EPA-540/1-86-026
oEPA
environmeniai riuieiuun
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Superfund
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
HEALTH EFFECTS ASSESSMENT
FOR DDT
-------
EPA/540/1-86-026
September 1984
HEALTH EFFECTS ASSESSMENT
FOR DDT
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
-------
DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and 1t has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with DDT. All
estimates of acceptable Intakes and carcinogenic potency presented 1n this
document should be considered as preliminary and reflect limited resources
allocated to this project. Pertinent toxlcologlc and environmental data
were located through on-line literature searches of the Chemical Abstracts,
TOXLINE, CANCERLINE and the CHEMFATE/DATALOG data bases. The basic litera-
ture searched supporting this document Is current up to September, 1984.
Secondary sources of Information have also been relied upon 1n the prepara-
tion of this report and represent large-scale health assessment efforts that
entail extensive peer and Agency review. The following Office of Health and
Environmental Assessment (OHEA) sources have been extensively utilized:
U.S. EPA. 1980a. Hazard Assessment Report on DDT, ODD, DDE.
Environmental Criteria and Assessment Office, Cincinnati, OH.
Internal report.
U.S. EPA. 1980b. Ambient Water Quality Criteria for DDT.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-038. NTIS PB 81-117491.
U.S. EPA. 1985. The Carcinogen Assessment Group's Evaluation of
the Cardnogenlcity of Dicofol (Kelthane), DDT, DDE and DDD (TOE).
Prepared by the Carcinogen Assessment Group, OHEA, Washington, DC
for the Hazard Evaluation Division Office of Pesticide Programs.
EPA 600/6-85-002X. Internal Review Draft.
The Intent in these assessments is to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemical(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer is not the endpoint of concern).
The first, the AIS or acceptable intake subchronic, is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time interval (I.e., for an Interval that
does not constitute a significant portion of the Hfespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants in ambient air or water where lifetime exposure is
assumed. Animal data used for AIS estimates generally include exposures
with durations of 30-90 days. Subchronic human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, is similar In concept to the ADI
(acceptable dally Intake). It Is an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the llfespan [see U.S. EPA (1980c) for a discussion
of this concept]. The AIC Is route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes 1s Insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development is explained in U.S. EPA (1983).
For compounds for which there Is sufficient evidence of carcinogenlcity,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980c). Since cancer is a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and Inhalation data if available.
iv
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ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
U.S. EPA (1985) estimated
orally administered DDT based on
separate studies.
a human q-|*
the geometric
of 0.34
average of
(mg/kg/day) 1 for
potencies from six
Data are not available for the evaluation of the potential cardnogen-
1dty of DDT following Inhalation exposure.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Or. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was',the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
Page
1
, . . 2
. . . 2
2
, . . 3
3
. . . 3
3
. . . 3
. . . 3
. . . 7
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS.
4.
5.
3.4.
3.3.1. Oral
3.3.2. Inhalation ,
TOXICANT INTERACTIONS
CARCINOGENICITY ,
4.1.
4.2.
4.3.
4.4.
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation ,
BIOASSAYS '
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
7
8
8
11
11
11
11
11
11
17
17
18
19
vll
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 20
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 20
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 20
6.3. CARCINOGENIC POTENCY (q-|*) 20
6.3.1. Oral 20
6.3.2. Inhalation 26
7. REFERENCES 31
APPENDIX: Summary Table for DOT 43
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LIST OF TABLES
No. Title Page
3-1 Subchronlc Oral Toxldty of DDT in Rats 4
3-2 Chronic Oral Toxlclty of DDT 5
3-3 Reproductive Studies 9
4-1 Oral Carc1nogen1c1ty of DDT 12
6-1 Incidence of the Most Commonly Occurring Malignant Tumors
1n Each of Five Generations of BALB/c Mice Fed DDT 21
6-2 Incidence of Benign Liver Tumors 1n Each of Six
Generations of CF-1 Mice Fed DDT 23
6-3 Incidence of Benign Liver Tumors In BALB/C Mice Fed DDT
During a 2-Generat1on Experiment 25
6-4 Incidence of Liver Tumors (Benign and Malignant) In CF-1
Mice Fed DDT for a Single Generation 27
6-5 Incidence of Benign Liver Tumors 1n CF-1 Mice Fed DDT for
15 or 30 Weeks and then Sacrificed at 65, 95 and 120 Weeks. . 28
6-6 Incidence of Benign Liver Tumors 1n Rats Fed DDT 29
6-7 Summary of Quantitative Potency Estimates for DDT 30
1x
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BCF Bloconcentratlon factor
bw Body weight
CAS Chemical Abstract Service
CS Composite score
ppm Parts per million
SER Smooth endoplasmlc retlculum
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The physical and chemical properties and environmental fate of DDT (CAS
No. 50-29-3 for p.p'-DDT and 789-02-6 for o.p'-DDT) are as follows:
Chemical class:
Molecular weight:
Vapor pressure at 20°C:
Water solubility at 25°C:
Log octanol/water
partition coefficient:
BCF:
Half-life 1n
Water:
Soil:
pesticide (Callahan et al., 1979)
354.5 (Callahan et al., 1979)
1.5xlO~7 mm Hg for p.p'-DDT
5.5xlO"6 mm Hg for o.p'-DDT
(Callahan, et al., 1979)
1.2-25 yg/8. for p.p'-DDT
26-85 yg/i for o.p'-DDT
(Callahan et al., 1979)
3.98-6.19 (Callahan et al., 1979)
103 to 106 (Callahan et al., 1979)
56-110 days 1n lake water
(Zoeteman et al., 1980)
3-15 years (IARC, 1974)
The mobility of DDT In soils has been studied by various authors (U.S.
EPA, 1980a) and has been reported to be extremely slow. Therefore, the leach-
Ing of DDT from soil 1s expected to be very slow, particularly 1n soil with
high organic carbon content. Nevertheless, leaching of DDT from soil Into
groundwater at a frequency of 8-9% has been reported (Page, 1981).
The half-life of DDT In the atmosphere 1s uncertain. DDT 1s probably lost
from the atmosphere by ralnout, fallout or photochemical degradation (Spencer,
1975). The photolytlc half-life for the transformation of DDT to DDE and ODD
1n the atmosphere can be estimated to be -17 days (Crosby and Mollanen, 1977).
The fact that DDT has been found to participate 1n long distance aerial trans-
port (Callahan et al., 1979) Indicates that 1-t has a long half-life 1n the
atmosphere.
-1-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Jensen et al. (1957) reported that 95% of the Ingested DDT in rats Is
absorbed from the gastrointestinal tract. Over 65% of the labeled DOT was
recovered in the bile collected from rats for 9 days following DDT ingestion
(Jensen et al., 1957). More DDT is absorbed in rats when it is dissolved in
digestible vegetable oils than when it is suspended 1n water or dissolved in
indigestible mineral oils (Keller and Yeary, 1980).
In humans, the absorption of DOT follows the same pattern as the absorp-
tion of dietary fat, that is, absorption is relatively slow; however, absorp-
tion appears to be complete after 24 hours (Morgan and Roan, 1977).
2.2. INHALATION
Pertinent data regarding the absorption of DDT by Inhalation could not be
located in the available literature.
-2-
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Laug et al. (1950) exposed rats to different levels of DDT
(1-50 ppm) 1n the food and examined the histology of the liver 15-27 weeks
after the start of treatment. No effects were reported at an exposure of
1 ppm; however, at all the higher exposure levels (5-50 ppm), hepatic cell
hypertrophy appeared to be dose-related and minimal alterations In Hver
histology were reported at an exposure of 5 ppm (Laug et al., 1950). Hart and
Pouts (1965) reported Increased liver mlcrosomal enzyme activity 1n rats at 5
and 50 ppm. Ortega et al. (1956a,b) reported ultrastructural changes at 5 and
15 ppm 1n livers of male rats (Table 3-1).
3.1.2. Inhalation. Pertinent data regarding the inhalation of DDT could
not be located in the available literature.
3.2. CHRONIC
3.2.1. Oral. Exposure of rats to 200 ppm (10 mg/kg/day) DDT in the food
for 2 years resulted in Increased liver weight in the females (FHzhugh and
Nelson, 1947; FHzhugh, 1948). At higher doses (400-800 ppm), the liver
alterations became more severe and were present in both sexes. Liver lesions
were present at all dose levels tested, the lowest of which was 10 ppm (0.5
mg/kg/day) (Fltzhugh and Nelson, 1947; FHzhugh, 1948) (Table 3-2). In
chronic exposure studies with DDT, effects appeared to be most severe In
offspring exposed to DDT for their entire Hfespan, especially during in utero
development and nursing. This 1s demonstrated in the study of Treon and
Cleveland (1955) in which male rats exposed to 25 ppm (1.25 mg/kg/day) DDT in
the food for 2 years and 3 generations had increased liver weights. In mice,
lactation was decreased and the mortality of the offspring increased at an
exposure level of 100 ppm (13.0 mg/kg/day) for 6 generations (Keplinger et
al., 1968). The incidence of tumors was increased at exposure levels of 50
-3-
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TABLE 3-1
Subchrontc Oral Toxlclty of DDT In Rats
Dose*
Isomer
ppm
NR 50
10
5
1
NR 350
i
f NR 50
5
NR 15
5
NR 0.2
rag/kg/day
2.5
0.5
0.25
0.05
17.0
2.5
0.25
0.75
0.25
0.01
Duration of Sex
Exposure
15-27 weeks H/F
33-60 weeks NR
3 months NR
2-18 months NR
1-13 weeks NR
Number
Used
75/75
NR
NR
NR
NR
Effects
Hepatic cell hypertrophy was definitely present at
dose levels of 50 and 10 ppm, and minimally present
at 5 ppm. No effects were reported at 1 ppm.
No htstopathologlc alteration In the exposed as
compared with the control group.
Liver mlcrosomal enzyme activity was Increased at
both exposure levels.
Males had hlstopathologlc alterations (proliferation
of SER and concentric membrane arrays) In the liver
at both exposure levels.
Liver mlcrosomal enzyme activity was not Increased.
Reference
Laug et al.,
1950
Cameron and
Cheng, 1951
Hart and
Fouts, 1965
Ortega et al.,
19S6a,b
Klnoshtta
et al.. 1966
*The fraction of body weight consumed per day In food, called the food factor. Is 0.13 for mice and 0.05 for rats. Exposures given In ppm of
food are converted to mg/kg/day by multiplying the ppm exposure level by the food factor.
NR = Not reported
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TABLE 3-2
Chronic Oral Toxlclty of DDT
Isomer3
ppra
Technical 800
600
400
200
TOO
50
TO
0
Doseb
Duration of
mg/kg/day Exposure
40 2 years
30
20
TO
5
2.5
0.5
Species Sex
rat/ H/F
Osborne- H/F
Hendel H/F
H/F
H
NR
NR
H/F
Number
Used
24/24
24/24
24/12
24/12
T2
NR
NR
24/T2
Effects Reference
At 800 ppm there were Increased Fltzhugh and
mortality and liver lesions. In- Nelson, 1947;
creased liver weight occurred at Fltzhugh, 1948
200 ppm for females and at higher
doses for both males and females.
No second generation offspring
survived In animals exposed to 600
ppm. A reduction In survival of
preweanllng rats occurred at DDT
levels of >50 ppm. Liver lesions
were present at all dose levels,
but no reproductive effects were
reported at exposures of 10 ppm.
NR
i
en
i
Technical
Technical
Technical
25
12.5
2.5
0
200
250
50
10
250
20
1.25
0.625
0.125
10
32.5
6.5
1.3
32.5
2.6
2 years/
3 generations
rat
2 generations
2 generations
rat/
Sprague-
Dawley
mouse
4 generations
2 generations
mouse/
BALB/c
mouse/
BALB/c
H/F 40/40 Hales had Increased liver weights
H/F 40/40 at an exposure level of 25 ppm.
H/F 40/40 Although size of the litter and the
H/F 40/40 number of pregnancies remained un-
affected by DDT. the mortality of
the offspring was Increased at all
exposure levels.
NR NR Increased liver weight, but no
reproductive disturbance, was seen
In exposed animals.
NR NR There was an Increased Incidence of
liver tumors at all exposure levels
tested. At an exposure of 250 ppm,
there was Increased mortality In
the neonates, and reduced llfespan.
Tremors and convulsions occurred In
some animals.
NR NR Although no effects on reproduction
were reported, females suffered re-
NR NR duced llfespans In addition to gas-
trointestinal bleeding, convulsion
and Increased Incidence of tumors.
Treon and
Cleveland, 1955
Ottobonl, 1969
Tomatls et al..
1972
Terraclnl
et al., 1973a,b
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TABLE 3-2 (cont.)
Isomera
ppm
p.p'-DDT 100
50
Technical 200
p.p'-DDT 200
Technical 3200
2000
400
0
p.p'-DDT 1000
500
0
i
f Technical 1000
500
250
NR 500
250
125
Doseb
Duration of Species
mg/kg/day Exposure
13.0 2 years mouse
6.5
8.0 3.5-7.5 years monkey
8.0
128 39-40 months dog
80
16
80 44/48 weeks hamster
40
80 18 months hamster
40
20
40 llfespan hamster
20
10
Sex
NR
NR
M/F
H/F
H/F
H/F
H/F
H/F
H/F
NR
NR
NR
NR
Number
Used
NR
NR
7/7
2/2
1/1
1/1
25-30/
25-30
25-30/
25-30
79
NR
NR
NR
NR
Effects
The Incidence of liver tumors was
Increased at both exposure levels.
No observed effects reported.
No effects were observed at 400
ppm, but liver damage occurred at
2000 ppm and was more severe at
3200 ppm.
Increased mortality as well as
nervousness and convulsions were
observed In exposed animals.
Increased liver weight and enzyme
(glucose-6-phosphate dehydrogenase)
activity and decreased llfespan
were reported.
No observed effects on growth or
survival .
Reference
Thorpe and
Walker. 1973;
Walker et al..
1972
Durham et al. ,
1963
Lehman. 1952.
1965
Agthe et al..
1970
Gralllot
et al., 1975
Cabral and
Shublk. 1977
technical DDT consists of -77.IX p.p'-DDT. 14.9X o.p'-DDT, 0.3X p.p'-DDD, 0.1X o.p'-DDD, 4.OX p.p'-DDE, 0.1X o.p'-DDE and 3.5X unidentified
compounds (U.S. EPA. 1980a).
bThe fraction of body weight consumed per day In food, called the food factor. Is 0.13 for mice and 0.05 for rats. Exposures given In ppm
of food are converted to mg/kg/day by multiplying the ppm exposure level by the food factor.
NR = Not reported
-------
ppm (6.5 mg/kg/day) for 2 years (Thorpe and Walker, 1973; Walker et a!., 1972)
and at 20 ppm (2.6 mg/kg/day) 1n a 2-generatlon study (Terraclnl et al.,
1973a,b). The llfespan of the females that suffered from gastrointestinal
bleeding and convulsions was decreased at an exposure level of 20 ppm (2.6
mg/kg/day) for 2-4 generations (Terraclnl et al., 1973a,b). Durham et al.
(1963) reported that there was no observed effect In monkeys exposed to 200
ppm (8.0 mg/kg/day) DOT In the food for 3.5-7.5 years; however, the offspring
of dogs exposed to 1 ppm (0.04 mg/kg/day) DDT In the food for 3 generations
had consistently Increased liver weights (Ottobonl et al., 1977). Hamsters
were exposed to much higher levels of DDT, ranging from 125 ppm (10 mg/kg/day)
to 1000 ppm (80 mg/kg/day). At an exposure level of 500 ppm (40 mg/kg/day),
Agthe et al. (1970) reported nervousness, convulsions and Increased mortality
1n exposed animals; Gralllot et al. (1975) reported Increased liver weights;
and Cabral and Shublk (1977) reported that there was no effect on the growth
or survival of exposed hamsters.
3.2.2. Inhalation. Pertinent data regarding the chronic toxlclty of
Inhaled DDT could not be located In the available literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. When pregnant mice were exposed to 1 mg/kg bw on days 10, 12
and 17 of gestation, morphologic changes were seen In the gonads and the
fertility of the female offspring was reduced (McLachlan and Dlxon, 1972).
Although no teratogenesls was observed, 2.5 mg/kg given dally to pregnant mice
was significantly embryotoxlc, as well as blastotoxlc and fetotoxlc (Schmidt,
1973). Similarly 1n rabbits, Increased resorptlon, premature delivery and
reduced fetal growth, but no teratogenlclty, were caused by exposure to 50
mg/kg DDT on days 7, 8 and 9 of pregnancy. When rats were exposed to 7 ppm
DDT 1n the diet for 60 days before mating and for the duration of pregnancy,
fertility was decreased and the number of resorptlons Increased, but there was
-7-
-------
no evidence of teratogenidty (Green, 1969) (Table 3-3). Although there have
been no reports of any teratogenlc effects of DDT, with the possible exception
of ringtail occurring 1n rats exposed to 200 ppm DDT 1n the diet (Ottobonl,
1969), DDT has consistently caused a decrease in reproductive capacity in mice
(Keplingler et al., 1968; McLachlan and Dixon, 1972; Schmidt, 1973), rats
(Fltzhugh and Nelson, 1947; FHzhugh, 1948; Treon and Cleveland, 1955; Clement
and Okey, 1974; Oonsson et al., 1975) and dogs (Deichmann et al., 1971;
Deichmann and MacDonald, 1971). Some studies reported no observed effects on
reproduction 1n rats (Ware and Good, 1967; Duby et al., 1971) and dogs
(Ottoboni et al., 1977) (see Tables 3-2 and 3-3).
3.3.2. Inhalation. Pertinent data regarding the teratogenicity of inhaled
DDT were not located 1n the available literature.
3.4. TOXICANT INTERACTIONS
Although there is widespread concern about the synergistic Interaction of
DDT with other potentially hazardous chemicals, the interaction of DDT with
only a few chemicals has been studied. Welsburger and Weisburger (1968)
reported that 10 mg/day of DDT significantly increased the incidence of hepa-
tomas In rats, caused by the ingestlon of 1 mg/day N-fluorenacetamide (2-AAF).
They postulated that DDT exerted Us Influence by stimulating the hepatic
mixed function oxidase system (Welsburger and Weisburger, 1968). On the other
hand, after evaluating the Interaction of DDT, aramite, methoxychlor, thiourca
and aldrin, Deichmann et al. (1967) concluded that the chemicals did not act
synergistlcally, and, in fact, may have Interacted antagonistically. Although
there was no Increase in the overall Incidence of Hver tumors when mice were
exposed to 100 ppm DDT and 5 ppm dleldrln simultaneously, the hlstological
characteristics of the liver tumors were more malignant after the mice were
exposed to DDT and dieldrln simultaneously (Walker et al., 1972).
-8-
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TABLE 3-3
Reproductive Studies
i
10
Ooseb
Isomera
Technical
p.p'-DDT
o,p'-DDT
Technical
NR
p.D'-DOT
I* • r •*" •
o.o'-DDT
** t r "•* "
NR
NR
ppm
7
15
15
15
1
500
200
20
1000
200
20
150
75
7
0
Duration of Species
mg/kg/day Exposure
0.9 120 days mouse/
BALB/c
and CFW
0.75 2 generations rat
0.75
0.75
0.05 175 days
25 6 months rat
10
1
50 6 months rat
10
1
7.5 8-36 weeks rat
3.75
0.35 2 generations rat
Sex
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
Number
Used
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
NR
131
396
Effects
No observed effect on reproduction
was reported.
No effects on reproduction were
reported.
No effects were seen at the 20 ppm
dose level. Growth of offspring
was severely depressed at the 200
ppm dose level, and all offspring
died within 10 days of birth when
the animals were exposed to 500 ppm
p.p'-DDT.
The only effects on reproduction
were seen at the 1000 ppm dose
levels, which caused decreased
fertility and growth In exposed
animals.
An exposure level of 150 ppm caused
reproductive failure. At 75 ppm.
the number of pups/litter was not
changed, but there was a decreased
number of pregnant females.
None of the rats In the second gen-
eration were able to get pregnant.
Reference
Ware and Good,
1967
Duby et al..
1971
Clement and
Okey. 1974
Clement and
Okey, 1974
Jonsson et al..
1975
Green, 1969
Technical
NR
200
25
12.5
2.5
0
10
1.25
0.625
0.125
2 generations
2 years/
3 generations
rat/
Sprague-
Oawley
rat
There was decreased fertility and
Increased mortality In the first
generation.
NR NR No reproductive disturbance was
seen In exposed animals.
M/F 40/40 Although size of the litter and the
H/F 40/40 number of pregnancies remained un-
H/F 40/40 affected by DDT, the mortality of
H/F 40/40 the offspring was Increased at all
exposure levels.
Ottobonl. 1969
Treon and
Cleveland. 1955
-------
TABLE 3-3 (cont.)
o
i
Isomera
Technical
Technical
NR
p.p'-DDT
Technical
ppm
250
SO
10
250
20
250
100
25
10
5
1
Doseb
Duration of Species
mg/kg/day Exposure
32.5 2 generations mouse
6.5
1.3
32.5 4 generations mouse/
BALB/c
2.6 2 generations mouse/
BALB/c
32.5 6 generations mouse
13.0
3.25
12 5 times/week, dog
14 months
0.4 3 generations dog
0.2
0.04
Sex Number Effects
Used
NR NR At an exposure of 250 ppm, there
was Increased mortality In the
neonates, and reduced llfespan.
Tremors and convulsions occurred
In some animals.
NR NR No effects on reproduction were
reported.
NR NR
NR NR No reproductive effects were seen
NR NR at exposure levels of 25 ppm. At
NR NR an exposure level of 100 ppm lacta-
tion was reduced and mortality of
the offspring Increased. The
severity of the effects produced
at 100 ppm were greatly Increased
at 250 ppm.
H/F 4/3 Decreased male libido and delayed
female estrus were reported, as
well as Infertility, reduced lacta-
tion and mammary gland development,
and Increased maternal and fetal
mortality.
NR NR Except that estrus occurred earlier
In exposed dogs than In controls,
there were no observed effects on
reproduction. However, liver weights
were consistently higher In pups
exposed to DDT.
Reference
Tomatls et al..
1972
Terradnl
et al.. 1973a,b
Kepllnger
et al.. 1968
Delchmann
et al.. 1971;
Delchmann and
Mac Dona Id. 1971
Ottobonl
et al.. 1977
aTechn1cal DDT consists of -77.IX p.p'-DDT. 14.9X o.p'-DDT. 0.3X p,p'-DDD. 0.1X o.p'-DDD, 4.OX p.p'-DDE, 0.1X o.p'-DDE and 3.5X unidentified
compounds (U.S. EPA. 1980a).
DThe fraction of body weight consumed per day In food, called the food factor, Is 0.13 for mice, 0.05 for rats and 0.04 for dogs. Exposures
given In ppm of food are converted to mg/kg/day by multiplying the ppm exposure level by the food factor.
NR = Not reported
-------
4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. A group of prison volunteers Ingested dally doses of DDT (3.5
mg/man/day or 35 mg/man/day) for 21.5 months (Hayes et al., 1971). No 111
effects ascribed to DDT 1ngest1on were reported 4-5 years after the start of
the experiment.
4.1.2. Inhalation. Human data regarding the cardnogenlclty of DDT has
been collected from occupational exposure, which occurs chiefly through
Inhalation. In occupational exposures where doses ranged from an estimated
10-40 mg/man/day for 1-8 years (Ortelee, 1958) and 3-18 mg/man/day for an
average of 15 years (range, 11-19 years) (Laws et al., 1967), no Increased
Incidence of cancer was reported.
4.2. BIOASSAYS
4.2.1. Oral. The cardnogenlclty of DDT has been tested extensively 1n
mice, rats and hamsters. An NCI study, reported by Innes et al. (1969), found
Increased Incidence of hepatomas 1n male and female mice exposed to DDT
beginning at 7 days of age. At first the DDT was Introduced by gavage; after
weaning at 4 weeks the DDT was Incorporated 1n the diet. In addition to liver
tumors, females had an Increased Incidence of lymphomas (Innes et al., 1969)
(Table 4-1).
Tarjan and Kemeny (1969) studied five generations of BALB/c mice exposed
to DDT at a level of 2.8-3.0 ppm In the diet. A variety of tumors accounted
for the Increased Incidence of cancer 1n exposed (28.7%) as compared with
control (3.2%) groups. Lung carcinoma, which occurred In 116 of the 196
animals with tumors, was the predominant type. Leukemia was found 1n 23
females and 21 males of the 196 animals that developed tumors. Tumors were
also observed In the liver, kidney, spleen, ovary and other organs. The
-11-
-------
TABLE 4-1
Oral CarcinogenicHy of DDT
Vehicle Dose
NR 0 ppm
3.0 ppm
Length of
Treatment
llfespan
Length of Species
Experiment
5 generations mice/
BALB/c
Sex
H/F
N/F
Number
Tested
406
683
Effects
Combined tumor Incidence across 5
generations: lung tumors (16. 9X
treated, 1 .2% control), lymphomas
(4.8X treated, 1.05C control) and
leukemlas (12. 4X treated. 2.5X
control) occurred In the mice exposed
to DDT.
Reference
Tarjan and
Kemeny. 1969
no
I
Gelatin/
diet
Gelatin/
diet
NR
NR
NR
control 81 weeks NR mlce/Xa H/F 79/87
46.4 mg/kg/day, days 7-28/ M/F 18/18
18.2 mg/kg/day (140 ppm),
4-81 weeks
control 81 weeks NR m1ce/Yb M/F 90/8?
46.4 mg/kg/day. days 7-28/ N/F 18/18
18.2 mg/kg/day (140 ppm),
4-81 weeks
0 ppmc llfespan 2 generations mouse/ H/F 113/111
(0.26 mg/kg/day) 2 ppm CF1 H/F 124/105
(1.3 mg/kg/day) 10 ppm H/F 104/124
(6.5 mg/kg/day) 50 ppm M/F 127/104
(32.5 mg/kg/day) 250 ppm M/F 103/90
0 ppm 112 weeks NR mouse/ M/F 47/47
(6.5 mg/kg/day) 50 ppm CF1 H/F 32/30
(13.0 mg/kg/day)100 ppm H/F 32/32
0 ppm 110 weeks NR mouse/ H/F 45/44
100 ppro CF1 H/F 30/30
About 30X of the females died during Innes
treatment. Hepatomas occurred In et al., 1969
11/18 male and 4/18 female mice
exposed to DDT. whereas only 8/79
male and 0/87 female controls had
hepatomas.
About 30X of the females died during Innes
treatment. Hepatomas occurred In 7/18 et al.. 1969
male and 1/18 female mice exposed to
DDT. whereas only 5/90 male and 1/82
female controls had hepatomas.
The Incidence of hepatomas was slgnlf- Tomatts
Icantly Increased (p<0.01) In both et al., 1972
males and females exposed to 250 ppm
DDT. When the animals were aged past
60 weeks, the Increased Incidence of
liver tumors was significant (p<0.01)
at all dose levels In males, but not
females.
Liver tumors In mice on diets con- Walker
talnlng DDT at a dose of 0. 50 or 100 et al.. 1972
ppm occurred In 13, 37 and 53X of the
males, and 17. 50 and 76% of the
females, respectively.
Liver tumors In mice on diets con- Thorpe and
talnlng 0 or 100 ppm DDT occurred In Walker, 1983
24 and BOX of the males and 23 and 87X
of the females, respectively. Malig-
nant liver tumors occurred In 4.4 and
30X of the males and 0 and 40X of the
females.
-------
fABLE 4-1 (cont.)
CO
i
Vehicle
NR
NR
NR
Dose
0 ppm
(0.26 mg/kg) 2 ppm
(1.5 mg/kg) 10 ppm
(6.S mg/kg) 50 ppm
(32.5 mg/kg) 250 ppm
0 ppm
(0.26 mg/kg/day) 2 ppm
(2.6 mg/kg/day) 20 ppm
(32.5 mg/kg/day) 250 ppm
0 ppm
(32.5 mg/kg/day) 250 ppm
Length of Length of Species Sex
Treatment Experiment
lifetime 6 generations mouse/ H/F
CF1 H/F
H/F
H/F
H/F
2 generations llfespan mouse/ H/F
CF1 H/F
H/F
H/F
15-30 weeks 65, 95 and mouse/ H/F
120 weeks CF1 H/F
Number
Tested
328/340
354/339
362/355
383/328
350/293
107/131
112/136
106/128
106/121
481
713
Effects
Cumulative Incidence of hepatomas
males: 29.5. 50.5, 50.0. 55.9. 86. OX
for 0, 2, 10, 50 and 250 ppm, respec-
tively. Cumulative hepatomas females:
4.7. 3.5. 9.0, 13.1, 65. 5X for 0. 2,
10, 50 and 250 ppm, respectively.
Only liver tumors occurred more fre-
quently In treated as compared with
control animals. Hale mortality
caused by DDT toxic Hy was Increased
only In the group receiving a dose of
250 ppm. In males, those on diets of
0, 2. 20 and 250 ppm of DDT had Inci-
dences of liver tumors combined across
2 generations of 2/107. 3/112, 1/106.
15/106. For females, the corresponding
Incidences were 0/131. 0/136. 1/128 and
71/121.
Incidence of hepatomas In males
treated for 15 weeks or 30 weeks with
Reference
Turusov
et al.. 1973
Terraclnl et
al., 1973a.b
Tomatls
et al., 1974
NR
0 ppmd
(3.3 mg/kg/day) 22 ppm
(6.6 mg/kg/day) 44 ppm
0 ppm
(13.05 mg/kg/day) 87 ppm
(26.25 mg/kg/day) 175 ppm
78 weeks
93 weeks
mouse/
B6C3F1
H
H
H
F
F
F
20
-50
-50
20
-50
-50
DDT and killed 65. 95 and 120 weeks
after the start of the experiment was
13/60. 25/60. 25/60 and 38/60. 41/60
and 37/60, respectively. Corresponding
values for controls, were 12/70, 24/83
and 33/98. When females were treated
for 15 weeks or 30 weeks with DDT and
killed at 65, 95 and 120 weeks after
the start of the experiment, the Inci-
dence of hepatomas was 3/60, 11/60.
5/60 and 4/54. 11/65 and 11/54, respec-
tively. Corresponding control values
for females were 0/69. 0/72 and 1/90.
Mortality was significantly Increased
In treated females and the Increase
appeared dose-related. No other toxic
or carcinogenic effects were seen.
NCI. 1978
-------
TABLE 4-1 (cont.)
Vehicle
Oil
NR
NR
NR
NR
NR
NR
Dose Length of Length of
Treatment Experiment
0 ppm 18 months NR
5 mg/kg/day (100 ppm)
10 mg/kg/day (200 ppm)
20 mg/kg/day (400 ppm)
30 mg/kg/day (600 ppm)
40 mg/kg/day (800 ppm)
0 ppm 2 years NR
• ** rr* •
80 ppm
200 ppm
•.WU |#f«IH
0 ppm lifetime lifetime
(25 mg/kg/day) 500 ppm
15 rag/rat, 5 days/week 1 year 18 months
by gavage (612.24 ppm)
0 ppm 78 weeks 111 weeks
(16.05 mg/kg/day) 321 ppm
(32.1 mg/kg/day) 642 ppm
0 ppm
(10.05 mg/kg/day) 210 ppm
(21.0 mg/kg/day) 420 ppm
0 ppm lifetime lifetime
(6.25 mg/kg/day) 125 ppm
(12.5 mg/kg/day) 250 ppm
(25 mg/kg/day) 500 ppm
0 ppm NR NR
(10 mg/kg/day) 125 ppm
(20 mg/kg/day) 250 ppm
(40 mg/kg/day) 500 ppm
Species
rats/
Osborne-
Hendel
rats
rat/
Wlstar
rats/
Fischer
rat/
Osborne-
Ncndel
rats/MRC
Portion
hamster
Sex
H/F
M
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H
H
H
F
F
F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
H/F
Number
Tested
24/12
12
24/12
24/12
24/12
36/24
30/30
30/30
30/30
35/32
27/28
15/15
20
-50
-50
20
-50
-50
38/38
30/30
30/30
38/38
40/39
30/28
31/28
39/40
Effects
The authors concluded that there was
an Increased Incidence of liver tumor
formation, but did not relate the
effect to dose levels or sex. and did
not provide any statistical analysis.
Treatment began at weaning.
No difference In tumor Incidence
between treated and control groups,
except for bronchogenlc carcinomas
which occurred In 2/60 controls. 8/60
rats fed DDT at 80 ppm and 0/60 rats
fed 200 ppm.
Increased Incidence of liver tumors
were seen In males (9/27. 35%) and
females (15/28, 56X). No liver
tumors were seen In controls.
No liver tumors were seen.
No Increase In tumor Incidence or
signs of toxlclty were noted for DDT.
The Incidence of hepatomas In males
was 1/38, 0/30, 1/30 and 2/38 for the
0. 125, 250 and 500 ppro groups, re-
spectively. Corresponding Incidences
for females were 0/38. 2/30. 4/30 and
7/30.
No liver tumors were seen In hamsters
at any feeding level. There was a
significant trend In total number of
tumor -bearing females: 7.5. 16.6.
25.8 and 28. 2X for 0. 125. 250 and
500 ppm, respectively.
Reference
Fltzhugh and
Nelson. 1947
Delchmann et
al.. 1967;
Radomskl
et al.. 1965
Rossi
et al., 1977
Welsburger
*n«l
ana
Welsburger,
1968
NCI. 1978
Cabral et
al., 1982b
Cabral et
al.. 1982a
-------
TABLE 4-1 (cont.)
Vehicle Dose
NR 0 ppm
(BO mg/kg/day) 1000 ppm
Length of Length of Species Sex Number
Treatment Experiment Tested
NR NR hamster M/F 31/42
H/F 35/36
Effects
An Increased Incidence of liver tumors
was not seen. Incidences of adrenal
adenomas were significantly elevated
In females, but not males. Incidence
for males: 0 ppm. 8/31; 1000 ppm.
14/35 and for females: 0 ppm, 2/42;
1000 ppm, 10/36.
Reference
Rossi
et al., 1983
aCS7BL/6 females mated with C3H/Anf males
bCS7BL/6 females mated with AKR males
cThe fraction of body weight consumed per day In food, called the food factor, Is 0.13 for mice and 0.05 for rats. Exposures given In ppm of food are
converted to mg/kg/day by multiplying the ppm exposure level by the food factor.
dfloses given are the TWA dose computed by NCI.
tn
i
-------
authors emphasized that the transplacental and translactatlonal exposure to
DDT that occurred during the experiment may have had an Important, but unquan-
tlfled, effect upon the results.
Under the auspices of IARC, Tomatls et al. (1972), Terradni et al.
(1973a,b), Turusov et al. (1973) and Shabad et al. (1973) Investigated DDT
cardnogenldty 1n mice. Several mult1generat1on studies were conducted In
which mice were exposed continuously to DDT, Including transplacentally and
translactatlonally. Tomatls et al. (1972) found that mice of both sexes
exposed to 250 ppm DDT had a significantly higher Incidence of hepatomas.
When the mice exposed to lower doses of DDT (2-50 ppm) were allowed to age
past 60 weeks, the males, but not the females, had a significantly higher
Incidence of hepatomas. In another experiment, Tomatls et al. (1974) demon-
strated that hepatoma formation was dose-dependent and that exposure to DDT
early 1n life may result In tumor formation 1n the aging animal even after
removal of the source of DDT. Terradni et al. (1973a) found that the Inci-
dence of hepatomas was Increased 1n BALB/c mice exposed to DDT. In addition,
the mice exposed transplacentally and translactatlonally had an even higher
Incidence of liver tumors than the mice exposed after weaning only.
Walker et al. (1972) and Thorpe and Walker (1973) reported an Increased
Incidence of liver tumors 1n CF1 mice exposed to DDT In their food for 2
years. They divided the liver lesions into two hlstologlcal types. Subse-
quent analysis by Reuber (1974,1976) classified the lesions as hepatocellular
carcinomas and preneoplastlc lesions.
The NCI (1978) bioassay reported no carcinogenic effect from DDT exposure,
although the mortality of the female mice was significantly Increased 1n a
dose-related manner. The dose levels, however, were low in comparison with
other bloassays.
-16-
-------
In rats exposed to 100-800 ppm DDT In the diet for 18 months, the dose-
related changes Included hypertrophy of centrolobular hepatic cells, hyalinl-
zatlon of the cytoplasm and focal necrosis (Fltzhugh and Nelson, 1947). More
than half (111 out of 192) of the rats died during the experiment. Of the 81
that remained alive at the end of the treatment period. 4 had Hver carcinomas
and 11 had preneoplastlc hepatic lesions. No liver pathology was observed 1n
the control animals (Fltzhugh and Nelson, 1947). Rossi et al. (1977) reported
an Increased incidence of Hver tumors in rats exposed to 500 ppm DDT 1n their
diets. Other studies 1n rats on the carclnogenicity of DDT 1n doses ranging
from 210-642 ppm (NCI, 1978; Weisburger and Weisburger, 1968; Deichmann et
al., 1967; Radomski et al., 1965) reported no Increased incidence of liver
tumors.
None of the bioassays in hamsters revealed an increased Incidence of
tumors In DDT exposed animals (Agthe et al., 1970; Cabral and Shubik, 1977;
Graillot et al., 1975), and Graillot et al. (1975) reported a marked dose-
related decrease In the incidence of lymphosarcoma 1n the DDT exposed animals
as compared with controls.
4.2.2. Inhalation. Pertinent data regarding the carclnogenicity of inhaled
DDT could not be located In the available literature.
4.3. OTHER RELEVANT DATA
No Increase in the number of reverse mutants was caused by DDT in Salmo-
nella typhimurlum (strains TA1535, TA1536, TA1537 and TA1538) or Escherichia
coli (strains B/r try, WP2, WP2 try and her), regardless of the presence of
rat liver microsomes (Shirasu et al., 1976; Marshall et al., 1976). DDT
caused no significant Increase in recombination mutants 1n Bacillus subtilis
(Shirasu et al., 1976), 1n recessive lethal mutants 1n Neurospora crassa
(Clark, 1974; Luers, 1953) or in mutation frequency in Salmonella typhimurlum
-17-
-------
(Buselmaier et al., 1972). Chromosomal aberrations have been reported In
cultivated rat-kangaroo cells (Palmer et al., 1972} and human lymphocytes
(Lessa et al., 1976), but not 1n rat cells (Legator et al., 1973) and In mouse
bone marrow cells in vivo (Markaryan, 1966). An Increase 1n dominant lethal
mutations was caused by DDT in Drosophlla melanogaster (Clark, 1974), the
Swiss mouse (Clark, 1974) and the rat (Palmer et al., 1972), but not 1n the
CF1 mouse (Wallace et al., 1976) or the ICR/Ha mouse (Epstein et al., 1972).
4.4. WEIGHT OF EVIDENCE
DDT has been associated with liver tumors in mice (Innes et al., 1969;
Tomatis et al., 1972; Terradni et al., 1973a,b) and rats (Rossi et al.,
1977), and lymphomas and pulmonary tumors (Tarjan and Kemeny, 1969) in mice.
Based on inadequate evidence for cardnogenldty 1n humans and sufficient
evidence of cardnogenldty 1n animals 1n spite of inadequate evidence for
cardnogenldty 1n short-term tests (I.e., mutagenldty), DDT 1s most appro-
priately classified following the scheme proposed by the Carcinogen Assessment
Group of the U.S. EPA (Federal Register, 1984) as a Group B2 - Probable Human
Carcinogen.
-18-
-------
5. REGULATORY STANDARDS AND CRITERIA
The WHO (1971) recommended a maximum Interim ADI 1n food of 0.005 mg/kg/bw
for DDT. The ACGIH (1983) recommended a TLV-TWA of 1 mg/m3 and a TLV-STEL
of 3 mg/m3, based on analogy with Undane, which was judged to be twice as
toxic as DDT (ACGIH, 1980).
-19-
-------
6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
DDT is known to be an animal carcinogen and data are sufficient for
computing a q*. Therefore, H Is Inappropriate to calculate an oral or
Inhalation AIS for DDT.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
DDT Is a chemical known to be an animal carcinogen and for which data are
sufficient for computing a q *. Therefore, 1t 1s Inappropriate to calculate
an oral or Inhalation AIC for DDT.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. U.S. EPA (1985) has developed a quantitative estimate of the
carcinogenic potency of DDT. The studies selected for quantitative evaluation
were: Tarjan and Kemeny (1969), Turusov et al. (1973), Terradnl et al.
(1973), Thorpe and Walker (1973), Tomatls and Turusov (1975), Cabral et al.
(1982b) and Rossi et al. (1977).
The data used for estimation of a q * from the Tarjan and Kemeny (1969)
study as shown In U.S. EPA (1985) are presented In Table 6-1. Group sizes
were considered Inadequate for evaluation in the F, and F~ generations. A
potency estimate of 7.27 (mg/kg/day)'1 was estimated based on the geometric
mean of the potencies for generations F~-F5 for lung cancers and leukemia.
The data used for estimation of a q * from the Turusov et al. (1973)
study as shown in U.S. EPA (1985) are presented in Table 6-2. A geometric
mean of the potencies across six generations for liver tumors of 0.80
(mg/kg/day)'1 for males and 0.42 (mg/kg/day)'1 for females was estimated.
The data used for estimation of a q * from the Terradnl et al. (1973)
study as shown in U.S. EPA (1985) are presented in Table 6-3. A geometric
mean potency (q,*) of 0.082 (mg/kg/day)'1 for liver tumors was calculated
across sexes and two generations.
-20-
-------
TABLE 6-1
Incidence of the Host Commonly Occurring Malignant Tumors In Each of Five Generations
of BALB/c Mice Fed DDTa
I
ro
Incidence by Generation1* (combined
Site/Dose Group
F!
Lung (carcinomas)
Control 0/3 (00.0)
3 ppm DOTC 2/10 (20.0)
Significance11
qi*e
qi*f
f*
0/39 (00.0)
10/35 (28.5)
p=0.001
18.78
17.20
F3
3/51 (5.9)
13/69 (18.8)
p=0.007
9.09
9.95
male and female) (54)
F4
0/144 (00.0)
41/264 (15.5)
p<0.002
7.45
7.16
F5
2/169 (1
50/305 (16
p<0.001
7.37
7.68
• 2)
.4)
-------
TABLE 6-1 (cent.)
Site/Dose Group
Incidence by Generation0 (combined male and female) (%)
Leukemia
Control 2/3 (66.6)
3 ppm DDTC 4/10 (40.0)
Significance*1
-------
TABLE 6-2
Incidence of Benign Liver Tumors In Each of Six Generations of CF-1 Mice Fed DDTa
Benlqn Liver Tumor Incidence by Generation (%)**
Sex/Dose
Group
Hales
Control
2 ppmc
10 ppm
50 ppm
250 ppm
Parental
H/60 (24)
26/60 (44)
32/60 (53)
27/60 (45)
46/60 (76)
F!
13/60 (21)
29/60 (48)
28/60 (47)
35/60 (58)
51/60 (85)
F2
20/60 (34)
38/60 (63)
33/60 (55)
41/60 (69)
53/60 (89)
F3
21/60 (35)
30/60 (50)
36/60 (60)
36/60 (60)
53/60 (89)
F4
16/60 (26)
34/60 (57)
24/60 (40)
32/60 (53)
57/60 (95)
F5
23/60 (39)
25/60 (42)
26/60 (44)
28/60 (47)
48/60 (80)
CO
I
,*d
0.572
0.873
0.935
0.878
1.096
0.598
-------
TABLE 6-2 (cont.)
Benign Liver Tumor Incidence by Generation (54)b
Sex/Dose
Group
Females
Control
2 ppmc
10 ppm
50 ppm
250 ppm
qi*d
Parental
3/60
3/60
2/60
8/60
37/60
0.372
(5)
(5)
(3)
(13)
(61)
F!
2/60
1/60
8/60
7/60
43/60
0.471
(3)
(2)
(13)
(12)
(71)
F2
1/60
3/60
8/60
8/60
31/60
0.369
(2)
(5)
(13)
(13)
(52)
FS
2/60
5/60
3/60
9/60
40/60
0.434
(3)
(9)
(5)
(15)
(67)
F4
4/60
0/60
5/60
10/60
48/60
0.526
(7)
(0)
(8)
(16)
(80)
F5
5/60 (8)
0/60 (0)
6/60 (10)
7/60 (11)
38/60 (64)
0.370
aSource: U.S. EPA, 1985
bNumber of animals with tumors/number of animals examined (percent). The effective number of animals
was given by Turusov et al. (1973) as 50-60; 60 has been used for every group because the exact number
was not given.
cThe human equivalent doses are calculated by multiplying the ppm values by 0.13 and then by the cube
root of 0.030/70 (=0.0753949). No adjustment for time was made because these were lifetime tests and
CF-1 mice were fed DDT continuously during that time. For example, human equivalent doses are: 2 ppm =
0.0196, 10 ppm = 0.0980, 50 ppm = 0.4900 and 250 ppm = 2.45 mg/kg bw/day.
dThe qi*s of the upper-bound limits In units of (mg/kg bw/day of dietary exposure)'1 were calculated
using the multistage model.
-------
TABLE 6-3
Incidence of Benign Liver Tumors In BALB/c Mice Fed DOT During
a 2-Generat1on Experimenta»b
Incidence of Beniqn Liver Tumors by Generation0
Males
Dose Group
0 ppm
Trendd
2 ppm
20 ppm
250 ppm
qi*e
High dose q-|*
Parental + f-\
2/107
p<0
3/112
1/106
15/106
0.074
0.086
(1.9)
.001
(2.7)
(0.9)
(14.2)
Females
Parental F-j
0/62
p<0.
0/63
1/61
28/63
0.080
0.324
(0)
001
(0)
(1.6)
(44.4)
0/69
p<0.
0/73
0/67
43/58
0.094
0.718
(0)
001
(0)
(0)
(74.1)
aSource: U.S. EPA, 1985
bNumber of animals with tumors/number of animals examined (percent).
Malignant tumors were not observed 1n liver.
cThe numbers In the grups of males were reduced by fighting, so the 2
generations of males were pooled. Each high-dose group shown is statisti-
cally different from Us control group (p<0.001). Other palrwlse tests
were not significant.
dBeneath the control incidence 1s the p value for positive trend in Inci-
dence over the dose levels.
eThe q-|*s were calculated using the human equivalent dose. The "high-
dose q-j*" 1s the result of using only the controls and the high-dose
groups 1n the calculations. The human equivalent doses are calculated by
multiplying the ppm values by 0.13 and then by the cube root of 0.030/70
(=0.0753949). For example, 250 ppm = 2.45 mg/kg/day for humans.
-25-
-------
The data used for estimation of a q^ from the Thorpe and Walker (1983)
study as presented 1n U.S. EPA (1985) are shown In Table 6-4. q^ values
for the Incidence of malignant liver tumors 1n males and females were
calculated as 0.52 (mg/kg/day)'1 and 0.81 (mg/kg/day)'1, respectively.
The data used for estimation of a q * from the Tomatls and Turusov
(1975) study as presented In U.S. EPA (1985) are shown 1n Table 6-5. q^
values for benign liver tumors 1n males and females were 1.04 (mg/kg/day)'1
and 0.49 (mg/kg/day)'1, respectively.
The data used for estimation of a q * from the Cabral et al. (1982b)
study are shown 1n Table 6-6. A q, of 0.084 (mg/kg/day)'1 was calculated
for liver tumors 1n female rats. The data used for q^* estimation from
Rossi et al. (1977) are also shown 1n Table 6-6. q * values for liver
tumors 1n male and female rats of 0.16 and 0.27 (mg/kg/day)"1, respectively,
were calculated.
Table 6-7 presents a summary of the calculated potency estimates. Of
these values, the q * based on Tarjan and Kemeny (1969) was eliminated based
on the D1xon statistical criterion for rejecting outliers (p=0.01) and the
additional considerations that the study was from an unaudited laboratory and
that the feed was contaminated with DOT. A geometric average of the values
from the remaining six studies resulted 1n a final q * estimate for DOT of
0.34 (mg/kg/day)'1: (0.80 x 0.42 x 0.082 x 0.52 x 0.81 x 1.04 x 0.49 x
0.084 x 0.16 x 0.27)1/10 = 0.34.
6.3.2. Inhalation. Pertinent data regarding the cardnogenldty of Inhaled
DDT could not be located 1n the available literature.
-26-
-------
TABLE 6-4
Incidence of Liver Tumors (Benign and Malignant) In CF-1 Mice
Fed DDT for a Single Generation3
Dose Group Incidence of Benign Incidence of Malignant
Liver Tumors^ Liver Tumors'3
Males
Controls 11/45 (24%) 2/45 (4.4%)
100 ppm 23/30 (80%) 9/30 (30%)
q-|* ND 0.52
Females
Controls 10/44 (23%) 0/44 (0%)
100 ppm 26/30 (87%) 12/30 (40%)
qi* ND 0.81
aSource: U.S. EPA, 1985
^Benign Hver tumors in this study were referred to as "type a" and malig-
nant liver tumors as "type b."
ND = Not determined
-27-
-------
TABLE 6-5
Incidence of Benign Liver Tumors In CF-1 Mice Fed DOT for 15 or 30 Weeks and then Sacrificed
at 65, 95 and 120 Weeksa.°.c
ro
CO
i
Dose Group
Hales at Meek
Females at Week
65
95
120
65
95
120
0 ppmd
250 ppm for
15 weeks6
250 ppm for
30 weekse
qi*f values
all qi*
30 week
12/70 (17)
13/60 (22)
p=0.142
38/60 (63)
p<0.001
0.36
1.38
24/83 (29)
25/60 (42)
p=0.040
41/60 (68)
p<0.001
1.04
1.43
33/98 (34)
25/60 (42)
p-0.080
37/60 (62)
p<0.001
0.84
1.06
0/69 (0)
3/60 (5)
p=0.097
4/54 (7)
p-0.034
0.19
0.19
0/72 (0)
11/60 (14)
p<0.001
11/55 (20)
p<0.001
0.49
0.79
1/90 (1)
5/50 (10)
p=0.034
11/54 (20)
p<0.001
0.35
0.43
aSource: U.S. EPA, 1985
DNumber of animals with tumors/number of animals examined (percent).
C8orae groups were exposed for 15 weeks; other groups were exposed for 30 weeks. All groups were sacri-
ficed serially at 30, 65, 95 and 120 weeks.
dine human equivalent dose for 1 ppm for 15 weeks Is 0.4084 mg/kg/day and for 30 weeks Is 0.8168 mg/kg/
day. The human equivalent doses are calculated by multiplying the ppm values by 0.13 and then by the
cube root of 0.030/70 (=0.0753949). Adjustments for time consist of multiplying the 15-week dose by
15/90 and the 30-week exposure by 30/90.
eBcneath each dosed group Incidence Is the p value for comparison of the Incidence In the dose group
with that In the control group.
q^*s were calculated based on the human equivalent dose shown In footnote d. The term "all q^*" Indi-
cates that the dosed groups and the control group were used In the calculation. The "30 week" row
contains the results of using only the 30-week exposure cancer data with the control cancer data.
-------
TABLE 6-6
Incidence of Benign Liver Tumors 1n Rats Fed DDTa»b
Dose Group6
0 ppm
Trendr
125 ppm
250 ppm
500 ppm
qi*9
Cabral et
Males
1/38 (0)
NS
0.30 (0)
NS
1/30 (3.3)
NS
2/38 (5.3)
NS
NDn
al.. 1982bc
Females
0/38 (0)
p=0.003
2/30 (6.7)
NS
4/30 (13.3)
p=0.033
7/38 (18.4)
p=0.005
0.084
Rossi et
Males
0/35 (0)
--
—
9/27 (33.3)
p<0.001
0.16
al.. 1977d
Females
0/32 (0)
—
—
15/28 (53.6)
p<0.001
0.27
aSource: U.S. EPA, 1985
bNumber of animals with tumor/number of animals examined (percent).
cThese were Portion (Wlstar derived) rats.
dThese were Wlstar rats.
eThe human equivalent doses are calculated by multiplying the ppm values
by 0.0085499, which 1s 0.05 mg/kg/day (for rats) multiplied by the cube
root of 0.350/70 (=0.0753949). No adjustment for time was made because
rats were fed continuously for a lifetime.
fBeneath the control group Incidence 1s the p value for a positive trend
of Incidences as the dose Increases, when the p values 1s less than p=0.05,
otherwise NS (not significant). Beneath each dosed group Incidence 1s the
p value for the comparison of the Incidence 1n the dosed group with Us
control group when 1t 1s less than p=0.05, otherwise NS.
9The q-]*s were calculated using the human equivalent dose. For example,
500 ppm = 4.275 mg/kg/day for humans.
nNot calculated due to lack of statistical Increase 1n hepatomas.
NS = Not significant; NO = not determined
-29-
-------
TABLE 6-7
Summary of Quantitative Potency Estimates for DDT*
Species
Mouse
Mouse
Mouse
Mouse
Mouse
Rat
Rat
Tumor Site
lung/leukemia
liver
liver
liver
Hver
liver
liver
q-j* (mg/kg/day) 1
Males Females
7.27 (combined)
0.80 0.42
0.082 (combined)
0.52 0.81
1.04 0.49
0.084
0.16 0.27
Reference
Tarjan and
Kemeny, 1969
Turusov
et al.. 1973
Terraclni
et al., 1973
Thorpe and
Walker, 1983
Tomatls and
Turusov, 1975
Cabral
et al., 1982b
Rossi et al . ,
1977
*Source: Adapted from U.S. EPA, 1985
-30-
-------
7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienlsts). 1980.
Documentation of the Threshold Limit Values for Substances In Workroom A1r,
4th ed. with supplements through 1981. Cincinnati, OH. p. 117-118.
ACGIH {American Conference of Governmental Industrial Hygienlsts). 1983.
Threshold Limit Values for Chemical Substances and Physical Agents 1n the
Workroom Environment with Intended Changes for 1983-1984. Cincinnati, OH.
p. 16.
Agthe, C., H. Garcia, P. Shublk, L. Tomatls and E. Wenyon. 1970. Study of
the potential cardnogenlcity of DDT 1n the Syrian golden hamster (34740).
Proc. Soc. Exp. Med. 134: 113-116. (Cited In IARC, 1974; NIOSH, 1978)
Buselmaler, W. and G. Rohrborn and C. Propping. 1972. Mutagenltats-Unter-
suchungen mlt Pest1z1den 1m Host-mediated assay und m1t den Domlnanten Letal-
test an der Maus. Blol. Zentrablbl. 91: 307-325. (Ger.) (Cited In NIOSH,
1978)
Cabral, J.R.P. and P. Shublk. 1977. Lack of cardnogenlcity of DDT 1n
hamsters. Fed. Proc. 36: 1086. (Cited In NIOSH, 1978)
Cabral, J.R.P., R.K. Hall, L. Rossi, S.A. Bronczyk and K.P. Shublk. 1982a.
Lack of cardnogenlcity of DDT 1n hamsters. Tumorl. 68: 5-10. (Cited 1n
U.S. EPA, 1985)
-31-
-------
Cabral, J.R.P., R.K. Hall, L. Rossi, S.A. Bronczyk and K.P. Shubik. 1982b.
Effects of long-term Intake of DDT on rats. Tumor 1. 68: 11-17. (Cited in
U.S. EPA, 1985)
Callahan, M.A., M.W. Slimak, N.W. Gabel, et al. 1979. Water-Related Environ-
mental Fate of 129 Priority Pollutants, Vol. I. U.S. EPA, Office of Water
Planning and Standards, Office of Water and Waste Management, Washington, DC.
EPA 440/4-79-029.
Cameron, G.R. and K.K. Cheng. 1951. Failure of oral DDT to induce toxic
changes in rats. Br. Med. J. 2: 819-821. (Cited in NIOSH, 1978)
Clark, J.M. 1974. Mutagenicity of DDT in mice, Drosophila melanogaster and
Neurospora crassa. Aust. J. Biol. 27: 427-440. (Cited in NIOSH, 1978)
Clement, J.G. and A.B. Okey. 1974. Reproduction in female rats born to
DDT-treated parents. Bull. Environ. Contam. Toxicol. 12: 373-377. (Cited in
NIOSH, 1978)
Crosby, D.G. and K.W. Moilanen. 1977. Vapor-phase photodecomposition of DDT.
Chemosphere. 6: 167-172.
Deichmann, W.B. and W.E. MacDonald. 1971. Organochlorine pesticides and
human health. Food Cosmet. Toxicol. 9: 91-103. (Cited in NIOSH, 1978)
Deichmann, W.B., M. Keplinger, F. Sala and E. Glass. 1967. Synergism among
oral carcinogens: IV. The simultaneous feeding of four tumorigens to rats.
Toxicol. Appl. Pharmacol. 11: 88-103. (Cited in NIOSH, 1978; U.S. EPA, 1980a)
-32-
-------
Deichmann, W.B., W.E. MacDonald, A.G. Beasley and D. CubH. 1971. Subnormal
reproduction 1n beagle dogs Induced by DDT and aldrin. Ind. Med. 40: 10-20.
(Cited In NIOSH, 1978)
Duby, R.F., H.F. Travis and C.E. Terrill. 1971. Uterotrophlc activity of DDT
1n rats and mink and Us Influence on reproduction 1n the rat. Toxlcol. Appl.
Pharmacol. 8: 348-355. (Cited In NIOSH, 1978)
Durham, W.F., P. Ortega and H.3. Hayes, Jr. 1963. The effect of various
dietary levels of DDT on liver function, cell morphology, and DDT storage In
the rhesus monkey. Arch. Int. Pharmacodyn. Ther. 141: 111-129. (Cited 1n
NIOSH, 1978)
Epstein, S.S., E. Arnold, J. Andrea, W. Bass and Y. Bishop. 1972. Detection
of chemical mutagens by the dominant lethal assay in the mouse. Toxicol.
Appl. Pharmacol. 23: 288-325. (Cited in NIOSH, 1978)
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
Fltzhugh, O.G. 1948. Use of DOT insecticides on food products. Ind. Eng.
Chem. 40: 704-705. (Cited in NIOSH, 1978)
Fltzhugh, O.G. and A.A. Nelson. 1947. The chronic oral toxicity of DDT
(2,2-bis(p-chlorophenyl)-l,1,l-tr1chloroethane). J. Pharmacol. Exp. Ther.
89: 1830. (Cited in NIOSH, 1978)
-33-
-------
G'ralllot, C., J.C. Gak, C. Lacret, R. Truhaut, D. Fournler and C. Martin.
1975. Recherchers sur les modalHes et les mechanismes d'actlon toxlque des
Insecticides organochlores: II. Etude chez le hamster des effect de toxldte a
long terme du DDT. Eur. J. Toxlcol. 8: 353-359. (Fre.) (CHed in NIOSH,
1978)
Green, V.A. 1969. Effects of pesticides on rat and chick embryo. Proc.
Conf. Trace Substances. Environ. Health. 2: 183-209. (CHed In NIOSH, 1978)
Hart, L.G. and J.R. Fouts. 1965. Further studies on the stimulations of
hepatic mlcrosomal drug metabolizing enzymes by DDT and Its analogs. Naunyn-
Schmledebergs Arch. Path. Pharmacol. 249: 496-500. (CHed In NIOSH, 1978)
Hayes, W.J., Jr., W.E. Dale, and C.I. Plrkle. 1971. Evidence of safety of
long-term, high, oral doses of DDT for man. Arch. Environ. Health. 22:
119-136. (CHed In NIOSH, 1978)
Innes, J.R.M., et al. 1969. Bloassay of pesticides and Industrial chemicals
for tumorlgenidty In mice: A preliminary note. J. Natl. Cancer. Inst. 42:
1101. (CHed in U.S. EPA, 1980a)
IARC (International Agency for Research on Cancer). 1974. DDT. JJK Some
OrganochloMne Pesticides. IARC Monographs on the Evaluation of the Carcino-
genic Risk of Chemicals to Man. WHO, IARC, Lyon, France. Vol. 5, p. 83-124.
Jensen, J.A., et al. 1957. DDT metabolites 1n feces and bile of rats. J.
Agrlc. Food Chem. 5: 919. (CHed in U.S. EPA, 1980a)
-34-
-------
Jbnsson, H.T., Jr., J.E. Ke1l, R.G. Gaddy, C.B. Loadholt, G.R. Hennlgar and
E.M. Walker, Jr. 1975. Prolonged 1ngest1on of commercial DOT and PCB:
Effects on progesterone levels and reproduction 1n the mature female rat.
Arch. Environ. Contam. Toxlcol. 3: 479-490. (Cited In NIOSH, 1978)
Keller, W.C. and R.A. Yeary. 1980. A comparison of the effects of mineral
oil, vegetable oil and sodium sulfate on the Intestinal absorption of DDT In
rodents. CUn. Toxlcol. 16(2): 223. (Cited In U.S. EPA, 1980a)
KepHnger, M.L., W.B. Delchmann and F. Sala. 1968. Effects of combinations
of pesticides on reproduction 1n mice. In: Pesticides Symposia, W.B.
Delchmann, Ed. Halos and Associates, Inc., Miami, FL. p. 125-138. (Cited in
NIOSH, 1978)
Kinoshita, F.K., J.P. Frawley and K.P. Dubois. 1966. Quantitative measure-
ment of induction of hepatic microsomal enzymes by various dietary levels of
DDT and toxaphene in rats. Toxlcol. Appl. Pharmacol. 9: 505-513. (Cited in
NIOSH, 1978)
Laug, E.P., A.A. Nelson, O.G. Fithugh and F.M. Kunze. 1950. Liver cell
alteration and DDT storage in the fat of the rat induced by dietary levels of
1-50 ppm DDT. J. Pharmacol. Exp. Ther. 98: 268-273. (Cited in NIOSH, 1978)
Laws, E.R., A. Curley and F.J. Biros. 1967. Men with intensive occupational
exposure to DDT. Arch. Environ. Health. 15: 766-775. (Cited in NIOSH, 1978)
-35-
-------
Negator, M.S., K.A. Palmer and I-D. Adler. 1973. A collaborative study of in
vivo cytogenetlc analysis. Toxlcol. Appl. Pharmacol. 24: 337-370. (Cited In
NIOSH, 1978)
Lehman, A.J. 1952. Chemicals 1n foods — A Report to the Association of Food
and Drug Officials on Current Developments: II. Pesticides; III. Subacute and
chronic toxidty. Quart. Bull. Assoc. Food Drug Officials USA. 16: 47.
(Cited In IARC, 1974; NIOSH, 1978)
Lehman, A.L., Ed. 1965. DDT [a mixture of 1,1 ,l-trichloro-2,2-bis(p-chloro-
phenylJethane and 1,1 ,l-tr1chloro-2-(0-chlorophenyl)-2-(p-chlorophenyl)-
ethane]. In: Summaries of Pesticide Toxiclty, Food and Drug Administration,
U.S. DHEW, Washington, DC. U.S. GPO. p. 16-17. (Cited In IARC, 1974; NIOSH,
1978)
Lessa, J.M.M., W. Becak, M.N. Rabello, C.A.B. Pereira and M.T. Ungaro. 1976.
Cytogenetic study of DDT on human lymphocytes jji vitro. Mutat. Res. 40:
131-138. (Cited in NIOSH, 1978)
Luers, H. 1953. Untersuchung zur Frage der Mutagenitat des Kontaktinsekti-
zids DDT an DrosophlUa melangaster. Naturwiss. 40: 293. (Ger.) (Cited in
NIOSH, 1978)
Markaryan, D.S. 1966. Cytogenetlc effect of some chlororganlc insecticides
on the nuclei of mouse bone-marrow cells. Genetlka. 1: 132-137. (Cited in
NIOSH, 1978)
-36-
-------
Marshall, T.C., H. Dorough and H.E. Swim. 1976. Screening of pesticides for
mutagenlc potential using Salmonella typhlmurlum mutants. J. Agrlc. Food
Chem. 24: 560-563. (Cited In NIOSH. 1978)
McLachlan, J.A. and R.L. D1xon. 1972. Gonadal function In mice exposed
prenatally to p.p'-DDT. Toxlcol. Appl. Pharmacol. 22: 327. (Cited In NIOSH,
1978)
Morgan, O.P. and C.C. Roan. 1977. The metabolism of DDT In man. Essays
Toxlcol. 5: 139. (Cited In U.S. EPA, 1980a)
NCI (National Cancer Institute). 1978. Bloassays of DDT, TDE and p,p'-DOE
for possible cardnogenldty. CAS No. 50-29-3, 72-54-8, 72-55-9, NCI-CG-
TR-1321. U.S. DHEW. (Cited 1n U.S. EPA, 1980a)
NIOSH (National Institute for Occupational Safety and Health). 1978. Special
Occupational Hazard Review: DDT. U.S. DHEW (NIOSH) Publ. No. 78-200.
Ortega, P., W.J. Hayes, Jr. and W.F. Durham. 1956a. Pathologic changes 1n
the liver of rats after feeding low levels of various Insecticides. Am. Med.
Assoc. Arch. Pathol. 64: 614. (Cited In NIOSH, 1978)
Ortega, P., W.J. Hayes, Jr., W.F. Durham and A. Mattson. 1956b. DDT In the
diet of the rat: Its effect on DDT storage, liver function and cell morphol-
ogy. Publ. Health Mongr. No. 43. (Cited In NIOSH, 1978)
-37-
-------
Oftelee, M.F. 1958. Study of men with prolonged Intensive occupational
exposure to DDT. Arch. Ind. Health. 18: 433-439. (Cited In NIOSH, 1978)
Ottobonl, A. 1969. Effect of DDT on reproduction In the rat. Toxlcol. Appl.
Pharmacol. 14: 74-81. (Cited In NIOSH, 1978)
Ottobonl, A., G.D. Blssell and A.C. Hexter. 1977. Effects of DDT reproduc-
tion 1n multiple generations of beagle dogs. Arch. Environ. Contam. Toxicol.
6: 83-101. (Cited in NIOSH, 1978)
Page, G.W. 1981. Comparison of groundwater and surface water for patterns
and levels of contamination by toxic substances. Environ. Scl. Techno!. 15:
1475-1481.
Palmer, K.A., S. Green and M.S. Legator. 1972. Cytogenic effects DDT and
derivatives of DDT 1n a cultured mammalian cell line. Toxlcol. Appl.
Pharmacol. 22: 355-364. (Cited in NIOSH, 1978)
Radomski, J.L., W.B. Delchmann, W.E. MacDonald and E.M. Glass. 1965. Syner-
glsm among oral carcinogens. I. Results of the simultaneous feeding of four
tumoMgens to rats. Toxlcol. Appl. Pharmacol. 7: 652-656. (Cited in NIOSH,
1978; U.S. EPA, 1980a)
Reuber, M.D. 1974. Statement of testimony at public hearings on cancellation
of registrations of aldrin/d1eldr1n (EPA Exhibit 42). U.S. EPA, Washington,
DC. (Cited in NIOSH, 1978)
-38-
-------
Reuber, M.O. 1976. Hlstopathology of carcinomas of the liver 1n mice Ingest-
ing dleldrln or aldrln. Tumor 1. 62: 463-472. (CHed In NIOSH, 1978)
Rossi, L., M. Ravera, G. Repett! and L. Santi. 1977. Long-term administra-
tion of DOT or phenobarb1tal-Na 1n Wlstar rats. Int. J. Cancer. 19: 179-185.
(CHed 1n NIOSH, 1978)
Rossi, L., 0. BarbleM, M. Sangu1net1, J.R.P. Cabral, P. Bruzzl and L. Santi.
1983. Carclnogenldty study with technical-grade DDT and DDE 1n hamsters.
Cancer Res. 43: 776-781. (CUed 1n U.S. EPA, 1985)
Schmidt, R. 1973. Effect of 1,1,l-tr1chloro-2,2-b1s(p-chlorophenyl)-ethane
(DDT) on the prenatal development of the mouse (under consideration of
distribution of tritium-labeled and carbon-14-labeled DDT 1n pregnant mice).
(Ger.) B1ol. Rundsch. 11: 316-317. (CHed In NIOSH, 1978)
Shabad, L., T.S. Kolesnlchenko and T.V. Nlkonova. 1973. Transplacental and
combined long-term effect of DDT 1n five generations of A-stra1n mice. Int.
J. Cancer. 11: 688-693. (CHed In U.S. EPA, 1980a)
Shlrasu, Y., M. Morlya, K. Kato, A. Furuhashl and T. Kada. 1976. Mutagenlc-
Hy screening of pesticides 1n the mlcroblal system. Mutat. Res. 40: 19-30.
(CHed 1n NIOSH, 1978)
Spencer, W.W. 1975. Movement of DDT and Hs derivatives Into the atmosphere.
Res. Rev. 59: 91-117.
-39-
-------
farjan, R. and T. Kemeny. 1969. Multigeneratlon studies on DOT In mice.
Food Cosmet. Toxlcol. 7: 215-222. (CHed in NIOSH, 1978; U.S. EPA, 1980a)
Terracini, B., M.C. Testa, J.R. Cabral and N. Day. 1973a. The effects of
long-term feeding of DDT to BALB/c mice. Int. J. Cancer. 11: 747-764.
(Cited in NIOSH, 1978; U.S. EPA, 1980a)
Terracini, B., R.J. Cabral and M.C. Testa. 1973b. A multlgeneration study of
the effects of continuous administration of DDT to BALB/c mice. In: Pesti-
cides and the Environment: A Continuing Controversy, W.B. Delchmann, Ed.
Intercontinental Medical Book Corp., NY. p. 77-86. (Cited in NIOSH, 1978}
Thorpe, E. and A.I.T. Walker. 1973. The toxicology of dieldrin (HEOD): II.
Comparative long-term oral toxicity studies in mice with dieldrin, DDT, pheno-
barbitone, beta-BHC, and gamma-BHC. Food Cosmet. Toxlcol. 11: 433-442.
(Cited in NIOSH, 1978)
Tomatis, L., V. Turusov, N. Day and R.T. Charles. 1972. The effect of long-
term exposure to DDT on CF-1 mice. Int. J. Cancer. 10: 489-506. (Cited in
U.S. EPA, 1980a)
Tomatis, L., B. Turusov, N. Day and R.T. Charles. 1972. The effect of long-
term exposure to DDT on CF-1 mice. Int. J. Cancer. 10: 489-506. (Cited in
NIOSH, 1978; U.S. EPA, 1980a)
Tomatis, L., V. Turusov, R.T. Charles, M. Boiocchi and E. Gati. 1974. Liver
tumors in CF-1 mice exposed for limited periods to technical DDT. Z. Krebs-
forsch. 82: 25-35. (Cited in NIOSH, 1978)
-40-
-------
treon, J.F. and P.P. Cleveland. 1955. ToxIcHy of certain chlorinated hydro-
carbon Insecticides for laboratory animals, with special reference to aldrln
and dleldrln. Agrlc. Food Chem. 3: 402-408. (Cited In NIOSH, 1978; IARC,
1974}
Turusov, V.S., N.E. Day, L. Tomatls, E. Gat1 and R.T. Charles. 1973. Tumors
1n CF-1 mice exposed for six consecutive generations to DOT. 3. Natl. Cancer
Inst. 51: 983-995. (Cited In U.S. EPA, 1980a)
U.S. EPA. 1980a. Hazard Assessment Report on DDT, ODD, DOE. Environmental
Criteria and Assessment Office, Cincinnati, OH. Internal report.
U.S. EPA. 1980b. Ambient Water Quality Criteria for DDT. Environmental
Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-038. NTIS PB
81-117491.
U.S. EPA. 1980c. Guidelines and Methodology Used In the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45: 79347-79357.
U.S. EPA. 1983. Methodology and Guidelines for Reportable Quantity Determi-
nations Based on Chronic Toxldty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
-41-
-------
U'.S. EPA. 1985. The Carcinogen Assessment Group's Evaluation of the Carcino-
genlcity of Dlcofol (Kelthane), DOT, DDE and DOD (TDE). Prepared by the
Carcinogen Assessment Group, OHEA, Washington, DC for the Hazard Evaluation
Division Office of Pesticide Programs. EPA 600/6-85-002X. Internal Review
Draft.
Walker, A.I.T., E. Thorpe and D.E. Stevenson. 1972. The toxicology of
dleldrin (HEOD): I. Long-term oral toxldty studies In mice. Food Cosmet.
Toxlcol. 11: 415-432. (Cited In NIOSH, 1978; U.S. EPA, 1980a)
Wallace, M.E., P. Knights and A.O. Dye. 1976. Pilo-t study of the mutagenic-
Hy of DDT In mice. Environ. Pollut. 11: 217-222. (Cited In NIOSH, 1978)
Ware, G.W. and E.E. Good. 1967. Effects of Insecticides on reproduction In
the laboratory mouse: II. Mlrex, Telodrln and DDT. Toxlcol. Appl. Pharmacol.
10: 54-61. (Cited In NIOSH, 1978)
Welsburger, J.H. and E.K. Welsburger. 1968. Food additives and chemical
carcinogens: On the concept of zero tolerance. Food Cosmet. Toxlcol. 6: 235.
(Cited in U.S. EPA, 1980a)
WHO (World Health Organization). 1971. International Standards for Drinking
Water, 3rd ed. Geneva. (Cited in U.S. EPA, 1980a)
Zoeteman, B.C.J., K. Harmsen, J.B.H.J. Llnders, C.F.H. Morra and W. Slooff.
1980. Persistent organic pollutants in river water and groundwater of The
Netherlands. Chemosphere. 9: 231-249.
-42-
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APPENDIX
Summary Table for DDT
Species
Experimental
Dose/Exposure
Effect
Reference
Inhalation
AIS
AIC
Carcinogenic
potency
CO
1 Oral
AIS
AIC
Carcinogenic
potency
mice and
rats
combined data
from six studies
ND
ND
ND
Increased Incidence
of liver tumors
ND
ND
0.34
(mg/kg/day)"
U.S. EPA, 1985
ND '= Not derived
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