchus kisutch
Coho salmon, S U
Oncorhynchus kisutch
Coho salmon,
Oncorhynchus kisutch
Coho salmon, S U
Oncorhynchus kisutch
Chinook salmon, S U
Oncorhynchus tshawytscha
Cutthroat trout, S U
Salmo clarki
Cutthroat trout,
Salmo clarki
Rainbow trout, S U
Salmo gairdneri
Rainbow trout, S U
Salmo gairdneri
Rainbow trout, S U
Salmo gairdneri
Rainbow trout, S U
Salmo gairdnert
Rainbow trout, S U
Salmo gairdneri
Chemical
Description
DDT
i
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
Time
thrg)
96
96 ,
96
96
96
96
96
96
96
96
LC5o
(ug/i)
- 44
4
11.3
18.5
13
11.5
0.85
1.37
42
7
Adjusted
LCbO
(Uq/A)
24.05
2.19
6.18
10.11
7.11
6.29
0.46
0.75
22.96
3.83
hriterence
Katz, 1961
Macek &
McAllister,
1970
Post &
Schroeder,
1971
Post &
Schroeder,
1971
Schaumburg,
et al. 1967
Katz, 1961
Post &
Schroeder ,
1971
Post &
Schroeder,
1971
Katz, 1961
Macek &
McAllister,
1970
DDT
DDT
DDT
96
96
96
7.2 3.94 Macek &
Sanders, 1970
14 7.65 Marking, 1966
4.6 2.51 Marking. 1966
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Table 1. (Continued)
03
I
til
Organism M«
Rainbow crouc ,
Salmo gairdneri
Rainbow crouc,
Saimo gairdneri
Rainbow crouc,
Salmo gairdneri
Rainbow crouc,
Salmo gairdneri
Rainbow Crouc,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Rainbow Crouc,
Salmo gairdneri
Rainbow trout (fry),
Salmo gairdneri
Brown crouc (alevin) ,
Saimo Crucca
Brown crouc (f ingerling) .
Salmo Crucca
Brown crouc,
Salmo Crucca
Brown trout,
Salmo trutta
Brook trout,
Salvellnus foncinalis
Brook Crouc,
Salvelinus foncinalis
Brook CrouC,
.oassa>
"tiiod *
S
S
S
S
S
S
S
FT
FT
S
S
S
S
S
S
' Test Chemical Time
Cone .** Description (nrs)
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U - DDT 48
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U DDT 96
U DDT 96
LCbu
7.2
15
17
13
12
2.4
1.7
2.4
2.5
17.5
2
10.9
7.2
17
20
Adjusted
LCbO
(uq/il heterence
3.94
8.20
9.29
7.11
6.56
1.31
0.93
1.85
1.56
9.57
1.09
5.96
3.94
9.29
10.93
Marking. 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Post &
Schroeder,
1971
Tooby, et al.
1975
Alabaster,
1969
King, 1962
Macek &
McAllister,
1970
Marking, 1966
Marking. 1966
Marking, 1966
a
Marking. 1966
Salvelinus, foncinalis
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Table 1. (Continued)
Bioassay Test
1
I— '
NJ
Organism
Brook trout.
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Lake trout ,
Salvelinus namaycush
Lake trout,
Salvelinus namaycush
Northern pike,
Esox lucius
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish,
Carassius auratus
Goldfish.
Carassius auratus
Goldfish,
Carassius auratua
Goldfish.
Carassius auratus
Goldfish,
Cardbsius auratus
Metnod * Cone.**
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
U
u
u
u
u
u
u
u
u
u
u
u
u
u
u
Chemical
Description
DDT
• i
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
Time •
(nrs)
96
24
96
96
96
96
96
96
96
96
96
96
96
96
96
LCiL
fu-j/i)
1.8
54
7.4
11.9
9.1
9.5
1.7
21
76
27
32
180
40
35
21
Adjusted
LCiO
(uq/l|
0.98
19.48
4.05
6.51
4.97
5.19
0.93
11.48
41.55
14.76
17.49
98.41
21.87
19.13
11.48
Keterence
Marking, 1966
Miller &
Ogilvie, 1975
Post &
Schroeder,
1971
Post &
Schroeder,
1971
Marking, 1966
Marking, 1966
Marking, 1966
Macek &
McAllister,
1970
Marking, 1966
Marking, 1966
Marking, 1966
Marking. 1966
Marking. 1966
Marking. 1966
Marking, 1966
-------
Table 1. (Continued)
Bioabsay Test Chemical. Time
(nrs)
Adjusted
LCbO
(uq/i) Keterence
CD
V*!fc -*.****. ~* Ml f
Goldfish.
Carassius auratus
Northern redbelly dace,
Chrosomus eos
Carp,
Cyprinus carpto
Carp,
Cyprinus carpio
Carp,
Cyprinus carpio
Carp,
Cyprinus carpio
Carp,
Cyprinus carpio
Carp,
Cyprinus carpio
Carp,
Cyprinus carpio
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead minnow,
Pimephales promelas
Fathead • minnow ,
Pimep_hales promelas
Fathead minnow,
Pimephales promelas
S
S
S
S
S
S
S
S
S
FT
S
S
S
S
S
U
U
U
U
U
U
U
U
U
M
U
U
U
U
U
. DDT
1
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
96
96
96
.
96
96
96
96
96
96
96
48
96
96
96
96
.*.•*.. =^«-
36
68
10
9.2
4.0
11.3
12
6.9
6
48
7.4
19
19.9
58
42
19.68
37.18
5.47
5.03
2.19
6.18
6.56
3.77
3.28
48
3.28
10.39
10.88
31.71
22.96
Henderson, et
al. 1959
Marking, 1966
Macek &
McAllister.
1970
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Jarvinen, et
al 1977
Lincer, et al
1970
Macek &
McAllister.
1970
Macek &
Sanders, 1970
Priester,
1965
Henderson, et
al. 1959
-------
Table 1 (Continued)
Adjusted
Orcj.a,-ii3iri
Fathead minnow,
Pimephales promelaa
Fachead minnow,
Pimephales promelas
Fachead minnow,
Pirrephales promelas
Black bullhead,
Iccalurus melas
Black bullhead.
Iccalurus melas
03
1 Black bullhead,
^ Iccalurus melas
Black bullhead,
Iccalurus melas
Black bullhead,
Iccalurus melas
Channel catfish,
Ictalurus punctatua
Channel catfish.
Iccalurus punctatus
Channel catfish,
Iccalurus punctatus
Channel catfish.
Iccalurus punctatus
MosquiCof ish.
Gambubia affints
Guppy,
Lebistes reticulatus
Guppy,
bioafesay
Method*
S
S
S
s
s
s
s
s
s
s
s
s
s
s
s
Test
Cone,**
U
U
u
u
u
u
u
u
u
u
u
u
u
u
u
Chemical
Pescriftion
DDT -
i
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
Time
(nrs)
96
96
96
96
96
96
96
96
96
96
96
96
48
96
96
LCio
(u^/Il
45
26
^6
5
42
23.5
17
20
16
17.4
17.5
17.5
43
19.5
56
LCbO
(uq/H
24.60
14.21
14.21
2.73
22.96
12.85
9.29
10.93
8.75
9.51
9.57
9.57
19.04
10.66
30.62
hererence
Henderson, et
al. 1959
Henderson, et
al. 1959
Henderson, et
al. 1959
Macek &
McAllister,
1970
Marking, 1966
Marking, 1966
Marking. 1966
Marking, 1966
Macek &
McAllister,
1970
Macek &
Sanders, 1970
Marking, 1966
Marking, 1966
Dziuk &
Plapp, 1973
King, 1962
Henderson, et
Lebistes reciculatua
al. 1959
-------
Table 1. (Continued)
C3
I
M
(J\
Organism
Brook stickleback,
Eucalia inconstans
Green sunfish,
Lepomis cyanellus
Green sunfish,
Lepomis cyanellus
Green sunfish,
Lepomis cyanellus
Green sunfish,
Lepomis cyanellus
Green sunfish,
Lepomis cyanellua
Green sunfish,
Lepomis cyanellus
Green sunfish,
Lepomis cyanellua
Green sunfish,
Lepomis cyanellus
Pumpkinseed,
Lepomis gtbbosus
Pumpkinseed,
Lepomis gtbbosus
Pumpkinseed,
Lepomis gtbbosus
Pumpkinseed,
Lepomis gtbbosus
Pumpkinseed,
Lepomis gtbbosua
Bluegill,
Lepomis macrochirus
JdSSa
Jiod*
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
y Test
Cone,**
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
Chemical
Description
DDT
I
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
Time
Ifira)
96
96
96
96
96
96
96
96
96
96
96
96
96
96
96
LCbu
67
2.8
3
3.9
6.7
6.4
4.4
3.6
5
7.5
6.7
2.8
3.6
1.8
8
Adjusted
LCbO
(uq/i} Heterence
36.63
1.53
1.64
2.13
3.66
3.50
2.41
1.97
2.73
4.10
3.66
1.53
1.97
0.98
4.37
Marking ,
Marking,
Marking .
Marking,
Marking ,
Marking ,
Marking,
Marking,
Marking,
Marking ,
Marking,
Marking ,
Marking,
Marking,
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
1966
Macek & •
McAllister,
1970
-------
Table 1 (Continued)
r . s .
Organism
-T" • • =- 3£ ^f
Bluegill,
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
to Bluegill,
1 Lepomis macrochirus
H
<* Bluegill,
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Bluegill.
Leporais macrochirus
Bluegill.
Lepomis macrochirus
Longear sunfish,
Lepomis megalotis
Longear sunfish,
Lepomis megalocis
Redear sunfish.
Lepomis microlophus
Bioassay Test
Method* Cone,**
"; •- • < i ; :• JP
s u
s
s
s
s
s
s
s
s
s
s
s
s
s
s
u
u
u
u
u
u
u
u
u
u
u
u
u
u
Chemical
Debcription
DDT
i
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
-
Time
(nra)
96
96
96
96 '
96
96
96
96
96
96
96
96
96
96
96
Adjusted
LCSo LCbO
/U^/j)
9.5
4.3 -
3.6
1.7
1.2
3
4.6
7
9.4
7
2.8
21
4.9
12.5
5
(UCJ/ll
5.19
2.35
1.97
0.93
0.66
1.64
2.51
3.83
5.14
3.83
1.53
11.48
2.68
6.83
2.73
Keterence
Macek &
Sanders, 1970
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
Henderson, et
al. 1959
Marking, 1966
Marking. 1966
Macek &
McAllister,
-------
Table 1. (Continued)
to
i
biaassay Test
Organism Method*
Largemouth bass, S
Micropterus salmoides
Largemouch bass, S
Micropcerua salmoides
Largemouth bass, S
Micropterus salmoides
Yellow perch, S
Perca flavescens
Yellow perch. S
Perca flavescens
Yellow perch, S
Perca flavescens
Yellow perch, S
Perca flavescens
Freshwater drum, S
Aplodinotus grunniena
Cone,**
U
U
U
U
U
U
If
U
Chemical
Description
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
Time
tttzs)
96
96
96
1
96
96
96
96
96
Adjusted
LCbt. LCbO
(uq/H fuq/i)
2 1.09
1.8 0.98
0.8 0.44
9 4.92
0.8 0.44
0.6 0.33
1.5 . 0.82
10 5.47
Kererence
Macek &
McAllister.
1970
Macek &
Sanders, 1970
Marking, 1966
Macek &
McAllister,
1970
Marking, 1966
Marking, 1966
Marking, 1966
Marking, 1966
* S = static, FT - flow-through .
** U = unmeasured, M » measured
Geometric mean of adjusted values *• 5.05 ug/1 \ A -1.3 pg/1
Lov;est value from a flow-through test with measured concentrations *° 48 pg/1
-------
Table 2. Freshwater invertebrate acute values for DDT and metabolites
Adjusted '
Bioassay Test Chemical
Organism Method* Cone .** Description
Cladoceran. S U DDT
Daphnia magna ,
0)
1
H1
00
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia magna
Cladoceran,
Daphnia pulex
Cladoceran,
Daphnia pulex
Cladoceran,
Simocephalus serrulatus
Cladoceran,
Simocephalus serrulatus
Cladoceran,
Simocephalus serrulatus
Cladoceran,
Simocephalus serrulatus
Sowbug,
Asellus brevicaudus
Sowbug,
Asellus brevicaudus
Sowbug,
Asellus brevicaudus
Scud.
Cammarus fasciatus
Scud,
Gammarus fasciatus
Scud,
S
S
S
S
S
S
S
S
S
S
S
S
S
FT
U
U
U
U
U
U
U
U
U
U
U
U
U
U
DDT
DDT
DDT
TDE
DDT
DDT
TDE
TDE
DDT
DDT
TDE
DDT
DDT
DDT,
Time
HITS)
26
48
48
i
48
48
48
48
48
48
48
96
96
48
96
96
LCiO LCbO
(uq/1) (uq/1)
5.5
4
1.48
0.36
3.2
2.5
2.8
4.5
5.2
4.7
4
10
3.6
3.2
0.8
4.66
3.39
1.25
0.30
2.71
2.12
2.37
3.81
4.40
1.71
3.39
8.47
1.31
2.71
0.62
Ketereuce
Crosby, et
al. 1966
Macek &
Sanders, 1970
Priester, 1965
Sanders &
Cope, 1966
Sanders &
Cope, 1966
Sanders &
Cope. 1966
Sanders &
Cope, 1966
Sanders &
Cope, 1966
Sanders &
Cope, 1966
Macek &
Sanders, 1970
Sanders, 1972
Sanders, 1972
Macek &
Sanders, 1970
Sanders, 1972
Sanders. 1972
Gammarus fasciatus
-------
Table 2. (Continued)
Organism
Bioaseay Test Chemical Time
CoQCj** Description (nrs)
Adjusted
LC50 LOO
(ug/l) (ug/i> heterence
00
I
»-•
vo
Scud. S U
Gammarus fasciatus
Scud, S U
Gammarus fasciatus
Scud, S U
Gammarus fasciatus
Scud, S U
Ganunarus lacustris
Scud, S U
Gammarus lacustrts
Scud, S U
Gammarus lacuscrts
Seed shrimp, S U
Cypridopsts vidua
Glass shrimp, S U
Palaemonetes kadtakensis
Glass shrimp, S U
Palaemonetes kadtakenais
Glass shrimp, FT U
Palaemonetes kadtakensis
Glass shrimp, S U
Palaemonetes kadiakensts
Crayfish. S U
Orconectes nais
Crayfish (1-day-old), S U
Orconectes nais
Crayfish (1-wk-old), S U
Orconectes nais
Crayfish (2-wk-old). S U
Orconectes nais
DDT
TDE
TDE
DDT
DDT
TDE
DDT
DDT
DDT
DDT
TDE
DDT
DDT
DDT
DDT
96 1.8 1.52 Sanders, 1972
96 0.6 0.51 Sanders, 1972
96 0.86 0.73 Sanders, 1972
96 9 7.62 Gaufirt, et al.
1965
96 1 0.85 Sanders, 1969
96 0.64 0.54 Sanders, 1969
48 54 19.67 Macek &
Sanders, 1970
48 4.2 1.53 Macek &
Sanders, 1970
96 2.3 1.95 Sanders. 1972
96 3.5 2.70 Sanders, 1972
96 0.68 0.58 Sanders. 1972
96 100 84.70 Sanders. 1972
96 0.30 0.25 Sanders, 1972
96 0.18 0.15 Sanders. 1972
96 0.20 0.17 Sanders. 1972
-------
2. (Continued)
Adjusted
Bioassay
Organism Method
Crayfish (3-wk-old), S
Orconectes nais
CO
1
M
0
Crayfish (5-wk-old) ,
Orconectes nais
Crayfish (8-wk-old) ,
Orconectes nais
Crayfish (10-wk-old).
Orconectes nais
Crayfish,
Procambarus acutus
Mayfly.
Ephemerella grandts
Stonefly.
Acroneuria pacifica
Stonefly,
Acroneuria pacifica
Stonefly.
Claassenia sabulosa
Stonefly,
Pteronarcella badia
Stonefly,
Pteronarcys californica
Stonefly.
Pteronarcys californica
Stonefly,
Pteronarcys californica
Stonefly,
Pteronarcys californica
Damself ly.
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Test
Cone ,
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
Chemical
Description
DDT
i
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
DDT
TDE
DDT
'DDT
Time
IMS')
96
96
96
i
96
48
96
96
96
96
96
96
96
96
96
48
LCbO
-------
Taolc 2. (Continued)
09
Bioa&say Test
Organism Met-pod Cone .
Caddisfly, S U
Arctopsyche grandts
Caddisfly, S U
Hydropsyche callfomica
Planarian, S U
Polycelis felina
Planarian, S U
Polycelis felina
Planarian. S U
Polycelis felina
Chemical
Description
DDT
i
DDT
DDT
DDE
IDE
Adjusted
Time' LC50 LCbO
(hrfi) ("S/i> tuq/ii
96 175 148.23
96 48 40.66
96 1,230 1,041.81
,
96 1,050 889.35
96 740 626.78
keteirence
Gaufin. et al.
1965
Gaufin, et al.
1965
Kouyoumjian &
Uglow. 1974
Kouyoumjian &
Uglow, 1974
Kouyoumjian &
Uglow, 1974
* S - static. FT - flow-through
** U » unmeasured
8 57
Geometric mean of adjusted values - 8.57 ug/l ~j\~ " °'41 Mg/l
-------
Tacle 5. Freshwater fish chronic values for DDT and metabolites (Jarvinen, et al. 1977)
Ctiroiuc
Limits Value
Organism Test* lug/it (aq/il
Fathead minnow. LC 0.37-1.48 0.74
Pimephales promelas
* LC = life cycle or partial life cycle
Geometric mean of chronic values ° 0.74 Mg/1 •> S •» 0.11 pg/1
Lowest chronic value = 0.74 Mg/1
CD Application Factor Values
£j 96-hr LC50 MATC
Species (pg/1) (MB/1) AF
Fathead minnow, 48 0.74 0.015
Pimephales promelas
Geometric mean AF = 0.015 Geometric mean LC50 ° 48 pg/1
0.015 ^48 ug/1 x 1.3 ng/1 = 0.12
-------
Table 4. Freshwater plant effects for DDT and metabolites
to
i
M
U>
Organism
Alga.
Anacystis nidulans
Alga.
Chlorella sp.
Alga.
Scenedesmus
quadricaudata
Alga,
Selanascrura
capricornutum
Lowest plant value »
Concentration
Effect iuq/ll
Growth 800
Growth & 0.3
morphology
Growth 100
Photosynthesis 3.6
0.3 Mg/1
Reference
Batterton, et al. 1972
1 Sodergren, 1968
Stadnyk. et al. 1971
Lee, et al. 1976
-------
Organism
Tatle 5. Freshwater residues" for DDT and metabolites
f
Bioconcentration Factor '*•
Coontail,
Ceratophyllum demersum
Cladophora,
Cladophora sp.
Duckweed ,
Lemna minor
Water milfoil,
Myriophyllum sp.
Curly leaf pondweed,
Potamogeton cripus
Narrow- leaf pondweed,
Potamogeton foliosus
CO „
1 Sago pondweed,
NJ Potamogeton pectinatus
Soft stem bulrush,
Scirpus validus
Bur reed,
Sparganium eurycarpum
Bladderwort ,
Utricularia vulgaris
Mussel,
Anodonta grandis
Clams (five species composite) ,
Lamps! 11 s siliquoidea
Lamps! lis ventricosa
Lasmigona costata
Fusconaia flava
Ligumia recta
Cladoceran ,
Daphnia magna
Zooplankton (mixed) ,
1,950
21,580
1,210
1,870
14,280
781
6.360
495
623
2,200
2,400
12.500
9.923*
63,500
30
30
30
' 30
30
30
30
30
30
30
21
56
14
21
neterence
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Bedford & Zabik. 1973
Jarvinen, et al. 1977
Daphnia sp.
KeraceTla sp.
Priester. 1965
Hamelink & Waybrant. 1976
-------
03
I
K>
O1
Table 5.
Organism
Freshwater prawn,
Palaemonetes paludosus
Crayfish.
Orconectes punctata
Crayfish.
Procambarus alleni
Mayfly (nymph),
Ephemera danica
Dragonfly (nymph),
Tetragoneuria sp.
Bloodworm,
Tendipes sp.
Red leech,
Erpobdella punctata
Alewife,
Alosa pseudoharengus
Lake herring,
Coregonus artedt
Lake whitefish,
Coregonus clupeaformis
BloaCer,
Coregonus hoyi
Kiyi.
Coregonus kiyi
Cisco.
Coregonus sp.
Coho salmon,
Oncorhynchus kisutch
Rainbow trout,
Salmo gairdneri
Rainbow trout,
(Continued)
Bioconcentratlon Factor
7,000
5,060
1,947
4,075
2,700
4,750
7,520
1,296,666
2,236,666
260,000
2,870,000
4,426,666
368,777
1.563.571
181.000
11.607
JSa
field
30
field
, 5
20
30
30
field
field
field
field
field
field
field
108
field
Salmo gairdneri
Keference
Kolipinski, et al. 1971
Eberhardc, et al. 1971
Kolipinski, et al. 1971
Sodergren & Svensson, 1973
Uilkes & Weiss, 1971
Eberhardt, et al. 1971
Eberhardt, et al. 1971
Reinert. 1970
Reinert, 1970
Reinert. 1970
Reinert, 1970
Reinert, 1970
Miles & Harris, 1973
Lake Michigan Interstate
Pestic. Comm. 1972
Hamelink & Waybrant, 1976
Miles & Harris. 1973
-------
Table S. (Continued)
Organism
Bioconcent ration Factor
Meference
03
I
tvj
Rainbow crout,
Salmo galrdneri
Brown trout,
Salmo trutta
Lake trout,
Salvelinus namaycush
Lake trout,
Salvelinus namaycush
Lake trout,
Salvelinus namaycush
American smelt,
Osmerus roordax
Carp,
Cyprinus carpio
Common shiner (composite),
Nocropis cornutus
Northern redbelly dace,
Chrosomus eos
Fathead minnow,
Pimephales promelaa
White sucker,
CaEostomus commersoni
White sucker,
Cacostomus commersoni
Trout-perch,
Percopsis omiscomaycus
Flagfish,
Jordanella floridtae
Mosquitofish,
Gambusia affinis
Rock bass,
Ambloplites rupestris
Green sunfish,
Lepomib cyanellus
38.642
45.357
458.259
1,168,333
47,428
770,000
640,000
363,000
99,000
110,000
96,666
313.333
14.526
21.411
17.500
17,500
84
Reinert, et al. 1974
field Miles & Harris. 1973
field Miles & Harris, 1973
field Reinert, 1970
152 Reinert & Stone, 1974,
field Reinert, 1970
field Reinert, 1970
40 Hamelink, et al. 1971
266 Jarvinen, et al. 1977
field Miles & Harris. 1973
field Reinert, 1970
field Reinert. 1970
field Kolipinski, et al. 1971
field Kolipinski. et al. 1971
field Miles & Harris. 1973
15
Sanborn. et al.. 1975
-------
Ta£le 5 (Continued)
Organ! am
Green sunfish (composite)
Lepomis cyanellus
Pumpkinseed,
Lepomis gibbosus
Bluegill.
Lepomis macrochirus
Bluegill,
Lepomis macrochirus
Largemouth bass (young of
Micropterus salmotdes
Yellow perch,
Perca flavescens
Slimy sculpin,
? Cottus cognatus
-j
Organism
Man
Domestic animals
Mallard.
Anas platyrhynchos
Mallard,
Anas platyrhynchos
Black duck,
Anas rubripes
Black duck.
Anas rubripes
Sparrow hawk,
Falco sparverius
Sparrow hawk,
Falco sparverius
Time
Bioconcentratlon Factor (days)
59.210 80
-110,000 ' 60
16.071 field
1
year), 317,000 40
1.073,333 field
763.333 field
Maximum Permissible Tissue Concentration
Concentration
Action Level or Effect (mg/kg)
Edible fish and 5
shellfish
Animal feed 0.5
Eggshell thinning 3*
Eggshell thinning 3*
Eggshell thinning 3*
Reduced duckling survival 2.8
Eggshell thinning 3
Reduced survival 2.8
heference
Hame link, et al. 1971
Hame link & Waybrant, 1976
Miles & Harris. 1973
Haraelink, et al. 1971
Reinert, 1970
Reinert, 1970
Reference
U.S. FDA Admin. Guideline
7420.08, 1973
U.S. FDA Admin. Guideline
7426.04, 1977
Haseltine, et al. 1974
Heath, et al. 1969
Longcore, et al. 1971
Longcore & Stendell. 1977
Lincer, 1975
Porter & Wiemeyer, 1972
-------
Title 5 (Continued)
CO
I
N)
CO
Organism
Screech owl,
Otus asio
Brown pelican,
Pelecanus occidencalis
Brown pelican,
Pelecanus occidentalis
Coho salmon (flngerling).
Onchorhynchus kisucch
Chinook salmon
(fingerling).
Onchorhynchus tshawytscha
Cutthroat trout,
Salmo dark!
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Saltno gairdneri
Rainbow trout,
Salmo gairdneri
Brown trout,
Salmo trutta
Lake trout,
Salvelinus namaycuah
Action Level or Effect
Eggshell thinning
Eggshell thinning
Reduced productivity
Reduced survival
Reduced survival
Reduced sac fry survival
Inhibition of Na+-K4 ATPase
Reduced phenoxyethanol
anesthetic induction
and recovery times
Reduced light intensity
discrimination
Reduced fry survival
Reduced fry survival
Concentration
(nig/kg) reference
2.8 McLane & Hall, 1972
0.5 Blus, et al. 1972,1974
0.15 Anderson, et al. 1975
6.25 Buhler. et al. 1969
6.25 Buhler, et al. 1969
3 Allison, et al. 1963
2.75 Campbell, et al. 1974
11.36 Klaverkamp, eC al. 1976
9 McNicholl & Mackay, 1975
3.4 Burdick, et al. 1972
6 Burdick, et al. 1972
Value converted from dry weight to wet weight basis
Average fish bioconcentration factor - 640,000
Lowest permissible tissue concentration = 0.15 ing/kg
'000 = .00000023 irg/kg or .00023 pg/1
-------
Table 6 Other freshwater data for DDT and metabolites
Organism
Test
Duration Etl'ect
Result
jug/1)
CD
I
N)
VO
^Ciadoceran. 14 days
Daphnia magna
Ciadoceran, 14 days
Daphnia magna
Scud, 120 hrs
Gammarus fasciatus
Glass shrimp, 36 hrs
Palaemonetes
kadlakensis
LC50
50% inhibition
of total young
produced
LC50
LC50
Glass shrimp,
Palaemonetes
kadiakensis
120 hra LC50
Stonefly (naiad), 30 days
Acroneuria pacifica
Stonefly (naiad), 30 days
Pteronarcys California
Planarian, 24 days
Polycelis felina
Coho salmon,
Oncorhynchus kisutch
Coho salmon (juvenile), 7 days
Oncorhynchus kisutch
Coho salmon, 125 days
Oncorhynchus kisutch
Cutthroat trout,
Salmo clarki
Rainbow trout, 24 hrs
Salmo gairdneri
Rainbow trout, 5 hrs
S a lino gairdneri
LC50
LC50
Asexual fission
inhibition
Reduced fry
survival
Increased cough
frequency
Estimated median
survival time-
106 days
Reduced sac fry
survival
Uncontrolled
reflex reaction
Cough response
threshold
0.67 Makl & Johnson, 1975
0.50 Maki & Johnson, 1975
0.6 Sanders, 1972
4.5 Ferguson, et al. 1965b
1.3 Sanders. 1972
72 Jensen & Gaufin, 1964
265 Jensen & Gaufin, 1964
250 KouyoumjIan & Uglow, 1974
1.09 mg/kg Johnson & Pecor, 1969
in eggs
5 Schaumburg, 1967
1.27 mg/kg Buhler & Shanks. 1972
In food
>0.4 mg/kg Cuerrier, et al. 1967
in eggs
100
Peters & Weber. 1977
52-140 Lunn. et al. 1976
-------
Tabie 6. (Continued)
Organism
Test
Duration
Result
JU9/J) peter ei.ce
03
I
Ul
o
Rainbow trout,
Salmo gairdneri
Atlantic salmon 30 days
(gastrulae),
Salmo salar
Atlantic salmon, 24 hrs
Salmo salar
Atlantic salmon 24 hrs
Salmo salar
Atlantic salmon, 24 hrs
Salmo salar
Brook trout, 24 hrs
Salvelinus fontinalis
Brook trout, 24 hrs
Salvelinus fontinalis
Brook trout,
Salvelinus fontinalis
Brook trout, 24 hrs
Salvelinus fontinalis
Brook trout, 156 days
Salvelinus fontinalis
Brook trout, 24 hrs
Salvelinus fontinalls
Brook trout, 24 hrs
Salvelinus fontinalis
Lake trout (fry),
Salvelinus namaycush
Goldfish. 2.5 hrs
Carassius auratus
Reduced sac fry >0.4 trig/kg
survival in eggs
Retarded behavioral SO
development and
impaired balance
of alevins
Altered temperature 5
selection
Altered temperature 50
selection for 1 mo
Altered temperature 10
selection
Lateral line nerve 100
hypersensitivity
Visual conditioned 20
avoidance inhibition
Reduced sac >0.4 nig/kg
fry survival in eggs
Altered temperature 20
selection
Slight reduction in 2 mg/kg
sac fry survival in food
Altered temperature 10
selection
Altered temperature 100
selection
Reduced survival 2.9 mg/kg
in fry
Loss of balance 1.000-
and decreased
spontaneous electrical
activity of the
cerebellum
Cuerrier, et al. 1967
Dill & Saunders,'1974
Ogilvie & Anderson, 1965
Ogilvie & Miller, 19-76
Peterson, 1973
Anderson, 1968
Anderson & Peterson, 19691
Cuerrier, et al. 1967
Gardner, 1973
Macek, 1968
Miller & Ogilvie, 1975
Peterson, 1973
Burdick, et al. 1964
Aubin & Johansen, 1969
-------
Tacle 6 (Continued)
Test
Result
Organism
Ettgct
gef ergficfe
Goldfish,
Carassius auratus
Goldfxsh.
Carassius auratus
Golden shiner.
Notemigonus crysoleucas
Golden shiner,
Notemigonus crysoleucas
Fathead minnow,
Pimephales promelas
Black bullhead,
„ Ictalurus melas
u> Mosquitofish.
•"* Gambusia afflnis
Mosquitofish,
Gambusia affinis
Green sunfish,
Lepomis cyanellus
Bluegill,
Lepomis macrochirus
Bluegill.
Lepomis macrochirus
Toad (tadpole, 4-5-wk-
old).
Bufo woodhousei fowleri
Toad (tadpole. 4-5-wk-
pld),
Bufo woodhousei fowieri
Toad (tadpole. 6-wk-
4 days
7 days
24 hrs
36 hrs
266 days
36 hrs
36 hrs
40 min '
36 hrs
36 hrs
16 days
96 hrs
96 hrs
96 hrs
Exploratory
behavior inhibition
Schooling '
inhibition
Schooling
inhibition
LC50
Mg2* ATPase
inhibition
LC50
LC50
Succinic dehydrogenase
activity inhibition
LC50
LC50
Hyperactive locomotor
response
LC50
LC50 (TDE)
LC50
10
1
15
29.9
0.5
16.4
21.3
9 K 10"9
molar
23.5
28.7
0.008
1,000
140
100
Davy & Kleerekoper
Ueis & Wets, 1974
Baily, 1973
Ferguson, et al.
. 1973
1964
Desaiah, et al. 1975
Ferguson, et al. 1965a
Ferguson, et al. 1965a
Moffett & Yarbrough. 1972
Ferguson, et al. 1964
Ferguson, et al.
Ellgaard, et al.
Sanders, 1970
Sanders, 1970
Sanders, 1970
1964
1977
old).
Bufo woodhousei fowleri
-------
Tacle 6. (Concinued)
Test
to
I
to
to
OrqafUS.T.
Toad (tadpole, 7-wk- 96 hrs LC50
old).
Bufo wcodhousei fowleri
Frog (cadpole). 96 hrs LC50
Pseudacris crisertaca
Frog (cadpole). 96 hrs LC50 (TDE)
Pseudacris criseriaca
Result
X)
Frog (cadpole),
Rana clamicans
Turtle,
Chrysemys plcta
6 days Increased pituitary
melanocyte-sCirculating
hormone levels
30 min ATPase inhibition
30 Sanders, 1970
800 Sanders, 1970
400 Sanders, 1970
100 Peaslee. 1970
0.53 nM Phillips & Wells, 1974
Lowest value - 0.008 »g/l
-------
SALTWATER ORGANISMS
Introduction
' ' V
DDT, a chlorinated hydrocarbon insecticide, was at one time
the most widely used compound for the control of insect pests. It
"• f*
was applied for more than 30 years to a variety of environments,
including the aquatic environment, in many forms (such as powders,
emulsions, encapsulations).
- *
Despite the widespread use of DDT, relatively few data are
available that describe its chronic effects on aquatic animals.
No saltwater life-cycle toxicity test has been conducted* and only
one such study using a freshwater animal has been published.
i , t
• j'
Any examination of environmental contamination by a pesticide
must include a consideration of its persistence which may be
beneficial or harmful. Long-lived pesticides provide control of
target organisms over longer periods of time and reduce the need
for reapplication, but may also affect non-target flora and fauna
for long periods of time. DDT is recognized as a persistent
pesticide.
Because of its persistent nature, coupled with hydrophobic
properties and solubility in lipids, DDT and its metabolites are
concentrated by aquatic organisms from water, enter the food web
i
and are bioaccumulated by organisms at higher trophic levels.
DDT has several metabolites. In environmental samples, the
two most frequent metabolites reported are ODD (TDE or Rhothane)
and DDE. Rhothane was manufactured as an insecticide and used for
a number of years. Most of the available aquatic toxicity data
are for DDT. However, because of their widespread occurrence,
B-33
-------
ODD and DDE must be considered, particularly for their toxicities
to" -co'nsumer species and occurrence in monitoring programs.
°~- Thus, a derivation of a DDT criterion must consider not only
acute and chronic toxicity to aquatic organisms, but also 1) its
persistence, 2) its propensity for bioaccumulation , 3) its break-
dow.f) into longlived metabolites, and 4) the toxicity of DDT and
its metabolites to organisms at higher trophic levels, such as
bi,rds of prey, as a result of food chain bioaccumulation.
Toxicity, DDT
In flow-through exposures with unmeasured concentrations, the
unadjusted LC50 values (Table 7) for nine fish species ranged from
0.20 to 3.4 ug/1 (Schoettger, 1970; Lowe, unpublished data; Korn
««
and Earnest, 1974; Earnest and Benville, 1971).
Static tests results were also reported for nine 'species with
the adjusted LC50 values ranging from 0.2 to 4.2 ug/1 (Eisler,
1970a,b; Earnest and Benville, 1971). Two species were tested in
static and flow- through tests under similar temperature and salin-
ity conditions (Earnest and Benville, 1971) and a comparison of
the results indicates that LC50 values from static tests are ap-
proximately 15 times higher than those in flowthrough tests.
There f ore f the 0.71 adjustment factor for this test condition may
be too high for DDT.
Ad-justed LC50 values (Table 8) for flow-through tests with
OPT and invertebrate species ranged from 0.14 to 3.3 ug/1 (Lowe,
unpublished data; Schimmel and Patrick, 1975; Schoettger, 1970).
The adjusted 96-hour LC50 values for three invertebrate species
obtained from static tests ranged from 0.5 to 3.0 ug/1 (Eisler,
L969; Schoettger, 1970). The most sensitive saltwater invertebrate
B-34
-------
species tested were the commercially important white shrimp with
an LC50 value of 0.1 ug/1 (Lowe, unpublished data) and the Korean
shrimp with an LC50 of 0.13 ug/1 (Schoettger, 1970). The Korean
shrimp was exposed to DDT in both flow-through and static tests
under similar temperature and salinity conditions (Schoettger,
1970). The results indicated that the result of the static LC50
was more than five times greater than that in the flow-through
test. Thus, the invertebrate adjustment factor of 1.1 times the
static LC50.may be inappropriate.
Acute Toxicity, ODD and DDE
The acute toxicity of the DDT metabolite, ODD, to three
species of fish is reported in Table 7. In flow-through exposures
using unmeasured concentrations, the adjusted 96-hour LC50 values
for the three species ranged from 1.9 to 26.2 ug/1 (Lowe, unpub-
lished data; Korn and Earnest, 1974). Of the three species,
Morone saxatilis (Korn and Earnest, 1974), and Fundulus similis
(Lowe, unpublished data) were exposed to both ODD and DDE under
.similar temperature and salinity conditions. A comparison of the
results indicates that ODD was one-fifth to one-seventh as acutely
toxic to these species as was DDT.
Acute toxicity results for saltwater invertebrate species
exposed to ODD and DDE are reported in Table 8. Flow-through
adusted 48- or 96-hour EC50 or LC50 values for three invertebrate
species ranged from 1.2 to 19.3 ug DDD/1 (Lowe, unpublished data;
Schoettger, 1970). The 96-hour LC50 in static exposures of Korean
shrimp to DDD was 8.3 ug/1 and in flow-through exposures was 1.6
uq/1 (Schoettger, 1970). Flow-through adjusted LC50 values for
the Eastern oyster and the brown shrimp exposed to DDE were 10.8
B-35
-------
(96-hour) to 9.3 (48-hour) ug/1, respectively (Lowe, unpublished
data). Of the invertebrate species tested, the most sensitive to
DDT, ODD and DDE, appear to be the pink shrimp and the Korean
shrimp.
Chronic Toxicity
Concentrations of DDT affecting three saltwater invertebrate
species in long-term exposures did not differ greatly from 48- or
96-hour LC50 values. Concentrations of DDT affecting shell
de'position of the eastern oyster in seven days (10 ug/1; Butler,
1966) and DDT concentrations resulting in mortality of the blue
crab in 36 weeks (0.5 ug/1; Lowe, 1965) and pink shrimp in 28 days
(0'. 12 ug/1; Nimmo, et al. 1970) were similar to LC50 values in
acute exposures of two to four days duration (Table 8 and 11).
These data cannot be used to calculate an Invertebrate Chronic
Value because none of the above species were exposed during the
reproductive portions of their life-cycle.
Plant Effects
Information on the sensitivity of aquatic plants including
algae and rooted vascular plants, while limited, indicates that
they are much less sensitive to DDT than are fish or invertebrate
species (Table 9). DDT at concentrations of 10 ug/1 has been
found to reduce photosynthesis in saltwater diatoms, green algae,
and dinoflagellates (Wurster, 1968).
Res iduos
Several laboratory tests have investigated the bioconcentra-
tion of DDT in tissues of saltwater animals (Table 10). Biocon-
centration factors (BCF) in these studies ranged from 1,200 to
76,300 for fish or shellfish (Butler, 1966; Lowe et al., 1978;
t
B-36
-------
Nimmo, et al. 1970; and Hansen and Wilson, 1970). Eastern oysters
exhibited BCF values from 10,000 for a 12-day exposure (Butler,
1966) to 76,300 for a 168-day exposure (Lowe, et al. 1971); the
former study was probably not of sufficient duration for DDT to
accumulate to steady-state. Parrish (1974) exposed oysters to DDT
and metabolites for 392 days and reported a bioconcentration fac-
tor of 37,000 times the nominal exposure concentration (Table 11);
he noted that concentrations in tissues were a function of spawn-
ing activity (i.e., concentrations were highest immediately prior
to spawning and lowest after spawning).
Bioconcentration factors for DDT determined from saltv/ater
animals captured from their natural environments were comparable
with those from laboratory studies (Table 10). ,BCF's in these
studies ranged from 800 times for unspecified zooplankton
(Woodwell, et al. 1967) to 46,500 times for the dwarf perch,
Micrometrus minimus (Earnest and Benville, 1971).
Several studies have addressed the problem of concentrations
of DDT and metabolites in food and saltwater organisms and avian
predator species. Odum, et al. (1969) fed fiddler crabs a diet of
natural detritus containing DDT residues of 10 mg/kg. After five
days, crabs fed DDT-contaminated detritus exhibited extremely poor
coordination. Although no crabs died, such behavior would "almost
certainly affect survival under natural conditions." After eleven
days on the diet, the DDT and metabolites increased threefold in
their tissues to 0.885 mg/kg. Odum, et al. (1969) speculated that
the results of this study may help to explain the disappearance of
this species from a Long Island marsh sprayed with DDT for more
than 15 years.
B-37
-------
Avian species that feed on saltwater animals containing DDT
and metabolites (particularly DDE) have exhibited reductions in
their reproductive capacity. For example, a colony of Bermuda
petrels, a species which feeds primarily on cephalopods in the
North Atlantic, suffered a significant decline in their population
from 1958 to 1967 (Wurster, 1968). Analysis of unhatched eggs and
dead chicks revealed an average concentration of 6.4 mg/kg DDT and
metabolites (62 percent DDE). No data are available on the
concentrations of DDT and metabolites in 'the cephalopods consumed
by the petrels.
Two studies evaluated the effects of DDT and metabolites in
eggs of the brown pelican and the subsequent decrease in reproduc-
tive success. Blus, et al. (1974) reported that their reproduc-
tive 'success was normal only when concentrations of DDT (including
metabolites) and the insecticide, dieldrin, were less than 2.5
mg/kg and 0.54 mg/kg, respectively. Anderson, et al. (1975)
studied the breeding success of the brown pelican in relation to
residues of DDT and metabolites in their eggs and in their major
food source, the northern anchovy. Their analyses of data col-
j
lected from 1969 to 1974 included the following observations: (1)
residues of DDT and metabolites (the major compound was DDE) in
northern anchovies dropped steadily from a mean of 4.3 mg/kg (wet
weight) in 1969 to 0.15 mg/kg in 1974; (2) during that same per-
iod, DDT and metabolites in intact eggs averaged 907 mg/kg (lipid
weight) in 1969 to 97 mg/kg in 1974, and higher residues were as-
sociated with crushed eggs; and (3) productivity of pelicans in-
creased from a total of four young fledged in 1969 to 1,115
*
fledged in 1974, with a concurrent increase in eggshell thickness.
B-38
-------
Anderson, et al. (1975) stated that even the lowest concentration
of DDT and metabolites in northern anchovies (0.15 mg/kg) and the
subsequent 97 mg/kg concentration in pelican eggs were.unaccept-
ably high, because the pelican eggshell thickness was"below normal
and productivity was too low for population stability.
If data of Anderson, et al. (1975) are used to calculate a
Residue Limited Toxicant Concentration (RLTC), the maximum concen-
trations of DDT and metabolites allowable in fish would be less
than 0.15 mg/kg. The average fish BCF from Table 10 is 22,467.
The RLTC is, therefore, less than 0.0067 ug/1- Because the maxi-
mum concentration in fish is a concentration affecting pelicans, a
criterion based on this RLTC must be lower.
It is noteworthy that none of the fishes tested in Table 10
is a species that belong to the order Clupeiformes. Cluepeids are
a major food source for brown pelicans and are very high in lipid
content. Due to the lipophilic nature of DDT and its metabolites,
it is likely that these fishes would contain higher concentrations
of the insecticide than would fishes of lower lipid content such
as those listed in Table 10. Therefore, the average bioconcentra-
tion factor for fishes (22,467) listed in Table 10 may under-
estimate the concentration factors likely to occur in cluepeid
species. Because no no-effect concentration in food of pelicans
is known and because the bioconcentration factor for fish is prob-
ably too low, and RLTC based on these data is not likely to be
protective.
M iscellaneous
No other data from Table 11 suggest any more sensitive
effects.
B-39
-------
CRITERION FORMULATION
Saltwater-Aquatic Life
Summary of Available Data
The concentrations below have been rounded to two significant
figures.
Final Fish Acute Value =0.38 ug/1
Final Invertebrate Acute Value = 0.021 ug/1
Final Acute Value = 0.021 ug/1
Final Fish Chronic Value = not available
Final Invertebrate Chronic Value = not available
)•
Final Plant Value = 10 ug/1
Residue Limited Toxicant Concentration = 0.0067 ug/1
Final Chronic Value = 0.0067 ug/1
0.44 x Final Acute Value = 0.0092 ug/1
No saltwater criterion can be derived for DDT and metabolites
t,
using the Guidelines because no Final Chronic Value for either
fish or invertebrate species or a good substitute for either value
is available.
Results obtained with DDT and metabolites and freshwater or-
j
ganisms indicate how a criterion may be estimated for DDT and
metabolites and saltwater organisms.
For DDT and metabolites and freshwater organisms the Residue
Limited Toxicant Concentration is lower than the Final Fish
Chronic Value which is derived from results of a life cycle test
with the fathead minnow. Therefore, it seems reasonable to esti-
mate a criterion for DDT and metabolites and saltwater organisms
using the Residue Limited Toxicant Concentration as the Final
Chronic Value.
B-40
-------
The maximum concentration of DDT and metabolites is the Final
Acute Value of 0.021 ug/1 and the estimated 24-hour average con-
centration is the Final Chronic Value of 0.0067 ug/1. No impor-
tant adverse effects on saltwater aquatic organisms have been re-
ported to be caused by concentrations lower than the 24-hour aver-
age concentration.
CRITERION:, For DDT and metabolites the criterion to protect
saltwater aquatic life as derived using procedures other than the
Guidelines is 0.0067 ug/1 as a 24-hour average and the concentra-
tion should not exceed 0.021 ug/1 at any time.
B-41
-------
Table 7. Marine fish acute values for DDT and metabolites
Adjusted
Organisa
American eel,
Anguilla rostrata
Chinook salmon
Oncorhynchus tshawytscha
Sheepshead minnow,
Cyprinodon vartegatua
Sheepshead minnow,
Cyprinodon variegatus
Mummichog,
Funduius neteroclitus
Mummichog,
CO Funduius heteroclitus
1
£ Striped killifis'h,
Funduius majalis
Longnose killifish,
Funduius siroilis
'Longnose killifish,
Funduius similis
Atlantic silverside,
Menidia menidia
Striped bass,
Morone saxatilis
Striped bass,
Morone saxatilis
Pinfish,
Lagodon rhomboides
Spot,
Leiostomus xanthurus
Spot,
Bioaeeay
Method *
S
FT
FT
FT
S
S
S
FT
FT
S
FT
FT
FT
FT
FT
Test
Concur*
U
U
U
U
U
U
U
U
U
U
U
U
U
U
U
Time
iH£8)
96
96
48
48
96
96
96
48
48
96
96
96
48
48
48
LC50
4
0.68
3.2
2
3
5
1
42***
5.5
0.4
0.53
2.5***
0.32
1.8
20***
LC50
(uq/U
2.2
0.52
2
•1.2
1.6
2.7
0.55
26.2
3.4
0.2
0.41
1.9
0.20
l.l
12.5
hefer fence
Eisler, 1970b
Schoettger, 1970
Lowe, undated
Lowe, undated
Eisler, 1970a
Eisler, 197 Ob
Eisler. 1970b
Lowe, undated
Lowe, undated
Eisler, 1970b
Korn & Earnest, 1974
Korn & Earnest, 1974
Lowe, undated
Lowe, undated
Lowe, undated
Leiostomus xanthurus
-------
7. (Continued)
Adjusted
Organism
Shiner perch,
Cymatogaster aggregata
Shiner perch,
•Cymatogaster aggregata
Dwarf perch.
Micrometrus minimus
Dwarf perch,
Micrometrus minimus
Bluehead,
Thalassoma bifasciatum
Mullet,
CD Mugil cephalus
1
*J Mullet.
Mugil cephalua
Mullet, '
Hugil cephalus
Mullet.
Mugil cephalus
Mullet.
Mugil cephalus
Northern puffer,
Sphaeroid'es maculatus
Bioassay
Method *
S
FT
S
FT
S
S
S
FT
FT
FT
S
Test
Cone ,**
U
U
U
U
U
U
U
U
U
U
U
Time
thrs)
96
96
96
96
96
96
96
48
48
48
96
LC50
(uq/1)
7.6
1
0.45
4.6
0.26
7
0.9
3
0.4
0.55
0.4
89
CC50
4.2
0.35
2.5
.0.20
3.8
0.5
1.6
0.2
0.3
0.2
48.6
Kererei.ce
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville.
1971
Eisler, 1970b
Eisler, 1970b
Eisler, 1970b
Lowe, undated
Lowe, undated
Lowe, undated -
Eisler, 19705
* S. = static; FT - flow-through
.** M = measured; U = unmeasured
***DDD
Geometric mean of adjusted values = 1.37 jjg/1
" °-38 pg/1
-------
8 Marine invertebrate acute values for DDT and metabolites
Organism
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Brown shrimp,
Penaeus aztecus
Brown shrimp,
03 Penaeus aztecus
£ Brown shrimp,
Penaeus aztecus
Pink shrimp,
Penaeus duorarum
Pink shrimp.
Penaeus duorarum
White shrimp,
Penaeus setiferua
Grass shrimp,
Palaemonetes pugio
Grass shrimp,
Palaemonetes vulgaris
Sand shrimp,
Crangon aeptemspinosa
Korean shrimp,
Palaemon macrodactylus
Korean shrimp,
Palaemon macrodactylus
bicaseay Test
Metjiou* Cone. **
FT U
FT U
FT U
FT U
FT U
FT
FT
FT
FT
FT
FT
S
S
S
FT
M
U
U
Adjusted
Tine LC50 LC!>0
(nrs) (uo/il
-------
8. (Continued)
en
Organism
fiioassay Test Time
Method * CojiCj** (hrs)
Adjusted
LC50 LC50
(uq/l> (ug/Hfteterei.ce
CD
1
Korean shrimp, S U
Palaemon macrodaccylus
Korean shrimp, FT U
Palaemon macrodaccvlus
Blue crab, FT U
Callinectes sapidus
Hermit crab, S U
Pagurus longtcarpua
* 3 • static, FT - flow-through
** -'M ° measured; U - unmeasured
96 8.3*** 7 Schoettger, 1970
96 1.6*** 1.2 Schoettger, 1970
48 10 3.3 Lowe, undated
96 6 's.l Eisler, 1969
*** DDD
****DDE
Geometric mean of adjusted value - 1.01 ug/1 ^p - 0.021
Lowest value from flow-through test based on measured concentrations • 0.14 iig/1
1.01.
-------
09
I
*»
<3\
Table 9. Marine plant effects for DDT and metabolites (Wurster, 1968)
Concentration
Organism Effect
-------
Table 10. Marine residues for DDT and metabolites
CO
Organism
Zooplankton,
species not given
Mud snail,
Nassarius obsoletus
Hard clam,
Mercenaria mercenaria
Eastern oyster,
Crassostrea virginica
males
females
males and females
Gametes
eggs
sperm
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Pink shrimp,
Penaeus duorarum
Pink shrimp,
Penaeus duorarum
Shrimp,
species not given
Market crab,
Cancer magister
Market crab,
Cancer magister
American eel,
Bioconcentration Factot
.800*
5,200*
i
8,400*
20,000**
14,000**
10,000**
25,000**
9,000**
42,200**
76,300**
1.500**
1.200**
3,200*
14,250*
4,750*
5,600*
Time
Cdays)
field
field
field
1
12
12
12
12
12 '
252
168
13
56
field
field
field
field
Heterence
Uoodwell, et
Uoodwell, et
Uoodwell, et
Butler, 1966
Butler, 1966
Butler, 1966
Butler. 1966
Butler. 1966
Lowe, et al.
Lowe, et al.
Nimmo, et al
Nimmo, et al
Uoodwell. et
al. 1967
al. 1967
al. 1967
1970
1970
. 1970
. 1970
al.. 1967
Earnest & Benville. ;
1971
Earnest & Benville.
1971
Woodwell. et al. 1967
Anguilla rostrata
-------
00
I
*>.
CO
Tatle 10
Organism
Oyster toadfish,
Opsanus tau
Atlantic needlefish.
Strongylura marina
Sheepshead minnow,
Cyprinodon variegatus
Mummichog,
Fundulus heteroclltus
Atlantic silverside,
Menida men Ida
Threespine stickleback,
Gasterosteus aculeatus
Pinfish,
Lagodon rhomboides
Pinfish,
Lagodon rhomboides
Atlantic croaker,
Micropogon undulatus
Atlantic croaker,
Micropogon undulatus
Shiner perch,
Cymatogaster aggregata
Shiner perch,
Cymatogaster aggregata
Dwarf perch,
Micrometrus minimus
Dwarf perch,
Micrometrus minimus
White perch,
Phanerodon fureatua
White perch.
Phanerodon fureatus
(Continued)
Bioconcentration Factor
3,400*
41,400*
i
16,800*
24,800*
4,600*
5,200*
40,000**
11,000**
16,000**
12,200**
43,250*
34.750*
46.500*
37.000*
22,250*
29,250*
Time
(days)
field
field
field
field
field
field
14
14
21-35
14
field
field
field
field
field
field
neterence
Woodwell ,
Woodwell,
Woodwell ,
Woodwell,
Woodwell,
Woodwell,
Hans en, 1<
Hansen, 1!
Hans en, 1!
Hansen, V.
Earnest &
1971
Earnest &
1971
Earnest &
1971
Earnest &
1971
Earnest &
1971
Earnest &
1971
Benvilie,
Benville,
Benville,
Benville,
Benville,
Benville,
-------
Tatle 10. (Continued)
CO
Organism
Pile perch.
Racochilus vacca
Pile perch,
Raccochilus vacca
Staghorn sculpin,
Leptocotlus annatus
Staghorn sculpin,
Leptocotlus annatus
Summer flounder,
Paralichchys dentatus
Speckled sanddab,
Cithartchthys stigmaeua
Speckled sanddab,
Citharichthys stigmaeua
English sole,
Parophrys vetulus
English sole,
Parophrys vetulus
Starry flounder,
Platichthys stellatus
Starry flounder.-
Platichthys stellatus
Bioconcentratxon
26,750*
32,500*
17,000*
22,250*
25,600*
15,250*
12,250*
20,000*
13,000*
24,750*
23.750*
Time
Factor
field
field
1
field
field
i
field
field
field
field
field
field
field
Keterence
Earnest & Benville,
197L
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville.
1971
Woodwell. et al. 1967
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville,
1971
Earnest & Benville,
1971
Maximum Permissible Tissue Concentration
Organism
Man
Domestic animals
Action Level or Effect
Edible fish and shellfish
Animal feed
Concentration
(mR/kg)
5
0.5
Reference
U.S. FDA Admin. Guide lin
7420.08, 1973
U.S. FDA Admin. Guidelin
7426.04. 1977
Mallard.
Anas platyrhynchos
Eggshell thinning
llaseltine, et al. 1974
-------
Table 10. (Continued)
I
Ul
o
Organism
Mallard,
Anas platyrhynchos
Black duck,
Anas rubripes
Black duck,
Anas rubripes
Sparrow hawk,
Falco sparverius
Sparrow hawk,
Falco sparverius
Screech owl,
Ocus asio
Brown pelican,
Pelecanus occidentalis
Brown pelican,
Pelecanus occidentalta
Coho salmon
(fingerling),
Oncorhynchus kiautch
Chinnok salmon
(fingerling),
Oncorhynchus tshawytacha
Cucchroac trout,
Salmo clarkt
Rainbow trout,
Salmo gairdneri
Rainbow trout,
Salmo gairdneri
Action Level or Effect
Eggshell thinning
Eggshell thinning
Reduced duckling survival
Eggshell thinning
Reduced survival
Eggshell thinning
Eggshell thinning
Reduced productivity
Reduced survival
Reduced survival
Reduced sac fry survival
Inhibition of Na+-K+ ATPase
Rainbow trout,
Salmo gairdneri
Brown trout
Salmo trutta
Reduced phenoxyethanol
anesthetic induction
and recovery times
Reduced light intensity
discrimination
Reduced fry survival
Concentration
(mg/kg)
3***
3***
2.8
3
2.8
2.8
0.5
0.15
6.25
6.25
3
2.75
11.36
3.4
Reference
Heath, et al. 1969
Longcore, et al. 1971
Longcore & Stendell. 1977
Lincer, 1975
Porter & Wiemeyer, 1972
McLane & Hall, 1972
Blus, et al. 1972, 1974
Anderson, et al. 1975
Buhler, et al. 1969
Buhler. et al. 1969
Allison, et al. 1963
Campbell, et al. 1974
Klaverkamp. et al. 1976
McNicholl & Mackay, 1975
,Burdick. et al. 1972
-------
Tatle 10. (Continued)
Organism
Aceion Level or Effect
Lake trout. Reduced fry survival
Salvelinus namaycush
Concentration
(ing/kg)
Reference
Burdlck, et al. 1972
01
I
un
* Field data (including metabolites when given)
** Laboratory data (including metabolites when given)
*** Value converted from dry weight to wet weight basis
Average bioconcentration for fishes • 22,467
Average bioconcentration factor for pelecypods = 28,000
Lowest permissible tissue concentration "0.15 mg/kg
- 0.0000067 mg/kg or 0.0067 ng/1
-------
Table 11- Other marine data for DDT and metabolites
03
I
Ul
ro
Organ!am
Eastern oyster.
Crassostrea virglnica
Eastern oyster,
Crassostrea virgtnica
Pink shrimp,
Penaeus duorarum
Blue crabs,
Callinectes saptdus
Mummichog.
Fundulus heteroclitus
Mosquitofish.
Cambusia afftnis
Pink shrimp,
Penaeus duorarum
Test
Duration Effect
7 days Affected shell
deposition
392 days Bioconcentration '
factor • 37.000*
30 days Affected cation
concentrations in
hepatopancreas tissue.
36 wks Mortality
240 hrs LC50
24 hrs Affected salinity
selection
28 days LC100
Result x
lug/11 Reference
10 Butler, 1966
Parrish. 1974
0.05 Nlmrao & Blackman, 1972
i
0.50 Lowe, 1965
2.7 Eisler, 1970
5-20 Hansen, 1972
0,12 Nimroo, et al. 1970
* Result based on unmeasured water concentrations.
-------
DDT
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B-67
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Mammalian Toxicology and Human Health Effects
EXPOSURE
Introduction
DDT, first synthesized in Germany in 1874, has been
used extensively world-wide for public health and agricultural
programs. Its efficacy as a broad spectrum insecticide
and its low cost continue to make it the insecticide of
choice for those measures for most of the world.
Following an extensive review of health and environmental
hazards of the use of DDT, U.S. EPA decided to ban further
use of DDT. This decision was based on several properties
of DDT that had been well evidenced: (1) DDT and its meta-
bolites are toxicants with long-term persistence in soil
and water, (2) it is widely dispersed by erosion, runoff
and volatilization, (3) the low-water solubility and high
lipophilicity of DDT result in concentrated accumulation
of DDT in the fat of wildlife and humans which may be hazard-
ous. Agricultural use of DDT was canceled by the U.S. EPA
in December, 1972. Prior to this, DDT had been widely used
in the U.S. with a peak usage in 1959 of 80 million pounds.
This amount decreased steadily to less than 12 million pounds
by 1972. Since the 1972 ban, the use of DDT in the U.S.
has been effectively discontinued.
The purpose of this report is to briefly summarize
the published reviews in literature with special attention
to the mutagenic and carcinogenic effects of DDT and its
metabolites. Within the text, the following abbreviations
and their meanings are hereby noted.
C-l
-------
DDT refers to technical DDT, which is usually composed of:
77.1% p,p'-DDT
14.9% o,p'-DDT
0.3% p,p'-DDD
0.1% o,p'-DDD R-
4.0% p,p'-DDE
0.1% o,p'-DDE
3.5% unidentified compounds
DDT l,l'-(2,2,2-trichloroethyli-
de/ne) -bis/4-chlorobenzene/
DDE l,l'-(2,2-dichloroethenyli-
dene)-bis/4-chlorobenzene/
ODD 1,1'-(2,2-dichloroethylidene)
bis/4-chlorobenzene/
DDMU 1,1'-(2-chloroethenylidene)-
bis/4-chlorobenzene/
DDMS l,l'-(2-chloroethylidene)-
bis/4-chlorobenzene/
DDNU 1,1-bis(4-chlorophenyl)
ethylene
DDOH 2,2-bis(4-chlorophenyl)
ethanol
DDA 2,2-bis(4-chlorophenyl) -
acetic acid
R
-Cl
-Cl
-Cl
-Cl
-ci
-Cl
-Cl
-Cl
R'
-H
None
-H
None
-H
None
-H
-H
R"
-cci3
=cci2
-CHC12
-CHC1
-CH2C1
' =CH2
-CH2OH
-C(0)01
C-2
-------
Ingestion from Water
The solubility of DDT in water is approximately 1.2
ppb, although the presence of salts, colloid and particulate
material may increase this solubility. An examination of
Table 1 shows no instance of natural water approaching the
solubility limit (Bevenue, 1976). Lichtenberg, et al.
(1970) noted that residues in surface water peaked in 1966
and tapered down in 1967 and 1968, and this trend should
be continuing. Since the primary source of DDT residues
in surface waters is runoff from drainage areas, the varia-
tions seen in samplings range from non-detectable to 1 ppb
and are the result of variable seasonal runoff patterns,
sed-imentation rate-s, amount of pesticides on land areas,
and distance of travel from points of application.
By utilizing the guidelines for deriving water quality
criterion for the protection of aquatic life (43FR29028,
July 1978), maximum concentrations of DDT in fresh water
were calculated. To protect freshwater aquatic organisms
and consumers of these organisms, a twenty-four hour average
concentration of DDT of 0.00023 ug/1 and a maximum concentra-
tion of 0.41 ug/1 were proposed as standards. The chronic
levels proposed are near the limits of detection and subject
to significant analytical error (Gunther, 1969). The low
chronic level proposed may be a reflection of the large
bioaccumulation factor used in this model.
The National Academy of Sciences Safe Drinking Water
Committee estimates the carcinogenic risk to man to be an
excess death rate of 63 persons per year at a 10 ug/1 expo-
C-3
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TABLE 1
DDT and Metabolites in Waters of Different Areas
(Bevenue, 1976)
Water Sources
Time
Period
ppt
Range
Reference
Galveston Bay (Gulf
of Mexico)
Selected Western
Streams (USA)
Selected Western
Streams (USA)
Surface Waters of
United States
Region:
Northeast
Middle Atlantic
Southeast
Ohio Basin
Great Lakes
Missouri Basin
South Central
Southwest
Northwest
Iowa Rivers (USA)
Aransas Bay, Texas
(USA)
Big Creek, Ontario1,
Canada
Seawater, California
Current System
Hawaii:
potable waters
marine waters
Rivers, Southern
California Bight area
1964
1965-1966
1966-1968
1967-1968
1968-1970
1969
1970
1970
1971
1970-1971
N.D.-1,000
N.D.-120
N.D.-120
N.D.-30
N.D.-30
N.D.-60
N.D.-5
N.D.-270
N.D.-840
N.D.-110
N.D.-30
N.D.-20
N.D.-23
N.D.-100
3-67
2-6
ca 1
1-82
Casper (1967)
Brown and Nishioka (1967)
Manigold and Schulze
(1969)
Lichtenberg, et al.
(1970)
Johnson and Morris (1972)
Fay and Newland (1972)
Miles and Harris (1971)
Cox (1971)
Bevenue, et al. (1972)
Bevenue, et al. (1972)
1971-1972 120-880 SCCWRP (1972)
C-4
-------
sure. These calculations were for direct exposure from
water intake and do not account for bioconcentration effects.
In 1976, the U.S. EPA recommended that water levels not
exceed 0.001 jag/1 on the basis of bioaccumulation in food
and adverse effects in birds.
According to Lichtenberg, et al. (1970), fresh water
entering treatment plants contained DDT residues in amounts
1/10 to 1/500 of the permissible levels for public water
supplies as described in the Water Quality Criteria (Fed.
Water Pollut. Control Adm. 1968) of 50 ppt.
Assuming an average daily intake of 2 liters of water
per individual, Huang (1972) concluded that the maximum
daily ingestion would be 0.002 mg DDT, which is based on
the highest recorded levels in water. This would amount
to approximately 5 percent of the total daily dietary intake.
The preponderance of evidence indicates that DDT residues
in drinking water are 1 to 3 orders of magnitude less; there-
fore, it has been concluded that recorded DDT residues have
little significance when evaluating DDT effects on animal
populations, but may contribute to bioconcentration in aqua-
tic species and higher organisms in the food chain (Woodwell,
et al. 1967).
Ingestion from Food
The accumulation of DDT in different species of widely
different phylla has made it the classical compound for
study of biological magnification of pesticides. An abun-
dance of literature attests to the widespread movement of
persistent residues along food chains in natural environments
coupled with the biological concentration of the residue
at each' trophic level. Magnification of DDT occurs by two
C-5
-------
routes: (1) direct absorption from contaminated water for
aquatic organisms, (2) transfer of residues through sequen-
tial predator feeding.
Non-target species, such as predatory birds, have been
severely affected through reproductive loss due to eggshell
thinning. Although in no way comprehensive, the following
selected papers illustrate the relative magnitude of bio-
concentration of DDT. Johnson, et al. (1971) introduced
14
C-labeled DDT into fresh water; within 3 days from initial
e'xposure, the magnification factor in 2 groups of inverte-
brates (Cladocera and Diptera) ranged over 100,000 times;
in two others (Amphipoda and Ephemeroptera), in excesss
of 20,000; and in Decapoda and Odonata, up to 3000 magnifica-
tion. Cope (1971) calculated the accumulation of DDT in
comparison to water for several species. It was 70,000
v
times for oysters, 1,000,000 times for coho salmon, and
1200 to 317,000 in other fish. As a final example of biocon-
centration, Woodwell, et al. (1967) measured DDT residues
in a Long Island marsh area and observed the following ppm
on a whole body wet weight basis: for plankton, 0.04; water
plants, 0.08; snail, 0.26; shrimp, 0.16; minnow, 0.94; bill
fish, 2.07; heron, 3.5; cormorant, 26.4; gull, up to 75.5.
The primary route of human exposure to DDT is from
ingestion of small amounts in the diet. These residues
are transferred from agricultural soils, of which 5 percent
o£ the total area has been heavily treated and has an estimat-
ed average content of 2 ppm (Edwards, 1966). Since the
half-life of DDT is approximately 3 to 10 years (Menzie,
1972) and sandy soils can retain 39 percent at 17 years
C-6
-------
(Nash and Woolson, 1967), the presence of DDT residues in
foodstuffs derived from contaminated soils will continue
for some time.
Monitoring programs by the FDA have been conducted
in 80 markets nationwide in the period from 1965 to 1970
and the results are shown in Table 2 (Revenue, 1976). Meats,
fish, poultry and dairy products are the primary sources
of DDT residues.
As seen from these data, there have been continual
decreases in the overall levels of residues in all classes
from 1965 to 1970. Between 1970 and 1973, a significant
drop in residues of DDT and ODD occurred, constituting de-
creases of 86 and 89 percent respectively. DDE decreased
only 27 percent. These decreases are reflected in the chang-
ing amounts of estimated dietary intake: 1965 - 0.062 mg/man/
day, 1970 - 0.024 mg/man/day, 1973 - 0.008 mg/man/day (U.S.
EPA, 1975). This trend continued through 1977 as reported
by Johnson and Manske (1977). Compared to 49 percent of
the samples presently containing organochlorine residues,
54 percent were observed in 1971. DDE in meat, fish and
poultry has declined from 0.114 to 0.033 ppm, and in dairy
products from 0.043 to 0.017 ppm, while DDT remained constant
in meat residues at 0.017 ppm. The decreases in pesticide
residues in various food classes indicate that the ban on
DDT has indeed lowered the exposure of humans in the diet.
This decrease is paralleled by a lowering of the total DDT
equivalent in human tissues for the U.S. population average
from approximately 8 ppm to 5 ppm residue in fat from 1971
through 1974.
C-7
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TABLE 2
DDT and Metabolite Residues in Food and Feed*
(Duggan, et al. 1967; Duggan, 1968; Corneliussen, 1969, 1970, and 1972)
Product and
time period
Dairy products (
1965-1966
1967-1968
1968-1969
1969-1970
Meat, fish, and
1965-1966
1967-1968
1968-1969
1969-1970
Grains
1965-1966
1967-1968
1968-1969
1969-1970
Leafy vegetables
1965-1966
1967-1968
1968-1969
1969-1970
DDT
fat basis
0.040
0.030
0.023
0.017
poultry (
0.299
0.103
0.101
0.072
,
0.008
0.004
0.005
0.004
0.012
0.015
0.010
0.007
Garden fruits (tomatoes,
1965-1966
1967-1968
1968-1969
1969-1970
Fruits
1965-1966
1967-1968
1968-1969
1969-1970
Oils (salad oil,
1965-1966
1967-1968
1968-1969
1969-1970
0.027
0.029
0.028
0.019
0.009
0.009
0.009
0.021
Residue (ppm)
TDE DDE
, 8-13% fat)
0.015
0.019
0.012
0.005
fat basis, 17-23%
0.139
0.062
0.043
0.049
0.002
0.001
0.001
0.001
0.016
0.007
0.001
0.001
cucumbers, squash
0.017
0.015
0.012
0.016
0.003
0.001
0.004
0.001
margarine, peanut butter,
0.009
0.009
0.003
0.006
0.016
0.028
0.003
0.003
0.075
0.063
0.048
0.043
fat)
0.254
0.116
0.100
0.114
0.001
0.002
0.001
0.001
0.005
0.004
0.007
0.002
, etc. )
0.005
0.002
0.002
0.002
0.002
0.002
0.001
0.001
etc. )
0.005
0.018
0.003
0.002
Total
0.130
0.112
0.083
0.065
0.602
0.281
0.244
0.235
0.011
0.007
0.007
0.006
0.033
0.026
0.018
. 0.010
0.049
0.046
0.042
0.037
0.014
0.012
0.014
0.023
0.030
0.055
0.009
0.010
*Bevenue, 1976
C-8
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The acceptable daily intake of DDT established by WHO/FAO
is 0.005 mg/kg/day. Duggan and Corneliussen (1972) reported
the six-year average from 1965 through 1970 in the U.S.
diet of DDT and its metabolites to be almost tenfold less
at 0.0007 mg/kg/day.
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
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.
C-9
-------
Measured bioconcentration factors for DDT have been
obtained with many aquatic species, both in laboratory tests
and from field exposures, but only the species for which
the percent lipids could be estimated are used herein.
Many of the BCF values include metabolites of DDT, such
as DDE.
Species
Freshwater fish
BCF
Percent Adjusted
Lipids BCF
Reference
Alewife, 1,296,666 10. 298,000 Reinert, 1970
Alosa pseudoharengus
Lake herring,
Cor eg on us artedi
Lak'e whitefish,
Coregonus clupeaformis
Bloater ,
Coregonus hoyi
Cisco,
Coregonus
Rainbow trout,
Salmo gairdner i
Rainbow trout,
Salmo gairdner i
Brown trout,
Salmo trutta
Lake trout,
Salvelinus namaycush
Lake trout,
Salvelinus namaycush
3.3 156,000 Reinert, 1970
7.6 78,700 Reinert, 1970
2,236,666
260,000
2,870,000 20. 330,000 Reinert, 1970
368,777
11,607
38,642 12
45,357
458,259
1,168,333 10 269,000 Reinert, 1970
6.4 133,000 Miles, & Harris
1970
1.0 26,700 Miles & Harris,
1970
7,400 Reinert, et al.,
1974
1.8 58,000 Miles & Harris,
1973
4.4 240,000 Miles & Harris,
1973
C-10
-------
Species
American smelt,
Osmerus mordax
Carp,
Cyprinus carpio
Fathead minnow,
Pimephales promelas
White sucker,
Catostomus commersoni
i
Rock bass,
Ambloplites rupestris
Bluegill,
Lepomis macrochirus
Yellow perch,
Perca flavescens
Percent
BCF Lipids
Adjusted
BCF
770,000 3.9 454,000
640,000 6.2 237,000
99,000 8.0 28,000
110,000 2.8 90,000
17,500 4.0 10,000
16,071 4.0 9,200
1,073,333 7.9 312,000
Saltwater bivalve molluscs
Hard clam,
Mercenaria mercenaria
Eastern oyster,
Crassostrea virginica
Eastern oyster,
Crassostrea virginica
Saltwater decapods
Pink shrimp,
Penaeus duorarum
Shrimp,
species not given
Market crab,
Cancer magister
Market crab,
Cancer magister
Saltwater fish
Sheepshead minnow,
Cyprinodon variegatus
8,400 1.4 13,800
42,200 1.5 64,700
76,300 1.5 117,000
1,200 1.1 2,500
3,200 1.1 6,700
14,250 1.3 25,000
4,750 1.3 8,400
18,800 5.0 8,600
Reference
Reinert, 1970
Reinert, 1970
Jarvinen, et al,
1977
Miles & Harris,
1973
Miles & Harris,
1973
Mules & Harris,
1973
Reinert, 1970
Woodwell, et al.
1967
Lowe, et al. 1971
Lowe, et al. 1971
Nimmo, et al.
1970
Woodwell, et al.
1967
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Woodwell, et al,
1967
C-ll
-------
Species
Shiner perch,
Cymatogaster aggregata
Shiner perch,
Cymatogaster aggregata
Dwarf perch,
Micrometrus minimus
Dwarf perch,
Micrometrus minimus
White perch,
Phanerodon fureatus
White perch,
Phanerodon fureatus
Pile perch,
Racochilus vacca
Pile perch,
Raccochilus vacca
Staghorn sculpin,
Leptocotlus armatus
Staghorn sculpin,
Leptocotlus armatus
Summer flounder,
Paralichthys dentatus
Speckled sanddab,
Citharichthys stigmaeus
Speckled sanddab,
Citharichthys stigmaeus
English sole,
Parophrys vetulus
English sole,
Parophcys vetulus
Starry flounder,
Platichthys stellatus
Starry flounder,
Platichthys stellatus
Percent Adjusted
BCF Lipids BCF
43,250 3.4 29,000
34,750 3.4 23,500
46,500 6.4 16,700
37,000 6.4 13,300
22,250 2.8 18,300
29,250 2.8 24,000
26,750 4.4 14,000
32,500 4.4 17,000
17,000 1.9 27,000
22,250 1.9 27,000
25,600 0.9 65,400
15,250 2.7 13,000
12,250 2.7 10,400
20,000 2.0 23,000
13,000 2.0 15,000
24,750 2.5 22,800
23,750 2.5 21,800
Reference
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Woodwell, et al.
1967
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
Earnest &
Benville, 1971
C-12
-------
Each of these measured BCF's was adjusted from the percent
lipids of the species to the 2.3 percent lipids that is
the weighted average for consumed fish and shellfish. The
geometric mean was obtained for each species, and then for
all species. Thus the mean bioconcentration factor for
DDT and the edible portion of all aquatic organisms consumed
by Americans is calculated to be 39,000.
Inhalation
Levels of DDT found in,the air are far below levels
that add significantly to total human intake. Stanley,
et al. (1971) sampled air in 9 localities in both urban
and agricultural areas in the U.S. p,p'-DDT was found in
3 3
all localities in ranges from 1 ng/m of air to 2520 ng/m .
Generally, levels were highest in southern agricultural
areas and lower in urban areas. These samples were taken
during time of high usage of DDT. Most likely, air concentra-
tions are much lower today. Kraybill (1969) estimated the
concentration of DDT in the air to be 0.2 ng/m which is
in the lower range of Stanley's reported values.
In a study on plant workers, Wolfe and Armstrong (1971)
estimated respiratory exposure from the contamination of
filter pads placed within respirators. The highest exposures
reported were 33.8 mg/man/hour for the bagging operation,
with a mean 14.11 mg/man/hour. The authors concluded that
workers in fomulating plants not wearing respirators have
significant intake of DDT via inhalation. Wolfe, et al.
(1967) used a similar method to determine inhalation exposure
and found for airplane flaggers in dusting operations 0.1
to 0.2 mg/man/hour levels.
C-13
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Dermal
Absorption of DDT through skin is minimal. Several
factors can influence the rate of absorption, such as the
condition of the skin or external factors such as temperature.
Technical DDT was less toxic dermally to white rats than
a large percentage of other pesticides tested by Gaines
(1969). In Wolfe and Armstrong's study (1971), most of
the exposure was dermal with the exposure ranging from 5
to 993 mg/man/hour, but these high values did not correlate
with significant increases above the general population
in the urine of the workers. This led them to conclude
that there was a minimal absorption of DDT in -exposed skin
areas.
Hayes (1966) estimated the intake of DDT to be in the
following proportions: food - 0.04 mg/man/day, water -4.6
x 10- mg/man/day, and air - 9 x 10- mg/man/day. Wessel
<1972) calculated the daily dietary intake of DDT and ana-
logues to be 0.027 DDT, 0.018 DDE and 0.012 ppm ODD. Kraybill
(1969) estimated DDT dietary intake to be approximately
85 percent of the total exposure of 30 mg/year. Aerosols,
dust and cosmetic exposure were estimated as 5 mg/year,
with air and water intakes of 0.03 and 0.01 mg/year, respec-
tively.
From these estimates, it is concluded that the maximum
total intake of DDT and analogues does not exceed 0.1 mg/man/
day and is probably today considerably less, due to restric-
tion in its use. Since dermal, inhalatiori and water intake
account for less than 10 percent of the total dosage, and
in most recent estimates dietary intakes are 0.008 mg/man/
day, the actual total dose per day is estimated to be approxi-
mately 0.01 mg/man/day or 3.65 mg/year.
C-14
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PHARMACOKINETICS
Absorption
DDT and DDE are absorbed from the gastrointestinal
tract with high efficiency characteristic of dietary fat.
Maximum lipid solubilities reach 100,000 ppm. Inasmuch
as DDT and metabolites ingested are contained primarily
in fat-bearing foodstuffs, such as dairy products, meat
and poultry, the absorption of dietary DDT approaches the
95 percent absorptive values for these dietary fats. Over
65 percent of labeled DDT and metabolites were found in
the nine-day bile collections of treated rats (Jensen, et
al. 1957).
Determinations of absorption and assimilation of ingested
DDT in humans have, been studied by following the serum concen-
trations of the compound after ingestion (Morgan and Roan,
1971). Highest concentrations were found in the samples
taken 3 hours after ingestion of DDT. Serum concentrations
remained above pre-dose level for at least 14 hours but
returned to base level within 24 hours. Blood levels show
a relatively slow uptake and assimilation consistent with
physiological dependence on intestinal fat absorption.
However, absorption proceeded faster than transport out
of the vascular compartment into tissue storage with a dosage
oE 20 mg. Assimilation of the entire given dose was completed
within 24 hours. One subject ingested 2.82 g technical
DDT, with approximately 85 percent being stored or excreted
in the urine. The authors concluded that several factors
collectively cause storage values to underestimate absorptive
efficiency and that true intestinal absorption of DDT in
C-15
-------
man is essentially similar to fat.
Distribution
DDT and its metabolites have been found in virtually
all body tissues, approximately in proportion to respective
tissue content of extractable tissue lipid, except in the
brain. Adipose/blood ratios of DDT have been variously
estimated from 140 to -1000; more recent estimations indicate
that the ratio is approximately 280 fat: plasma (Morgan
and Roan, 1977). This ratio represents a dynamic equilibrium
between DDT in plasma lipoprotein and in triglycerides stored
in fat cells.
Long-term admininstration of DDT to mice and its storage
in various tissues have been reported by Tomatis, et al.
(19-71). Apart from o,p'-DDT, there is direct relationship
between the concentration of each metabolite in each organ
and the dose to which the animal was exposed. The highest
concentration of DDT and metabolites was found in fat tissue,
followed by reproductive organs, liver and kidney together,
and lastly, brain. The most prevalent stored compound was
unaltered p,p'-DDT. Storage levels of o,p'-DDT were propor-
tionally higher in animals receiving the control diet or
exposed to the lowest DDT dose. In the reproductive organs
and fat, females had considerably greater levels of all
three compounds than males, with no storage differences
in kidney, brain and liver.
In Rhesus monkeys, Durham, et al. (1963) noted that
dosage levels from .25 to 10 mg/kg/day technical DDT in
the diet produced a maximum storage in fat by 6 months,
which was not increased by feeding for an additional period
C-16
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of 7 years. Of interest is the fact that no DDE'was detected
in the fat of these monkeys. However, high levels of DDE
storage were found in monkeys fed DDE, indicating an inability
to convert DDT to DDE.
Human adipose storage decreases in the order DDE>p,p'-
DDT>DDD. Serum and adipose concentrations of DDE rise
slowly to DDT ingestion with the peak some months following
termination of dosing. In contrast, levels of DDT, ODD and
o,p'-DDT decline more rapidly. Fitted exponential curves
in man suggest that 25 percent of stored material should
be lost within a year after the last administration. Elimina-
tion of very low levels from storage of DDT proceeds much
more slowly than disposition of the large stores of DDT
accumulated by occupationally exposed or dosed volunteers.
Thus, when DDT in fat amounts to 100 ppm, the chemical is
lost at a rate of 4.1 mg/day or 0.24 percent of the total
store. When, after 2 years, the load has decreased to 40
ppm, the loss rate falls to 0.2 mg/day or 0.10 percent of
store; projected to 5 ppm, storage loss is 0.03 mg/day DDT
or only 0.04 percent of body stores (Morgan and Roan, 1971).
Hayes, et al. (1971) have shown that subjects ingesting
high doses up to 35 mg/kg/day DDT reach a storage plateau
sometime between 18 to 22 months (Figure 1). Volunteers
had mean adipose concentrations of 281 ppm with a high of
619 over a 21-month period. DDE reached levels as high
as 71 ppm with a mean of 25.8 ppm in 21 months, but the
values increased during recovery to a peak of 563 ppm approxi-
mately two years after dosing, and fell only slightly to
50.8 after a 3-year recovery. Over a 5-year recovery period,
C-17
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1000
500-
0
5
O 35 mg. pp'-DDT/man/day
• 3.5mg. pp'-DDT/man /day
100
200 300 400
Time of treatment, days
FIGURE 1
500
600
Increase of the Concentration of PP'-DDT in the Bodyfat
of Men with Continuing Intake of PP'-DDT*
(Based on Hayes, et al. 1971)
C-18
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the concentration of DDE in fat as a percentage of all DDT
derived material rose from 26 to 47 percent.
The preceding data are consistent with the known fact
that DDE is very slowly eliminated from the body and has
the higher affinity for storage. The average North American
adult, with 17 kg of body fat, contains approximately 25
mg of DDT and 75 mg of DDE. Storage loss data predict that,
if dietary intake were eliminated, most of the DDT would
be lost-within one or two decades, but DDE would require
an entire lifespan.
It has been suggested by a number of investigators
that DDT levels reflect recent exposure to DDT, while DDE
levels correlate well with long-term exposure and storage
capacity of the human body (Roan and Morgan, 1971; Edmundson,
et al. 1969b). In occupationally exposed workers, Laws,,
et al. (1967) determined the concentrations in fat of DDE
expressed as DDT to be 25 to 63 percent of total DDT related
material. This is in contrast with 72 to 92 percent found
in the general population.
Tissue storages of DDE in the general population origin-
ate almost entirely from dietary DDE rather than DDT converson
(Roan and Morgan, 1971).
A comparison of DDT and DDE storage in the U.S population
is shown in Table 3 (U.S. EPA, 1975). Mean levels of DDT
in human adipose tissue show a downward trend from 7.95
ppm in 1971 to 5.89 ppm in 1973. Overall DDE levels on
the other hand, do not show a similar trend; and long-term
storage is reflected in the slightly increased percentage
of the total DDT found as DDE.
C-19
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TABLE 3
National Summary of Total DDT Equivalent
Residues in Human Adipose Tissue*
(Total US Population Basis)
FY 1970 FY 1971 FY 1972 FY 1973
1,412
99.3%
7.87 ppm
77.15%
1,616
99.75%
7.95 ppm
79.71%
1,916
99.95%
6.88 ppm
80.33%
1,092
100.00%
5.89 ppm
81.19%
Sample size
Frequency
Geometric mean
Percent DDT found as DDE
Total DDT equivalent = (o,p'-DDT + p,p'-DDT)
+ 1.114 (o,p'-DDD + p,p'-DDD +
p,p'-DDE + 0,p'-DDE)
*U.S. EPA, 1975
C-20
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A simple linear model has been developed by Durham,
et al.-(1965b) to describe the relationship between the
concentration of DDT in the body fat of man and the daily
dose of this compound. The equation is: log C, = 0.7 log
I + 1.3, where C, is the fat storage of DDT in ppm and I
is the DDT intake in mg/man/day. This equation gives good
agreement with storage found by other investigators and
is represented in graphical form in Figure 2.
At high levels of exposure, human volunteers have demon-
strated a steady state of storage or plateau which is exponen-
tially approached within 18 months. This plateau level
is proportional to the dose administered (Figure 1).
Metabolism
. The metabolism 6f DDT'has been well established in>
several mammalian species. Generally, two separate reductive
pathways produce the primary endpoint metabolites, DDE and
DDA. As seen in Figure 3, a generalized outline of the
metabolism of DDT, the predominant conversion is of DDT
to ODD via dechlorination. This is the first product in
a series which results in metabolites which are later excreted,
The other primary pathway proceeds via reductive dehydrochlor-
ination which results in the formation of DDE, the major
storage product in animals and humans.
Peterson and Robison (1964) showed convincingly that
ODD was the intermediate metabolite leading to DDA. Adult
male rats were treated acutely by gavage with 100 mg/kg
purified DDT and sacrificed 4 to 60 hours later. Liver
samples yielded primarily DDT and ODD, in a ratio of 14:1.
C-21
-------
1500.0
I
o
o
100.0
e
o
o>
g
o
O
10.0
1.0
O Mean.
T standard error of mean
0.01
0.1 1.0
Daily dose of DDT, mg/day
10.0
35.0
FIGURE 2
Relationship Between the Concentration of DDT in the Bodyfat
of Man and the Daily Dose of that Compound*
(Based on Hayes, et al. 1971 and Durham, et al. 1965b)
C-22
-------
H—C—Cl
DDT
DDD
DDMU"
«--c--ci
H—C—Cl
"DDMU"
•DDMS'
DDNU"
II
H-C-H
•DDNl"
Cl -
•DDOH-
-Cl
CHO
Probable inter-
mediate aldehyde
n-
Probable intor-
nirdinio aldehyde
(O)
COOH
DDA
FIGURE 3
Metabolic Products of P,P'-DDT in the Rat
(Peterson and Robison, 1964)
C-23
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Rats fed a diet of 1SOO ppm purified DDT were sampled at
6 days; the livers yielded DDT, ODD and DDE in the ratios
of approximately 3:5:1. Additional rats given 1000 mg/kg
ODD in identical manner of the DDT treatment showed ODD
and DDMU in a ratio of 1:13. Liver and kidney samples
of DDE-treated rats yielded only unchanged DDE, and the
urine from a two-week diet of a 1000 ppm DDE showed no detect-
able DDA. Furthermore, rats treated acutely with DDMU were
able to biologically convert this compound to DDMS. Similarly,
DDMS administration produced DDNU in ratios of 2:5 in the
kidney and 3:1 in the liver.
The final conversion step of DDNU to DDA by hydroxy-
lation occurs more slowly. Short-term 6-hour exposure to
DDNU produced minimal amounts of DDOH. However, analyses
of liver and kidney tissue from rats fed 500 ppm DDNU diet
contained equal quantities of DDNU and DDOH, and the urine
collected provided identification of DDA. Each degradation
product from DDT to DDNU when fed to rats was able to eventu-
ally exhibit DDOH and DDA in the urine. The aldehyde showa
in Figure 3 was postulated by the authors as a briefly exist-
ing intermediate between DDOH and DDA in mice.
Recent studies with pregnant rats using radiolabeled
14
C-p,p'-DDT give evidence of the sites in which a metabolite
conversion occurs. Thin layer chromatography of various
14
tissues following treatment with 0.9 mg C-DDT was utilized
to determine the relative percentages of the metabolites
produced. In the liver, from 12 to 24 hours the ratio of
DDT, ODD and DDE was unchanged at approximately 3:3:1, a
ratio similar to that found by Peterson and Robison (1964)
of 3:5:1 in male rats. Liver activity for DDT conversion
C-24
-------
is much higher in the adults in comparison to neonates.
The results for the metabolites recovered from different
tissues and fetuses 8 to 10 hours post exposure are shown
in Tables 4 and 5 (Fang, et al. 1977). DDE was the major
metabolite in all tissues. ODD was a minor metabolite,
with the exception of spleen, in which ODD and DDE were
equal. DDA was detected in high levels in lung, intestine,
kidney and blood, in lower levels in spleen, placenta and
fetus; and was undetected in muscle, heart, pancreas and
brain. These observations suggest that enzymatic activity
for the dehydrochlorination and reductive dechlorination
reactions transforming DDT to DDD and DDE are present in
all tissues, whereas the enzymes involved in the hydrogenation
and hydroxylation steps changing DDD to DDA are absent in
brain, heart, pancreas and muscle of the rat.
The metabolism of o,p'-DDT in rats shows no striking
differences to that of p,p'-DDT. Feil, et al. (1973) were
able to detect 13 different metabolites in the rat excreta
by nuclear magnetic resonance spectra. Besides o,p'-DDD
and o,p'-DDA, a number of additional ring hydroxylated DDA
\
forms were present. Serine and glycine conjugants and o,p'-
dichloro-benz-hydrol were identified in the rat urine.
These results indicate that o,p'-DDT is extensively metabolized,
Radiolabeled o,p'-DDD given orally in a 100 mg dose
to rats yielded, in both feces and urine, o,p'-DDA, aromatic
3-, 4-monohydroxy and 3, 4-dihydroxy substituted o,p'-DDA.
Comparison of urinary excretion of o,p'-DDD metabolites
of rats and humans are fundamentally similar. Hydroxylation
C-25
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TABLE 4
Concentration of 14C-DDT and its Metabolites in the Tissues of Infant Rats after Consumed Milk from Dam
Receiving an Oral Dose of 0.9 mg C-DDT and of the Dams (ug DDT and Equivalent per g Dry Tissue)
n
Elapsed
time
(days)
Stomach
content
(milk)
Stomach
Blood
Liver
Kidney
Intestine
Lung
Heart
Brain
Carcass
Infant Rats
l(4)a
2(4)
3(4)
4(4)
7(4)
11(2)
14(3)
21(2)
28(2)
14
28(2)
15.
4.
3.
3.
1.
1.
0.
1.
0.
26+3. 27b
56+ .46
49+1.09
73+ .35
62+ .18
73
75
33
48
-
-
4.82
2. 81+. 13
2. 31+. 06
2. 18+. 15
1.59+. 28
1.42
1.03
0.99
0.70
-
-
.72+. 34
1.59+.52
1.70+.15
1.59+. 34
1.23+.29
1.21
0.44
0.40
0
0
0
13.93+2.50
14.23+6.94
12.13+4.26
8.29+1.73
5.96+1.78
5.93
4.64
2.39
1.11
0.68
0.50
2.50+ .53
4.35+ .84
4.73+ .71
3.52+1.23
3.08+ .72
3.13
2.22
0.76
0.20
.07
.12
13.64+3.37
13.48+6.36
11.09+3.72
8.42+2.36
8.07+3.19
5.98
5.42
1.95
0.95
Dams
.20
.78
3.30+ .97
5.05+1.60
6.23+1.78
5.25+ .75
4.26+ .79
4.25
1.97
1.13
0.52
1.12
.40
1.21+. 22
1.57+. 56
1.91+.64
2. 00+. 85
1.13+. 26
1.81
1.04
0.60
0.18
.28
0
1.23+.35
2.24+.94
1.83+.94
1.83+.72
1.11+.62
1.30
0.62
0.28
0.14
.06
.10
6.34+2.
9.11+1.
10.98+1.
9.64+ .
7.09+ .
6.16
4.39
2.42
1.87
-
-
22
12
63
57
57
?Number of neonates used
Values are means +_ standard deviation
Fang, et al. 1977
-------
14
TABLE 5
C-DDT and its Labeled Metabolites in Different Tissues, of
••A **. C -L »/
Pregnant Rats 8 or 10 hr after Receiving an Oral Dose of C-DDT
Tissue
Blood
Brain
Fetus
Heart
Intestine
Kidney
Lung
Muscle
Pancreas '
Placenta
Spleen
Radioactivity
recovered
(meOH: hexane)
(%)
83
100
86
100
93
88
100
99
100
100
83
.02-. 04
DDA
26
0
8
0
39
24
41
0
0
4
11
RF
.36-. 43
ODD
10
18
20
10
18
5
6
0
5
9
32
Values
.46-. 52
DDT
31
36
25
67
11
24
8
9
15
5
14
„ i
.56-. 61
DDE
33
46
35
20
31
34
32
72
59
49
36
f
75
1
0
12
3
1
13
14
19
21
27
0
Fang, et al. 1977
C-27
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occurs primarily at the 3 and 4 positions. Humans show
a higher percentage of total dose excreted in the urine
than rats, 10 to 50 percent versus 3 to 7 percent. Serine
and glycine conjugates are excreted in the urine of man
and rat (Reif and Sinsheimer, 1975).
The metabolism of DDT in mouse follows essentially
the same pathways as the rat (Gingell and Wallcave, 1976).
No species differences in overall rates of metabolism of
14
DPT, as measured by urinary excretion of C were observed.
Further studies investigating chronic exposure up to 4 months,
have demonstrated fundamental differences in the metabolic
and physiological handling of DDT among other rodent species.
Both Swiss and CF, mice produce small but significant amounts
of -DDE in urine, whereas none was found in hamster urine
(Gingell, 1976). With long-term feeding experiences, the
mouse increasingly eliminates DDE, and at the termination
of the experiment, nearly as much DDE as DDA was found (Gingell
and Wallcave, 1976). The authors suggest that DDE may be
the proximate hepatotumorigenic metabolite in mice, inasmuch
as hamsters are not susceptible to DDT tumorigenesis and
do not form DDE. Additionally, hamsters are resistant to
toxic effects of DDT up to 2100 mg/kg (Agthe, et al. 1970).
Two major studies by Hayes, et al. (1971) and Roan
and Morgan (1977) are the basis for what is known of the
metabolism o£ DDT in man and are here described. Hayes,
et al. (1971) performed two studies, exposing volunteers
from a U.S. penitentiary to technical or recrystallized
p,p'-DDT at rates from 3.5 mg to 35 mg/man/day. In the
first study, ten subjects were studied: three for one year
C-28
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at 3.5 mg/man/day and seven for one year at 35 mg/man/day.
In the second study, 24 men could be followed for a period ,
of over four years. They consisted of four groups: Gl
- a control, whose diet was estimated as having 0.18 mg/man/
day DDT; G2 - receiving 3.5 mg technical DDT (85 percent
p,p'-DDT); G3 - receiving 35 mg technical DDT (85 percent
p,p'-DDT); and G4 - receiving 35 mg recrystallized p,p'-DDT.
Roan, et al. (1971) and Morgan and Roan (1977) measured
the concentrations of p,p'-DDE, p,p'-DDD and p,p'7DDA in
blood, fat and urine in response to oral dosing with these
compounds. Four volunteers ingested technical DDT doses
ranging from five to 20 mg/day for up to six months. The
total dose ingested ranged from 0.06 g to 2.82 g. Two volun-
teers ingested a total dose of 0.45 g p,p'-DDE in a three-
month period. A single volunteer was used for each dosing
of ODD and DDA for total dosages of 0.41 g and 0.105 g,
respectively.
»
From these studies, Morgan and Roan (1977) concluded
that the conversion of DDT to DDE occurs with considerable
latency. The magnitude of conversion at these levels was
estimated to be less than 20 percent conversion in the course
of three years. An upper trend in DDT fat storage over
this time course may be due to release of stored DDT and
further conversion to DDE, but no more than one-fifth of
the absorbed DDT ultimately undergoes this conversion.
The o,p'-isomer was not found to be present in fat and blood
of the subjects. DDE-dosed subjects did not exhibit any
significant excretion'of p,p'-DDA in excess of predose values.
Dose-dependent increases in ODD blood levels with DDT dosing
indicated the existence of this metabolic pathway. Urinary
C-29
-------
DDA excretion and serum ODD concentrations showed increases
with DDT dosage and declined after dosing ended. Conversely,
DDE exhibited an upward trend for months after dosing.
These facts further support the mutally exclusive role of
ODD, rather than DDE, in the formation of the urinary metabo-
lite, DDA. Taken together, these results strongly confirm
that the metabolism of DDT in man is identical to the pathways
reported by Peterson and Robison (1964) for the mouse.
Metabolic conversion of DDT by dechlorination to DDA proceeds
more rapidly and accounts for approximately one-fifth of
the DDT load, which is excreted in the urine. DDE, or the
storage metabolite, is produced from DDT more slowly, via
dehydrochlorination, and overall conversion will be approxi-
mately 20 percent 'in three years.
Excretion
Studies were conducted by Wallcave, et al. (1974)
«
on the excretion of DDT metabolites in hamsters and mice.
Of the ingested dose of between 22 to 29 mg per animal over
a four-month period, 12 to 14 percent was reco'vered in the .
urine as DDA or DDE. Steadily increasing amounts of DDE
excretion were observed in mice with long-term feeding,
whereas the hamster had no DDE present. Approximately 9
percent of ingested DDT was found in fecal excretion as
ODD or DDT in mice, as compared to 3 percent in hamsters.
These species seem to have less biliary excretion than the
rat, in which 65 percent of a DDT dose can be found in the
bile collections and large amounts of DDT conjugate are
found in the feces (Jensen, et al. 1957).
C-30
-------
The excretion of DDT was investigated in human volunteer
studies of Hayes, et al. (1971) and Roan, et al. (1971) ,
previously described. Excretion of DDA in the urine increased
rapidly in the first few days with a following gradual increase
in the subjects dosed with 35 mg/man/day to a steady level
of approximately 13 to 16 percent of the daily dose. DDA
excretion fell rapidly following cessation of dosing. Since
storage levels did not increase after reaching steady state,
these volunteers were apparently able to excrete 35 mg/day
of the amount they had ingested. This is probably due pri-
marily to excretion of DDT from the gut inasmuch as only
5.7 mg/day of all DDT isomers found in urine. Gut organisms
have a demonstrated capacity for degradation of DDT to ODD
and DDA and may be important in fecal excretion.
Occupationally exposed workers have been shown to have
significantly increased levels of DDA excretion in the urine.
Ortelee (1958) classified individuals as heavy, moderate
and slight exposure groups in formulating plants and found
a good correlation between exposure and DDA in the urine.
Laws, et al. (1967) were not able to find DDA in urine
samples from all persons of the general population due to
insensitivity of analytical methods at the time. In workers,
increased levels of DDA excretion were found, but paradoxical-
ly, DDE was found in only slightly higher concentrations
in exposed workers versus the general population with no
correlation with increasing work exposure. Estimations
of total intake of DDT based on DDA in urine are in good
agreement with estimations of intake based on the calculations
of DDT in fat by Durham, et al. (1965a).
C-31
-------
Morgan and Roan (1977) have calculated from excretion
measurements in disappearance curves the following rank
order of loss rates from storage from fastest to slowest:
DDA, ODD, o,p'-DDT, p,p'-DDT and p,p'-DDE. Differences
in excretability from one end of the scale to the other
are very great, water solubility being a possible important
variable. Interspecies differences also exist in the capacity
for unloading stored DDT. Man, as compared to the rat,
dog or monkey, exhibits a considerable slower rate of loss,
which may be related to differences in renal handling of
the pesticide. If dietary intake were completely eliminated,
most of the DDT would be lost in 10 to 20 years but DDE
would require almost an entire lifespan for removal.
EFFECTS
Acute, Sub-acute, and Chronic Toxicity
Acute toxic effects show central nervous system symptoms,
such as hyperexcitability, generalized trembling,- convulsions
and paralysis within five to ten minutes following i.v.
administration and a latent period of several hours for
oral dosing in experimental animals. LD5Q for rats typically
range from 100 to 400 mg/kg orally and 40 to 60 mg/kg i.v.
(Negherbon, 1959; Hayes, 1963). Dermal exposure in rats
was toxic at 3000 mg/kg. DDE has an oral LD5Q in rats of
380 mg/kg in males and 1240 mg/kg in females; DDA, 740 mg/kg
in males and 600 mg/kg in females (Hayes, et al. 1965).
The oral LDcQ of DDT is 60 to 75 mg/kg in dogs; in rabbits,
250-400 mg/kg; and in mice, 200 mg/kg (Pimentel, 1971).
Studies on acute toxicities in animals indicate that
the correlation between pathological symptomatic effect
C-32
-------
and pesticide level is highest in the brain. Dale, et al.
(1963) observed tremors in male rats four hours after adminis-
tration of DDT, when the brain concentration reached 287
ppm on a lipid basis.
Acute poisoning in man is a rare event and no well-
described case of fatal uncomplicated DDT poisoning has
been reported. General symptoms are similar to those found
in animals and include dizziness, confusion, and most char-
acteristically, tremors. In severe poisoning, convulsions
and parasthesia of extremities may intervene.
Single ingestion of 10 mg/kg produces illness in some,
but not all, subjects. Smaller doses generally produce
, i '
no illness. Convulsions and nausea frequently occur in
dosages greater than 16 mg/kg. Dosages as high as 285 mg/kg
have been taken without fatal result but such large ,dosages
are usually followed promptly by vomiting, so the amount
retained is variable (Hayes, 1963).
Although a number of pathological changes have been
noted in experimental animals, the most consistent finding.
in life-time feeding studies has been an increase in the
size of liver, kidneys and spleen, extensive degenerative
changes in the liver and an increased mortality rate. In
rats, Laug, et al. (1950) observed hepatic alteration with
feedings in diet at 5 ppm DDT. At dose levels of 600 and
800 ppm, significant decreases in weight gain and increased
mortality were observed in rats (Fitzhugh and Nelson, 1947).
The observation that increased mortality results from doses
above 100 ppm DDT in the diet is well established in mice.
(Walker, et al. 1972).
C-33
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In contrast to the rodent models, Rhesus monkeys, fed
diets with up to 200 ppm DDT, showed no liver histopathology,
decrease in weight gain or food consumption, or clinical
signs of illness. Several monkeys fed 5000 ppm in the diet
had some weight loss, prior to early death due to DDT poison-
ing (Durham, et al. 1963) . In one animal, liver pathology
consistent with DDT poisoning in other animals was found.
No clinical or laboratory evidence of injury to man
by repeated exposure to DDT has been reported. Volunteers
ingesting up to 35 mg/day for 21 months had no alterations
in neurological signs, hematocrit, hemoglobin and white
blood cell counts. No changes in cardiovascular status
or liver function tests were noted (Hayes, et al. 1971).
'Studies of exposed workers by Laws, et al. (1967),
Wolfe and Armstrong (1971), Almeida, et al. (1975) have
demonstrated no ill-effects from long-term high levels of
exposure, as judged by physical examination and chest X-
ray.
Furthermore, the dermal toxicity of DDT is practically .
nil. A few cases of allergenic reaction have been observed,
which are probably due to an extreme sensitivity of the
individual.
Synergism and/or Antagonism
One of the primary concerns about pesticide residues
is the possibility that they may act synergistically with
other chemicals over a long period to produce cancer. • The
accumulation and summation of carcinogenic exposure from
various sources may present a health problem of great signi-
ficance.
C-34
-------
DDT, a strong inducer in the mixed function oxidase
system, potentially could enhance the biological effects
of other chemicals by activation, or diminish their activities
through detoxification mechanisms. Weisburger and Weisburger
(1968) were able to enhance the incidence of hepatomas in
rats caused by N-fluorenacetamide (2-AAF) by co-administration
of DDT. They had previously shown that 2AAF is metabolized
by a mixed function oxidase system to the hydroxy intermediate
which is carcinogenic. By stimulating liver metabolism
with 10 mg/day DDT which, by itself, causes no hepatomas,
the percentage of animals bearing tumors from a dose of
1 mg/day 2-AAF for up to 52 weeks rose from 67 to 90 percent
*
in males and from 7 to 33 percent in females.
Conney (1967) observed decreases in phenobarbital induced
sleeping times proportional to the dose of DDT given to
rats two days earlier. Doses of 1 and 2 mg/kg of body fat
caused a 25 and 50 percent reduction in sleeping time, res-
pectively. This response is due to the greater capacity
of the MFO system to detoxify phenobarbital to a more readily
excretable form. Similar effects have been seen for Librium,
methyprylon and meprobamate in rats (Datta and Nelson, 1968).
Enhancement of metabolic activity has been demonstrated
in workers occupationally exposed to several insecticides,
DDT included (Kolmodin, et al. 1969). In these workers,
the half-life of antipyrine was significantly decreased
in comparison to controls.
Deichmann, et al. (1967) evaluated the synergistic
effects of aramite (200 ppm), DDT (200 ppm), methoxychlor
(1000 ppm), thiourea (50 ppm) and aldrin (5 ppm) given singly
C-35
-------
or in combination to rats. These dosages were approximately
50 percent of the levels reported to induce liver tumors.
Rats fed combinations of aramite, DDT, methoxychlor and
thiourea, with a total tumorigenic dose of 200 percent had
a 17 percent tumor incidence. Similarly, a combination
of aramite, DDT, methoxychlor and aldrin had a 10 percent
tumor incidence. Single chemical feedings had the following
incidences of tumors: aramite - 23 percent; DDT - 17 percent;
methoxychlor - 18 percent; thiourea - 28 percent; and aldrin
- 25 percent. Control rats had 23 percent tumors. Since
both total tumors,and liver tumors were essentially the
same in control versus experimental groups, those authors
concluded that the compounds did not act in an additive
manner and further, suggested that the mixtures might have
an antagonistic effect in the reduction of tumors below
control.
Walker, et al. (1972) produced liver tumors in mice
with either 100 ppm DDT or 5 ppm dieldrin. Two types of
histology were scored: simple nodular growth of parenchymal
cells (A), and papilliform adenoid growth of tumor cells
(B). Combination of the two chemicals showed an overall
increase in tumor numbers in males only, 53 to 88, when
compared to 100 ppm DDT alone. What is most striking, however,
is that for both males and females, there was a significant
shift in proportion to the more tumorigenic type B phenotype
•with the combined feeding.
The induction of the hepatic enzymes occurs in animal
models and possibly in occupationally exposed workers, as
shown by increased drug metabolism. However, the tumorigeni-
city data present inconsistent findings with respect to
C-36
-------
activation or detoxification, depending on the agent used.
This is not an uncommon paradox when dealing with metabolic ~
induction. The effects on human health as a- result of low '
level exposure and synergistic/antagonistic interactions
with other chemicals are unknown. '-,''•
Teratogenicity
Minimal teratogenic effects have been reported following
high acute dosages. Hart, et al. (1971) showed that'DDT
has an effect on prematurity and causes an increase in the-
number of fetal resorptions in rabbits given 50 mg/kg on
days 7, 8 and 9 of gestation. In the experimental group,
25 percent of the implantations suffered reabsorption'Ijn :
utero in comparison to 2 percent in the control. "The weight
of the viable fetuses was significantly lower in-th^ treated
animals. The dose used in the experiment corresponds' to
1/6 to 1/10 of the acute LDcQ for the species. ;
Low level exposure to DDT exerts an adverse effect3
on reproduction of several avian species. While data for -
mammalian species are meager, published reports to date
indicate that dietary intake has little or no effect on " -'
the reproductive success of laboratory animals. Dietary
DDT at 7 ppm was fed to BALB/C and CFW strains of Swiss
mice for 30 days prior and 90 days post-breeding. In the
BALB/C strains, there was a slight reduction in overall
fertility, but fecundity (litter size) was greater than ' ' •' *
control values. With the CFW strain, no differences in -
fertility or fecundity were noted (Ware and 'Good; 1967)".-
Ottoboni (1969) studied the effect of DDT at levels
of 0, 20 and 200 ppm on fertility, fecundity, neonatal morbid-
ity, and mortality through two successive generations in'
C-37
-------
Sprague-Dawley rats. No alteration in sex ratios nor any
evidence of teratogenic effect was found among live or still-
born young. Litter size, weights at birth and weaning showed
no differences between treated and control. Poor survival
of the ypung to weaning pups in the 200 ppm group was observed.
This finding was compromised by large losses in the control,
yet the 20 ppm diet group was unaffected. Viability of
young was high for all three groups in the F, generation
breedings. Of the other indices studied, fecundity, fertility
and" mortality, none was significantly affected. The only
significant finding w.as an increase in ring tail, a constric-
tion of the tail followed by amputation, in the offspring
of mothers whose diets contained 200 ppm DDT.
•Krause, et al." (1975) noted a damaging effect on sperma-
togenesis in rats which was somewhat persistent for 90 days,
and fertility was markedly reduced. This followed acute
500 mg/kg dose on days 4 and 5 of life or 200 mg/kg from
day 4 to day 23, In this experiment the administered dosages
are close to the LDcg for the species; therefore, these
results cannot be considered conclusive, since acute toxicity
will alter other physiological parameters that could affect
fertility.
Both p,p'-DDT and o,p'-DDT have been shown to possess
estrogenic activity in rodents and birds (Welch, et al.
1969; Bittman, et al. 1968). Increases in uterine wet weight,
j
and' uptake of labeled glucose into various precursors which
are in competition with estrodiol 17B for uterine binding
9
sites have been demonstrated.
The importance of the estrogenic activity of low level
DDT exposure is difficult to estimate. Since fertility
C-38
-------
in the mammalian female and male is dependent upon complex
hormonal interactions, chemical interference may represent
a hazard. As an example, Ottoboni (1969) suggested that
20 ppm of DDT in the diet had an adverse effect on the sub-
i
fertile females in reproductive prime and observed a greater
fertility or protective effect in aging female rats as com-
pared to controls. In a later study by Wrenn, et al. (1970)
long-term feeding of o,p'-DDT to rats did not interfere
with normal reproduction nor were estrogen sensitive physio-
logical parameters significantly affected.
Mutagenicity < , .
DDT has not shown mutagenic activity in any of the
bacterial test systems thus far studied. McCann, et al.
(19-75) found no increased frequency of reversions in Salmonella
typhimurium strains TA-1535, 1537, 98 or 100 with 4 ug/plate
DDT. In addition, DDE was nonmutagenic in this system;
neither DDT nor DDE were positive with S-9 microsomal acti-
vation. Marshall, et al. (1976) confirmed these studies
with doses up to 2500 ^ig/plate DDT and 1000 jag/plate DDE.
No inhibition of growth was seen in the E. coli Pol-A strains
with 500 pg of DDT and the metabolites ODD and DDE (FlucK,
et al. 1976). DDT was also negative in the rec-assy with
Bacillus subtilis (Shirasu, et al. 1976).
Fahrig (1974) reviewed the activity of DDT and its
metabolites DDE, ODD, DDOH and DDA in several other bacterial,
systems. All metabolites were negative, as judged by resis-
tance to 5-methyltrptophane and streptomycin in liquid holding
tests. Back mutation to prototrophy was negative in two
strains of Escherichia marcescens, and was negative to galac-
C-39
-------
tose prototrophy in E. coli.
The only positive result found in any of the bacterial
test systems was reported by Buselmaier, et al. (1972)
upon the administration of ODD to mice and assaying for
back mutation of Salmonella typhimurium and E. marcescens
following incubation in the peritonium in the host-mediated
assay. However/ DDT, DDE and DDA were found negative by
this method.
In summary, with the exception of one metabolite -ODD
- in the host-mediated assay, no genetic activity has been
detected in the prokaryotic test systems.
Tests on eukaryotic yeast cells have been uniformly
negative. Fahrig (1974) investigated the effect of DDT
and various metabolites on mitotic gene conversion in Saccharo-
myces cerevisiae, which detects single strand breaks of
the DNA. Host-mediated studies with DDT, ODD and DDE of
cells incubated in testis, liver and lung of rats were also
negative. Clark (1974) found no significant increases in
mutagenicity of conidia of Neurospora crassa incubated ir\
vitro and in vivo with the host-mediated assay.
Vogel (1972) measured X-linked recessive lethal muta-
tions in Drosophila melanogaster and found activity for
DDT and DDA, with negative results for DDE, ODD and DDOH.
Clark (1974) examined the relationship between sperma-
togenesis stages in D. melanogaster and the effect of DDT
on dominant lethality and chromosome abnormalities. Sequen-
tial breedings of the treated males with virgin females
at three day intervals indicated that DDT causes an increase
in dominant lethality in early spermatid and spermatocyte
stages. This increased lethal effect was correlated with
C-40
-------
an increase in non-disjunction.
In mammalian systems, the mutagenic activity of DDT
and its metabolites is relatively weak. This is evidenced
by the fact that depending upon the dose and route of adminis-
tration, and the species sensitivity of the test organism,
reported studies are negative or marginally positive.
High doses of technical DDT administered orally to
mice at 150 mg/kg/day for two days (acute) or 100 mg/kg
DDT twice weekly for 10 weeks (chronic) showed significant
increase in the number of dead implants per female. Acute
treatment showed maximum sensitivity in induction of dominant
/
lethals in week 5 and chronic treatment in week 2, with
continued increases above control through week 6. Chronic,
but not acute dosing, caused significant reductions in sperm
viability and a reduction of cell numbers in all stages
of spermatogenesis (Clark, 1974) .
Oral feeding of two strains of mice at lower levels
(1.05 mg/kg/day) showed little effects in reproductive response,
Both CFW and BALB/C strains of Swiss mice fed DDT showed
lesser parent mortality than control. Neither fertility,
as measured by pairs producing young, or fecundity, as measured
by litter size, was statistically different from the contol.
Number of litters per pair was not diminished (Ware and
Good, 1967).
Two additional studies have been reported with negative
results for dominant lethality in mice (Epstein and Shaffner,
1968; Buselmaier, et al. 1972). Intraperitoneally treated
male rats in doses up to 80 mg/kg for five days showed no
effect in dominant lethality or fertility (Palmer, et al.
C-41
-------
1973). Five-day oral doses of 25, 50 or 100 mg/kg given
to males bred sequentially for six weeks, showed a statisti-
cally significant effect in implantation loss only in week
three at 100 mg/kg level.
Oral feeding of technical DDT at 20 and 200 ppm/body
weight in the diet of Sprague-Dawley rats for two generations
produced no apparent effect on fertility, fecundity, neo-
natal morbidity or mortality through two generations (Ottoboni,
1969). By contrast, juvenile male rats of the Wistar Han
strain, fed 500 mg/kg on days four and five after birth
(acute) and 200 mg/kg pure DDT daily from day four to 23
(chronic) showed damaging effects on spermatogenesis: testi-
cular weight, tubular diameter, wall thickness and number
of spermatogonia (JKrause, et al. 1975) .
There are relatively few papers reporting the effect
of DDT and metabolites on mammalian chromosomes. Johnson
and Jalal (1973) studied the effect of DDT on the bone marrow
of i.p. injected BALB/C mice exposed to one single admin-
istration of 100, 150, 200, 300 and 400 ppm/body weight.
Doses from 150 ppm up caused a significant increase in the
number of cells with fragments; sticky cells were signifi-
cantly increased at all concentrations. Smaller doses were
tested by Larsen and Jalal (1974) in brown and BALB/C mice:
25, 50, 100 and 250 ppm did not significantly affect the
number of gaps, stickiness or mitotic indices, but deletions
and gaps plus deletions were significantly higher or approached
the significant levels at 50 ppm and higher concentrations.
Rats treated by i.p. or by gavage with doses ranging
from 20 up to 100 ppm/body weight did not show a dose-response
C-42
-------
relationship or an increase in percent aberrations over
the controls (Legator, et al. 1973).
DDE, but not DDT, caused an increase in chromosome
aberrations in a Chinese hamster cell line (V79) at 30 and
35 ,ug/ml (Kelly-Garvert and Legator, 1973).
Palmer, et al. (1972) found a significant increase
in cells with structural aberrations when an established
cell line of the kangaroo rat, Potorus tridactylis apicalis
was exposed to 10 ;jg/ml p,p' and o,p'-DDT, pp1 and op'ODD
and pp'DDE. The p,p'DDA was the least toxic among DDT metabo-
lites, since only a concentration of 200 /ig/ml caused a
cytopathic effect, whereas DDT, ODD and DDE - p,p' and o,p'-
were toxic at 20 and 50 jug/ml. Mitotic inhibition was intense
in cultures treated with o,p' and p,p'DDT (40 percent and
35 percent more, respectively, than in the control). Cultures
exposed to p,p' and o,p' ODD and DDE had indices of 20 to
i
25 percent below the control; almost no inhibition was observed
with p,p'-DDA. The rate of chromosomal aberrations depended
upon the isomer used: p,p'-DDT, ODD and DDE caused a two-
fold increase as compared to the o,p' isomers. At 10 jug/ml
f
p,p'-DDT, ODD and DDE caused chromosome damage to 22.4,
15.5 and 13.7 percent of the cells, respectively. Approxi-
mately 12 percent of the abnormal cells produced by p,p'-
DDT and p,p'-DDE had rearrangements. Only 1/10 of the cells
treated with p,p'-DDD had rearrangements. The o,p' isomers
did not produce exchanges.
Mahr and Miltenburger (1976) confirmed the fact that
DDA is the least effective of DDT metabolites in producing
cytogenetic damage and inhibiting proliferation in the Chinese
C-43
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hamster cell line B14F28. The proliferation rate after
a four-hour treatment was inhibited most strongly by ODD
(at 75, 45 and 22 ppm), followed by DDT (81 ppm) and DDE
(88 ppm); 100 ppm DDA did not produce any effect. The contin-
uous presence of DDT (8 ppm) in the medium over three months
did not result in an altered proliferation rate in cultures.
Chromosome damage was observed with 41 and 81 ppm DDT, 45
and 75 ppm ODD and 44 and 88 ppm DDE. Here again DDA was
the least effective in producing abnormal cells at 41, 68
and 100 ppm; at the highest concentration gaps, but not
breaks, were increased. No induction of configuration anoma-
lies was found in the experiment.
Hart, et al. (1972) found no increase in chromosomal
aberrations in human or rabbit lymphocyte cultures exposed
to 1, 5, 10, 30, 50 and 100 jug/ml DDT based on the analysis
of 25 metaphases per level in the human cultures. Liver
cells from rabbit fetuses whose mothers had been treated
with DDT during, pregnancy showed no difference as to chromo-
some damage when compared to non-treated controls.
Lessa, et al. (1976) exposed human lymphocytes in
vitro to very low concentrations of technical DDT ranging
from 0.06 to 0.20 jug/ml and from 1 to 15 jug/ml. The lowest
concentrations (0.06 to 0.20 jug/ml) are similar to those
found in the plasma of individuals of the general population
in Brazil. No correlation was found between DDT dose and
cells with chromosomal aberrations. At 0.20, 4.05 and 8.72
jug/ml the proportion of cells with structural aberrations
were significantly greater than in controls. It is interesting
to note, though, that higher concentrations of approximately
C-44
-------
12 and 15 ppm produced no such effect. Such fact may be
caused by precipitation of DDT in the culture medium or
may reflect a difference in the amount of binding of DDT
and metabolites to the lipid moiety in the serum, or e*ven
differences in cell permeability.
Yoder, et al. (1973) reported an increase in chromatid
t
lesions in blood cultures from a group of 42 men occupationally
exposed to several pesticides, DDT included, during the
spraying season, as compared with cultures made six months
before when the same indiviudals had not been in contact
with the pesticides for 30 days.
Rabello, et al. (1975) compared the frequency of cells
with chromosomal aberrations in workers from three DDT plants,
directly and indirectly exposed to DDT. There was no signifi-
cant difference between these two groups. The total DDT
and DDE levels in the plasma were determined. In the 25
workers in direct contact with DDT, the levels ranged from
0.16 /ag/ml to 3.25 jug/ml (mean 1.03 jug/ml + 0.79) total
DDT and 0.03 to 1.77 >ag/ml (mean 0.48 + 0.52) p,p'-DDE.
In these 25 indiviudals not in direct contact with the compound
they ranged from 0.03 to 1.46 jug/ml (mean 0.38 jug/ml + 0.15)
total" DDT and 0.01 to 0.41 jug/ml (mean 0.15 + 0.02) p,p'-
DDE. In one of the plants, though, not being in direct
contact with DDT did not prevent the workers from having
DDT plasma levels as high as those in workers who actually
manipulated the substance. A second comparison was then
made between the groups with high and low DDT plasma concen-
trations, which showed an increase in cells with chromatid
aberrations in the highly exposed group.
C-45
-------
When another group of eight plant workers with total
DDT plasma levels ranging from 0.09 to 0.54 jig/ml (mean
0.24 ;ug/ml + 0.15) and DDE levels ranging from 0.02 to 0.09
jug/ml (mean 0.041 + 0.02) was compared to 10 individuals
of the general population with no detectable o,p" or p,p'-
DDT and DDE levels ranging from 0.02 to 0.04 jug/ml (mean
0;029 pg/ml + 0.01), no significant difference was found
in the cytogenetic analysis. A positive correlation was
found between DDT levels and length of exposure of all indi-
viduals, but there was no correlation between DDT levels
in the plasma and frequency of cells having any type of
aberrations (numerical or structural).
No effect on unscheduled DNA synthesis was seen in
S-V-40 transformed human cells with concentrations up to
1000 uM DDT either with or without S-9 microsomal metabolic
activation (Ahmed, et al. 1977).
In summary, the evidence in prokaryotic and fungal
systems indicates that DDT and its metabolites do not produce
point mutations. Although the evidence is somewhat contradic-
tory in the dominant lethal studies, in vivo and in vitro
cytogenetic studies seem to indicated that DDT is a clastogenic
(phromosome breaking) substance.
Carcinogenicity
Fitzhugh and Nelson (1947) were the first to investi-
gate the carcinogenic potential of chronic feeding of DDT
in rodents. Osborne-Mandel weanling rats were fed diets
containing 0, 10.0, 20.0, 40.0 and 80.0 mg/kg/day technical
DDT for a period of two years. Pathologic examination revealed
that the chief lesion was a moderate degree of liver damage
046
-------
of a characteristic type, which consisted of hypertrophy
of centrolobular hepatic cells, hyalinization of the cytoplasm
and focal necrosis. Although no information as to dosage
or sex of the tumor-bearing animals was given, the authors
concluded that definite but minimal hepatic tumor formation
was evident. This conclusion was based on comparison to
many hundreds of similar aged rats which spontaneously showed
distinct hepatic tumors at a frequency of one percent.
By contrast, of the 75 rats surviving to eighteen months,
15 exhibited either large adenomas or nodular ademonatous
hyperplasia with similar microscopic morphologies, differing
chiefly in size. Chronic feeding produced degenerative
changes in the liver at all doses. Acute admininstration
of 1000 ppm in the" diet for twelve weeks produced the char-
acteristic pathology which peprsisted for two weeks and
reverted to a normal appearance when examined at weeks four,
six', eight and ten post dosing.
Laug, et al. (1950) followed this study by administering
lower doses of technical DDT in the diet for periods of
15 to 27 weeks to weanling rats. No hepatic cell altera-
tions were noted in control and 1 ppm levels, with minimal
effects at 5 ppm. At doses of 10 and 50 ppm, definite hepatic
hypertrophy was observed, but gross alterations such as
necrosis were not present. Ortega, et al. (1956) confirmed
that liver alterations can be observed in rats with DDT
levels as low as 5 ppm. However, this pathology was reversed
to normal once the administration of the compound was stopped.
C-47
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The next major report on the carcinogenicity of DDT
was the work of Tarjan and Kemeny (1969) with BALB/C mice.
Six generations of mice were fed either the control diet,
contaminated with 0.2 to 0.4 ppm DDT, or the test diet of
2.8 to 3.0 ppm p,p'-DDT. The control group was comprised
of 106 mice and the test group had 683 mice with a daily
intake of 0.4 to 0.7,mg/kg. A striking increase in the
incidence of leukemias was seen in the experimentally DDT
treated mice, beginning at the F3 generation. Myeloid,
lymphoid and aleukemias were found in 85 treated animals
(12.4 percent) but only the latter two types were found
in 10 controls (2.5 percent). In the F4 and F5 generations,
myeloid leukemias accounted for one-third of the total.
The authors further noted that in BALB/C mice spontaneous
leukemia is unknown. The induction of tumors in the experi-
mental group was significant in the F2 generation and increased
almost logarithmically in successive generations from F3.
A total of 196 animals (28.7 percent) versus 13 (3.2 percent)
were found to have tumors in the exposed and control series,
respectively. The predominant tumor type was pulmonary
carcinoma (116/196 animals), and the authors claim that
prior observation of their colony shows incidence of malignant
pulmonary tumors to be below 0.1 percent. A variety of
tumors was observed widely dispersed throughout the body
and included malignant vascular tumors (22/196) and reticulo-
sarcomas 27/196 of liver, kidney, spleen, ovary and other
organs. The authors noted that these positive findings
were somewhat complicated by the fact that fetal exposure
via placental passage and newborn intake through breast
C-48
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milk may heighten adverse effects.
In a survey of 120 selected pesticides and industrial
chemicals to determine their potential carcinogenicity,
five pesticides, p,p'-DDT included, were among the eleven
compounds that showed significant increases in tumor incidence
(Inhes, et al. 1969). Two hybrid strains of mice were
bred by crossing C-57BL/6 with either C3HANF or AKR strains;
Fl generations were designated strain X and Y, respectively.
From day 7 to 28, the animals were treated by gavage, at
the maximum tolerated dose of 46.4 mg/kg in a 0.5 percent
gelatin suspension. From four weeks to 18 months, the chemical
was mixed directly in the diet, to approximate this dose;
-' l r • '-»'. ?
the concentration of DDT was calculated to be 21 mg/kg/day.
The' frequency of mice with hepatomas in both strains as
compared to controls is given in Table, 6. Pulmonary, tumors,,,, •
and lymphomas occurred in lower frequencies but are not
presented in the table. "
The pattern of tumor type among several experimental
compounds was similar to the positive carcinogenic control
compounds with the major evidence for tumorigenicity arising
from the increased incidence of hepatomas. These increases
were significant at the 0.01 level for the sum of both sexes
and both strains, the sum of males of both strains and for
the males of each separate strain of the hybrids. Although
incidence of lung and lymphatic tissue tumors showed fewer
increases than hepatoma, the incidence of lymphomas was
significantly above negative controls for p,p'-DDT. The
pulmonary tumors consisted primarily of adenomas.
C-49
-------
TABLE 6
Frequency of Animals with Hepatomas in Two Hybrid
Strains of Mice Exposed to 21.0 mg/kg/day p,p'-DDT
and to a Control Diet Without DDT.
Strain
Group
Total Number
of animals
Number of
animals with
hepatomas
C57 BL/6 x C3H/AWF
Exposed
Control
M
18
79
F
18
87
M
11
22
F
5
8
C57 BL/6 x AKR
Exposed
Control
18
90
82
7
5
0
1
C-50
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In 1967, the International Agency for Research on Cancer
(lARC) initiated a large investigation on the potential
carcinogenicity of DDT in rodents. Studies were conducted
in three different strains of mice in Lyon, France, by Tomatis,
et al. (CFl);> in Moscow (USSR) by Shabad, et al. (strain A);
and by Terracini, et al. in Milan (Italy) with BALB/C.
In addition, a study was performed on white rats in Leningrad
(USSR). Although the rat study was negative, the long-term
administration of DDT to mice induced a significant increase
in the frequency of liver tumors, which constituted the
strongest evidence to date for the possible tumorigenicity
of DDT. Tomatis, et al. (1972) and Turusov, et al. (1973)
fed six consecutive generations of CFl mice technical DDT
in -the diet, at doses of 0.3, 1.5, 7.5 and 37.5 mg/kg/day
over the lifespan. CFl mice are characterized by a rather
high incidence of spontaneous tumors mainly of the lung,
haematopoietic system, bone and, in males, hepatomas. The
percentage of animals bearing tumors of all types in DDT
treated males (89 to 94 percent) was somewhat higher than
in the male controls (78 percent). The females had similar
incidence in the controls (89 percent) and in the DDT treated
(85 to 90 percent). Only liver tumor incidence was clearly
affected by DDT treattment. DDT treated male mice showed
increases in liver hepatoma at all treatment levels, with
the peak at 37.5 mg/kg/day (301/350) and similar incidence
of 179/354, 181/362 and 214/383 (50 percent to 56 percent)
for the three lower doses. Control males by contrast had
30 percent liver tumor frequency (97/328). In the females,
no effect was seen at 0.3 and 3.0 mg/kg/day, but at the
C-51
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higher dose levels, tumor rates were significantly increased
at 7.5/mg/kg/day (43/328) and 37.5 mg/kg/day (192/293).
Liver tumors appeared earlier in the Fl through F5 generations
than in the parental at higher dosages, but tumor incidence
did not show consistent increases with consecutive generations
as previously reported in BALB/C mice (Tarjan and Keraeny,
1969) .
Comparable lifetime studies were performed by Shabad,
et al. (1973) in A-strain mice. Technical DDT was given
via gavage in daily dosages of 1.5 and 7.5 mg/kg/day for
the parent lifetime and 10 ppm for consecutive generations,
Fl through F5. DDT in 0.1 ml sunflower oil dosing began
,-
at 6 to 8 weeks of age for each generation. Strain A, which
is susceptible to spontaneous lung adenomas, had an overall
incidence of 7 percent in the control group. The parental
generation, which received the highest dose, showed 37 percent
incidence of lung adenomas. The frequencies of lung tumor
formation in generations from FO to F5 treated at 1.5 mg/kg/da,y
were 19, 15, 24, 46, 43 and 13 percent respectively. Animals
dying prior to six months in all of the control and FO and
Fl treated groups showed no tumors, whereas earlier appearance
of tumors in treated F2 to F5 was seen in animals dying
prior to six months. No other tumors, including liver tumors,
were detected.
, A third multigeneration study on mice was performed
by Terracini, et al. (1973). Three dose levels of technical
DDT to 0.3, 3.0 and 37.5 mg/kg/day DDT in the diet was admin-
t
istered to two separate colonies of BALB/C mice, beginning
at four to five weeks of age, for their Iifespan. The liver
/ i
was the only target organ to show significant increases
\
C-52
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in the proportion of animals bearing tumors. Both males
and females showed higher percentages at the 37.5 mg/kg/day
level, with no excess tumorigenicity at 0.3 and 3.0 mg/kg/day.
Liver tumors were present in 28/63 of the female parents
and 43/58 of the first generation females, at the high dose
only. Both colonies of mice showed identical results at
this dosage. Incidence of malignant lymphomas was approxi-
mately 50 percent in the control, 0.3 or 3.0 mg/kg/day treated
mice. At highest dosages, this incidence fell to 14 percent
in one colony and 36 percent in the other. The incidence
of lung adenomas was not affected by DDT treatment.
In order to determine if the liver tumors of mice would
progress of regress after cessation of dosing, Tomatis,
et a'i. (1974) treated CF-1 mice with dietary DDT of 37.5
mg/kg/day for 15 or 30 weeks. Autopsy was performed at
65, 95 and 120 weeks from the beginning of the experiment.
The data indicated that a limited period of exposure to
37.5 mg/kg/day results in an increased and early appearance
of hepatomas, similar to that caused by lifespan exposure.
The shorter the period of exposure, the lower the incidence
of liver tumors. In males treated for 15 weeks and killed
at 65, 95 and 120 weeks after, the incidence of hepatomas
was 13/60, 25/60 and 25/60, respectively. In males treated
for 30 weeks the corresponding values were 38/60, 41/60
and 37/60, whereas the values for the controls in the same
periods were 12/70, 24/83 and 33/98. In females, the incidence
of hepatomas increased from the 65th to the 120th week.
Those treated for 15 weeks showed 3/60, 11/60 and 5/60 after
65, 90 and 120 weeks respectively; the corresponding values
C-53
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for the 30-week treated were: 4/54, 11/65 and 11/54; control
values were: 0/69, 0/72 and 1/90,
The size and multiplicity of the hepatomas were also
correlated with the duration of exposure and time of autopsy.
In this study, as in the mouse studies previously cited,
the histology of the hepatomas rarely shows signs of metas.tases
and local invasiveness.
/
Further confirmation of the tumorigenicity of DDT to
mouse livers was reported by Walker, et al. (1972) and
by Thorpe and Walker (1973) in CF-1 strains. Incidences
of tumors increased from 13 percent in controls to 37 percent
at 7.5 mg/kg/day and 53 percent at 15 mg/kg/day with slightly
higher increases in females (control, 17 percent; 15 mg/kg/day/
76 percent). In the second study, Thorpe and Walker (1973),
over 26 months, control values for both males and females
were approximately 23 percent, and rose to 77 percent for
males and 87 percent for females when fed 15 mg/kg/day in
the diet. In contrast to the considerable shortening of
lifespan seen in all previous mouse studies, minimal reduction
was observed in this study.
Lifespan studies of the effect of chronic exposure
to the metabolites DDE and ODD at 37.5 mg/kg/day in the
diet and a mixture of 18.75 mg/kg/day each have recently
been reported (Tomatis, et al. 1974). DDE showed marked
effects in females CFl mice on liver tumors increasing from
1 percent (1/90) to 98 percent (54/55) in control versus
treated; male incidence rose from 34 (33/98) to 74 percent
.(39/53) . ODD showed slight increases in males only, but
lung adenomas were markedly increased in both sexes. Control
C-54
-------
values for lung adenomas were 54 and 41 percent for males
and females, respectively. Treatment with DDE or ODD plus
DDE showed a decrease to approximately 15 percent of female
mice with lung tumors. DDE reduced male incidence to 36
percent but continued treatment had no effect. The combi-
nation of ODD and DDE increased hepatoma incidence in both
sexes to approximately 75 percent.
i
Since the most significant evidence implicating DDT
as a possible carcinogen to date has been the formation
of hepatic tumors in the mouse, some criticism of the use
of this model with high dosages has been expressed (Deichmann,
1972). The use of animals with high spontaneous rate of
tumor formation confers an added sensitivity if increases
are found following exposure; the use of animal models with
none or low spontaneous tumor incidences may be more indicative
of actual risk.
Breslow, et al. (1974) reviewed the multigeneration
studies by the IARC group to determine associations between
tumor types following DDT exposure. A negative correlation
was seen between lymphomas and lung, mammary, and ovarian
tumors, possibly due to competing risk mortality of the
diseases. Despite some spurious results caused by grouping
of animals, or age specific tumor prevalence, significant
associations remained. Positive association between lymphoma
and bone tumor formation could be a reflection of viral
factors. Viruses isolated from some tumors of CFl mice
have produced tumors in neonate mice. Hepatoma formation
was less affected by lymphoma mortality. Histological examin-
ation of liver tumors in the CFl mice showed that this hepato-
blastoma is similar in morphological resemblance to human
C-55
-------
hepatoblastoma* These tumors were found in association
with the ordinary type of hepatoma and isolated primarily
from older animals., The hepatoblastoma proved to be more
highly malignant than the hepatoma, with metastases occurring
in 10 to 20 percent versus 1 to 2 percent for hepatomas.
A progression from hyperplasia to neoplasia can occur sponta-
neously with age in mice. The phenomena of induction of
hyperplasia could be attributable to age and spontaneous
tumor formation, or associated with early induction by DDT
activity.
One othec positive report on the possible carcinocjeni-
city of DDT in other species should be noted. Halver, et
al. (1962) have observed an increase in evidence of hepatomas
in rainbow trout being grown for lake stock. Following
determinations of toxicity in rodents, dose fractions or
multiples 1/16, 1/4, 1, 4 and 16 times were fed in a synthetic
diet of caseine gellatin, minerals, etc. High doses of
DDT, 2-AAF, carbon tetrachloride and other substances exhibited
toxic effects. Histopathologically confirmed hepatomas
appeared in the intermediate levels of DDT, DBS and DMN.
In a parallel study of fatty extracts from commercial ratios
fed to fish, fish developed tumors also resembling mammalian
hepatoma histologically.
In contrast to the positive results found in the rat,
mouse and fish studies previously cited, a number of other
studies have shown no significant increase in tumor formation
following DDT exposure. Lifetime feeding studies with Syrian
Golden Hamster at 75 and 150 mg/kg/day DDT were conducted
by Agthe, et al. (1970) . No increases in tumor incidences
C-56
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A number of negative studies have been reported for
various rat strains. Cameron and Cheng (1951) gave daily
doses of 0.36, 3.6 and 36 mg/kg in oil for times up to 63
weeks. Of the characteristic lesions described by Fitzhugh
and Nelson (1947) and Laug, et al. (1950), only two female
rats showed the centrolobular necrosis, and no significant
differences in the extent of the other pathological changes
could be made between treated and untreated groups.
Two long-term feeding studies utilizing Osborne-Mendel
rats have shown no significant tumorigenic response to three
dosage levels of DDT. In the first (Radomski, et al. 1965),
DDT was fed at 7.5 and 12 mg/kg/day in the diet for two
years. At 7.5 mg/kg/day, a slight, but not significant,
increase in hepatic tumor was noted; at 12 mg/kg/day no
liver tumors were noted, and no differences were found between
control and treated rats in tumors of other sites. In addition,
DDT was fed in a mixture with 12 mg/kg/day each of aramite,
methoxychlor and thiourea for 2 years, and no additive or
synergistic effect for tumor formation was found.
In a similar fashion, Deichmann, et al. (1967) repeated
these studies with a higher dosage of DDT - 30 mg/kg/day
for 27 months. Despite the fact that the treated animals
displayed increased liver weights and the characteristic
liver pathology, actual tumor incidence in DDT-fed rats
was less than in the control. The majority of tumors were
mammary tumors in both control and treated animals. Liver
tumors were found only in rats fed DDT, aramite or a mixture
of these plus methoxychlor and thiourea. Mixtures of these
C-57
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tumorigens also had no significant effect in tumor incidence.
In order to determine the effect of diet and DDT on
the development of leukemia, Kimbrough, et al. (1964) fed
rats a purified high fat, purified normal fat, and normal
diets with and without DDT, for varying time periods. Of
the seven animals developing leukemia, four were on the
high fat diet, two were on purified high fat and 35 mg/day
pp'DDT, and one was on normal fat diet and DDT. No animals
fed DDT and normal ratios developed leukemias. The authors
concluded that chloroleukemic development in Sherman rats
was a consequence of diet and unrelated to DDT treatment.
Weisburger and Weisburger (1968) fed weanling Fisher
rats 10 mg DDT per day by gavage and found no liver tumors
nor evident hepatotoxicity. In combination with 0.1 mg
per day 2AAF, hepatoma incidence increased from 67 to 90
percent in males and 7 to 33 percent in females compared
to treatment with 2AAF alone.
Rossie, et al. were able to induce non-invasive nodular
liver tumors in wistar rats by administering dietarily approxi-
mately 35 mg/kg/day of either technical DDT or sodium pheno-
barbital. None of the tumors were metastatic and extrahyratic
tumors were slightly higher in controls than in treated
animals. For DDT, liver tumor incidences of 45 percent
(24 of 53 animals) were observed in treated rats while controls
exhibited no liver tumors. Interestingly, sodium phenobarbital
at the same dosage level shewed a similar hisopathologic
liver change in 44 percent (22/50) of the rats. A compilation
of long-term tumorigenicity studies in rats is given.in
Table 7.
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TABLE 7
Long Terra Tumorigenicity Studies in Rats
Dose Range
Mg/kg/day
5-40
0.36-36.0
.12-1.2
1-2
o
i
Ul
* 7.5-12
10
30-100
35
10-32
Method
In diet
In oil by
Gavage
In diet
In diet
In diet
In diet
In diet
In diet
In diet
Strain
Osborne-
Mendel
Osborne-
Mendel
Carworth
Sherman
Osborne-
Mendel
Osborne-
Mendel
Fischer
Wistar
Osborne-
Mendel
Duration
2 years
63 weeks
2 years
Variable
2 years
2.25 yrs
1 year
'2.9 yrs
78 weeks
Results
Increase in liver tumors at
unspecified close.
No effect.
No effect.
No increase in leukemia
incidence.
12 mg/kg/day. No effect.
Slight increase liver tumor
incidence at 7.5 mg/kg/day.
No effect
No effect.
Liver tumors in 45%
of animals.
PPDDT and PPDDE -
No significant tumor incidences
Reference
Ftizhugh and Nelson
(1947)
Cameron and Cheng
(1950)
Traeon and Cleveland
(1955)
Kimbrough, et al. (1964)
Raolomski, et al. (1965)
Deichman, et al. (1977)
Weissburger and
Weissburger (1968)
Rossi, et al. (1977)
NCI (1978)
PPDDD - Increased thyroid tumors.
-------
In a recent published report of the National Cancer
Institute (1978), bioassays of DDT, ODD and DDE were conducted
in male and female Osborne-Mendel rats and B6C3F1 mice by
long-term feeding. Approximately 50 animals of each sex
were treated and 20 animals of each sex served as controls.
The dosing period consisted of 78 weeks in which there were
dosage changes during the course of the study and dosing
was reported as time-weighted averages. High and low dietary
concentrations of DDT were, respectively, 32.1 and 16.05
mg/kg/day for male rats, 21.0 and 10.5 for females; for ODD,
males were fed 164.7 and 82.4 mg/kg/day and females 85.0
and 42.5 mg/kg/day. For DDE, males were fed 41.95 and 21.85
mg/kg/day and females 23.1 and 12.1 mg/kg/day. Increased
mortality was seen in both sexes of rats dosed with DDE.
No evidence of carcinogenicity was found for DDT or DDE
in either sex at the given doses. ODD had no carcinogenic
effects in the females but a significant increase in the
low dose males of follicular cell adenomas and carcinomas
of the thyroid was observed. Because of high variation
of thyroid lesions in control male rats/ these findings
are considered only suggestive of a chemical related effect.
Among dosed rats no significant increases in other neoplasms
were seen as compared to controls. Administration of DDE
did not result in significant incidences of liver tumors,
but the compound was hepatotoxic, inducing centrolobular
necrosis and fatty metamorphosis.
Time-weighted average high and low dietary concentrations
of DDT for the mice were, respectively, 6.6 and 3.3 mg/kg/day
for male mice, and 26.25 and 13.05 mg/kg/day for female
C-60
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mice; high and low average doses of ODD were 123.3 and 61.65
nig/kg/day ppm for male and female mice; average high and
low doses of DDE were 39.15 mg/kg/day and 22.2 mg/kg/day
for male and female mice. Significant positive associations
between increased doses and greater mortality in female
mice dosed with DDT and DDE were observed. Poor survival
was seen in control and dosed male mice in the bioassays
of DDT and DDE. The only neoplasms occurring in statistically
significant increased incidence were hepatocellular carcinomas
among groups receiving DDE. The incidences of these tumors
in control low-dosed and high-dosed males were 0/19, 7/41
(17 percent) and 17/47 (36 percent), respectively. Corres-
ponding figures for females were 0/19, 19/47 (40 percent),
and 34/48 (71 percent).
The NCI study presented no evidence for the carcinogeni-
city of DDT in rats and mice, of ODD in female rats or mice
of either sex, or of p,p'-DDE in rats although hepatotoxicity
was evident. A possible carcinogenic effect of ODD in induc-
ing follicular cell tumors of the thyroid of male rats was
suggested. DDE was carcinogenic in B6C3F1 mice, causing
hepatocellular carcinomas in both sexes (Natl. Cancer Inst.,1978).
Durham, et al. (1963) found no liver pathology in Rhesus
monkeys fed 100 mg/kg/day or less for up to 7% years. Monkeys
dosed at 2500 mg/kg/day had cytoplasmic inclusions and necro-
sis in the liver and brain pathology. These animals died
in less than six months from DDT poisoning.
There is evidence that DDT is an inhibitor of tumor
takes in transplant. Mice exposed to 5.5 mg/kg/day in the
diet were subjected to experimental transplantation of an
C-61
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ependymonao Compared to controls, treated animals were
less susceptible to ttmor transplantation and had increased
longevity upon implantation (Laws, 1971).
In summary? the evidence for carcinogenicity of DDT
in laboratory animals has been demonstrated only for the
mouse in the production of liver tumors. In several other
species, such as rat, monkey, and hamster, no tumorigenic
effect for DDT has been shown at doses less than 50 ppm.
At doses higher than that level evidence is equivocal for
the rat (Fitzhugh and Nelson, 1947; Radomski, et al. 1965;
Deichmann, et al. 1967; Natl. Cancer Inst., 1978).
The epidemiological studies in man to date cannot be
considered conclusive in view of the small number of indi-
viduals studied. Ortelee (1958) reported on a group of
40 men with extensive and prolonged occupational exposure
to DDT in manufacturing or formulating plants. An exposure
rate was given to each individual based on observation on
the job. The highest exposure rate was estimated to be
absorbed doses of approximately 42 mg/man/day. With the
exception of minor skin irritations, physical, neurological
and laboratory findings were within normal ranges and no
correlation between DDT exposure and frequency and distribu-
tion of the few abnormalities were seen. Laws, et al.
(1967) found no evidence of adverse health effects in 35
men with 11 to 19 years of high occupational exposure (3.6
to 18 mg/man/day). No case of cancer was found.
Almeida, et al. (1975) have conducted a surveillance
of workers exposed to DDT for six or more years as spray
men in a malaria eradication campaign in Brazil. Although
C-62
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significant increases in DDT and DDE residues in the blood
serum levels were observed, physical examination showed
no significant increases in adverse health effects for the
exposed versus control groups.
Edmundson, et al. (1969a) studied 154 individuals with
occupational exposure to DDT and observed significant dif-
ferences associated with race and type of occupation. Non-
white formulators and agricultural sprayers showed greatly
elevated serum concentrations but during the two-year time
of study no clinical effects related to DDT exposure were
observed.
Hayes, et al. (1971) administered doses up to 35 mg/man/day
to volunteers for 21.5 months. Liver function studies of
SCOT, plasma cholrnesterase, and BSP retention exhibited
no significant change from normal for these volunteers.
A number of other health parameters were studied and no
definite chemical or laboratory evidence of injury by DDT
was found at the prevailing levels of intake. This led the
/
authors to conclude that DDT had a considerable degree of
safety for the general population.
Several authors have examined the storage of DDT in
persons with various diseases. Maier-Bode (I960) found
t
no differences in storage of DDT or DDE in 21 persons who
died of cancer and 39 others who died of other diseases.
The difficulty in making these kinds of associations
is illustrated by the results of Radomski, et al. (1968).
Pesticide concentrations were determined in fat and liver
at autopsy for 271 patients previously exhibiting various
pathology of liver, brain and other tissues. Another group
C-63
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that had previously had infectious diseases was examined.
High significant elevations of DDT and DDE were found in
carcinomas of varying tissues. Fat concentrations of DDE,
DDT, DDD and dieldrin were consistently elevated in cases
of hypertension. These observations were clouded by the
great individual variability of pesticide levels regardless
of the disease category.
Two further studies (Hoffman, et al. 1967; Cassarett,
et al. 1968) have been conducted on the levels of DDT in
tissues of patients with cancer and other chronic diseases.
One showed higher DDT residues in cancer patients (Cassarett,
et al. 1968). No conclusions can be made from these studies
as to a possible causal relationship.
Sanchez-Medal, et al. (1963) noted 20 cases of aplastic
anemia over an eight-year period in a Mexico City Hospital.
In 16 out of 20 cases, the patients had repeated contact
with pesticides during the prior six months. Insecticides
implicated were DDT alone or DDT in association with lindane,
dieldrin or DDVP. One 13-year old boy had been exposed
repeatedly to DDT alone for two years and exposure was inten-
sified to every other day in the prior four months. He
was accidentally exposed to 10 percent DDT spray in the
hospital and died thirty hours later due to a worsening
blood discrasia. The American Medical Association Registry
on Blood Discrasia reported 44 cases of aplastic anemia
associated with pesticide exposure through 1963. Of these
cases, 19 were related to DDT and in three DDT was the sole
agent (Erslev, 1964)
C-64
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At the present time, no evidence of neoplasia has been
found in the studies performed in occupationally exposed
or dosed volunteer subjects. Medical histories have been
essentially normal. However, these studies do not constitute
an adequate basis to make conclusions regarding human carcino-
genicity because of small sample,size and short duration
in terms of average human life-span.
C-65
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CRITERION FORMULATION
Existing Guidelines and Standards
iE-n 1958., U.S. Department of Agriculture began to phase
out -the use of DDT in insect control programs. Spraying
was reduced from 4.9 million acres in 1957 to just over
IDO^QPO acres in 1967, and DDT was used as a persistent
pesticide thereafter only in the absence of an effective
alternative. In 1964, the Secretary of Interior issued
a directive that use of chlorinated hydrocarbons should
be avoided in interior lands. This was extended in 1970 /
when 16 pesticides, including DDT, were completely banned
for use on Department of -Interior lands. By 1969, DDT regis-
tration and usage was curtailed by the USDA in various areas
of the cooperative Federal State pest control program.
In November 1969, the USDA announced its intention to discon-
tinue all uses of DDT non-essential to human health and
for which there were safe and effective substitutes. In
1970, a major cancellation of Federal registrations of DDT
products by the USDA on 50 food crops, domestic animals,
finished wood and lumber products, and use around commercial,
institutional, and industrial establishments was completed.
Major responsibility for Federal regulation of pesticides
under the Federal Insecticide, Fungicide and Rodenticide
Act (1947) was transferred to the U.S. EPA. In January,
1971, U.S. EPA issued notices of intent to cancel all remain-
ing Federal registrations of products containing DDT. A
hearing on the cancellation of Federal registration of pro-
ducts containing DDT was held beginning in August, 1971
and concluding in March, 1972. The principal parties to
C-66
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the hearing were 31 DDT formulating companies, the USDA,
the Environmental Defense Fund, and the U.S. EPA. This
hearing and other evidence from four Government reports
including the December 1969 Mrak Commission Report were
instrumental in the final cancellation of all remaining
crop usages of DDT in the U.S., effective December 31, 1972.
During the same period (October 1972), a Federal Environmental
Pesticide Control Act (FEPCA) was enacted which provided
EPA with more effective pesticide regulation mechanisms.
The cancellation order was appealed by the pesticides industry
in several U.S. courts. On December 13, 1973, the U.S.
Court of Appeals for the District of Columbia ruled there
was substantial evidence in the record to support the U.S.
EPA ban on DDT. In April 1973 the U.S. EPA, in accordance
with authority granted by FEPCA, required that all products
containing DDT be registered with the Agency by June 10,
1973. Since that time, the U.S. EPA has granted requests
to the states of Washington and Idaho and to the Forest
Services to use DDT on the basis of economic emergency and
no effective alternative to DDT being available.
Authority to regulate hazards arising from the manufac-
turing and formulation of pesticides and other chemicals
resides with the Occupational Safety and Health Administration
(OSHA). Under the terms of the Occupational Safety and
Health Act of 1970, the National Institute of Occupational
Safety and Health has been responsible for setting guidelines,
criteria, and standards for occupational exposure. The
2
OSHA exposure limit for DDT on skin has been set a 1.0 mg/m .
Further, DDT has been classified as a suspected occupational
carcinogen that should be cautiously handled in the workplace.
C-67
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The decision to ban DDT was extensively reviewed /relative
to scientific and economic aspects in 1-975 (U.S,. EPA, J.975) .
No new evidence was found contradicting the original finding
of the Administrator in 1972,.
Year agency Org.
1971 WHO
1976 U.S. EPA
1977 Natl. Acad.
Sci0, Natl.
Res. Counc.
1978 Occup. Safety
Health Admin.
1978 U.S. EPA
Standard
0..005 .mg/kg
body weight
0.001 jug/1
1
0.41 jug/1
0.00023 jug/1
Remarks
Maximum Acceptable Daily Intake
in food
Quality Criteria for Water
In light .of carcinogenic risk
projecti.on, suggested strict
criteria for DDT and DDE in
drinking water
Skin exposure
Final acute and chronic values
for water quality criteria -for
protection of acquatic life
(fresh water)
Current Levels of Exposure
Most of the reported DDT concentrations in air are
associated with high usage of DDT prior to 1972. Stanley,
et al. (1971) analyzed air samples from nine localities.
DDT levels ranged from 0.1 ng/m. to 20 ng/m . Air samples
collected in July 1970 had 0..00007 -ng/ra (Prospero and Seba,
1972) over the Atlantic Ocean. The actual levels of DDT
in the ambient air at the present time are difficult to
estimate but are probably at the "lowest ranges ^f Stanley's
estimates. The significance of pesticide levels in the
air have been carefully reviewed and the consensus is that
the levels of DDT found in the ambient air are far below
levels that might add significantly to the total human intake
(Spencer, 1975).
C-68
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Kenaga (1972) gave the following relative values for
residues for DDT and its metabolites found in various types
of waters: rain water, 0.2 jug/1; fresh water, 0.02 jug/1;
sea water, 0.001 jug/1. Assuming average daily intake of
water to be 2 liters in any given year, maximal DDT intake
from water would be 0.007 mg. This figure is equivalent
to the estimated dietary intake of DDT in a single day for
a 19-year-old male (U.S. EPA, 1975). Therefore, it is con-
cluded that DDT'intake from potable water does not contribute
significantly to the overall exposure.
Duggan and Corneliussen (1972) calculated the average
daily intake of total DDT residues in 1965 as 0.0009 mg/kg
and decreasing to 0.0004 mg/kg in 1970. Market basket studies
have shown significant declines between 1970 and 1973 of
DDT and ODD residues of 86 and 89 percent, respectively.
DDE decreased by 25 percent over this period of time. Dairy,
meat, fish and poultry constitute 95 percent of the total
ingested DDT sources with dairy products contributing 30
percent of this amount. .Average human fat storage for the
time period of 1970 to 1973 has decreased from approximately
8 ppm to 6 ppm in the U.S. population. Based on these de-
clines and the most current figures of of 1973 for intakes
it is estimated that current levels of dietary intake are
approximately 0.0001 mg/kg/day with DDE comprising over
80 percent of this amount. Assuming the average male weighs
70 kg the average daily intake would be 0.007 mg/day or
2.56 mg/year.
Human exposure to DDT is primarily by ingestion of
contaminated food. Air and water intake is negligible and
amounts to probably less than 0.01 mg/year. Therefore,
C-69
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by our estimate, total intake of DDT per year for t.he average
U.S., resident will be less than 3 mg/year.
Special Groups at Risk
The entire population of the U.S. has some low level
exposure to dietary contaminants. Minimal exposure fxom
air and water sources, however, may be more important in
previously heavily sprayed agricultural areas, where large
amounts of residues may still be present.
In 1975, estimated DDT production was 30 to -49 .million
pounds (Natl. Inst. Occup. Safety Health, 1978). The primary
producer of DDT in the U.S. is the Montrose Chemical Co.
It is assumed that there are other companies involved in
the formulation of their products with DDT, but no data
are available.
Groups at special risk are workmen in manufacturing
plants and formulating plants and applicators, handlers
and sprayerSo
During such times as exceptions are granted by the
U.S. EPA for crop usage or during use for public health
measures, those involved in handling or applying DDT may
have considerable exposure.
Estimating the number of iridiviuduals at high risk
due to occupational exposure is difficult. It is estimated
that 8700 workers are involved in formulating or manufacturing
all pesticides. Since DDT constitutes much less than 10
percent of the total, the maximal number of exposed workers
would be approximately 500. Since usage of DDT is severely
limited, persons exposed by application would probably be
fewer.
C-70
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Basis and Derivation of Criterion
Since no epidemiological evidence for the carcinogeni-
city of DDT in man has been reported, the results of animal
carcinogenicity.studies conducted by feeding DDT or its
metabolites over the lifespan of the animal are regarded
as the most pertinent data. Although a number of studies
have been reported for various species, the major evidence
for the tumorigenicity of DDT is its ability to induce liver
tumors in mice.
Under the Consent Decree in NRDC vs. Train, criteria
are to state "recommended maximum permissible concentrations
(including where appropriate, zero) consistent with the
protection of aquatic organisms, human health, and recreation-
al activities." DDT is suspected of being a human carcinogen.
Because there is no recognized safe concentration for a
human carcinogen, the recommended concentration of DDT in
water for maximum protection of human health is zero.
Because attaining a zero concentration level may be
infeasible in some cases and in order to assist the Agency •
and States in the possible future development of water quality
regulations, the concentrations of DDT corresponding to
several incremental lifetime cancer risk levels have been
estimated. A cancer risk level provides an estimate of
the additional incidence of cancer that may be expected
in an exposed population. A risk of 10~ for example, indi-
cates a probability of one additional case of cancer for
every 100,000 people exposed, a risk of 10~ indicates one
additional case of cancer for every million people exposed,
and so forth.
C-71
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In the federal Register notice of availability of draft
ambient water quality criteria, EPA stated that it is con-
sidering setting criteria at an interim target risk level
of 10" , 10 or 10 as shown in the table below.
Exposure Assumptions Risk Levels and Corresponding Criteria^ '
(per :day) J lo'7 "^ lo"5
2 liters of drinking water 0.0098 ng/1 0.098 ng/1 0.98 ng/1
and consumption of 18.7
grams of fish and shellfish (2)
Consumption of fish 0.0098 ng/1 0.098 ng/1 0.98 ng/1
and shellfish only.
(1) Calculated by applying a modified "one hit" extrapolation
model described in the PR 15926, 1979, to the animal
bioassay data presented in Appendix I. Since the
extrapolation model is linear at low doses, the addi-
tional lifetime risk is directly proportional to the
water concentration. Therefore, water concentrations
corresponding to other risk levels can be derived
by multiplying or dividing one of the risk levels
and corresponding water concentrations shown in the
table by factors such as 10, 100, 1,000, and so forth.
(2) Greater than 99 percent of the DDT exposure results
from the consumption of aquatic organisms which exhibit
an average bioconcentration potential of 39,000 fold.
The remaining less than one percent of DDT exposure
results from drinking water.
C-72
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Concentration levels were derived assuming a lifetime
exposure to various amounts of DDT (1) occurring from the
consumption of both drinking water and aquatic life grown
in water containing the corresponding DDT concentrations
and, (2) occurring solely from the consumption of aquatic
life grown in the waters containing the corresponding DDT
concentrations. Although total exposure information for
DDT is discussed and an estimate of the contributions from
other sources of exposure can be made, this data will not
be factored into the ambient water quality criteria formula-
tion because of the tenuous estimates. The criteria presented,
therefore, assume an incremental risk from ambient water
exposure only.
' The case of DDT and its possible role as a human carcin-
ogen is complicated by several factors. Despite widespread
use and exposure over thirty years, no positive associations
with human cancer have been found to date, although the
number of individuals studied is not statistically large.
It is a chemical with high efficacy and has been extremely
effective all over the world for public health measures.
However, its slow biodegradability and propensity to accumu-
late in nontarget species have made it particularly hazardous
for many fish and bird species. For mammals, however, it
has a low acute toxicity as compared to other alternate
pesticides.
DDT has not been shown to produce point mutations or
teratogenic effects in a wide battery of tests. Some evidence
for its clastogenic properties, however, make it suspect.
C-73
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The primary evidence for the carcinogenicity of DDT and
metabolites to date has been the induction of liver tumors
in mice,. Studies in other species have consistently shown
little or no effect and in the mice only liver tumors have
shown an increase. The evidence for the carcinogenicity
of DDT would be much more convincing if other species or
sites of tumorigenic action could be conclusively demon-
strated. This is in light of the fact that DDT has been
probably the most extensively studied compound in modern
science.
Current levels of exposure would seem to pose extremely
small risk to persons in the U.S. DDT and DDE are preferentially
stored in fatty compartments that are not actively dividing
and subject to carcinogenic changes.
The use of DDT has been restricted in several countries
because of its impact on the environment and its tumorigenic
effect in mice. This is a reasonable proposition based
on numerous reports. Therefore, the levels proposed in
this document should ensure the health of wildlife and the .
co-existing human population.
C-74
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APPENDIX I
Summary and Conclusions Regarding the Carcinogenicity
of DDT*
DDT is a synthetic, chlorinated hydrocarbon insecticide
which has broad-spectrum insecticidal activity. DDT residues
have been detected in a wide variety of fruits, vegetables,
meat, fish and poultry, and will probably continue to be
present in agricultural produce indefinitely as a consequence
of the persistence of DDT in soil. DDT is absorbed completely
after inhalation and ingestion and absorbed poorly through
skin. DDT has not been found to be mutagenic in bacterial
test systems, either with or without metabolic activation.
The evidence from mammalian test systems ir\ vitro and in
vivo is inconclusive.
There is no epidemiological evidence relating to the
carcinogenicity of DDT, but there are a number of carcino-
genicity studies conducted by feeding DDT to animals. A
number of chronic studies have been reported in various
species, but the major evidences for tumorigenicity in mice
and rats are described below. In mice, DDT increased tumor
incidence significantly in experimental groups as compared
to controls in liver (Innes, et al. 1969; Walker, et al.
1972; Turusov, et al. 1973; Terracini, et al. 1973; Thorpe
and Walker, 1973), lungs (Tarjan and Kemeny, 1969; Shabad,
*This summary has been prepared and approved by the Carcino-
gens Assessment Group of EPA on July 25, 1979.
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et al. 1963) and lymphoreticular tissue tumors (Innes, et
alo 1969 and Tarjan and Kemeny, 1969). In rats, liver tumors
were significantly increased in the experimental group as
compared to controls in two studies (Fitzhugh and Nelson,
1947; Rossi, et al. 1977).
The negative NCI mouse study might be explained on
the basis of shorter duration of exposure, low dose in male
mice, and the use of a strain different from the other positive
studies. The negative NCI rat study might be explained
on the basis of shorter duration of exposure and lower dose
compared to that used in the Fitzhugh study. There are
other negative carcinogenicity studies in mice, rats, hamsters,
dogs, and monkeys.
The water quality criterion for DDT is based on a com-
parison of the cancer rates in Israel, where DDT exposure
has been high for an extended period of time, and the United
States (Tursov, et al. 1973). It concluded that if water
alone is consumed, the water concentration should be less
than 0.36 micrograms per liter in order to keep the lifetime
cancer risk below 10~ . If fish and water are consumed,
the water concentration should be less than 0.98 nanograms
per liter to achieve the same risk level.
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Summary of Pertinent Data
The water quality criterion for DDT can be derived
on the basis of two independent sets of data, neither of
which is completely satisfactory. The first method is based
on the most sensitive animal chronic bioassay available,
which is the six-generation study by Turusov, et al. (Jour.
Nat. Cancer Inst., 1973) in CF-1 mice. The second method
is based on a comparison of the lifetime incidence of nervous
system cancer cases between residents of New York State
(except New York City) and residents of Israel who were
born in Europe or America.
The first method results in water quality concentrations
so low that over 95 percent of surface water in the U.S.
would fail to meet the criteria. This method also implies
that the lifetime risk from current ambient concentrations
is approximately three percent, which seems unrealistically
high for DDT exposure alone in view of the absence of reported
carcinogenic effects in heavily exposed populations. The
second method is based on extremely tenous assumptions,
but it does use human data to put an upper limit on the
carcinogenic effectiveness of DDT.
METHOD 1
In the Turusov mouse study, the six generations of
the lowest dose group (2 ppm) of males had 179 animals with
hepatomas out of 354 animals analyzed, whereas in controls
97 out of 328 animals had hepatomas. The data used for
the criterion are:
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nfc = 179 d = 2 X 0.13 = 0.26 mg/kg/day
N = 354 w = 0.030 kg
n = 97 L = 104 weeks
c
NC = 328 R = 39,000
Le = 104 weeks F = 0.0187 kg/day
le = 104 weeks
With these values the slope parameter is BH = 18.055
(ing/kg/day)" . The result of the calculation is that if
\
fish and water are consumed the water concentration should
be less than 0.053 ng/1 in order to keep the individual
lifetime risk below 10~ . If only water were consumed
(F = 0) the corresponding concentration is 20 ng/1.
METHOD 2
There is strong evidence that method 1 overstates the
DDT risk, either because the animal experiments overstate
the human risk or because most people do not eat fish contam-
inated to the extent assumed in the model. The basis for
stating this is that countries like Israel where the levels
of DDT exposure have been high and widespread have experienced
no excess cancer incidence as compared to the United States.
As an upper limit estimate of cancer risk from DDT exposure,
we can make the unsupported assumption that DDT does cause
human cancer with some probability which is proportional
to the lifetime exposure and we can make the reductio ad
absurdum argument that cancer incidence in the organ site
where the largest excess in incidence occurs in Israel is
due solely to DDT, which of course is not true. Taking
the nervous system as a reasonable candidate site for the
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action of DDT, we can make the following estimate which
is intended only to put upper bounds on the carcinogenic
effectiveness of DDT.
The high exposure in Israel is reflected in the higher
fat levels measured by Wasserman, et al. According to their
data the average level in Israel is 16.33 ppm (based on
three studies), whereas in the United States it is 9.04
ppm (based on ten studies). Using the following relationship,
developed by Hayes, et al. and Durham, et al. between the
daily dose I(mg/day), and the concentration, C (ppm) in
body fat:
log I = (1/0.7)(log C -1.3),
the difference in the average daily doses between in Israel
and the United States was calculated to be 0.751 - 0.323
= 0.428 mg/day. The lifetime incidence of cancer for Israel
and New York State is tabulated below from Table 8.3.
Lifetime Incidence (percent)
Nervous
Population (males) System All Sites
New York State 0.5 28.8
Israel:
All Jews 1.1 24.9
Born Israel 1.3 21.4
Born Europe or America 1.1 24.1
Born Africa or Asia 0.7 18.6
Non - Jews 0.5 15.3
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Relative to New Yauk, the exaess lifetime risk of nervous
system cancer in wigranrbs -to larafil ffitom Europe and America
is 1.1 - 0.5 * ,0v€ p^nwmt. 'Thi-s is caused by an excess
intake of 0.42B ing/day. Therefor**, the intake I resulting
_c
in 10 risk is
I = (10"~5/O.JOO&) X. 0,428 * ^,..13 X 10~4 mg/day
If this intake comes frswi jE.iah and *tater, the concentration
of water would .be-:
C = 7.13 X ID"4/ (-2 + 39,00.0 X O.JQJL87)
=0.98 ng/1
If the intake comes from water alone, -the concentration
would J>e:
—.4 '
C = ?'132- ^ — - 0.3S7
Therefore, according ±o -atetteod 2, if fish and water
are con-sumed, the water concentration should be less than
0.98 ng/1 in order to ke*^> i*e iaad,iv:idual lifetime risk
below 10" . if only water is consutsed, .the corxe spending
concentration is 0.36 ug/1. The «quivalent slo.pe factor
for method 2 is:
70 X 10^ ,
H ~ 2 x 3.57 X 10"4 = °-m <»B/*g/day) ~
Method 2 is recommemted beceuse it gives some basis
for avoiding the unreal iat ica'ULy low concen-fcrations impoaed
by considering only the artimaH -j
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