EPA 600-6-87-007c
PB88-127121
Investigation of Cancer Risk
Assessment Methods
Volume 2. Bioassay Data Base
Clement Associates, Inc., Ruston, LA
Prepared for
Environmental Protection Agency, Washington, DC
Sep 87
L
1LS. DtpvtuMit of Convntrcf
Niteul TtcMul InfornutMn Sonnet
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Pfadtt-12/121
EPA/600/6-87/007C
September 1987
Investigation of Cancer
Risk Assessment Methods;
Volume 2. BJG assay Data Base
Prepared by
Bruce C. Allan
Annette M. Shipp
Kenny S. Crump
Bryan Kilian
Mary Lee Hogg
Joe Tudor
Barbara Keller
Clement Associate*. Inc.
1201 Gaines Street
Ruston. Louisiana 71270
Prepared for
U. S. Environmental Protection Agency
Contract f68-01-6807
Research Triangle Institute, Prime Contractor
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, DC 20460
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DISCLAIMER
This document has been reviewed in accordance with the U.S. Environmental
Protection Agency's peer and administrative review policies and approved for
publication. Mention of i-iade names or commercial products does not constitute
endorsement or recommendation for use. The information in this document has
been funded by the U.S. Environmental Protection Agency, the Department of
Defense (through Interagency Agreement Number RW97075101), the Electric
Power.Research Institute, and the Risk Science Institute.
n
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CONTENTS
Section Page
1 BIOASSAY DATA COLLECTION AND SUMMARIZATION
Background 1-1
Data Abstraction 1-1
Discussion 1-3
2 DATA BASE CONTENTS
Introduction 2-1
Acrylonitrile 2-1
Aflatoxin 2-2
Ally! Chloride 2-2
4-Aminobiphenyl 2-2
Arsenic 2-3
Asbestos 2-3
Benzene 2-3
Benzidine 2-*
Benzo[a]pyrene 2-4
Cadmium 2-4
Carbon Tetrachloride 2-5
Chloranbucil 2-5
ChlorCane 2-5
Chloroform 2-5
Chromium 2-6
Cigarette Smoke 2- 6
3,3-Dichlorobenzidene 2-9
1,2-Dichloroethane 2-10
Dichloromethane 2-10
Diethylstilbestrol 2-10
Diphenylhydrazine 2-11
Epichlorohydrin 2-11
Estrogen 2-11
Cthylene Dibromide 2-12
Ethylene Oxide 2-12
Formaldehyde 2-12
Hexachlorobenzene 2-12
Hydrazine 2-13
Isoniazid 2-13
Lead 2-13
Melphalan 2-14
Methotrexate 2-14
Mustard Gas 2-14
2-Nophthylomine 2-14
Nickel 2-14
Nitrilotriacetic Acid 2-15
Phenocetin 2-13
Polychlorinated Biphenyls 2-15
Reserpine 2-16
Saccharin 2-16
2,3,7,8-Tetrachlorodibenzo-p-Dioxin ?-16
TetrachlorAethylene 2-16
Toxaphene 2-17
iii
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CONTENTS
Section Poge
Trichloroethylene 2-17
2,<»,6-Trichlorophenol 2-17
Vinyl Chloride 2-17
Vinylidene Chloride 2-17
IV
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TABLES
Table Page
1-1 Data Item* Abstracted From Animal Bioassays 1-5
1-2 The Responses of Interest in Humans for Chemicals 1-12
With Suitable Human Data
2-1 Summary of Carcinogenic Data Sets for Acryloni.tri.le 2-18
2-2 Summary of Acrylonitrile Carcinogenic Bioassay Data 2-19
2-3 Summary of Carcinogenic Data Sets for Aflatoxin 2-23
2-4 Summary of Aflatoxin Carcinogenic Bioassay Data 2-24
2-5 Summary of Carcinogenic Data Sets for Allyl Chloride 2-31
2-6 Summary of Allyl Chloride Carcinogenic Bioassay Data 2-32
2-7 Summary of Carcinogenic Data Sets for
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TAB) ES
Toble
2-23 Suflirary of Carcinogenic Data Sets for C'hlorambucil 2-65
2-24 Summary of Chlorambucil Carcinogenic Bioassay Data 2-66
2-25 Summary of Carcinogenic Data Sets for Chlordane 2-67
2-26 Summary of Chlordane Carcinogenic Bioassay Data 2-68
2-27 Summary of Carcinogenic Data Sets for Chloroform 2-70
2-28 Summary of Chloroform Carcinogenic Bioassay Data 2-71
2-29 Summary of Carcinogenic Data Sets for Chromium 2-75
2-30 Summary of Chromium Carcinogenic Bioasscy Data 2-76
2-31 Summary of Carcinogenic Data Sets for Cigarette Smoke 2-78
2-32 Summary of Cigarette Smoke Carcinogenic Bioasscy Data 2-79
2-33 Summary of Carcinogenic Data Sets for 3.3-Oictilorobenzidene 2-81
2-34 Summary of 3,3-Dichlorobenzidine Carcinogenic Bioassay Data 2-82
2-35 Summary of Carcinogenic Data Sets for 1,2-Dichloroethane 2-83
2-36 Summary of 1,2-Dichloroethane Carcinogenic Biocssay Data 2-84
2-37 Summary of Carcinogenic Data Sets for Dichloromethone 2-88
2-38 Summary of Dichloromethane Carcinogenic Bioassay Data 2-89
2-39 Summary of Carcinogenic Data Sets for Diethylstilbestrol 2-92
2-40 Summary of Diethylstilbestrol Carcinogenic Bioassay Data 2-93
2-41 Summary of Carcinogenic Data Sets for Diphenylhydrazine 2-38
2-42 Summary of Diphenylhydrazine Carcinogenic Bioassay Data 2-99
2-43 Summary of Carcinogenic Data Sets for Epichlorohydrin 2-100
2-44 Summary of Epichlorohydrin Carcinogenic Bioassay Data 2-101
2-45 Summary of Carcinogenic Data Sets for Estrogen 2-1O5
2-46 Summary of Estrogen Carcinogenic Bioasscy Data 2-103
2-47 Summary of Carcinogenic Data Sets for Ethylene Dibromide 2-104
vi
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TABLES
Toble Page
2-48 Summary of Ethylene Dibromide Carcinogenic Bioassay Data 2-105
2-49 Summary of Carcinogenic Data Sets for Ethylene Oxide 2-108
2-50 Summary of Ethvlene Oxide Carcinogenic Bioassay Data 2-109
2-51 Summary of Carcinogenic Data Sets for Forrraldehyde 2-112
2-52 Summary of Formaldehyde Carcinogenic Biuassay Data 2-113
2-53 Summary of Carcinogenic Data Sets for Hexachlcrobenzene ?-116
2-54 Summary of Hexachlorobenzene Carcinogenic Bioassay Data 2-117
2-55 Summary of Carcinogenic Data Sets for Hydrazine 2-119
2-S6 Summary of Kydrazine Carcinogenic Bioassay Data 2-120
2-57 Summary of Carcinogenic Data Sets for Isoniazid 2-124
2-58 Summary of Isoniazid Carcinogenic Bioassay Data 2-125
2-59 Summary of Carcinogenic Data Sets for Lead 2-133
2-60 Summary of Lead Carcinogenic Bioassay Data 2-13«>.
2-61 Summary of Carcinogenic Data Sets for Melphalan 2-137
2-62 Summary of Melphalan Carcinogenle 3ioasscy Data 2-138
2-63 Summary of Carcinogenic Data Sets for Methotrexate 2-139
2-64 Summary of Methotrexate Carcinogenic Bioassay Data 2-140
2-65 Summary of Carcinogenic Data Sets for Mustard Gas 2-142
2-66 Summary of Mustard Gas Carcinogenic Bioassay Data 2-143
2-67 Summary of Carcinogenic Data Sets for 2-Naphthylamine 2-144
2-68 Summary of 2-Naphtliylomine Carcinogenic Bioassay Data 2-145
2-69 Summary of Carcinogenic Data Sets for Nickel 2-149
2-70 Summary of Nickel Carcinogenic Bioassay Data 2-150
2-71 Summary of Carcinogenic Data Sets for Nitrilotriactic Acid 2-156
2-72 Summary of Nitrilotriactic Acid Carcinogenic Bioassay Data 2-157
vii
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TABLES
Toble Page
2-73 Summary of Carcinogenic Data Sets for Phenacetin 2-160
2-74 Summary of Phenacetin Carcinogenic Bioassay Data 2-161
2-75 Summary of Carcinogenic Data Sets for 2-163
Polychlorinated Biphenyls
2-76 Summary of Polychlorinated Biphenyls Carcinogenic 2-164
Bioassay Data
2-77 Summary of Carcinogenic Data Sets for Reserpine 2-165
2-78 Summary of Reserpine Carcinogenic Bioassay Data 2-166
2-79 Summary of Carcinogenic Data Sets for Saccharin 2-167
2-80 Summary of SaccEtarin Carcinogenic dioassay Data 2-168
2-81 Summary of Carcinogenic Data Sets for 2-172
2,3,7,8-Tetrachlorodibenzo-p-dioxin
2-82 Summary of 2,3.7,8-Tetrachlorodibenzo-p-dioxin 2-17?
Carcinogenic Bioassay Data
2-83 Summary of Carcinogenic Data Sets for Tetrachloroethylene 2-176
2-G4 Summary of Tetrachloroethylene Carcinogenic Bioassay Data 2-177
2-85 Summary of Carcinogenic Data Sets for Toxaphene 2-179
2-86 Summary of Toxaphene Carcinogenic Bioassay Data 2-180
2-87 Summary of Carcinogenic Ootn Sets for Trichloroethylene 2-182
2-88 Summary of Trichloroethylene Carcinogenic Bioassay Data 2-183
2-89 Summary of Carcinogenic Data Sets for 2,4,6-Trichlorophenol 2-187
2-90 Sun«iKiry of 2,4,6-Trich)oropher,ol Carcinogenic Bioassay Data 2-188
2-91 Summary of Carcinogenic Data Sets for Vinyl Chloride 2-189
2-92 Summary of Vinyl Chloride Carcinogenic Biocssay Data 2-190
2-93 Summary of Carcinogenic Data Sets for Vinylidene Chloride 2-202
2-94 Summary of Vinylidene Chloride Carcinogenic Bioassay Data 2-203
viii
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Section 1
BIOASSAY DATA COLLECTION AND SUMMARIZATION
BACKGROUND
The goal of '.he study is to characterize the uncertainty associated with
various components of bioassay-based risk assessment. This is accom-
plished by constructing a data base of bioassays and applying a number
of different analyses to that data base. Differences that result from
different analyses inform the characterization of uncertainty.
For each chemical selected for inclusion in the study (as described in
Volume 1), the available bioassay literature was acquired and, when
appropriate, abstracted for entry into the data base. In this manner, a
source of data that has uniform format and the flexibility to support an
array of different types of analyses has been created. This section
describes the manner in which bioassny data was summarized. The
following section provides details of the contents of the data base for
each chemical represented.
DATA ABSTRACTION
The data from an experiment are included in the data base if the experi-
ment is a chronic carcinogenicity bioassay satisfying the following
conditions:
• the test species is a non-human mammalian species;
• the protocol includes matched controls, preferably vehicle (or
shsm inhalation) treated animals;
• dosing is consistent within a dose group, with dosages and
dosing patterns clearly stated;
1-1
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• a single route of exposure is employed;
• th<» test compound is administered alone or in an acceptable
vehicle, without pretreatment or concurrent treatment of any
kind;
* tumor incidence is reported as number of tumor-bearing animals
as opposed to number of tumors.
Since it was decided early in the course of the project not to include
in the analysis experiments that exposed the test animals by skin
painting or subcutaneous injection, the data base does not include some
such experiments that would be otherwise eligible.
Table 1-1 lists the data that were abstracted from each acceptable
experiment. The coding of the responses deserves further comment. For
each experiment, each tumor occurring significantly more often in a
dosed group compared to the control group (as determined by the original
authors or by Fisher's exact test at the 0.05 level) was included. If
there were no such responses, the tumor type that was most nearly
significant was coded. In addition, an attempt was made to code the
number of animals in each dose group with the following carcinogenic
responses:
• the combination of all significantly increased tumors (as
defined above), coded with the code 1000-7000/
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Any on* of these additional responses could be coded only if that
response was specifically reported in the study, if only one tumor type
occurred, or if individual animal pathologies were presented. It is not
appropriate, for example, to add together the number of animals with
individual responses oecause a single animal may have multiple
responses.
Certain tumor types have not been considered in the definition of "all"
tumors or •all* malignant tumors. They are interstitial cell tumors of
the testes in mala F344 rats, mammary gland benign tumors in female
Sprague-Dawley rats, malignant lymphomas in AKR and AKR/J mice, and
mammary tumors in MTV+ mice. These tumors have high background rates in
the indicated strains. Inclusion of such responses in the •all* cate-
gory would tend to obscure any dose-related effect that is manifested in
many sites or as many tumor types, which is the very effect we are
attempting to capture by the use of the "oil" categories. When it has
not been possible to separate the above-mentioned tumors from others in
the definition of total tumor-bearing (or total ir.alignancy-bearing)
animals, the response has been caded as 1001-8000/4 (or 1001-8000/3).
The "1001" codes are not included in the analyses.
DISCUSSION
The manner in which the bioassay data has been abstracted influences the
use of the data base. Consider, for example, the coding of the r!rv,ing
pattern for each dose group. The form of the data included in the data
base includes the week when a particular regimen wa« started as well as
its frequency and its intensity. It is possible, therefore, to indicate
all the changes in dosing pattern that occurred in any dose group
throughout an experiment. Consequently, many possible manipulations of
the exposure calculations con be examined. There are, however, limita-
:ons imposed by the choice of weeks (as opposed to days, for example)
. the unit of time for indicating dosing changes. A bioassay with two
o groups, one administered a single dose of chemical on the ninth
the other administered the same dose on the thirteenth day of
peri merit, provides an example of *he limitation. Both dose groups
n coded in the same manner to indicate a single dose given in the
1-3
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second week. In some cases, such as transplacental exposure to DES, the
four-day difference in timing of exposure could be very important. It
is not expected, for the gross differences in analysis approaches that
are the subject of this project, that these limitations will unduly
influence the results. Any future plans for the data base should
consider possible limitations posed by the form of the data collected
and the manner in which it was coded.
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Table 1-1
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Data Item Description. Values
Chemical Cod* CAS* number of the chemical under
investigation.
Study Code Numerical code for source of
data; corresponding cod* on
original research article.
Animal Code Code which will specify species.
strain, and sex of the
animal model. The first
digit will represent
species -
0-3: mouse
4-6: rat
7-9: other
Route Code for route of exposure
1 • oral, food
2 • gavage
3 * intracolonic
% • intragastric
5 - injection
6 • implant
7 • intramuscular injection
8 • intranostril
9 • inhalation
10 « intrathoracic
11 * intraperitoneal
injection
12 - intratrachidl
13 » subcutaneous
1* • skin paint
15 • orol. water
16 - orol, peros
17 • transplacental
18 • introfemoral
19 - intropleural injection
20 • poranasal injection
21 • intrarenal injection
22 • mouth pointing
23 • intraocular injection
2
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Table 1-1 (continued)
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Data Item_
Description. Values
Routs (continued)
Length of Experiment
Individual Pathologies
Number Dote Group*
Number Responses
Chemical Class
Code for route of exposure
(continued):
25 * intravenous
26 • tronsplacentol, then
oral
27 • transplacental, then
transmammary
28 » transmammary
29 - intrahepatic injection
As stated, expressed in weeks.
Flag to indicate presence or
absence of individual
pathologies
0 • no pathologies
1 • pathologies present
Number of dose groups in the
experiment.
Number of carcinogenic
responses coded; two digit
number between 01 and 99,
inclusive.
Chemical class of the compound
being tested
01 » Aromatic hydrocarbon
02 - Aromatic amine
03 • Aromatic halogenated
hydrocarbon
0* • Aliphatic halogenated
hydrocarbon
05 • Natural product
06 * Inorganic polymer
07 • Inorganic metal
08 • Mustard
09 - Hormone
10 • Polycyclic aromatic
hydrocarbon
11 • Aldehyde
1-6
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Tobl* 1-1 (continued)
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Data Item
Description. Values
Mechanism of Action
XARC Close
Response
Dot* Group
Initial Number of Animals
Average Age at Start
Median Time to Death
Number of Do*e Levels
Code to describe the putative
mechanism of carcinogenic
action
1 - Genetic, direct
2 • Genetic, procarcinogen
3 • Epigenetic
% • Genetic and epigenetic
5 - Unknown
The classification of the
chemical done by IARC:
1 • IARC Class 1
2 • IARC Class 2A
3 • IARC Class 2B
% . IARC Class 3
5 • No IARC Class
Code for a carcinogenic response
noted in the experiment.
The code will be based on
the ICDO code of 1976 and
will include topography and
morphology, including degree
of malignancy.
Number identifying the dose
group The control group
will always be given the
number 1.
The number of animals orig-
inally assigned to the dose
group.
Average age (in weeks) of the
dose group at start of
experiment.
Week by which time ho1* the dose
group had died.
Number of distinct dose regimens
for the dose group <-number
of dose changes plus one).
1-7
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Table 1-1 (continued)
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Data Item
Description. Values
Tim* Started Do»e
Dose Level
Units
Frequency
Number of Weight
Measurements
Number of Food Intake
.Measurements
The week (counting from start of
experiment) in which a
particular dose started.
Number of units of dose received
at one administration.
Code for units of dose measure-
ment:
1 * mg
2 • mg/kg
3 » ppm air
* - ppm food
5 • ppm water
6 • K food
7 « % water
10 • g
11 - g/kg
12 * ng/kg
13 • ppt air
14 - mg/m3
15 • jtg/fl
16 - ng
Code for frequency of admini-
stration of dose. Code* to
indicate the number of
administrations per unit of
time, the number of hours
per administration (for
inhalation route), or con-
tinuous exposure situations.
Nuirber of times an avorage
weight measurement is
recorded for th« dose
group.
Number of times an average food
intake measurument is
recorded for *che dose group.
1-8
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Table 1-1 (continued)
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Data Item
.Description^.. Values
Weight Units
Food Intake Units
Average Weight
Time of Weight
Measurement
Average Food Intake
Time of Food Intake
Measurement
Flag
Number Eligible
Tim* to First Response
Units for expressing weight!
01 - grams
02 • pounds
Units for expressing food intake
• wgt. of food/animal/wk.
01 • grams
02 • pounds
03 • grams per kilogram
body weight
0% • pounds per pound body
Average weight of dose group.
Week from start of experiment in
which a measurement was
mod*.
Averuge food intake of the dose
group.
Week from start of experiment
in which a measurement
was mode.
Flag indicating whether the
fallowing five variables are
known with certainty or
whether w* had to estimate
what some of them were:
0 • estimated
1 • known with certainty
Number of animals in the dose
group who were examined for
the response of interest.
Time in weeks from start of
experiment until devel-
opment of this response in
this dose group.
1-9
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Table l-l (continued)
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Data
Description. Values
Number Alive at First
Re«pon»e
Number Eligible at First
Response
Number of Responses
Number of Responses Without
Sacrifices
Animal Identification
Week of Death
Cause of Decth
Number of animals in the dose
group wno were alive just
prior to the first death of
any animal in any dose group
due to the response of
interest.
Number of animals in the dose
group who were alive (and
examined for the response)
Just prior to the first
death of any animal due to
the response of interest.
Number of animals in the dose
group who demonstrated the
response of interest.
Number of animals in the dose
group demonstrating the
response, excluding those
animals who died from
scheduled sacrifices.
Identifying number for on
individual animal if indi-
vidual pathologies are
available.
Week from start of experiment to
death of individual animal.
Code for cause of death
1 • Natural death
2 • Moribund sacrifice
3 • Interim sacrifice
* - Terminal sacrifice
5 <• Accident
9 • Unknown
1-10
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Table 1-1 (continued)
DATA ITEMS ABSTRACTED FROM ANIMAL BIOASSAYS
Poto Item Description, ^Values
Response indicator In column (i+11) of the
•Individual Pathology Card"
i* an indicator for response
i for a particular animal;
value* arc a* follow*
2 • positive for response
of interest
1 • negative for response
of interest
0 • animal not examined for
the response of
interest
1-11
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Table 1-2
THE RESPONSES OF INTEREST IN HUMANS
FOR CHEMICALS WITH SUITABLE HUMAN DATA
Chemical
Response
Aflatoxin
Arsenic
Asbestos
Benzene
Benzidine
Cadmium
Cigarette smoke
Chlorambucii
Chromium
DES
Epichlorohydrin
Estrogens
Ethylene oxide
Isoriazid
Melpholan
Methylene chlorid*
Nickel
PCBs
Phenacetin
Reserpine
Saccharin
Trichloroethylnne
Vinyl chloride
Liver Cancer
Lung Cancer
Mesothelioma; Lung Cancer
Leukemia
Bladder Cancer
Prostate of Lung Cancer
Lung Cancer
Leukemia
Pharynx or Lung Cancer
Cancer of the Genital Tract
All Malignant Neoplams
Mammary. Endometrial, or
Uterine Cancer
Leukemia
All Malignant Neoplasms
Leukemia
All Malignant Neoplasms
Nasal or Lung Cancer
All Malignant Neoplasms
Bladder or Renal Pelvis Cancer
Breast Cancer
Bladder Cancer
All Malignant Neoplasms
Angiosarcoma of the Liver
1-12
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Section 2
DATA BASE CONTENTS
INTRODUCTION
This section contains a brief description of the experiments that have
been reviewed for inclusion in the bioassay data base. N«t all experi-
ments are suitable for. the purposes of this project. Nevertheless, a
summary of the entire literature reviewed, what we have called the data
matrix, is provided as well as a more complete description of the
bioaisays that satisfy the inclusion criteria. The text of this section
describes any special situations encountered wit.-! **espect to calculation
of dosage, route of administrrticn, or identity of chemical.
It should be noted that several of the chemicals under investigation,
especially the metals, exist in more than one form or complex. For
example, studies exist for nickel subsulfide and fcr nickel carbonyl.
Each form or complex is identified by a unique Chemical Abstract Service
(CAS) number so that it is possible to treat each form as a separate
chemical. In accordance with this possibility, the data on dosages
applies to the complex rather than the corresponding element. Thus, for
an experiment testing nickel subsulfide, a dose coded as 1 mg/kg/doy
indicates that 1 mg/kg/doy of nickel subsulfide, not nickel itself, was
administered. No calculation of the amount of the elemental form in the
complex was undertaken. The different forms of a chemical have been
grouped together in this summary of data base contents and in the
analyses.
ACRYLONITRZLE
A summary of the data sets in the data matrix for acrylonitrile is
presented in Table 2-1. Nineteen carcinogenicity bioassay data sets
are included in the data matrix, all of which are considered suitable
2-1
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for risk assessment and all of which tested rats. This ccircinogenicity
bioassay data is summarized in Table 2-2.
AFLATQXIN
There are a total of eighty-six carcinogenicity bicassay data sets
included in the data matrix, of which 33 are suitable for risk assess-
ment (Table 2-3). Although an abundance of data or* available for non-
mammalian species, only studies utilizing mammalian species were
abstracted and included in the quantitative risk assessment. These
studies are summarized in Table 2-4.
Several types of aflatoxin exist in nature including aflatcxins B-|, 82.
GI , 62, MI. In some experimental studies, the specific type of
aflatoxin tested is identified and was assigned a unique CAS registry
number. In studies where the type of aflatoxin was unspecified or a
combination of aflatoxins was used, the term "general aflatoxin* was
applied. The molecular weight of this "general aflatoxin* was derived
by determining the arithmetic'mean of the specific forms of aflatoxin.
ALLYL CHLORIDE
Six carcinogenicity data sets are included in the data matrix (Table
2-5). Of these data sets, four are suitable for risk assessment, and
are summarized in Table 2-6.
4-AMINOBIPHENYL
Carcinogenicity bioassay data sets for
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ARSENIC
Thirty-three carcinogenicity bioassay data sets are included in the data
matrix and are summarized in Table 2-9. S aen of these data sets
are suitable for risk analysis (Table 2-10).
Various forms of arsenic were used in the bioassays. In abstracting
data for analysis, each form was identified by a unique CAS number.
The arsenic compounds included sodium orsenate, lead arsenate, calcium
arsenate and arsenic trioxide, as well as elemental arsenic itself
ASBESTOS
The data sets in the data matrix for asbestos are summarized in Table
2-11. There are a total of eighty-four carcinogenicity bioassay data sets
in the data matrix. Of these, sixty-four are considered suitable for
analysis, none of them testi'ig mice. A summary of this carcinogenicity
bioassay data is presented in Table 2-12.
Asbestos is a term applied to a group of compounds which exist in
fibrous form with various possible types or sizes of fibers, rather than
a single unique substance. In some of the studies from which data sets
were taken, the type of asbestos was not clearly defined and was
assigned a CAS number for unspecified asbestos. An average molecular
weight for this general class of asbestos was derived from the molecular
weight of the individual types. Those studies which did state the type
or types of asbestos used were treated as separate data sets with
different CAS numbers employed as a means of identification. Hence
analysis is possible for specific asbestos types (amosite, chryuotile
and crocidolite being the primary examples) or for the asbestos class as
a whole.
BENZENE
A total of twenty-six carcinogenicity bioassays for benzene were
obtained and entered into the data matrix (Table 2-13). Of these.
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fifteen data sets are considered suitable for quantitative risk
estirration. These dctc sets ore summarized in Table 2-14.
BENZIDINE
Ten carcinogenesis bioassay data sets were selected from the literature
for benzidene and are summarized in Table 2-15. Only three are
considered suitable for carcinogenic potency estimation. These data
sets are summarized in Table 2-16. The studies not considered suitable
for inclusion in the data base were flawed by poor exposure information
or contained only one animal per dose group without concurrent controls.
BEN20[A]PYRENE
A •urr,.nry of the data sets for benzo[a]pyrene in the data matrix is
presented in Table 2-17. Fifty-one carcinogenicity bioassay data sets
are included in the matrix, and of these, fourteen are considered suit-
able for risk assessment. This corcinogenicity bioassay data is summa-
rized in Table 2-18. Twenty-six of the fifty-one data sets available
for analysis employed subcutaneous injection or skin painting. These
experiments were not included in the data base ever if they met the
inclusion criteria.
CADMIUM
The data sets in the data matrix for cadmium are summarized in Table
2-19. Thirty carcinogenicity bioasscy data sets ere included in the
data matrix. Of these, eight are considered suitable for analysis. A
summary of this corcinogenicity bioassay data is presented >.,: Table
2-20. Sixteen of the thirty data sets included in the data matrix
employed subcutaneous injection as the route of exposure and were not
coded. An additional six data sets did not employ suitable controls and
could therefore not be analyzed.
2-4
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rise this chemical classification,
niufli oxide and cadmium chloride. These
AS nu.Tibers, enabling analysis of the
group a* a whole.
001 tetrachloride included in the data matrix are
2-21. Twenty-one carcinogenicity bioassay data sets
a data matrix; six are considered suitable for our
y of this carcinogenicity bioassay data is presented
the twenty-cne data sets available for analysis,
ocutaneou* injection as the route of administration and
d in the data base. Some aata sets were excluded due to
controls.
..ett in the data matrix for chlorambucil are summarized in
-23. Six carcinogenicity bioassay data sets are included in the
matrix. Only one is suitable for analysis. A summary o-f this
assay is presented in Table 2-2*>.
CHLORDANE
The data sets in the data matrix for chlordane are summarized in Table
2-25. Eight ccrcinogenicity bioassay data sets are included in the data
matrix. All of these are abstracted for analysis. This data is summa-
rized in Table 2-26.
CHLOROFORM
Thirty-one carcinogenicity bioassoy data sets are included in the data
matrix (Table 2-27). Twenty of these ore suitable for risk assessment.
2-5
-------
The remaining studies are unsuitable due to poor experimental protocols
(no controls, reporting of number of tumors rather than number of
animals with tumors, etc.) or were not coded because chloroform was
administered by subcutaneous injection. The experimental protocols for
the cata sets included in the data base are summarized in Table 2-28.
CHROMIUM
Sixteen carcinogenicity bioassays are included in the data matrix (Table
2-29). Of those, eight are suitable for risk assessment and are summa-
rized in Table 2-50. Several of the data sets presented the data in a
form that could not be used (such as number of tumors as opposed to
number of animals with tumors) or did not have a control group.
Various forms of chromium were administered in the bioassays. Each form
is identified by a unique CAS number. The different forms of chromium
include calcium chrornate, strontium chromotw, zinc chrornate, sodium
dichrornate, chromium acetate and chromium itself.
CIGARETTE SMOKE
The data sets in the data matrix for cigarette smoke are summarized in
Table 2-31. Forty-one carcinogenicity bioassay data sets are included
for this chemical in the data matrix. However, only nine are considered
suitable for risk assessment. A summary of this carcinogenicity bioassay
data is presented in Table 2-32. Derivations of RROs from selected data
sets are presented below. These derivations are presented in more detail
than those for other chemicals because of the special dosing considera-
tions for cigarette smoke and because several RRDs calculated from
animal data are smaller than epidemiologically derived estimates, which
is contrary to the possibly pr*vailing opinion that cigarette smoke is a
less potent carcinogen in animals than in humans.
Twenty-four of the forty-one data sets available for analysis employed
skin painting as the route of exposure, frequently with benzene or other
unacceptable solvents as the vehicle. These twenty-four data sets have
2-6
-------
not been entered in the data bat*. In some studies, a particular frac-
tion of cigarette smoke condensete, rather than whole smoke, was admin-
istered. The data base includes only those studies (or portions of
studies) that dosed with whole smoke or whole tar. Several studies
either had no controls or treated animals with tumor-promoting agents.
These studies were also excluded from the data base.
There was not a clearly-defined, uniform method of expressing dosages
among the inhalation studies. For those data sets considered suitable
for analysis, the following method was employed when necessary to
calculate dosages.
Standard cigarette smoke values (1_) include
weight of cigarette smoke per cigarette - 505.6 mg
butt length - 30 mm
number of puffs per cigarette * 10
volume per puff • 38.9 ml.
Therefore, the weight (in mg) of cigarette smoke administered is deter-
mined using one or a combination of the following:
weight(mg)/puff -
std. puff weight (50.6 mg) x experimental puff vol (in mi) (2-1)
std. puff vol (38.9 mi)
mg/day cigarette smoke •
puff weight (mg) x breathing rate (m3/hour) x hours exposed. (2-2)
chamber volume(md) day
(Hours exposure per day is derived by using the reported puff duration
times the number of puffs per exposure times exposures/day.)
Of the nine experiments testing cigarette smoke, the study yielding the
smallest RRO estimates (lower bound, MLE, and upper bound) is that by
Stanton et al. (2). This was a 107-week study with only one noncontrol
2-7
-------
dose group of 105 rot*. Cigarette smoke eondensate mixed with beeswax
was injected into the lunge of the animals. The total dost was 24 mo, of
cigarette smoke that leached out of the beeswax over the entire two
years of the experiment. Consequently the calculated tiaily dose was
24 mg/0.35 kg/749 days - 0.09 mg/kg/dcy, which is a relatively small
dose when compared to dose groups in other cigarette smoke experiments.
Nevertheless, 14 of the 58 eligible dosed animals developed epidermoid
carcinoma so that the lower bound, maximum likelihood, and upper bound
estimates of dose corresponding to an extra risk of one in four are
1.34X10-2, 2.02x10-2, and 3.25x10~2 mg/kg/day, respectively, when
mg/m^/day are the units used in animal-to-humon extrapolation. For
comparison, the lower bound, maximum likelihood, and upper bound
estimates obtained directly from the epidemiclogical investigation are
2.79x102, 6.41x102, and 1.47x105, respectively.
Of the inhalation studies, that by Hammond et al. (3) provided the
smallest RRO estimates. In this ease male beagles were given trochees-
tomies, so that they coulf smoke cigarettes directly through the holes
in their trochees. The control group, consisting of 8 dogs, got
tracheostomies but no cigarettes. Over the entire 125 weeks of the
experiment, a low dose group received an average of 1754.6 mg/day and a
high dose group received 3452.7 mg/day of cigarette smoke. These doses
were calculated using data given in the study about, the weight of smcke
per cigarette and the number of cigarettes per day. Lung cancers
appeared significantly more often in the dosed group: only 2 out of 8
controls developed lung cancers (nonmalignant), whereas 7 of 12 low-dose
animals and 19 of 24 high-dose animals developed lung cancer (0 of 12,
and 10 of 24, respectively, had malignant lung tumors). Adjusting for
the shortness of the experiment (312 weeks is considered a standard
duration for a dog experiment) the calculated RRO lower bound. MLE. and
upper bound are 1.73, 3.11, and 8.39 mg/kg/day. respectively, when
mg/m2/day are the units used in animal-to-human extrapolation.
If attention is limited to inhalation experiments of fairly long dura-
tion, the one by Bernfeld et al. (4) yields the smallest RRO estimates.
This experiment utilized a smoking machine to expose male hamsters to
the smoke of four cigarettes twice a day. five days per week. Equations
2-1 and 2-2 were used to calculate an average daily dose of 150
2-8
-------
for the single exposed group. In that group, laryngeal tumors
developed in 9 of the 29 eligible animals compared to 0 of the 13 eligi-
ble- controls. Again, if on* uses mg/m^/day as the units for animal-to-
human extrapolation the lower bound. MLE, and upper bound RRDs are 9.95,
I.65xl01, and S.lSxlO1 mg/kg/day, respectively, values closer to those
derived from the epidemiology than those reported for previous studies.
If mg/kg/day are the units assumed to give equivalence between animals
and hwnans, the three RRO estimates are 6.98x10^, 1.16x10.2, and
2.23x1O2, which are even closer to the epidetniologically derived values.
One further example will serve to confirm that several bioassays
performed using various species in our data base underestimate RROs for
cigarette smoke in comparison with the direct epidemiological estimates.
(Note, however, that some, for example the inhalation study of rats by
Dalbey et ol. (5) in which subcutaneous sarcoma was the only signifi-
cantly increased tumor among treated animals, do yield estimates that
are larger than the epidemiologically based estimates). DiPaolo and
Levin (6) tested female mice by painting the oral cavity with a solution
of whole tar. The daily dose (for 5 days per week. 63 weeks of the 82
week experiment) was 26 mg of whole tar. Although only the lungs were
examined for carcinogenesis, the treated group of 81 animals contained
52 that developed lung tumors whereas 20 of 89 control animals developed
such cancers. The calculation of RROs, including adjustment for the
length of the experiment (82 as opposed to the standard 10<> weeks),
yields values of 6.03, 8.22, and 1.21X101 ing/kg/day as the lower bound,
maximum likelihood, and upper bound estimates corresponding to a one-in-
four risk. Again, mg/m2/day are the units used in the animal-to-human
extrapolation.
3.3-OICHLOROBENZIDENE
Eight carcinogenicity bioossay data sets are included in the data matrix
(Table 2-33). Five of these data sets, all employing tns oral route of
exposure, are suitable for risk assessment (Table 2-34). None of the
experiments in the data base tested mice.
2-9
-------
1,2-DICHLOROETHANE (ETHYLENE DICHLORIDE)
Fourteen corcinogenieity bioossoy data sets arw included in the data
matrix (Table 2-35); eight are considered suitable for risk assessment
(Table 2-38). The remaining data sets were excluded because dosing
information was non-specific. Skin pointing experiments have not been
included.
OZCHLOROMETHANE
Fourteen carcinogenic bioassoy data sets ore included in the data matrix
(Table 2-37). Of these, twelve were considered suitable for risk
assessment (Table 2-38).
DIETHYLSTILBESTROL
The data sets for diethylttilbestrol in the data matrix are summarized
in Table 2-39. Eighty-one carcinogenicity bioossay data sets are
represented in the data matrix and, of these, sixteen were abstracted
for analysis. A summary of these data sets is presented in Table 2-40.
Of the eighty-one data vets available for analysis, ten employed
subcutaneous injection as the route of exposure and were not coded.
Thirty-six data sets employed implantation of diethyJstilbestrol
pellets, with only five of these data sets considered suitable for
analysis. Many of these implantation studies did not use adequate
controls or did not sufficiently identify dosing. Several studies
employed unacceptable vehicles or used inappropriate animals, such as
castratee males or carriers of the mammary tumor virus.
The transf, \ocentol studies from which data were abstracted present some
unique problems in determination of exposure. It is necessary first to
assume that 100* of the administered dose crossed the placental barrier,
and that the entire dose was equally divided among the fetuses with 1000
absorption by each fetus. The dose por dam is then divided by the actual
litter siz«, if stated, or the average litter size for the species
2-10
-------
tested. If the odministered dose was expressed in units/body weight of
the dam, this it fir»t converted to simple uni-» (by multiplying by the
average dam body weight) before dividing by litter size, rather than
attempting to report dosage in b.^its/dom body weight/fetus.
DIPHENYLHYORA2INE
A summary of the data sets in the data matrix for diphenylhydrazine is
presented in Table 2-41. There is very little information available on
this chemical and only two carcinogenicity experiments are included in
the data matrix. Although the route of administration employed in one
study was subcutaneous injection, this data set is included in the
analysis due to the lack of data available for this chemical. The data
set is summarized in Table 2-42.
EPICHLOROHYDRIN
Seven carcinogenicity bioassoy data sets ore included in the data matrix
(Table 2-43) three of which are suitable for risk assessment (Table
2-44). The retraining data sets were either subcutaneous injection or
skin painting studies.
ESTROGEN
The data sets in the data matrix for estrogen are summarized in Table
2-45. Thirty-four carcinogenicity bioassay data sets are included in
the data matrix; only two are considered suitable for analysis. A
summary of these two experiments is presented in Table 2-46.
Of the thirty-four data sets available for analysis, twelve were
excluded due to lack of appropriate controls. An additional ten data
sets were excluded because of insufficient dosing information. Two
specific types of estrogen (17-B-estradiol, mestranol) ore included in
the data matrix in addition to the general designation estrogen, and are
identified by unique CAS numbers.
2-11
-------
ETHYLENE DIBROMIDE
The data sets in the data matrix for ethylene dibromide are summarized
in Table 2-47. Nineteen carcinogenieity bioa««ay data »et» are included
in the data matrix, ten of which were abstracted for analytic and
summarized in Table 2-48.
Four of the nineteen data sett were obtained from o study which gave no
length of experiment. The remaining data sets that were not selected
for analysis were taken from abstracts of articles and did not provide
sufficient information for analysis.
ETHYLENE OXIDE
A summary of the ethylene oxide bioassays in th» data matrix is
presented in Table 2-49. Fifteen carcinogenieity bioassay data sets are
included in the data matrix. Of these, ten are considered suitable ior
risk assessment and are summarized in Table 2-50. All experiments in
the data base employed rats as the test species.
FORMALDEHYDE
There are fifteen carcinogenic bioossoy dotn sets included in the data
matrix (Table 2-51) of which ten are suitable for risk assessment.
Those that are suitable for risk assessment were cbstracted.for analysis
and are summarized in Table 2-52.
HEXACHLOROBEN2ENE
Seven carcinogenieity bioassay data sets are listed in the data matrix
(Table 2-59). six of which are suitable for risk assessment. These six
are described in Table 2-54.
2-12
-------
HYDRA2INE
Thirty-one carcinogenicity bioassay data set* are included in the data
matrix (Table 2-55); 19 were abstracted for analysis. These data sets
are summarized in Table 2-56. The remaining data set* were not consi-
dered suitable due to lack of specific tumor data, or lack of control
groups.
ISONIAZID
A total of sixty-six carcinogenicity bioassay data sets are included in
the data matrix (Table 2-57), forty of which are suitable for risk
assessment. These latter are summarized in Table 2-58. The remaining
data sets were excluded due to the routes of exposure (subcutaneous
injection), insufficient information (no number of animals, no specific
tumor incidences) or poor experimental protocols (no controls,
unacceptable vehicle).
LEAD
A summary of the data sets in the data matrix for lead compounds is
presented in Table 2-59. Thirty-three careinogenicity bioassay data
sets are included in the data matrix. Of these, fifteen are abstracted
for analysis. This bioassay data is summarized in Fable 2-60.
Studies were excluded from analysis due to one or more of several
deficiencies, such as lack of appropriate controls or multiple routes of
exposure. In several studies, the number of tumors rather than the
number of animals with a particular tumor was reported. Several lead
compounds are included in this chemical classification, and are identi-
fied with unique CAS numbers, enabling examination of the group as a
generic entity or as the individual compounds. Lead arsenate studies
are not included in this group, but are instead classified under the
arsenic group.
2-13
-------
MELPHALAN
The data sets in the data matrix for melphalan or* summarized in Table
2-61. Seven earcinogenicity bioaseays or* included in the data matrix,
and of these, one it considered suitable for analysis. This corcino-
genicity bioossay it summarized in Table 2-62.
METHOTREXATE
Methotrexate data sets included in the data matrix ere summarized in
Table 2-99. There are a total of sixteen data sets of which six are
considered suitable for risk assessment. These data sets are summarized
in Table 2-81.
MUSTARD GAS
Of the available information on the carcinogenicity of mustard gas in
animal bioassays, four data sets were abstracted from the literature and
included in the data matrix (Table 2-63). The data sets that are
included in risk assessment analyses are summarized in Table 2-66.
2-NAPHTHYLAMZNE
A summary of the data sets in the data matrix for 2-naphthylomine is
presented in Table 2-67. Thirty-seven coreinogenieity bioassay data
sets are included in the data matrix. Many of these studies are older
(pre-1960) studies, and many utilized dogs as the .test animal and were
poorly controlled. Twenty-one are considered suitable for risk assess-
ment. This careinogenicity bioassay data is summarized in Table 2-68.
NICKEL
Seventy-seven carcinogenicity bioossay data sets are listed in the data
matrix (Table 2-69), of which 28 were suitable for risk assessment
(Table 2-70). The data sets that are not suitable for this risk
2-U
-------
analysis or* those that did not use control animals, reported number of
tumors instead of number of animals with tumors, or did not report the
number of animals being tested.
Only a small number of the data sets used for risk analysis involved the
use of elemental nickel. Therefore, data sets which utilized nickel
compounds are abstracted for analysis. These nickel compounds include
nickel carbonyl, nickel subsulfide, nickel acetate, nickel monosulfide
and nickel-iron-sulfide matte. Each compound is identified by its own
CAS number.
NXTRXLOTRXACETIC ACID
Eighteen carcinogenic bioassay data sets are listed in the data matrix
(Table 2-71). Of these, fifteen are suitable for risk assessment and
are summarized in Table 2-72.
PHENACETIN
The data sets in the data matrix for phenocetin are summarized in Table
2-73. Twenty-one carcinogenicity bioassay data sets ore included in the
data matrix. Of these, twelve or* considered suitable for analysis. A
summary of this carcinogenicity bioassay data is presented in Table
2-7*.
POLYCHLORINATED BIPHENYLS
The data sets in the data matrix for polychlorinated biphenyls are
summarized in Table 2-75. Twelve carcinogenicity bioassay data sets are
included in the matrix, and of these, six are considered suitable for
our analysis. A summary of this carcir.ogenicity bioassay data is
presented in Table 2-76. The data sets which were abstracted for
analysis are primarily studies on Aroclor 1254 or Aroclor 1260 (Aroclor
is the registered trademark of the Monsanto Chemical Company for their
polychlorinated biphenyls).
2-15
-------
RESERPINE
The reserpine experiments in the data matrix are summarized in Table
2-77. There is little data available for this chemical. Six carcino-
genicity bioassay data sets aro included in the data matrix, of which
four were abstracted for analysis. A summary of the suitable bioassay
data is presented in Table 2-78.
SACCHARIN
A summary of the data sets in the data matrix for saccharin is presented
in Table 2-79. Twenty-seven carcinogenicity bioassay data sets are
included in the data matrix and, of these, eighteen war? abstracted for
analysis. The appropriate bioassay data is summarized in Table 2-80.
The bioassay reported by R. A. Squire in "Histopathological Evaluation
of Rat Urinary Bladders from the IROC Two-Generation Bioassay of Sodium
Saccharin" (Fd.^hem. Toxie. 23{4/5):*91-497) was inadvertently omitted.
2.3,7,8-TETRACHLORODlBENZO-P-DIOXlN (TCOD)
A summary of the data *ets in the data matrix for TCDO is presented in
Table 2-81. Nineteen carcinogenicity bioassay data set* are included in
the data matrix. Of these, ten were abstracted for analysis. This
carcinogenicity bioassay data is summarized in Table 2-82. Most of the
data sets which were excluded from the analysis employed subcutaneous
injection as the route of administration. There are two studies
abstracted for analysis which employed dermal exposure, the route
determined to be most pertinent to human exposure for this chemical.
TETRACHLOROETHYLENE
The tetrachloroethylene experiments in the data matrix are summarized in
Table 2-83. Fourteen carcinogenicity bioassay data sets are included in
the matrix, of which eight are considered suitable for risk assessment.
A summary of the suitable data is presented in Table 2-84.
2-16
-------
TOXAPHENE
Only one study, containing four carcinogenicit/ bioassays, is listed in
the data matrix (Table 2-85). All four of these data sets were
abstracted for analysis and are summarized in Table 2-86.
TRICHLOROETHYLENE
The data sets in the data matrix for trichloroethylene are summarized in
Table 2-87. Thirty-four carcinogenicity bioassay data sets are included
in the matrix and, of these, twenty-two were abstracted for analysis.
The abstracted bioassay data are summarized in Table 2-88.
2, <>, 6-TRICHLOROPHENOL
The data sets for trichlorophenol that are included in the data matrix
are sumtiarized in Table 2-89 and those data sets included in the data
base are summarized in Table 2-90.
VINYL CHLORIDE
Data matrix information on vinyl chloride is summarized in Table 2-91.
Sixty-five carcinogenesis bioassay data sets are included in the data
matrix. Of these, fifty-six were abstracted for the data base, and are
summarized in Table 2-92. Twenty-seven of those data sets abstracted
for analysis are taken from Experimental Research on Vinyl Chloride
Corcinogenesis (7).
VINYLIDENE CHLORIDE
A summary of the data sets in the data matrix for vinylidene chloride is
presented in Table 2-93. Forty-six carcinogenicity bioassay data sets
are included in the data matrix. Of these, thirty-two were abstracted
for analysis. This carcinogenicity bioassay data is summarized in Table
2-94.
2-17
-------
Animal Model
Table 2-1
SUMMARY OF CARCINOGENIC DATA SETS FOR ACRYLONITRILEa
Rente of Administration
Species Sex Oral Govoge Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Ttouse
Rot
Rot
Rot
Other
Other
Other
Mole
Female
Mixed"
Male
Female
Mixed
Male
Female
Mixed
0
0
0
*(%)«
5(5)
0
0
0
0
0
0
0
2(2)
2(2)
0
0
0
0
0
0
0
3(3)
3(3)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
c
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
aThere were a total of 19 data sets of which 19 were considered suitable for risk
assessment.
bThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
cThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
2-18
-------
Table 2-2
SUMMARY OF ACRYLONITRILE CARCINOGENIC BIOASSAY DATA
Species
Rat
Spartan
Sprague-
Dawley
Male
Rat
Spartan
Sprague-
Dawley
Female
Rat
Spartan
Sprogue-
Dawley
Male
Pat
Spartan
Sprague-
Dowley
Female
Rat
Fischer
3
Bio/
Dynamics,
in EPA
(§)
Bio/
Dynamics,
in EPA
(§>
2-19
-------
Table 2-2 (continued)
SUMMARY OP ACRYLONITRILE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat
Fischer
344
Femalo
Rat
Charles
River
Femaifl
Oral-water
Oral-water
Rat
Sprogue-
Dawley
Mole
Oral-water
Rat
Sprague-
Oawley
Female
Oral-water
0, 1, 3, 10, 30 and 1 ppm
100 ppm continuously
for length of experi-
ment (99 weeks); 200
controls, 100/dose
group.
Brain
0, 100, 500 ppm water
continuously for 20
weeKs; length of ex-
periment 45 weeks; 39
controls, 39 dosed
(100 ppm), 42 dosed
(500 ppm).
0 or 35 ppm contin-
uously for length of
experiment; 85 or 210
ppm continuously for
3 weeks, then raised to
100 or 300 ppm, respec-
tively for remainder
of experiment; length
of experiment 106 weeks
80 controls, 48/dose
group.
0 or 35 ppm contin- 35 ppm
uously for length of
experiment; 85 or 210
ppm continuously for
3 weeks, then raised to
100 or 300 ppm, respec-
tively for remainder of
experiment; length of
experiment 106 weeks; 80
controls. 48/dose
group.
100 ppm Brain
35 ppm Stomach
Mammary
gland
Bio/
Dynamics,
in EPA
(§)
Belilos
et al.,
in EPA
<§>
Ouast
et ol.,
in EPA
<§)
Quast
•t ol..
in EPA
<§>
2-20
-------
Table 2-2 (continued)
SUMMARY OF ACRYLONITRILE CARCINOGENIC BIOASSAY DATA
Soecies
Rat
Spartan
Sprague-
Oawley
Male
Rat
Spartan
Sprague-
Oawley
Female
Rot
Sprague-
Dawley
Male
Rat
Sprague-
Dawley
Female
Rat
Sprague-
Dawley
Male
Rat
Sprague-
Dowley
Female
Route of Lowest Highly
Adminis- Nature of Effective Affected
tration Exposure Dose Qrqan(s)
Oral-water 0, 1 or 100 ppm con- 1 ppm Brain
tinuously for length
of experiment (94
weeks); 100 controls,
100/dose group.
Oral-water 0, 1 or 100 ppm con- 1 ppm Brain
tinuously for length
of experiment (81
weeks); 100 controls.
100/dose group.
Inhalation 0, 5, 10, 20 or 40 ppm — None
4 hrs/day, 5 days /week
for 52 weeks; length of
experiment 134 weeks);
30 controls, 30/dose
group .
Inhalation 0, 5, 10, 20 or 40 ppm — None
4 hrs/day, 5 days/week
for 52 weeks; length of
experiment 134 weeks;
30 controls, 30/dose
group .
Gavage 0 or 5 mg/kg 3 times a — None
week for 52 weeks; length
of experiment 130 weeks;
75 controls, 40 dosed.
Govage 0 or 5 mg/kg 3 times a — None
week for 52 weeks;
length of experiment
130 weeks; 75 controls,
40 dosed.
Reference
Bio/
Dynamics,
in EPA
(§)
Bio/
Dynamics,
in EPA
<§)
Maltoni
et al.
(§)
•
Maltoni
et al.
Maltoni
et al.
(1>
Moltoni
et al.
<§)
2-21
-------
Table 2-2 (continued)
SUMMARY OF ACRYLONITRILE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Rat Inhalation 0, 5, 10, 20 or 40
Sprogue- ppm 5 days/week, 4
Dowley hrs/day for 52 weeks;
Mole length of experiment
136 weeks; 30/dose
group.
Rat Inhalation 0, 5, 10, 20 or 40 5 ppm
Sprague- ppm 5 days/week, 4
Dawley hrs/day for 52 weeks;
Female length oC experiment
136 weeks; 30/dose
group.
Rat Gavage 0 or 5 mg/kg 3 times a
Sprague- week for 52 weeks;
Dawley length of experiment
Male 131 weeks; 77 controls,
40 dosed.
Rat Gavage 0 or 5 mg/kg 3 times a
Sprague- week for 52 weeks;
Dawley length of experiment
Female 131 weeks; 62 controls.
40 dosed.
20 ppm None
None
None
None
Maltoni
et ol.
(10)
Maltoni
et ol.
(10)
Maltoni
et al.
(10)
Maltoni
et ol.
(10)
2-22
-------
Animo1 Modal
Table 2-9
SUMMARY OF CARCINOGENIC DATA SETS FOR AFLATOXIN0
Route of Administration
Species
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Sex
Male
Female
MixedC
Male
Female
Mixed
Male
Female
Mixed
Oral
0
0
0
23(1*)
6(4)
7(5)
3(1)
4(1 )
15(1)
Govoge
KDb
0
0
10(2)
3(1)
0
0
0
1(0)
Inhalation
KD
0
0
0
0
0
0
0
0
Subcu-
taneous
KD
0
0
1(0)
0
0
0
0
0
Skin
Painting
0
0
0
0
0
0
0
0
2(0)
Injection
KD
2(0)
0
5(0)
0
0
0
0
0
Instil-
lation
0
0
0
0
0
0
0
0
0
TP
0
0
0
0
0
0
0
0
0
°There were a total of 86 data sets of which S3 were considered suitable for"risk
assessment.
°The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
eThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-23
-------
Toble 2-
-------
Table 2-4 (continued)
SUMMARY OF AFLATOXIN CARCINOGENIC BIOASSAY DATA
Species
Rot
Wistor-
Porton
Female
Rat
Pitcher
Mole
Rot
Fischer
Female
Rat
Porton
Albino
Male
Monkey
Rhesus 4
Cynomol-
gus
Male 1
Female
Rat
Charle*
River CO
Male
Route of
Adminis-
tration
Qavoge
Oral -food
Oral -food
Oral -food
Oral-food
« intra-
peritoneal
injection
Oral-food
Lowest Highly
Nature of Effective Affected
Exposure Dose Oraan(s)
0. 5.1 or 7.69 mg/kg 5.1 mg/kg Liver
as a single dose. 19
controls, 18 in the
mid dose. 16 in the
high dose. Length
of experiment was
139 weeks.
0, 1, 0.3 or 0.015 0.015 ppm Liver
pom for 82 weeks and
killed; 1 pom for 3
weeks and observed
for 80 weeks. 25/
dose group.
0, 1. 0.3 or 0.015 0.015 ppm Liver
ppm for 82 weeks and
killed; 1 ppm for 3
weeks and observed
for 80 weeks. 25/
dose group.
0 or 10 ppm continu- 10 ppm Liver
ous dosing for 9
weeks, then control
diet to 104 weeks. 10
controls. 20/dose group.
0 or 1.78 mg dosing 1.78 trig Gall
once a week for bladder;
length of experiment Liver
(676 weeks). 211
controls, 21 dosed.
0 or 1 ppm continuous 1 ppm Liver
dosing for length of
experiment (60 weeks).
10 /dose group.
Reference
Carnaghan
(14)
Wogan and
Newberne
(15)
Wogan and
Newberne
(15)
McLean and
Marshall
Sieber
•t ol.
(12)
Newberne
et ol.
(1§)
2-25
-------
Table 2-it (continued)
SUMMARY OF AFLATOXIN CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Hig'ily
Affected
Organ (s)
Reference
Rat
Charles
River CD
Male
Rat
Long
Evans
Male
Rat
Long
Evans
Male
Rot
Fischer
Oral -food
Oral-food
Oral-food
Oral -food
0 or 0.2 ppm continu- 0.2 ppm Liver
ously for length of
experiment (71 weeks).
20 controls, 35 dosed.
0 or 0.018 or 0.184 — None
ppm for 52 weeks.
Terminated at 77
weeks. 10/group.
Female
0, 0.552 or 0.736
ppm for 51 weeks
(length of experi-
ment). 10 controls,
10 in low dose, 15
in high dose.
0 or 2 ppm for 75 weeks —
(length of experiment).
12 in controls, 19 in
treated.
0.552 ppm Kidney
None
Newberne £
Williams
(19)
Lee
et al
(20)
Lee
et al
(20)
Ward
et at.
Rat
Fischer
Oral-food
Male
Rat
Wittar
Male
Oral-food
0 or 2 ppm for 75 weeks —
(length of experiment).
6/dose group.
None
0, 0.25. 0.5 or 1.0
ppm for 21 week*.
Observed for 131
weeks (life). 26
controls, 17 in low
dose, 18 in mid
dose, and 16 in high
dose.
0.25 ppm Liver
Word
et al
(?J.)
Epstein
et al.
2-26
-------
Toble 2-4 (continued)
SUMMARY OF AFLATOXZN CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Monkey
Cynomol-
gus
Male
Oral-food
Monkey
Cynomol-
gus
Female
Oral-food
Rat
MRC
Male *
Female
Oral-water
Rat
MRC
Male A
Female
Oral-water
0 or 0.07, up to 0.36
or 1.8 ppm for 160 weeks
(length of experi-
ment). 2 controls,
2 in low and mid
dose. -4 in high
dose.
0 or 0.07, up to 0.3S
or 1.8 pom for 160 weeks
(length of experi-
ment). 3 controls,
2 in low and mid
dose, 3 in high
dose.
None
Cuthbertson
et ol.
(23)
None
0 or 0.1 mg 5 days/
week for 10 weeks or
0.02 mg 5 days/week
for 20 weeks (length
of experiment, 100
weeks). 30 controls,
10 in low dose and
30 in high dose.
0 or 0.02 mg. 5 days/
week for 10 weeks;
length of experiment
100 weeks; 30 con-
trols, 10 dosed.
Cuthbertson
et al.
(23)
0.02 mg Liver
Butler
et ol,
(2*)
None
Butler
• t al
2-27
-------
Table 2-* (continued)
SUMMARY OF AFLATOXIN CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Oraon(s) Reference
Rat
MRC
Male i
Female
Oral-water
Rat
Fischer
Oral-food
Male
Rat
Porton
Male
Oral-food
Mat
Porton
Female
Oral-food
0 or 0.02 mg 5 days
week for 10 weeks or
0.02 mg 5 days/week
for 20 weeks, 0.08 mg
5 days/week for 20
weeks. 30 controls,
10 in low dose for
10 weeks. 30 in low
dose for 20 weeks,
and 28 in high dose;
observed 100 weeks.
0 or 5C' ppb for 32
weeks; observed for
m w**ks, 20/dose
group.
0, 0.1 or 0.9 pp«i
for 130 weeks, 51
in control, 48 in
0.1 ppm group and 38
in 0.5 ppm group;
other groups fed 5
ppm for 1, 3. 6 or
9 weeks ond
observed for 130
weeks, 15 in 1 week
group, 20 in 3
weeks, 22 in 6
weeks, ond 6 in 9
weeks.
0, 0.1 or 0.5 ppm
for 130 weeks, 36/
dose group.
0.06 ing Liver
Butler
•t cl.
50 ppb Liver
5 ppm Liver
(6 weeks)
Nixon
et ol.
(25)
Butler
and
Barnes
(26)
0.1 ppm Liver
Butler and
Barnes
(26)
2-28
-------
Table 2-k (continued)
SUMMARY OF AFLATOXIN CARCINOGENIC BIOASSAY DATA
Species
Rat
Pitcher
344
Male A
Female
Rat
Fischer
Ski*
Male
Rat
use
Male
Rat
use
Female
Mouse
Swiss
Male
Mouse
Swiss
Male
Rat
Charles
River
Male
Route of
Adminis-
tration
Oral-per os
Oral-food
Oral-food
Oral-food
Oavage
Subcutan-
eous in-
jection
Oral-food
Lowest
Nature of Effective
Exposure Oose
0 or 0.025 mg for 20 0.025 mg
weeks, observed 77
weeks, 28 controls.
37 dosed.
0, 1, 5, ''5, 50 and 50 ppb
100 ppb for up to 109
weeks (length of ex-
periment). 18 controls
2 1-28 /dose group.
0, 1 or 10 ppb for
10* weeks (length of
experiment). 24/
dose group.
0, 1 or 10 ppb for
104 weeks (length of
experiment). 2k/
dose group.
0 or 0.1 mg 5 days/ 0.1
week for 52 weeks
(length of experi-
ment). 37 controls,
14 dosed.
0 or 0.1 mg 5 days/
week for 52 weeks
(length of experi-
ment), 37 controls,
15 dosed.
0, 0.4 or 1.5 ppm 0.4 ppm
for up to 87 weeks
(length of experi-
ment). 9 controls,
20 low dose, 10 in
high dose.
Highly
Affected
Oraan(s) Reference
Liver Chedid
et ol.
(27)
Liver Wogan
et ol.
(28)
None Alfin-Sloter
et al .
(29)
None Alfin-Slater
et ol .
(29)
Uympha- Lour i a
tics et ol.
(«)
None Louria
et al.
(30)
Liver Newberne
ee ol.
(11)
2-29
-------
Table 2-4 (continued)
SUMMARY OF AFLATOXIN CARCINOGENIC 8IOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Highly
Affected
Organ(s) Reference
Rot
Fischer
Male
Gavoge
Rat
Fischer
Male
Govoge
Mouse
Swiss
Male
Inhalation
0 or 25 M9/doy, 5
days/week for 8
weeks. Length of
experiment 100
weeks. 15 controls,
30 dosed.
0 or 25 M9/doy 5
days/week for 8
weeks. Length of
experiment 100 weeks
(dosed animals
killed at S3 weeks).
15 controls, 10
dosed.
0 or 1 mg of aerosol
2 times/day for 3
months, then 1 time/
day for 9 months.
37 controls, 22
dosed. Length of
experiment 12
months.
None
25
Liver
Wogan and
Paglialunga
(32)
Wogan and
Poglialunga
(32)
1 mg
Lympha-
tics
Louria
•t ol.
(30)
2-30
-------
Animal Model
Table 2-5
SUMMARY OF CARCINOGENIC DATA SETS FOR ALLYL CHLORIDE0
Route of Administration
Species Sex Oral Govage Inhalation
Subcu- Skin Instil-
toneous Painting Injection lotion
°There were a total of 6 data sets of which
assessment .
were considered suitable for risk
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
1(1 )b
KD
0
KD
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risK assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-31
-------
Table 2-6
SUMMARY OF ALLYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqon(s)
Reference
Rat
Osborne-
Mendel
Male
Gavage
Rat
Osborne-
Mendel
Female
Gavago
Mice
B6C3F-)
Male
Gavage
Mice
B6C3F-J
Female
Gavagf
Animals received
time-weighted average
doses of 0, 57 or 77
ing/kg 5 days/week for
78 weel's; length of
experiment 113 weeks;
animals/control, 50/
dose group.
None
NCI (33)
20
Animals received
time-weighted average
doses of 0, 55 or 73
mg/kg 5 days/week for
78 weeks; length of ex-
periment 110 weeks; 20
animals/control, SO/
dose group.
Animals received
time-weighted average
doses of 0, 172 or
199 mg/kg 5 days/week
for 78 weeks; length
of experiment 91 weeks;
20/control. 50/dose
group.
Animals received
time-weighted average
doses of 0, 129 or
258 mg/kg 5 days/week
for 90 weeks; length of
experiment 92 weeks,
20/control, 50/dose
group.
None
NCI (33)
None
NCI (3.3)
None
NCI (3_3)
2-32
-------
Animal Modal
Table 2-7
SUMMARY OF CARCINOGENIC DATA SETS FOR <*-AMINOBIPHENYLQ
Route of Administration
Species
Mouse
Mouse
Mouse
Rat
Rat
Rot
Other
Other
Other
Sex Oral
Male 1(1)b
Female 1(1)
Mixed6 0
Male 1(0)
Female 0
Mixed 0
Male 0
Female 3(0)
Mixed 2( 1 )
Gavage
0
0
0
0
0
0
0
0
0
Inhalation
0
0
0
0
0
0
0
0
0
Subcu-
taneous
0
0
0
0
0
0
0
0
0
Skin
Painting
0
0
0
0
0
0
0
0
0
Injection
0
0
0
0
0
0
0
0
0
Instil-
lation
0
0
0
0
0
0
0
0
0
TP
0
0
0
0
0
0
0
0
0
°There were a total of 8 data sets of which 2 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe 'mixed" sex indicates that either both sexes wero tested, but results were not
reported separately, or sex of test animal was unknown.
2-35
-------
Table 2-8
SUWIAKY OF 4-AMINOBIPHENYL CARCINOGENIC 8IOASSAY DATA
Species
Route nf
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Mouse Oral-water 0, 7, 14, 28, 55, 55 ppm Bladder; Schiefer-
BALB/c 110 and 220 ppm in Subcut- stein
StCrlf drinking water; aneous et al.
CjHf/ serial sacrifices tissue (34)
Nctr at 13, 26, 39, 52
Male and 96 weeks (length
of experiment); only
natural deaths and
terminal sacrifice
information utilized;
approximately 30-60/
dose group died
natural deaths or
were sacrificed at
96 weeks.
Mouse Oral-water 0, 7, 19, 38, 75, 150 75 ppm Liver; Schiefer-
BALB/c or 300 ppm in drinking Subcut- stein
StCrlf water; serial sacri- aneous et al.
C3Hf/ fices at 13. 26, 39 tissue (34)
Nctr 52 and 96 weeks (length
Female of experiment); only
natural deaths and
terminal sacrifice
information utilized;
approximately 30-60/
dose group died natural
deaths or were sacri-
ficed at 96 weeks.
2-34
-------
Animal Model
Table 2-9
SUMMARY OF CARCINOGENIC DATA SETS FOR ARSENIC0
Route of Administration
Specie* Sex Oral Qovoqe Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mou»*
•louse
Mou*e
Rat
Rat
Rat
Other
Other
Other
Male 2(0)b
Female 6(1)
Mixed0 3(1}
Male 3(2)
Female 3(2)
Mixed *(3)
Male 0
Female 0
Mixed 2(0)
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(1)
1(1)
0
0
0
0
0
0
0
0
0
0
1(1)
1(1)
1(1)
0
0
1(0)
0
0
0
2(2)
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
°There were a total of 33 data set* of which 17 were considered suitable for risk
assessment.
''The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-35
-------
Table 2-10 (continued)
SUMMARY OF ARSENIC CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration.
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ (s ) Reference
Rat
Wistor-
King
Albino
Male
Nice
C3H/St
Female
Hamster
Syrian
Golden-
Female
nice
Swiss
Male *
Female
Intratro-
ch«al in-
stillation
Oral-water
Intratra-
cheal in-
stillation
oral-per os
0 or 0.26 mg once a — None
week for 15 weeks;
length of experiment
97 weeks; 23 controls,
14 dosed.
0 or 2 ppm in water — None
continuously for
length of experiment
(86 weeks); 30/dose
group.
Instilled once a week 0.25 mg Lung
according to follow-
ing schedule:
0 mg for 15 weeks;
1 mg for 1 week, then
0.5 mg for 3 weeks,
then 0.25 mg for 11
weeks; or 0.25 mg for
15 weeks; observed 105
weeks total; 50 con-
trols, 20 or 30/dose
group.
Ishinishi
et ol.
Schrauzer
et ol.
Ishinishi
et ol.
0 or 0.38 mg/kg/
day continuously
for length of ex-
periment (140
weeks); 198 controls,
108 dosed.
None
Kanisawa
and
Schroeder
2-38
-------
Table 2-11
SUMMARY OF CARCINOGENIC DATA SETS FOR ASBESTOS0
Animol Modal
Route of Administration
Specie* Sax Orol Govoqe Inhalation
Subcu- Shin Instil-
toneou* Painting Injection lotion
TP
Mouse
Mouse
Mouse
Rot
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
0
0
0
0
2(1)
6(4)
4(4)
0
0
0
0
0
0
0
0
0
0
0
0
0
KD
0
12(10)
0
0
10(9)
0
1(0)
0
0
0
0
0
0
0
1(0)*
0
0
0
0
0
0
0
0
0
3(0)
0
1(0)
2(2)
12(12)
1(0)
0
12(9)
0
0
0
0
3(0)
3(3)
1(1)
0
9(8}
0
0
0
0
0
0
0
0
0
°There were a total of 84 data set* of which 64 were considered suitable for risk
assessment.
&The number in parenthesis indicates the number of data set:: that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
GThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-39
-------
Table 2-12
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Rat
Fischer
344
Male *
Femnl*
Rat
Wistar
Male i
Female
Oral-food
Inhalation
Rat
Wistar
Male i
Female
Inhalation
0 or 10* in food
for length of ex-
periment (135
weeks); 121 con-
trols, 240 dosed.
0 or 12.5 mg/m9
for one day; 12.6
mg/m9 for 12
weeks; 10.7 mg/m9
for 25 weeks; 10.6
mg/m9 for 5 weeks;
10.3 mg/m9 for 103
weeks; 15% controls,
20-50/dose group.
Dosing was 5 days/
week, 7 hrs/day;
length of experi-
ment 135 weeks.
0 or 14.1 mg/m9
for one day; 12.4
mg/m9 for 12 weeks:
11.2 mg/m9 for 23
weeks; 10.B mg/m9
for 51 weeks; or
10.6 mg/m9 for 103
weeks; 154 controls,
18-45/dose group.
Dosing was 5 days/
w««k, 7 hrs/day;
length of «wp«rim«nt
143 weeks.
None
Donham
ee al.
10.6
mg/m9
Lung
Wagner
et al
(46)
10.6
mg/m9
Lung
Wagner
et al
(46)
2-40
-------
Table 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rot
Wistar
Mole •
Female
Inhalation
Rat
Wistar
Male i
Female
Inhalation
Hamster
Syrian
Golden
Oral -water
Oral -water
Go).
Groups received 10.8
0 or 12.2 mg/m3 for mg/m3
one day; 12.2 mg/m3
for 12 weeks; 10.5
mg/m3 for 25 we«fcs;
10.8 mg/m3 for 51
weeks; or 10.6 mg/m3
for 105 weeks; 15% con-
trols. 38-87/dose
group. Dosing was 5
days /week, 7 hrs/day;
length of experiment
weeks.
11.%
mg/m3
Lung
Wagner
et ol,
Groups received 0 or
12.8 mg/m3 for one
tfay; 13.5 mg/m3 for
12 weeks; 10.9
mg/m3 for 25 weeks;
11.% mg/m3 for 51
weeks; or 10.6 mg/m3
for 103 weeks; 15% con-
trols, 1S-%5/dose
group; dosing 5 days/
week, 7 hrs/day;
length of experiment
1%3 weeks.
0, 0.675, 0.068 or
0.007 mg/day for
length of experi-
ment (93 weeks);
60 controls. 30/dose
group.
0, 0.675. 0.068 or
0.007 mq/day for
length of experi-
men*. (86 weeks); 60
controls. 30/dos«
group .
Lung
Wogner
et ol.
(46)
None
Smith
et ol
None
Smith
at si
-------
Table 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOAS&AY DATA
Specie*
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(t)
Reference
Rat Inhalation 2 or 10 mg/m'
SPF chrysotile 5 days/
Wan week, 7 hrt/day
Male A for 52 weeks, 20
Female untreated controls,
48/dose group.
Length of experi-
ment 123 weeks.
10 mg/m3 omotite 5
days/week, 7 hrs/
day for S2 weeks,
20 untreated con-
trols, *7 dosed.
Length of experi-
ment 123 weeks.
5 or 10 mg/m' cro-
cidolite 5 days/
week, 7 hrs/day for
52 weeks, 20 un-
treated controls,
kB dosed. Length
of experiment 123
weeks.a
Rat Intro- 0 or 20 mg amosit*
Wistar pleural in- in a single injec-
Male A Jection tion. 96/dose group.
Female length of experi-
ment 165 weeks.
Rot Intra-
Sprogue- pleurol in-
Oawley jection
Male *
Female
0 or 20 mg omosite
in a single injec-
tion 85/dose group,
length of exper-
iment 158 weeks.
Rat Intro- 0 or 20 mg ehryso-
Wistar pleurel in- tile in a single
Male a jection injection, 9d/dose
Femole group, length of
experiment 165 weeks,
2 mg/m5 Lung
Davis
et ol
None
Davis
et ol
Lung
Davis
et al
20 mg
Pleura
Wagner
and Berry
20 mg
Pleura
Wagner
and Berry
20 mg
Pleura
Wagner
and Berry
-------
Table 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Route of
Adminis-
Scecies tration
Nature of
Exposure
Lowest Highly
Effective Affected
Pose Organ ( s ) Reference
Rat Intra-
Sprogue- pleural in-
Oawley jection
Male *
Female
Rot Intra-
Wisv.ar pleural in-
Main « jection
0 or 20 mg chryso- 20 mg Pleura Wagner
tile in a single and Berry
injection, 85 con- (49)
trols, 90 dosed,
length of experiment
158 weeks.
0 or 20 mg crocido- 20 mg Pleura Wagner
lite in a single and Berry
injection, 96 con- (49)
trols, 189 dosed,
length of experi-
ment 165 weeks.
Rat Intra-
Sprague- pleural in-
Oawley jection
Male i
Female
0 or 20 r.!j crocido-
lite in a single
injection, 85 con-
trols. 180 dosed,
length of experi-
ment 158 weeks.
20 mg
Pleura
Wagner
and Berry
Hamster Intra- 0 or 0.25 mg once
Syrian tracheol a week for 25 weeks,
Golden injection length of experiment
Male 43 weeks, 10/dose
group.
Hamster Oral-food 0 or 1* amosite in
Syrian food for length of
Golden experiment (135
Male weeks); 127 con-
trols, 252 dosed.
Hamster Oral-food 0 or 1* amosite in
Syrian food for length of
Golden experiment (108
Female weeks); 126 con-
trols. 254 doited.
None
None
Miller
et ol.
(50)
NTP (5J.)
None
NTP (51)
2-43
-------
Table 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orqan(s) Reference
Hamster Oral-food
Syrian
Golden
Male
Hamster Oral-food
Syrian
Golden
Female
Hamster Oral-food
Syrian
Golden
Male
Hamster Oral-food
Syrian
Golden
Female
Rat Intrafe-
Osborne- moral in-
Mendel jection
Male
Rat Intrapleural
Osborne- injection
Mendel
Female
0 or 10 chrysotile
in food for length
of experiment (130
weeks); 126 con-
trols, 253 dosed.
0 or 10 chrysotile
in food for length
of experiment (103
weeks); 126 con-
trols. 252 dosed.
0 or 10 chrysotile
in food for length
of experiment (139
weeks); 126 con-
trols, 251 dosed.
0 or 10 chrysotile
in food for length
of experiment (98
weeks); 126 con-
trols, 252 dosed.
0 or 0.58 mg in a
single injection, 25
controls, 25 dosed.
Length of experi-
ment 104 weeks.
0 or 0.58 SKJ injected
once a month for 6
months, 25/dose group.
Length of experi-
ment 104 weeks.
None
NTP (51.)
None
NTP (5J.)
None
NTP (51)
None
NTP (5J.)
None
None
Hueper
(38)
Hueper
2-44
-------
Toble 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Rat Injection
Ocborne- into para-
Mendel nasal
Male sinuses
Rat
Charles
River CO
Male *
Female
Inhalation
Rabbit
Male *
Female
Inhalation
0 or 29 mg injected
once every 2 months
for total of 3 injec-
tions, 20/dose group.
Length of experi-
ment 10% weeks.
0 or i*8.2 mg/m3 amosite
4 hrs/day, 4 days/week
for life, 10 controls,
77 dosed; 0 or 48.7 mg/
m3 crocidolite 4 hrs/
day, 4 days/week for
life, 10 controls, 69
dosed; 0 or 47.4 mg/m5
chrysotile 4 hrs/day, 4
days/week for life, 10
controls, 60 dosed.
Each of these 3 experi-
ments lasted 156 weeks.0
0 or 48.2 mg/m3 amosite
4 hrs/day, 4 days/week
for life, 10 controls,
38 dosed; 0 or 48.7
mg/m3 crocidolite 4 hrs/
day, 4 days/week for
life, 10 controls. 32
dosed; 0 or 47.4 mg/m3
chrysotile 4 hrs/day, 4
days/week for life, 10
controls, 36 dosed.
Each of these 3 experi-
ments lasted 156 weeks.9
None
Hueper
(38)
Hone
Reeves
et al.
(52)
None
Reeves
et al.
(52)
2-45
-------
Table 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orggn(s) Reference
Guinea Inhalation 0 or 48.2 mg/m5 amosite
Pig 4 hrs/day, 4 days/week
Hartley for life, 12 controls,
Male i 45 dosed; 0 or 48.7 mg/
Female m3 crocidolite 4 hrs/
day, 4 days/week for
life, 12 controls, 50
dosed; 0 or 47.4 chry-
sotile mg/m3 4 hrs/day,
4 days/week for life,
12 controls, 44 dosed.
Each of these 3 experi-
ments lasted 156 weeks.0
Hamster Inhalation 0 or 48.2 mg/m3 amosite
Syrian 4 hrs/day, 4 days/week
Golden for life, 8 controls,
Male t 73 dosed; 0 or 48.7 mg/
Female m3 crocidolite 4 hrs/day,
4 days/week for life, 8
controls. 67 dosed; 0 or
47.4 mg/m5 chrysotile 4
hrs/day, 4 days/week for
life, 8 controls, 74
dosed. Each of these 3
experiments lasted 104
weeks.0
Rat Intratra- Single injection of
Charles cheal in- either 0 or 6 mg of
River jection amosite, crocidylite
CD or chrysotile asbes-
Male It tos, 10 controls, 13-
Female 16/dose group. Each of
these 3 experiments
lasted 156 weeks.0
None
Reeves
at al.
(52)
None
Reeves
9t al.
(52)
None
Reeves
at al.
(§2)
2-46
-------
Tobl9 2-12 (continued)
SUMMARY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration^
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Qrgon(s)
Reference
Rabbit Intratra- Single injection of
Male 4 cheal in- either 0 or 10 mg of
Female jaction otnosite, crocitiylite
or chrysotile as.les-
tos, 10 controls, *2-
15/dos* group. Each of
these 5 experiments
lasted 156 weeks.0
None
Reeves
et al.
(52)
Guinea Intratro-
Pig cheal in-
Hartley jection
Male i
Female
Single injection of
either 0 or 6 mg of
amosite. crocidylite
or chrysotile asbes-
tos, 12 controls, 15-
16/dose group. Each of
these 3 experiments
lasted 156 weeks.0
None
Reeves
et al.
Hamster Intratra- Single injection of
Syrian cheal in- either 0 or k mg of
Golden jection amosite or crocidy-
Male « lite asbestos, 8
Female controls, 10-13/
dose group. Both of
these experiments
lasted 10
-------
Toble 2-12 (continued)
SUWURY OF ASBESTOS CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly.
Affected
OrqanCs)
Reference
Rabbit Intro- Single injection of
Male I ploural either 0 or 16 mg of
Female injection amoeite, crocidylite
or chrysotile asbes-
tos, 10 controls, 13-
14/dcse group. Each of
these 3 experiments
lasted 156 weeks.0
None
Reeves
et ol.
(52)
Guinea Intra-
Pig pleural
Hartley injection
Male «
Female
Single injection of
either 0 or 10 mg of
omosite, crocidylite
or chrysotile asbes-
tos, 12 controls, 11-
17/dose group. Each of
these 3 experiments
lasted 10i» weeks.0
None
Reeves
et al.
(§2)
Hamster Intro- Single injection of
Syrian pleural either 0 or 10 mg of
Golden injection amosite, crocidylite
Male it 01 chrysotile asbes-
Female tos, 8 controls, 9-
14/dose group. Each of
these 3 experiments
lasted 104 weeks.0
None
Reeves
et al
Rat Intro-
Cnorles peritoneal
River injection
CD
mole *
Female
Single injection of
either 0 or 20 mg of
omosit.*. crocidylite
or chrysotile asbes-
tos. 10 controls. 11-
13/dose group. Each of
these 3 experiments
lasted 10<» weeks.0
None
Reeves
et ol
(52)
°Abstracted as three data sets; cne for each asbestos compound tested.
"Abstracted as two data sets; one for each asbestos compound tested.
2-48
-------
Table 2-13
SUMMARY OF CARCINOGENIC DATA SETS FOR BENZENE0
Animal Model
Route of Administration
Species Sex Oral Govoqe Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
0
0
3(0)
0
0
0
0
0
0
Ki)»
1(1)
0
3(3)
3(3)
0
0
0
0
3(3)
2(1)
KO)
2(1)
2(1)
0
0
0
0
2(1)
2(0)
0
0
0
0
0
0
0
0
0
KO)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 26 data set* of which IS were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" ssx indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
-------
Table 2-14
SUMMARY OF BENZENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s^
Reference
Mouse
B6C3F-J
Male
Mouse
B6C3F-I
Female
Rat
F344
Male
Rat
F344
Female
Rat
Sprague
Dow lay
Female
Gavage
Gavage
Gavage
Gavage
Inhalation
Rat
Sprague
Dawlay
Male
Gavage
0. 25. 50 or 100 25 mg/
mg/kg/day for 104 kg/day
weeks (length of
experiment); SO/
dose group.
0, 25, 50, or 100 i.3 mg/
mg/kg/day for 104 kg/day
weeks (length of
experiment; 50/dose
group.
0, 50, 100 or 200 50 mg/
mg/kg/day for 104 kg/day
weeks (length of
experiment); SO/
dose group.
0. 50. 100 or 200 50 mg/
mg/kg/day for 104 kg/day
w*eks (length of
experiment); SO/
group.
0 or 200 ppm 5 days/
week. 4 hr/day for 19
weeks; then 500 ppm 5
days/week, 4 hr/day
for 85 weeks; length
of experiment 150
weeks; 54/dose
group.
0, 50 or 250 mg/kg/
day for 51 weeks;
length of experiment
144 weeks; 30-35/dose
group.
Preputial, NTP (53)
Harderian,
A Zymbal's
gland
Liver; NTP (53)
Ovary;
Lung
Oral
cavity;
Zymbal's
gland;
Skin
Zymbal's
gland;
Oral
cavity
None
None
NTP (53)
NTP (53)
Maltoni
et al.
(54>
Malt.oni
at al.
(54)
2-50
-------
Toble 2-14 (continued)
SUMMARY OF BENZENE CARCINOGENIC BIOAS5AY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Sprague-
Dawley
Female
Mouse
C57BL/6J
Male
Mouse
AKR/J
Male
Mouse
C57BL/6N
Male
Gavage
Inhalation
Inhalation
Subcutan-
eous in-
jection
Rat
Sprague-
Oawley
Male
Mouse
AKR/J
Male
Inhalation
Inhalation
0. 50 or 250 mg/kg/ 250 mg/ Zymbal's Maltoni
day for 51 weeks; kg/day gland et al.
length of experiment (§J»)
144 weeks; 30-35/dose
group.
0 or 300 ppm 5 days/ — None Snyder
week, 4 hr/day for 70 et al.
weeks (length of exper- (55)
iifont); 40/dose group.
0 or 100 ppm 5 days/ — None Snyder
week, 5 hr/day for 72 et al.
weeks (length of exper- (55)
iment); 50/dose group.
0 or 13.2-39.6 ml 2 — None Ward
times/week for i et al.
weeks, or 52.8 ml 1 (56)
time/week for 9 weeks;
length of experiment
104 weeks; 20/dose
group.
0 or 300 ppm, 5 days/ — None Snyder
week, 6 hr/doy for et al.
99 weeks (length of (57)
experiment); 27 con-
trols. 45/dos* group.
0 or 300 ppm, 5 days/ — None Snyder
we*: , 6 hr/day for 28 et al.
weeks; length of exper- (57)
iment 52 weeks; 60/dose
group.
2-51
-------
Table 2-14 (continued)
SUMMARY OF BENZENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Loves t
Effective
Dose
Highly
Affected
Orqan(e)
Reference
Mouse Inhalation 0 or 300 ppm 5 days/ 300 ppm Lympha- Cronkite
C57BL/6 week, 6 hr/day for 16 tics et al.
Female weeks; length of ex- (58)
periment approximately
99 weeks; approximately
90/dcse group.
Rat Gavage 0 or 500 mg/kg 5
Sprogue- days week for 92
Dawley weeks; length of
Male experiment 1<>1
weeks; 50 controls,
tO dosed.
Rat Gavage 0 or 500 mg/kg 5 500 mg/ Zymbol's Maltoni
Sprogue- days week for 92 kg/day gland; et al.
Dawley weeks; length of Oral (54)
Female experiment 1*1 cavity
weeks; 50 controls,
40 dosed.
500 mg/
kg/day
Zymbal ' s
gland;
Oral
cavity;
Skin
Moltoni
et al.
(§4)
2-52
-------
Animal Model
Table 2-15
SUMMARY OF CARCINOGENIC DATA SETS FOR BEN2IDINEa
Rout* of Administration
Species Sex Oral Gavcae Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed*
Male
Female
Mixed
Male
Female
Mixed
0
0
0
1(0)
1(0)
0
1(0)
2(0)
2(0)
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(1)*
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 10 data sets of which 3 were considered suitable for risk
assessment.
bThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
cThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
2-53
-------
Table 2-16
SUMMARY OF BENZIDINE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Orqon(s) Reference
Mouse Subcuton- 0 c • S ing, 2 days/
Unspeci- ecu* in- we»k for 52 \*«ekft;
fied jection length of experiment
Male A 98 weeks; SO/dose
Female group.
Mixed
Rat Gavage 0, 1.2, 2.5, 3.5 or
Sprague- 5.0 mg every 3rd
Dowley day for 4 weeks;
Female length of experiment
36 weeks; 10-20/dose
group, 140 controls.
None
Bonser
et ol,
(59)
None
Griswold
et ol.
(60)
Rat
Sherman
Male •
Female
Mixed
Subcutan-
eous in-
jection
0 or 15 mg * day /week 15 mg
for 42 weeks; 50/con-
trols; length of ex-
periment 130 weeks;
385 /dose group.
Zymbol's
gland
Spitz
et ol.
(SI)
2-54
-------
Tcbl» 2-17
SUWARY OF CAPClNOiiENIC DATA SETS FOR 8EN2Q£A)PYR£.NEG
of Administration
Sp»ci»* Sex Oral
Mouftft
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Mel*
Fecxjle
Mixed0
Mole
Femole
Mixed
Mole
Female
Mixed
C
0
2(0)
0
e
0
KO)
0
0
Qovaq* Innslotson
0
2(2)
0
0
KD
0
n
0
0
0
0
0
0
c
0
0
0
0
Suocu-
Skin
tsn*»os,
0
0
0
0
0
0
0
0
0
°Th«r» w«r« a total of 51 data **t* of whicn id w«r« con*id«r«d *uitapl« for risk
as««csm«nt.
numb«r in par«nth«*it indicate* th« numb«r of data ««t« that wer* considered
suitable for risk as««*»ni«nt. and w«r« further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-55
-------
Table 2-18
SUMMARY OF BENZO(AJPYRENt CARCINOGENIC 8IQA3SAY DATA
Soecits
Mouse
Ha/ICR
Female
Hamster
Syrian
Golden
Combined
Rat
Fischer
Male
Rat
Wistar
Albino
Male
Rat
Sprague-
Dawley
Female
Rat
Sprague-
Oowley
Female
Route of
Adminis-
tration
Gavage
Intratra-
cheal in-
stillation
Intramus-
cular in-
jection
Intratra-
cheal in-
stil\ation
Subcutane-
ous injec-
tion
Gavage
Lowest
Nature of Effective
Exposure Dose
0 or 252 M9 3 times/ 252 j»9
week for 6 weeks.
Observed 41 weeks,
20 controls, 17
dosed.
0 or 1 mg/week for 10
weeks. Observed 60
weeks, 30 controls,
30 dosed.
0 or 10 mg injected 10 mg
one time into thighs
(1/2 of dose in each
thigh). Observed 104
weeks. 30 controls,
30 dosed.
0 or 0.4 mg instilled
once a week for 15
weeks. Observed 150
weeks. 23 controls.
21 dosed.
0, 3, 12.5, 25, 50, 3 Mg
100, 200 or 400 M9 in
sescme oil every 2
days for 30 doses (60
days). Observed 54
weeks, 20/dose group.
0 or 100 mg as c sin- 20 mg
gle dose, or 20 mg (x5)
every week for 5
weeks. 40 controls,
20/dose group. Length
of experiment 54 weeks.
Highly
Affected
Organ(s) Reference
Cardia
(fore-
stomach )
None
Thigh
(injec-
tion site)
None
Thigh
(injec-
tion site)
Mammary
gland
Wattenberg
et al .
(§2)
Kobayashi
and
Okamoto
(63)
Maenza
et al.
(64)
Ishinishi
et al.
(M>
Sydnor
et al.
(§5)
Sydnor
et ol.
(65)
2-56
-------
Table 2-18 (continued)
SUMMARY OF BENZO(A)PYRENE CARCINOGENIC BIOASSAY DATA
Species
Hamster
Syrian
Golden
Male
Hamster
Syrian
Golden
Moie
Hamster
Syrian
Golden
Female
Hamster
Syrian
Golden
Male It
Female
Hamster
Syrian
Golden
Male 4
Female
Route of
Adminis-
tration
Intratra-
cheal in-
jection
Intratra-
cheal in-
jection
Intratra-
cheal in-
jection
Intratra-
cheal in-
jection
Intratra-
cheal in-
jection
Lowest Highly
Nature of Effective Affected
Exposure Dose Organ(s)
0 or 0.5 mg in "Tween 0.5 mg Lung
60" once/week for
25 weeks, observed
until 214 days
(0.5), or 300 days
(control), 10/dose
group.
0, 0.5 or 1.0 mg once 0.5 mg Lung
a week for 52 weeks;
observed to 105
weeks; 70 animals
for 0.5, 105 ani-
mals for 1.0, 35 .
controls.
0, 0.5 or 1.0 mg once 0.5 mg Lung
a week for 52 weeks;
observed to 105
weeks; 70 animals
for 0.5, 105 ani-
mals for 1 .0, 35
controls.
0 or 3 mg in saline 3 mg Fore-
one e a week for 20 stomach
weeks, observed un-
til death,
-------
Table 2-18 (continued)
SuMHARY OF BENZO(A)PYRENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
E^oosure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Mouse Subcutan- 0 or 55 j*g once at 35 pg Lung Pietra
Swiss eous in- birth (single in- et ol.
Albino jection jection), observed (68)
Male t until natural deuth,
Female 32 dosed, 17 controls.
Mouse Intraperi- 0 or 35 pg once at 35 ng Lung; Pietra
Swiss toneal in- birth (single in- Lymphoma et al.
Albino jection jection), observed (68)
Male £ until natural death,
Female 2k dosed, 20 controls.
Mouse Gavage 0 or 50 pg in single 50 pg Fore- Roe
Swiss dose; observed for stomach at ol.
Albino 77 weeks (length of (69)
Female experiment). 50 per
group.
2-58
-------
Animp1 Modal
Table 2-19
SUMMAR* OF CARCINOGENIC DATA SETS FOR CADMIUM0
Route of Administration
Species Sex Oral Govaqe Inhalation
Subcu- Skin Inst.il-
t oneoii s Pa i n t i n g I n j ec t i on lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
0
1(0)
KD
KD
2(1)
0
0
0
KDb
0
0
1(1)
0
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
3(0)
0
0
8(0)
2(0)
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
1(1)
1(0)
2(0)
3(0)
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 30 data sets of which 8 were considered suitable for risk
assessment.
"The number in parenthesis indicates the numoer of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-59
-------
Table 2-20
SUMMARY OF CADMIUM CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Rat Inhalation 0, 0.003, 0.006 or O.OC3 Lung Takenaka
Wistar 0.012 ppm (air) con- ppm et al.
Mais tinously for 78 (70)
weeks; obc'wed an
additional 56 weeks.
40/dose group, 41
controls.
Rat Intratra- 0 or 25 M9 ot age 70 75 pg Mammary Sanders
Fischer cheal days (48 animals), 25 fibro- and
344 instilla- pg at age 70 and 100 adenoma Mahoffey
Male tion days for 50 pg total (71)
(46 animals); or 25
Mg ot age 70, 100 and
130 days for 75 pg
total (50 animals);
all observed until
natural death (130
weeks).
Mice Intra- 0, 0.3 or 0.61 mg/kg — None Stoner
A/Strong peritoneal 3 times/week fcr 8 at ol.
Mole & injection weeks for a total of (72)
Female 23 injections, 20/
dose group, observed
for 30 weeks.
Rat Oral-food 0, 1, 3, 10 or 50 3 ppm Adrenals Loser
SPF- ppm continuously for (75)
Wistar length of experiment.
Male Observed 104 weeks,
100 controls, 50/dose
group.
Rat Oral-food 0, 1, 3, 10 or 50 -- None Loser
SPF- ppm continuously for (73)
Wistar length of experiment.
Female Observed 104 wesks,
100 controls, 50/dose
group.
2-60
-------
Table 2-20 (continued)
SUMMARY OF CADMIUM CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Rot Oral-food 0 or 359 pg/kg/day for —
Long length of experiment
Evans (167 weeks). 34 ron-
Male ft trols, V7 dosed.
Female
Rat Govoge 0. 0.087. 0.18 or
CB 0.35 mg/kg cadmium
Male in distilled water
one time a week for
length of experi-
ment (104 week*).
90 controls.
30/dose group.
Mice Gavage 0, 0.44, 0.88 or
Swiss 1.75 mg/kg in dis-
Male tilled water once a
week for 77 weeks.
Length of experi-
ment 86 weeks. 150
controls, SO/dose
group.
None
None
Kanisawa
and
irhroeder
(35)
Levy and
Clack
(2fi>
None
Levy
•t ol.
2-61
-------
Table 2-21
SUMMARY OF CARCINOGENIC DATA SETS FOR CARBON TETRACHLORIDE0
Animal Model
Rout* of Administration
Species
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Sex
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
Oral
0
0
0
0
0
0
0
0
1(0}
Gavage
3(2)**
3(2)
0
2(1)
2(1)
0
1(0)
KO)
0
Inhalation
0
0
0
0
0
0
0
0
0
Subcu-
taneous
1(0)
1(0)
0
6(0)
0
0
0
0
0
Skin
Painting
0
0
0
0
0
0
0
0
0
Injection
0
0
0
0
0
0
0
0
0
Instil-
lation
0
0
0
0
0
0
0
0
0
TP
0
0
0
0
0
0
0
0
0
°There were a total of 21 data sett of which 6 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-62
-------
Table 2-22
SUMMARY OF CARBON TETRACHLORIOE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Mouse
C3H
male
Gavage
0 mg once/week for
20 weeks or 4 mg
once/week for 2
weeks, then 6 mg
once/week for 17
weeks; length of
experiment 40 weeks;
45 controls. 77
dosed.
6 mg/
week
Liver
Andervont
(25)
Mouse
C3H
Female
Gavage
Mouse
B6C3F-I
Male
Mouse
B6C3F-,
Female
Gavage
Gavage
0 mg once/week for 6 mg/ Liver Andervont
20 weeks or 4 mg wes.X (75)
once/week for 2
weeks, then 6 mg
once/week for 17
weeks; length of
experiment 43 weeks;
30 controls, 37
dosed.
0, 1250 or 2500 mg/ 12'JO Liver NCI (76)
kg once/day. 5 days/ mg/kg
ws«k for 78 weeks-,
length of experi-
ment 90 weeks; 20
controls, 5C/
dose group.
0, 1250 or 2500 mg/ 1250 Liver NCI (76)
kg once/day, 5 days/ mg/kg
week for 78 weeks;
length of experi-
ment 90 weeks; 20
controls, 50/
dose group.
2-63
-------
Table 2-22 (continued)
SUMMARY OF CARBON TETRACHLORIDE CARCINOGENIC BIOASSAY DATA
Route of
Adminis-
Species tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat Gavage
Osborne-
Mendel
Male
Rat Gavnge
Osborne-
Mend'il
Fe.nole
Dose* administered
once/day, 5 days/week
according to follow-
ing schedule: 0 mg/
kg for 78 weeks; 25
mg/kg for 10 weeks,
then 50 mg/kg for 68
weeks; 50 mg/kg for
10 weeks, then 100
mg/kg for- 68 weeks;
length of experi-
ment 111 weeks; 20
controls, SO/dose
group.
Doses administered
once/day, 5 days/week
according to follow-
ing schedule: 0 mg/
kg for 78 weeks; 100
mg/kg for 1
-------
Animal Modal
Table 2-23
SUMMARY OF CARCINOGENIC DATA SETS FOR CHl_ORAMBUCILa
Route of Administration
Species Sex Oral Gavage Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
KO}"
2(0)
1(1)
1(0)
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
c
0
°Th«re were a total of 6 data sets of which 1 was considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent cnalyses.
°The "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of te*& animal was unknown.
2-65
-------
Table 2-24
SUWIARY OF CHLORAM8JCIL CARCINOGENIC 8IOASSAY DATA
Spades
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Mouse
Mole ft
Female
Intraperi-
toneal in-
jection
0, 0.80, 3.09,
12.5 or 35 mg/kg
3 times/week for
weeks; observed
39 weeks total;
330 controls, 45
60/dose group.
0.80
mg/Kg
Lung
Shimkin
et al.
(ZZ>
2-66
-------
Animal Model
Table 2-25
SUMMAPV OF CARCINOGENIC DATA SETS FOR CHLORDAN£°
Rout* of Admfnistration
Species Sax Oral GOVOQ*
Mous*
Mous*
Mous*
Rat
Rat
Rat
Oth*r
Ot**'"
Oth*r
Mai*
Female
Mixed0
Mai*
Female
Mixed
Mole
Female
Mixed
3(3)"
3(3)
0
KD
1(1 )
0
0
0
0
0
0
0
0
0
0
0
0
0
Inhalation
0
0
0
3
0
0
0
0
0
Subcu-
taneous
0
0
0
0
0
0
0
0
0
Skin
Pointing
0
0
t'
0
0
0
0
0
0
Injection
0
0
0
0
0
0
0
0
0
Instil-
lation
C
0
0
0
0
0
0
0
0
TP
0
0
0
0
0
0
0
0
0
aTn*r* w*r* a total of 8 data sets, all of which were con*id*r*d *uitabl* for risk
assessment.
bTh* number in parenthesis indicate* th* number of data s*ts that were considered
suitobl* for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cTh* "mixed" sex indicates that either both sexes were tested, but results were >*at
reported separately, or sex of test animal was unknown.
2 6/
-------
Tabl9 2-26
SUMMARY OF CHLORDANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Oraan(s)
Reference
Mouse
Charles
River
CD-I
Male
Mouse
Charles
River
CD-I
Female
Mouse
B6C3F-,
Male
Oral-food
Oral-food
Oral-food
Mouse
B6C3F1
Female
Oral-food
0, 5. 25 or 50 ppm
continuously for
length of experi-
ment (77 weeks),
100 controls, 100/
dose group.
0, 5, 25 or 50 ppm
continuously for
length of experi-
ment (77 weeks),
100 controls, TOO/
dose group.
0 ppm continuously
for length of experi-
ment; 20 ppm for 1
week, then 30 ppm for
79 weeks; 40 ppm for 16
weeks, then 60 pom for
65 weeks; length of
experiment 91 weeks;
20 controls, 50/dose
group.
None
None
30 ppm Liver
IRDC,
in Epstein
(Z§>
IRDC,
in Epstein
(78)
NCI (79)
0 ppm continuously
for length of experi-
ment; <»0 ppm for 1
week, then 30 ppm for
79 weeks; 80 ppm for 16
weeks, then 60 ppm for
65 weeks; length of
experiment 91 weeks; 20
controls, 50/dose
group.
30 ppm Liver
NCI (79)
2-68
-------
Table 2-26 (continued)
SUMMARY OF CHLOROANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Rat
Osborne-
Mendel
Male
Oral-food
Rat
Osborne-
Mendel
Female
Oral-food
Mouse
ICR
Male
Mouse
ICR
Female
Oral-food
Oral-food
Dosage administered 800 /
as follows: 0 ppffl 200/
continuously; 400 ppm 100
for 33 weeks, then ppm
100 ppm for 1* weeks,
then 50 ppm for 35
weeks; 800 ppm for 33
weeks, then 200 ppm for
1* weeks, then 100 ppm
for 33 weeks; length of
experiment 109 weeks;
10 controls, 50/dose
group .
Dosage administered
as follows: 0 ppm
continuously; 200 ppm
for 33 weeks, then
100 ppm for 1*
weeks, then 50 ppm
for 33 weeks; 400
ppm for 33 weeks,
then 200 ppm for 14
weeks, then 100 opm
for 33 weeks; length
of experiment 109
weeks; 10 controls,
50/dose group.
Thyroid NCI (79)
None
NCI (79)
0, 1, 5 or 12.5 ppm
continuously for
length of experi-
ment (106 weeks),
80 /cose group.
0, 1, 5 or 12.5 ppm
continuously for
length of experi-
ment ( 105 weeks),
80/dose group.
1 ppm
Skin;
Liver
None
Velsicol
Chemical
Corp.
(80)
Velsicol
Chemical
Corp.
(§0)
2-69
-------
Animol Modal
Table 2-27
SUMMARY OF CARCINOGENIC DATA SETS FOR CHLOROFORM0
Route of Administrotion
Species Sax Orol Govoge Inhalation
Subeu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other .
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
KD
0
KD
0
0
1(1)
'(1 )
0
10(9)b
5(10
0
3(2)
2(1)
1(0)
0
0
0
1(0)
1(0)
0
0
0
0
0
0
0
1(0)
1(0)
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
aThere were a total of 31 data sets of which 20 were considered suitable for ris
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
oase and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-70
-------
Table 2-28
SUMMARY OF CHLOROFORM CARCINOGENIC BIOASSAY DATA
Route of
Adminis-
Species trot ion
Mouse Gavage
C8A
Male
Mouse Gavage
C57BL
Male
Mouse Gavage
CF-1
Male
Mouse Gavage
ICI
Male
Mouse Gavage
SPF
CFLP
Male
Mouse Gavage
ICI
Albino
Male
Mouse Gavage
ICI
Albino
Female
Lowest Highly
Nature of Effective Affected
Exposure Dose Orgon(s) Reference
0 or 60 mg/kg, 6 — None
days /week for 80
weeks; observed 104
weeks; 52 controls,
52 dosed.
0 or 60 mg/kg, 6 — None
days /week for 80
weeks ; observed 1 04
weeks; 52 controls.
52 dosed.
0 or 60 mg/kg, 6 — None
days /week for 80
weeks; observed 93
weeks; 52 controls,
52 dosed.
0 or 60 mg/kg, 6 — None
days/week for 80
weeks; observed 98
weeks; 52 controls,
52 dosed.
0 or 60 mg/kg, 6 — None
'days /week for 80
weeks; observed 96
weeks, 260 controls.
52 dosed.
0, 17 or 60 mg/kg — None
6 days /week for 80
weeks; observed 96
weeks; 104 controls.
52/dose group.
0, 17 or 60 mg/kg — None
6 days/week for 80
weeks; observed 96
weeks; 104 controls,
52/dose group.
Roe et
(§1)
Roe et
(§1)
Roe et
(§1)
Roe et
<§!>
Roe et
(81 )
Roe et
(§1)
Roe et
(§1)
al
al
al
al
al
al
al
2-71
-------
Table 2-28 (continued)
SUMMARY OF CHLOROFORM CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Oose
Highly
Affected
Orqan(s)
Reference
Mouse
ICI
Ma 16
Rot
SPF
Sprague-
Dawley
Male
Gavage
Gavage
0 or 60 mg/kg 6
days/week for 80
weeks; observed 98
weeks; 52 controls,
52/dose group.
0 or 60 mg/kg 6
days/weeks for length
of experiment (95
week.*); 50 controls,
50 dosed.
None
None
Roe et al
(§1)
Palmer
et ol.
(82)
Rat
SPF
Sprogue-
Ocwley
Female
Gavage
0 or 60 ng/kg 6
days/weexs for length
of experiment (95
weaka); SO controls,
50 dosed.
None
Palmer
et al.
(§2)
Dog
Beagle
Male
Dog
Beagle
Female
Orel- per os
Oral- per os
Rat
Osborne-
Mendel
Male
Gavage
0, 15 or SO mg/kg -- None Heywood
6 days/week for 390 et al.
weeks; observed 420 (85)
weeks; 16 controls,
8/dose group.
0, 15 or 30 mg/kg — None Heywood
6 days/week for 390 et al.
weeks; observed 420 (83)
weeks; 16 controls,
8/dose group.
0, 90 or 180 mg/kg/ 90 mg/ Kidney NCI (84)
day, 5 days/week for kg/day
79 weeks; observed 111
weeks; 20 controls,
50/dose group.
2-72
-------
Table 2-28 (continued)
SUMMARY OP CHLOROFORM CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(s) Reference
Rat
Osborne-
Mendel
Female
Gavage
Mouse
B6C3F-!
Male
Gavage
Mouse
B6C3F-I
Female
Gavage
Dosages administered
5 days/week according
to following schedule:
0 mg/kg for 78
weeks; 125 mg/kg for
22 weeks, then 90
mg/kg for 56 weeks;
250 mg/kg for 22
weeks, then 180 mg/
kg for 56 weeks;
observed 111 weeks;
20 controls, 50/dose
group.
Dosages administered • 100/150
5 days/week according mg/kg
to following schedule:
0 mg/kg for 78 weeks;
100 mg/kg for 18 weeks.
then 150 mg/kg for 60
weeks; 200 mg/kg for 18
weeks, then 300 mg/kg for
60 weeks; 20 con-
trols. 50/dose group.
Length of experiment
93 weeks.
None
NCI (8ft)
Liver
NCI (8ft)
Dosages administered
5 days/week according
to following schedule:
0 mg/kg for 78 weeks;
200 mg/kg for 18 weeks,
then 250 mg/kg for 80
weeks;
-------
Table 2-28 (continued)
SUMMARY OF CHLOROFORM CARCINOGENIC BIOASSAY DATA
Species
Mouse
Strain
Male
Route of
Adminis-
tration
Gavage
A
Lowest
Nature of Effective
Exposure Dose
0, 0.1 or 0.2 cc/kg in
corn oil every 4 days
for 30 doses, then
observed for one month;
5 animals/group.
Highly
Affected
Organ(s)
None
Reference
Eschen-
brenner
(85)
Mouse Gavage
Strain A
Female
Mouse Oral-water
Osborne-
Mendel
Female
Mouse Oral-water
Osborne-
Mendel
Male
0, 0.1, 0.2, 0.4 or
0.8 cc/kg in corn oil
every 4 days for 30
doses, then observed
for one month; 5 ani-
mals/group.
0, 200, 400, 900 or
1800 ppm continuously
for length of experi-
ment (104 weeks). 50
controls, 50-430/dos*
group.
0, 209. 400, 900 or
1800 ppm continuously
for length of experi-
ment (104 weeks). 50
controls, 50-330/dos*
group.
None
Eschen-
brenner
(85)
200 ppm Liver
Jorgenson
et al .
(86)
200 ppm Kidney
Jorgenson
et al .
(66)
2-74
-------
Animal Model
Table 2-29
SUMMARY OF CARCINOGENIC DATA SETS FOR CHROMIUM0
Route of Administration
Species Sex Oral Gavaqe Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixedc
Male
Female
Mixed
Male
Female
Mixed
1(0)
0
1(0}
0
0
2(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(1)
2(2)
1(0)
1(1)
0
0
0
0
0
1(0)
0
0
6(3)
0
0
0
0
0
0
0
0
0
0
0
0
aThere were a total of 16 data sets of which 8 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
°The "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-75
-------
Table 2-30
SUMMARY OF CHROMIUM CARCINOGENIC BIQASSAY DATA
Species
Rat
CB
Male
Route of
Adminis-
tration
Intramus-
cular in-
jection
Lowest
Nature of Effective
Exposure Dose
0 mg once a week 0.5 mg
for 20 weeks; or
5 mg once o week for
2 weeks, then 0.5 mg
once a week for 18
weeks. Length of
experiment 63 weeks,
16 controls, 24
dosed .
Highly
Affected
Orqan{s)
Right
flank
(injec-
tion
site)
Reference
Roe and
Carter
(§7)
Rat Intra- 0 or 2 mg sodium
Bethesda pleural dichromate once a
Black injection month for 16 months,
Male it observed to 24
Female months, 60 untreated
controls, 39 dosed.
Rat Intra- 0 or 2 mg of calcium
Bethesda tracheal chrornate, strontium
Black chromate, or zinc
Male & chromate0 once every 2
Female months for a total of 5
administrations;
length of experiment
104 weeks. 3 experi-
ments: 35 controls, 85
in calcium chromate
group, 60 in strontium
chromate group, 73 in
zinc chromate group.
Rat Oral-food 0 or 364 mg chromium
Long acetote/kg/day for
Evans length of experiment
Male & (170 weeks); 34 con-
Female trols, 56 dosed.
None
Hueper and
Payne
(§8)
None
Hueper and
Payne
(§8)
None
Kanisawa and
Schroeder
(35)
2-76
-------
Table 2-30 (continued)
SUMMARY OF CHROMIUM CARCINOGENIC 8IOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Mouse
Strong/A
Male *
Female
Rat
Fischer
344
Male
Intra-
peritoneal
injection
Intramus-
cular in-
jection
0, 20, 50 or 100
mg/kg 3 times a week
for 8 weeks (24 injec-
tions); observed 30
weeks, 20 controls,
20/dose group.
0, 0.5, 1.0, 2.0 or
4.0 mg in a single
injection, length of
experiment 104 weeks,
60 controls, 15/dose
group.
None
Stoner
et al.
(72)
None
Sunderman
et al.
(§9)
Abstracted as three data sets; one for each chromium compound tested.
2-77
-------
Animal Model
Table 2-31
SUMMARY OF CARCINOGENIC DATA SETS FOR CIGARETTE SMOKEa
Route of Administration
Species Sex Oral Gavoge Inhalation
Subcu- Skin Instil"
taneous Painting Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
1(0)"
KD
2(2)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
KO)
HO)
*(2)
1(1)
2(1)
KO)
2(0)
0
0
0
0
0
0
0
0
0
1(0)
16(0)
6(0)
0
0
1(0)
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
2(1)
0
0
2(1)
0
0
0
0
0
0
0
0
0
0
°There were a total of 41 data sets of which 9 were considered suitable for risk
assessment.
number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-78
-------
Table 2-32
SUMMARY OF CIGARETTE SMOKE CARCINOGENIC BIOASSAY DATA
Species
Rat
Wistar
SPF
Female
Route of
Adminis-
tration
Inhalation
Nature of
Exposure
1 cigarette (11
puffs 25 ml ea)
2 times/day, 5
times/week (234 mg/
Lowest
Effective
Dose
—
Highly
Affected
Orqan(s)
None
Reference
Davis
et a.l.
(90)
day, 5 days/week);
sham controls; 102
controls, 408 dosed.
Dosed for length of
experiment (160 weeks).
Rat Intra- 0 or 24 mg ciga- 24 mg Lung Stanton
Osborne- pleural rette smoke con- et al.
Mendel implant densate in pellet; (2)
CD/SPF length of experi-
Female ment 107 weeks;
108 controls,
105 dosed.
Rat Inhalation 0 or 416 mg/day, 7 — None Haag
White days/week for length et ol.
Male ft of experiment (148 (91.)
Female weeks); controls
sham-exposed for
first 400 days,
then unexposed;
16 animals/group.
Mouse Oral 0 or 25 mg 5 times/ 25 mg Lung DiPaolo
Swiss painting week for 56 wks; and
ICR/Ha length of experi- Moore
Male ft ment 78 weeks; 50 (92)
Female animals/group.
Rat Inhalation 0 or 598 mg/day, 5 598 mg Dermis Dalbey
F344 days/week for 126 (subcu- et al.
Female weeks; length of taneous (5)
experiment 152 sarcoma)
weeks; 30 controls
(sham) and 80 dosed.
2-79
-------
Toble 2-32 (continued)
SUiVMARY OF CIGARETTE SMOKE CARCINOGENIC BIOASSAY DATA
Species
Hamster
Syrian
BIO
Male
Route of
Adminis-
tration
Inhalation
Nature of
Exposure
0 or 12.43 mg/day,
5 days /week for
length of experi-
ment (100 weeks).
22 controls, 60
dosed.
Lowest
Effective
Dose
12.43
mg
Highly
Affected
Organ(s)
Larynx
Reference
Bernfeld
et al.
(4)
Mouse Oral-mouth 0 or 26.4 mg, 5 26.4
Swiss painting times/week for 64 mg
ICR/Ha weeks; observed 82
Female weeks; 100 controls,
100 dosed.
Mouse Oral-mouth 0 or 30 mg, 6 days/ 30 mg
Mixed painting . weeks for 20 weeks;
Strain length of experi-
Male A ment 52 weeks; 40
Female controls, 60 dosed.
Dog Inhalation Untreated (non- High
Beagle smoking) controls; dose,
Male 5 treatment groups unfil-
exposed to ciga- tered
rette smoke from 1 ciga-
filtered cigarette/ rettes
day increasing to 4/
day by week 8 (ap-
proximately 486 mg/
cigarette); these 3
groups then exposed to
variable number of
unfiltered ciga-
rettes/day (approxi-
mately 504 mg/cigar-
ette), ranging from
3 to 9/day, for
length of experiment.
125 weeks.
Lung
Bladder
Lung
DiPaolo
and
Levin
(6)
Holsti
and
Ermala
(£3)
Hammond
et al.
(3) and
Auerbach
et al.
(94)
2-80
-------
Animal Model
Table 2-33
SUMMARY OF CARCINOGENIC DATA SETS FOR 3,3-OICHLOROBENZIDENE°
Route of Administration
Species
Mouse
Mouse
Mouse
Rot
Rat
Rat
Other
Other
Other
Sex
Male
Female
Mixedb
Male
Female
Mixed
Male
Female
Mixed
Oral
0
0
0
3(3)c
1(1)
KO)
KO)
2(1)
0
Gavaqe
0
0
0
0
0
0
0
0
0
Inhalation
0
0
0
0
0
0
0
0
0
Subcu-
taneous
0
0
0
0
0
0
0
0
0
Skin
Pointinq
.0
0
0
0
0
0
0
0
0
Injection
0
0
0
0
0
0
0
0
0
Instil-
lation
0
0
0
0
0
0
0
0
0
TP
0
0
0
0
0
0
0
0
0
aThere were a total of 8 data sets of which 5 were considered suitable for risk
assessment.
bThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
°The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
2-81
-------
Table 2-34
SUMMARY OF 3,3-DICHLOROBENZIDENE CARCINOGENIC BIOASSAY DATA
Species
Dog
Beagle
Female
Route of
Adminis-
tration
Orol-per os
Nature of
Exposure
0 (untreated con-
trols) or 100 mg 3
times/week for 6
Lowest
Effective
Oose
100 mg
Highly
Affected
Organ(sJ
Livfl.
Reference
«':«.
weeks, then 100 mg
5 times/week until
end (7 years for
treated dogs); 6/
dose group; length
of experiment 9
years .
Rot Oral-food
Sprogue-
Dowley
Charles
River CO
Male
Rot Oral -food
Sprogue-
Dawley
Charles
River CO
Female
Rot Oral-food
Wistar
Male
Rat Oral-food
Wistar
Male
0 or 1000 ppm con- 1000 ppm
tinuously for length
of experiment (104
weeks}; 44 controls.
44 dosed.
0 or 1000 ppm con- 1000 ppm
tinuously for length
of experiment (105
weeks); 44 controls,
44 dosed.
0 or 0.03* continu-
ously for length of
experiment (40 weeks);
18/dose group.
0 or 0.03* continu-
ously from weeks 12-
16; length of exper-
iment 40 weeks; 12
controls, 22 dosed.
Hemopoie-
tic sys-
tem j«
Mammary *
Zymbal
Glands
Mammary
gland
None
None
Stula
et al.
(S§)
Stula
et al.
(96)
Tsuda
et ol.
(12)
Tatematsu
ec ol.
(98)
2-82
-------
AnimpI Model
Table 2-35
SUMMARY OF CARCINOGENIC DATA SETS FOR 1,2-OICHLORO£THANEa
Route of Administration
Species Sex Oral Savage Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
0
0
0
0
0
0
0
0
0
2(1)b
2(1)
0
2(1)
2(1)
0
0
0
0
KD
1(1)
0
1(1)
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of
assessment.
data sets of which 8 were considered suitable for risk
''The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-83
-------
Table 2-36
SUMMARY OF 1,2-DICHLOROETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Oose
Highly
Affected
Orqan(s)
Reference
Rat Govoge Dosages odminis-
Osborne- tered 5 days/week
Mendel for number of weeks
Male indicated: Group
1: 0 mg/kg for 78
weeks; Group 2: 50
mg/kg for 59 weeks.
75 mg/kg for 10
weeks; Group 3: 100
mg/kg for 59 weeks,
150 mg/kg for 10
weeks; length of
experiment 110
weeks, 20 controls,
50/dose group.
50/75
Stomach NCI (99)
Rot Gavage Dosages odminis-
Osborne- tered 5 days/week
Mendel for number of weeks
Female indicated: Group
1: 0 mg/kg for 78
weeks; Group 2: 50
mg/kg for 59 weeks,
75 mg/kg for 10
weeks; Group 3: 100
mg/kg for 59 weeks,
150 mg/kg for 10
weeks; length of
experiment 110
weeks, 20 controls,
50"/dose group.
50/75
mg/kg
Mammary
gland
NCI (99)
2-84
-------
Table 2-36 (continued)
SUMMARY OF 1,2-DICHLOROETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqon(s)
Reference
Mouse G^vage Dosages adminis- 75/100 lung NCI (99)
B6C3F-, tered 5 days/week mg/kg
Mole according to follow-
ing schedule: Group
1: 0 mg/kg for 78
weeks; Group 2: 75
mg/kg for 8 weeks,
100 mg/kg for 70
weeks; Group 3, 150
mg/kg for 8 weeks.
200 mg/kg for 70
weeks; length of
experiment 90 weeks,
20 controls,
SO/dose group.
Mouse Gavage Dosages adminis- 125/200 Lung; NCI (99)
B6C3F-] tered 5 days/week mg/kg Mammary
Female according to follow- (low gland
ing schedule: Group dose)
1: 0 mg/kg for 78
weeks; Group 2: 125
mg/kg for 8 weeks,
200 mg/kg for 3
weeks, 150 mg for
67 weeks; Group 3,
250 mg/kg for 8
weeks, 400 mg/kg
for 3 weeks, 300
mg/kg for 67 weeks;
length of experi-
ment 90 weeks, 20
controls, 50/dose
group.
2-85
-------
Table 2-36 (continued)
SUMMARY OF 1,2-OICHLOROETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Mouse
Swiss
Male
Inhalation
Mouse
Swiss
Female
Inhalation
Rot
Sprogue-
Dawley
Male
Inhalation
0, 5, 10 or 50 ppm
5 days/week, 7 hrs/
day for 78 weeks or
250 ppm 5 days/
week, 7 hrs/day for
3 weeks, then re-
duced to 150 ppm
for 76 weeks;
length of experi-
ment 119 weeks, 115
controls, 90/dose
group.
0, 5, 10 or 50 ppm
5 days/week, 7 hrs/
day for 78 weeks or
250 ppm 5 days/
week, 7 hrs/day for
3 weeks, then re-
duced to 150 ppm
for 76 weeks;
length of experi-
ment 119 weeks, 134
controls, 90/dose
group.
0, 5, 10 or 50 ppm
5 days/week, 7 hrs/
day for 78 weeks or
250 ppm 5 days/
week, 7 hrs/day for
3 weeks, then re-
duced to 150 ppm
for 76 weeks;
length of experi-
ment T*S weeks, 90
controls, 90/dose
group.
None
Maltoni
et ol.
(100)
Non<
Maltoni
et ol.
(100)
None
Maltoni
at ol.
(100)
2-86
-------
Table 2-36 (continued)
SUMMARY OF 1,2-DICHLOROETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqon(s) Reference
Rat
Sprague-
Dawley
Female
Inhalation
0, 5, 10 or SO ppfn
5 days/week, 7 hrs/
day for 78 weeks, or
250 ppm 5 days/week,
7 hrs/day for 3
weeks, then re-
duced to 150 ppm
for 76 weeks;
length of experi-
ment 148 weeks,
90 controls, 90/
dose group.
5 ppm
Mammary
gland
Maltoni
•t al.
(100)
2-87
-------
Animol Model
Table 2-37
SUMMARY OF CARCINOGENIC DATA SETS FOR DICHLOROMETHANE0
Route of Administration
Species Sex Oral Savage Inhalation
Subcu- Skin Instil-
toneeus Painting Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
1
-------
Table 2-38
SUMMARY OF DICHLOROMETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Rat Inhalation 0, 100, 2000 or 4000
F344/N ppm 5 days/week, 6
Male hr«/day for 102
weeks; length of
experiment 104
weeks; 50 controls,
50/dose group.
Rat Inhalation 0, 100, 2000 or 4000
F344/N ppm 5 days/week, 6
Female hrs/day for 102 weeks;
length of experiment
104 weeks; 50 con-
trols, 50/dose
group.
Mouse Inhalation 0, 2000 or 4000 ppm
B6C3F-J 5 days/week, 6 hrs/
Male day for 102 weeks;
length of experiment
104 weeks; 50 con-
trols, 50/dose
group.
Mouse Inhalation 0, 2000 or 4000 ppm
B6C3F-J 5 days/week, 6 hrs/
Female day for 102 weeks;
length of experiment
104 weeks; 50 con-
trols, 50/dose
group.
Rat Inhalation 0, 500, 1.500 or 3,500
Sprague- ppm 5 days/week, 6
Dawley hrs/day for length
Male of experiment (104
weeks); 129 con-
trols, 129/dose
group.
None
NTP (101)
1000 ppm Mammary
gland
NTP (101)
2000 ppm
Liver;
Lung
NTP (101)
2000 ppm
Liver;
Lung
NTP (101)
1500 ppm
Salivary
gland
region
Burek
•t al.
(102)
2-89
-------
Table 2-38 (continued)
SUMMARY OF DICHLOROMETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration^
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat Inhalation
Sprague-
Daw ley
Female
Mice
B6C3F-,
Male
Oral-water
Mice
B6C3F-I
Female
Oral-water
Rat
Sprague-
Dawley
Male
Inhalation
0, 500, 1,500 or 5,500
ppm 5 days/week, 6
hrs/day for length
of experiment (104
weeks); 129 con-
trols. 129/dose
group.
0, 60.6, 124, 177 or
234 mg/kg/day for
length of experi-
ment (104 weeks);
125 controls, 100-
200/dose group.
0, 59.5, 118, 172 or
238 mg/kg/day for
length of experi-
ment (104 weeks);
100 controls, 50-
100/dose group.
0, 50, 200 or 500
ppm 6 hrs/day. 5
days /week for
length of experi-
ment (87 weeks); 70
controls, 70 dose
group.
None
Burek
et ol.
(102)
None
NCA (103)
None
NCA (103)
None
Nitschke
et ol.
(104)
2-90
-------
Table 2-38 (continued)
SUMMARY OF DICHIOROMETHANE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Qrp,an(s)
Reference
Rat Inhalation Exposures were for 50 ppm Mammary Nitschke
Sprogue- 6 hrs/doy, 5 days/ gland et al.
Oawley week for time in- (10ft)
Female dicated: 0 ppm - 104
weeks, or SO ppm -104
weeks, or 200 pom - 104
weeks, or 500 ppm - 104
weeks, or 500 ppm - 52
weeks, then 0 ppm for 52
weeks; or 0 - 52 weeks,
then 500 ppm for 52
weeks; observed 104
weeks; 70 controls. 25-
70/dose group.
Rat Oral-water 0, 5.65. 52.3. 125, — None NCA (105)
Fischer or 235 mg/kg/day for
344 104 weeks or 232 mg/
Male kg/day for 78 weeks;
observed 104 weeks;
135 controls, 25-B5/
dose group.
Rat Oral-water 0, 6.47, 58.3, 136, — None NCA (105)
Fischer . or 263 mg/kg/day for
344 104 weeks or 269 mg/
Female kg/day for 78 weeks;
observed 104 weeks;
135 controls, 25-B5/
dose group.
2-91
-------
Table 2-33
SUMMARY OF CARCINOGENIC DATA SETS FOR DIETHYLSTILBESTROL0
Animal Model
Species Sex Oral Gavaqe
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
5(Ob
6(1)
1(0)
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Route of Administration
Inhalation
0
0
0
0
0
0
0
0
0
Subcu-
Skin
taneous Painting
0
1(0)
0
2(0)
0
0
5(0)
0
2(0)
0
0
0
0
0
0
0
0
0
Injection
0
1(0)
0
0
0
0
1(0)
2(0)
0
Instil
lotion
8(0)
0
0
7(0)
9(2)
1(0)
6(3)
2(0)
0
-
TP
1(0)
11(8)
KD
0
2(0)
1(0)
0
3(0)
1(0)
aThere were a total of 81 data sets of which 16 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-92
-------
Table 2-40
SUMMARY OF OIETHYLSTILBESTROL (DES) CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
0.006 ppm Mammary
gland
Mouse Oral-food 0, 0.006, 0.013, 0.013 ppm
C3H 0.025, 0.05, 0.1,
Male 0.5 and 1.0 ppm con-
tinuously for length
of experiment (85
weeks}; 115 controls,
58-71/dose group.
Mouse Oral-food 0, 0.006, 0.013,
C3H 0.025. 0.05, 0.1,
Female 0.5 and 1.0 ppm con-
tinuously for length of
experiment (85 weeks);
121 controls, S6-68/
dose group.
Rat Pellet 20 mg pellet im-
ACI implant planted at start
Female in intrascrapular
region. (Dosed animals
received 2.9 ng DES/
day.) Observed 31
weeks; 10 controls, 10
dosed.
Mammary
gland
Gas* et al
(106)
Gass et
(106)
al
2.9 M9/
day
Mammary
gland
Stone
•t al
(107)
Rat
Sprague-
Dawley
Female
Hamster
Syrian
Golden
Male
Pellet
implant
Pellet
implant
20 mg pellet im-
planted at start
in intrascrapular
region. (Dosed animals
received 2,*» M9 DES/
day.) Observed 31
weeks; 10 controls, 6
dosed.
None
25 mg pellet im-
planted every 5
months. (Controls
received only the
implanting operation
with no pellet.) Ob-
served 108 weeks; 15
controls, 50 dosed.
25 mg
every
5 months
Adeno-
hypo-
physis
Stone
et al.
(107)
Reznik-
Schuller
(108)
2-93
-------
Table 2-40 (continued)
SUMMARY OF DIETHYLSTILBESTROL (DES) CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exoosure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Hamster
European
Kale
Pellet
implant
Hamster
Syrian
Male
Mouse
CD-I
Female
Pellet
implant
Trans-
placental
25 mg pellet im- 25 mg
planted every 5 every
months. (Controls 5 months
received only the
implanting operation
with no pellet.) Ob-
served 108 weeks; 15
controls, 50 dosed.
0 or 36 mg implanted 36 mg
at start and at 3
months; observed
25 weeks; 10 con-
trols, 15 dosed.
Adeno-
hypo-
physis
Kidney
None
The following doses
were administered by
subcutaneous injec-
tion to pregnant mice
on days 9-16 of
gestation: 0, 0.01, 1,
10, 100 MQ/kg/day.
Dose received by fetus
estimated by:
[Maternal dose x avg. maternal weight (50
Reznik-
Schuller
(108)
Liehr and
Wheeler,
(109)
McLocMlan
•t al.
(110)
avg. litter size
Estimated fetal
doses: 0, 0.036
ng/day, 3.75 ng/
day, 37.5 ng/day,
375 ng/day. Ob-
served 54 weeks;
11 controls, 4-
15/dose group.
(8)
2-94
-------
Table 2-40 (continued)
SUMMARY OF DIETHYLSTILBESTROL (DES) CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(s) Reference
Mouse
CD-1
Female
Mouse
CD-1
Female
MOUSD
CD-1
Female
Trons-
placental
Trans-
placental
Trans-
placental
Maternal, subcutan-
eous injection on
days 9-16 of gesta-
tion. Maternal
dose: 0, 0.01, 1,
2.5, 5, 10 or 100
>g/kg/day. Esti-
mated fetal doses:
0, 0.038, 3.75,
9.38, 18.8. 37.5 or
375 ng/day. Ob-
served 58 weeks, 31
controls, 3-12/
dose group.
Maternal, subcutan-
eous injection on
days 9-16 of gesta-
tion. Maternal
dose: 0, 1 or 100
MQ/kg/day. Esti-
mated fetal doses:
0, 3.75 or 375
ng/day. Observed
63 weeks, 4 con-
trols, 1/dose
group.
Maternal, subcutan-
eous injection on
days 9-16 of gesta-
tion. Maternal dose:
0, 0.01 or 5 M9/
kg/day. Estimated
fetal doses: 0,
0.038 or 18.8 ng/day.
Observed 67 weeks,
4 controls, 1-2/
dose group.
None
McLachlan
et ol.
None
McLachlan
et al.
(110)
None
McLachlan
et al .
(110)
2-95
-------
Table 2-40 (continued)
SUMMARY OF DIETHYLSTILBESTROL (DES) CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
.Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Mouse
CD-1
Female
Mouse
CD-1
Female
Mouse
CD-I
Female
Trans-
placental
Trons-
placental
Trons-
placental
Maternal, subcutan-
eous injection on
days 9-16 of gesta-
tion . Maternal
dose: 0, 1, 2.5, 5
or 10 fig/kg/day.
Estimated fetal
doses: 0, 3.75,
9.38 18.8 or 37.5
ng/day. Observed
71 weeks, 4 con-
trols, 1-2/dose
group.
Maternal, subcutan-
eous injection on
days 9-16 of gesta-
tion. Maternal
dose: 0, 0.01, 2.5,
5, 10 or 100 pg/
kg/day. Estimated
fetal doses: 0,
0.038, 9.38. 18.8,
37.5 or 375 ng/
day. Observed 76
weeks, 7 controls,
1-7/dose group.
Maternal, subcutan-
eous injection on
days 9-16 of gesta-
tion. Maternal
dose: 0, 1, 2.5, 5
or 10 M9/kg/day.
Estimated fetal
doses: 0, 3.75,
9.38, 18.8 or 37.5,
ng/day. Observed
80 weeks, 24 con-
trols, 4-12/dose
group.
None
McLachlan
et al.
(110)
None
McLachlan
0t al.
(110)
None
McLochlan
et al.
(110)
2-96
-------
Table 2-
-------
Animal Model
Table 2-
-------
Table 2-42
Sr?«1ARY OF DIPHENYLHYQRAZINE CARCINOGENIC BIOASSAY DATA
Route of Lowest Highly
Adminis- Nature of Effective Affected
^^ trot ion Exposure Dose Orgon(s) Reference
Rat Subcutan- 0 or 60 mg injec- -- None Spitz
Sherman eous in- ted once weekly et al.
Male £ jection until spontan- (61)
Female eous death; length
of experiment 130
weeks, 50 controls,
52 dosed.
2-99
-------
Animp1 Model
Table 2-43
SUMMARY OF CARCINOGENIC DATA SETS FOR EPICHLOROHYDRINa
Route of Administration
Species Sex Oral Govoge Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixedc
Male
Female
Mixed
Male
Female
Mixed
0
0
0
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2(2)
0
0
0
0
0
0
2(0)"
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
aThere were a total of 7 data sets of which 3 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-100
-------
Table 2-44
SUMMARY OF EPICHLOROHYDRIN CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(s) Reference
Rat Inhalation 0 or 100 ppm 6 hrs/
Sprague- day for 30 days,
Dawley examined until
Male week 144, 100 con-
trols, 140/dosed.
Rat Oral-water 0, 375, 750 or 1500
Wistar ppm administered con-
Male tinuously with
periodic cessation
of dosing according
to the following
schedule: 0 ppm -
uninterrupted; 375
ppm - 77 weeks dos-
ing, 4 weeks inter-
ruptions; 750 ppm -
79 weeks dosing, 2
weeks interrup-
tions; 1500 ppm -
76 weeks dosing, 5
weeks interrup-
tions; observed 81
weeks, 18 controls,
18/dose group.
Rat Inhalation 0, 10 or 30 ppm, 6
Sprague- hr/day, 5 days/week
Dawley for life (144 weeks).
Male 100 animals/group.
100 ppm
Nasal
cavity
750 ppm
Fore-
stomach
(cardia)
Laskin
et ol.
(112)
Konishi
et ol.
(113)
None
Laskin
at al.
(112)
2-101
-------
Table 2-45
SUMMARY OF CARCINOGENIC DATA SETS FOR ESTROGEN0
Animal Model
Route of Administration
Soecies Sex Oral Gavaqe Inhalation
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
0
3(0)
0
1(0)
2(1)
0
0
1(0)
KO)
0
0
0
0
0
0
0
2(0)
0
0
0
0
0
0
0
0
0
0
Subcu-
Skin
taneous Painting
0
3(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Injection
1(0)b
1(0)
0
0
0
0
0
0
2(0)
Instil-
lation
3(0)
1(0)
0
1(0)
3(0)
KO)
6(1)
2(0)
0
TP
0
0
0
0
0
0
0
0
0
°There were a total of 34 data sets of which 2 were considered suitable for risk
assessment.
*>The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-102
-------
Table 2-46
SUMMARY OF ESTROGEN CARCINOGENIC BIOASSAY DATA
Species
Hamster
Syrian
Male
Route of
Adminis-
tration
Pellet
implant
Nature of
Exposure
0 or 27 . 9 mg im-
planted at start,
then 0 or 40.5 mg
implanted at week
13; observed 28
weeks; 10 con-
trols, 25 dosed.
Lowest
Effective
Dose
27. 9/
40.5 mg
Highly
Affected
Organ(s)
Kidney
Reference
Liehr and
Wheeler
(109)
Rot Oral-food
McCollum
Female
0 M9/kg in diet,
60 controls; 30
dosed - 30 pg/kg/
day for 26 weeks,
then 60 M9/kg/day
for 79 weeks,
sacrificed.
None
McKinney
et al.
2-103
-------
Table 2-V7
SUMMARY OF CARCINOGENIC DATA SETS FOR ETHYLENE DIBROMIDEa
Animal Model
Route of Administration
Species Sex Oral Gavoqe Inhalation
Subcu- Skin
toneous Pointing
Instil-
Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
0
1(0)
0
0
1(0)
0
0
0
2(1)b
2(1)
1(0)
2(1)
2(1)
KO)
0
0
0
KD
KD
0
2(2)
2(2)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of .19 data sets of which 10 were considered suitable for risk
assessment.
''The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes wero tested, but results were not
reported separately, or sex of test animal was unknown.
-------
Toble 2-48
SUMMARY OF ETHYLENE DIBROMIDE CARCINOGENIC BIOASSAY DATA
Soacies
Rat
Sprague-
Dawley
Male
Rat
Sprague-
D awl ay
Female
Rat
F344
Male
Route of
Admin is- Nature of
tration Exposure
Inhalation 0 or 20 ppm 5 days/
week, 7 hr/day for
length of experi-
ment (77 weeks);
48 controls, 48
dosed .
Inhalation 0 or 20 ppm 5 days/
week, 7 hr/day for
length of experi-
ment (77 weeks); 48
controls, 48 dosed.
Inhalation 0, 10 or 40 ppm 5
days/week, 6 hr/
day for length of
Lowest Highly
Effective Affected
Dose Orqan(s)
20 ppm Supra-
renal
gland;
Subcu-
taneous
connec-
tive
tissue
20 ppm Mammary
gland
10 ppm Nasal
cavity;
Testes
Reference
Wong et al .
(115)
Wong at ol .
(115)
NCI and NTP
(116)
Rat
F344
Female
Inhalation
Mouse
B6C3F-I
Male
Inhalation
experiment; ob-
served 106 weeks
(high-dose group
observed 89 weeks);
50 controls, SO/
dose group.
0, 10 or 40 ppm 5
days/week, 6 hr/
day for longth of
experiment; ob-
served 106 weeks
(high-dose group
observed 92 weeks);
50 controls, SO/
dose group.
0, 10 or 40 ppm 5
days/week, 6 hr/
day for length of
experiment; ob-
served 79 weeks; 50
controls, 50/dose
group.
10 ppm
Nasal
cavity;
Mammary
gland
10 ppm Lung
NCI and NTP
(116)
NCI and NTP
2-105
-------
Table 2-48 (continued)
SUMMARY OF ETHYLENE DIBROMIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
10 ppin Lung
Mouse Inhalation 0, 10 or 40 ppm 5
B6C3F-J days/week, 6 hr/
Female day for length of
experiment; ob-
served 106 weeks
(high-dose group
observed 91 weeks);
50 controls, SO/
dose group.
Rat Gavage 20 vehicle controls 40 mg/kg
Osborne- treated for 49 weeks, (low
Mendel 5 days/week, then dose)
Male untreated for 14 weeks;
sacrificed at 63 weeks.
Dose groups treated 5
days/week on variable
regimens for length of
experiment, with ini-
tial dosages 40 and 80
mg/kg; sacrificed at 49
weeks (50 animals/
group).
Rat Gavage Controls treated 5 40 mg/kg
Osborne- days/week for 61 (low
Mendel weeks, then untreated dose)
Female for 2 weeks; sacri-
ficed at 63 weeks
(20 animals). Dose
groups treated 5 days/
week on variable regi-
mens for length of
experiment with initial
dosages of 40 and 80
mg/kg; sacrificed at 61
weeks (50 animals/
group).
NCI and NTP
(116)
Fore-
stomach ;
Circula-
tory
system
NCI (117)
Fore-
stomach ;
Circula-
tory
system
NCI (117)
2-106
-------
Table 2-48 (continued)
SUMMARY OF ETHYLENE OIBROMIDE CARCINOGENIC BIOASSAY DATA
Species
Mouse
B6C3Fi
Male
Route of
Adminis-
tration
Gavage
Nature of
Exposure
Controls treated 5
days/week for 53
weeks, then untreated
Lowest
Effective
Dose
60 mg/kg
(low
dose)
Highly
Affected
Organ(s)
Lung;
Stomach
Reference
NCI (117)
for 6 weeks; sacrificed
at 59 wks (20 animals).
Dose groups treated 5
days/week on variable
regimens for length of
experiment with initial
dosages of 60 and 120
mg/kg; sacrificed at
77-78 weeks (50
animals/ group).
Mouse Gavage Controls treated 5 60 mg/kg
B6C3F-J days/week for 53 (low
Female weeks, then untreated dose)
for 7 weeks; sacri-
ficed at 60 weeks (20
animals). Dose groups
treated 5 days/week on
variable regimens for
length of experiment
with initial dosages of
60 and 120 mg/kg;
sacrificed at 90 weeks
(low dose) or 78 weeks
(high dose).
Lung;
Stomach
NCI (117)
2-107
-------
Animal Model
Table 2-49
SUMMARY OF CARCINOGENIC DATA SETS FOR ETHYLENE OXIDEa
Route of Administration
Species Sex Oral Gavoge Inhalation
Subcu- Skin Instil-
taneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
6(5)
5(4)
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
1(0)°
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 15 data sets of which 10 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
eThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-108
-------
Table 2-50
SUMMARY OF ETHYLENE OXIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration^
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orqon(s) Reference
Rat
Fischer
Albino
Male
Inhalation
Rat
Fischer
344
Male
Inhalation
Rat
Fischer
344
Female
Inhalation
Rat
Fischer
344
Male
Inhalation
Rat
Fischer
344
Female
Inhalation
0, 50 or 100 ppm
5 days/week, 7
hrs/day for length
of experiment; ob-
served 105 weeks;
40 controls, 80/
dose group.
0, 10, 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 104 weeks;
240 controls, 120/
dose group.
0, 10, 33 or 100
ppm 5 days/week. 6
hrs/doy for length
of experiment; ob-
served 104 weeks;
240 controls, 120/
dose group.
0, 10, 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 78 weeks;
240 controls (40
examined), 120/
dose group (20
examined/group).
0, 10, 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 78 weeks;
240 controls (40
examined), 120/
dose group (20
examined/group).
50 ppm
Peri-
toneum
Lynch
et al.
(118)
10 ppm
Peri-
toneum
Snellings
et al.
(119)
10 ppm
Spleen Snellings
(leukemia) et al.
(119)
None
Snellings
et al.
(119)
None
Snellings
et al.
(119)
2-109
-------
Table 2-50 (continued)
SUWIARY OF ETHYLENE OXIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat
Fischer
344
Male
Inhalation
Rat
Fischer
344
Female
Inhalation
Rat
Fischer
344
Male
Inhalation
Rat
Fischer
344
Female
Inhalation
0, 10, 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 52 weeks;
240 controls (20
examined), 120/
dose group (10
examined/group).
0, 10, 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 52 weeks;
240 controls (20
examined), 120/
dose group (10
examined/group).
0, 10. 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 26 weeks;
240 controls (20
examined), 120/
dose group (10
examined/group).
0, 10. 33 or 100
ppm 5 days/week, 6
hrs/day for length
of experiment; ob-
served 26 weeks;
240 controls (20
examined), 120/
dose group (10
examined/group).
None
Snellings
•t al.
(119)
None
Snellings
et al.
(119)
None
Snellings
et al.
(119)
None
Snellings
et al.
(119)
2-110
-------
Table 2-50 (continued)
SUMMARY OF ETHYLENE OXIDE CARCINOGENIC BIOASSAY DATA
Route of Lowest Highly
Adminis- Nature of Effective Affected
Species trotion Exposure Dose Orqon(s) Reference
Rat Gavage 0, 7.5 or 30 mg/kg 7.5 Fore- Dunkelberg
Sprague- body weight, 2 times mg/kg stomach (120)
Dawley per week for length
Female of experiment (150
weeks); 50/dose
group.
2-111
-------
Animp1 Model
Table 2-51
SUMMARY OF CARCINOGENIC DATA SETS FOR FORMALDEHYDE0
Route of Administration
Species Sex Orol Gavoge Inhalation
Subcu- Skin Instil-
tgnegus Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2(1 >b
2(1)
2(2)
5(3)
2(1)
1(1)
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
c
0
0
0
0
0
0
0
°The-e were a total of 15 data sets of which 10 were considered suitable for risk
assessment.
DThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
°The "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-112
-------
Table 2-52
SUMMARY OF FORMALDEHYDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose QrapnCs)
Reference
Rat
Fischer
344
Male i
Female
Hamster
Syrian
Golden
Male
Inhalation
Mouse
C3H
Male t
Female
Mouse
C3H
Mole «
Female
Inhalation
Inhalation
Inhalation
0, 2, 6 or 15 ppm
6 hrs/day, 5 days/
week for length of
experiment (78
weeks); 42 to 84/
dose group.
0 or 10 ppm 5 days/
week, 5 hrs/day or
30 ppm 1 day/week,
5 hrs/day for
length of experi-
ment (118 weeks};
132 controls, 88
and 50/dose group,
respectively.
0 or 50 mg/m3
3 days/week, 1 hr/
day for 35 weeks,
then 0 or 150 mg/m3
3 days/week, 1 hr/
day for 35 weeks;
length of experi-
ment 70 weeks; 30
controls. 60 dosed.
0 or 100 mg/m3
3 days/week, 1 hr/
day for length
of experiment, or
200 mg/m3 3 days/
week, 1 hr/day for
4 weeks; length of
experiment 35
weeks; 59 controls,
60 in 100 mg/m3. 42
in 200 mg/m3.
15 ppm
Nasal
cavity
None
Swenberg
et al.
(121)
Dalbey (122)
None
Horton
ee al.
(123)
None
Horton
• C al .
(125)
2-113
-------
Table 2-52 (continued)
SUMMARY OF FORMALDEHYDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat Inhalation 0 or 14.8 ppm, 5 14.8 ppm Nasal Sellakumar
Sprague- days/week, 6 hrs/ cavity at ol.
Dawley day for length (12k)
Male- of experiment
(130 weeks); 100
controls. 100
dosed.
Mouse Inhalation 0, 2. 6 or 15 ppm — None CUT (124)
B6C3F-I 5 days/week, 6 hrs/
Male day for length of
experiment (104
weeks); 100/dose
group (interim
sacrifices ex-
cluded) .
Mouse Inhalation 0. 2, 6 or 15 ppm — None CUT (124)
B6C3F-) 5 days/week, 6 hrs/
Female day for length of
experiment (104 weeks);
60-62 animals/dose
group (interim
sacrifices excluded).
Rat Inhalation 0. 2, 6 or 15 ppm 15 ppm Nose CUT (124)
Fischer 5 days/week. 6 hrs/
344 day for length
Male of experiment
(104 weeks); 60-70/
dose group (in-
terim sacrifices
excluded).
2-114
-------
Table 2-52 (continued)
SUMMARY OF FORMALDEHYDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat
Fischer
344
Male
Inhalation
Rat
Fischer
344
Male
Inhalation
0, 2, 6 or 15 ppm
5 days/week, 6 hrs/
day for length
of experiment
(104 weeks); 60/
dose group for 0,
2, or 6 ppm, 80/
dose group for 15
ppm (interim sacri-
fices excluded).
0, 0.3, 2 or 15 ppm
6 hrs/day, 5 days/
week for length
of experiment
(121 weeks); 17/
group for 0, 0.3,
2 ppm; 20/group
for 15 ppm; (in-
terim sacrifices
excluded).
15 ppm Nose
CUT (124)
15 ppm Nasal Tobe et ol
(squamous (126)
cell car-
cinoma)
2-115
-------
Animal Model
Species Sex
Table 2-53
SUMMARY OF CARCINOGENIC DATA SETS FOR HEXACHLOROBENZENE8
Route of Administration
Oral Gavoqe Inholgtion,
Subcu- Skin Instil-
tgneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
KDb
KD
0
0
2(2)
0
KD
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
aThere were a total of 7 data sets of which 6 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
°The "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-116
-------
Table 2-5<»
SUMMARY OF HEXACHLOROBEN2ENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Ham&ter
Syrian
Golden
Male
Hamster
Syrian
Golden
Female
Mouse
Swiss
Male
Mouse
Swiss
Female
Rat
Wistar
Female
Oral-food
Oral-food
Oral-food
Oral-food
Oral-food
0, 50, 100 or 200
ppm continuously
for length of
experiment (70
weeks); kO controls,
30-59/dose group.
0, 50, 100 or 200
ppm continuously
for length of
experiment {70
weeks);
-------
Table 2-54 (continued)
SUMMARY OF HEXACHLOROBEN2ENE CARCINOGENIC 8IOASSAY DATA
Route of Lowest Highly
Adminis- Nature of Effective Affected
Species trotion Exposure Dose Organ(s) Reference
Rat Oral-food 0 or 100 ppm con- 100 ppm Liver Smith and
Agus tinuously for length Cabral
Female of experiment (90 (129)
weeks); 12 con-
trols, 1% doeed.
2-118
-------
Animal Model
Table 2-55
SUMMARY OF CARCINOGENIC DATA SETS FOR HYDRA2INE°
Route of Administration
Species Sex Oral Govoqe Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rot
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
5(4)b
5(3)
KO)
0
0
0
KO)
KO)
0
3(3)
6(4)
KD
2(2)
2(2)
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
KO)
0
2(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 31 data sets of which 19 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-119
-------
Table 2-56
SUMMARY OF HYDRAZINE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(s) Reference
Mouse
A/J
Male
Oral-water
Gavage
Gavage
Mouse
BALB/
Cb/Se
Male
Mouse
BALB/
Cb/Se
Female
Mouse Gavage
CBA/Cbl
Se
Male
Mouse Gavage
CBA/Cbl
Se
Female
Mouse
C3H
Male
Oral-water
0 or 0.033* in
drinking water for
48 weeks, 20 con-
trols, 38 dosed;
length of experi-
ment 48 .weeks.
0 or 1.14 mg/day
for 4 weeks, 22
controls, 10 dosed;
length of experi-
ment 105 weeks.
0 or 1.14 mg/day
for 4 weeks, 23
controls. 10
dosed; length of
experiment 99
weeks.
0 or 1.12 mg/doy
for 36 weeks,
length of exper-
iment weeks; 37
controls, 21 dosed.
0 or 1.12 mg/day
for 36 weeks, length
of experiment 110
weeks, 47 controls,
21 dosed.
0 or 0.012* con-
tinuously for
lengtn of experi-
ment (104 weeks);
30 controls. 41
dosed.
0.033* Lung
1.14 Lung
mg/day
1.14 Lung
mg/doy
1.12 Lung;
mg/day Liver
1.12 Lung;
mg/day Liver
0.012* Lung
Yommamoto
and
Weisburger
(130)
Biancifiori
et ol.
(131)
Biancifiori
et ol.
(131)
Biancifiori
et 02.
(131)
Biancifiori
et ol.
(131)
Toth (132)
2-120
-------
Table 2-56 (continued)
SUMMARY OF HYDRAZINE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ (..») Reference
Mouse
C3H
Female
Oral-water
Mouse
Swiss
Male
Oral-water
Mouse
Swiss
Female
Oral-water
0 or 0.012* con-
tinuously for
length of experi-
ment (84 weeks);
30 controls, 41
dosed.
0 or 0.0120 con-
tinuously for
length of experi-
ment (104 weeks);
110 controls, 50
dosed.
0 or 0.0120 con-
tinuously for
length of experi-
ment (114 weeks);
110 controls, 50
dosed.
None
Toth, 19R9
0.0120
Lung
Toth (132)
0.0120
Lung
Toth (132)
Rat
CBRI/Sf
Male
Gavoge
Rat
CBHI/Se
Female
Gavage
0 or 56.9 mg once 56.9 Lung
weekly for 68 mg/week
weeks, length of
experiment 109
weeeks, 28 controls,
14 dosed.
0 or 37.9 mg once 37.9 Lung
weekly for 68 mg/week
weeks, length of
experiment 109
weeks, 22 controls,
18 dosed.
Biancifiori
et ol.
(133)
Biancifiori
et ol.
(133)
Mouse
CBA/Cb/
Se
Male
Gavage
0 or 1.13 mg/day
for 36 weeks; length
of experiment 148
weeks; 37 controls,
21 dosed.
1.13
mg/day
Lung
Severi and
Biancifiori
(134)
2-121
-------
Table 2-56 (continued)
SUMMARY OF HYDRAZINE CARCINOGENIC BIOASSAY DATA
Route of
Adminis-
Species tration
Mouse Govage
CBA/Cb/
Se
Female
Rat Gavage
CB/Se
Male
Rat Gavage
C8/Se
Female
Mouse Gavage
BALB/c/
Cb/Se
Female
Mouse Gavage
CBA/Cb/
Se
Male *
Female
Mouse oral -water
Swiss
Male
Nature of
Exposure
0 or 1.13 mg/day
for 36 weeks; length
of experiment 99
weeks; *7 controls,
21 dosed.
0, 12 or 18 mg/
day for 68 weeks;
length of experi-
ment 109 weeks; 28
controls, 13 dosed
(12 mg/doy), U»
dosed (18 mg/day).
0. 12 or 18 mg/day
doily for 68 weeks;
length of experi-
ment 109 weeks; 22
controls, 13 dosed
(12 mg/day) 18
dosed (18 mg/day ).
0 or 1.13 mg/day,
5 days /week for 30
weeks; length of
experiment 102
weeks; 25 controls,
22 dosed.
0, O.U, 0.28,
0.56 or 1.13 mg/
day 6 days/week
for 25 weeks;
length of experi-
ment 100 weeks, 59
controls, *9-51/
dose group.
0 or 0.001* (10
ppm) continuously
for life (120
Lowest Highly
Effective Affected
Dose Orqan(s)
1.13 Lung
mg/day
12 mg/ Liver;
day Lung
12 mg/ Lung
day
1.13 Lung
mg/day
0.1* Liver
mg/day
10 ppm Lung
Reference
Sever i and
Biancifiori
(15fr)
Severi and
Biancifiori
(15fi>
Severi and
Biancifiori
O3M
Biancifiori
(135)
Biancif iori
(135)
Toth (136)
weeks); 110 con-
trols, 50 dosed.
2-122
-------
Table 2-56 (continued)
SUfWARY OF HYDRAZINE CARCINOGENIC BIOASSAY DATA
Route of Lowest Highly
Adminis- Nature of Effective Affected
Speciestrotion Exposure Dose Orgon(s)Reference
Mouse Oral-water 0 or 0.001* {10 10 ppm Lung Toth (136)
Swiss ppm) continuously
Female for life (120
weeks); 110 con-
trols, 50 dosed.
2-123
-------
Animol Modal
Species Sex
Table 2-57
SUMMARY OF CARCINOGENIC DATA SETS FOR ISONIAZID0
Route of Administration
Oral Govoge Inhalation
Subcu- Skin Instil-
to neous Pointing Injection lotion
TP
nous*
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
10(9)"
n<8)
1(0)
5(2)
0(2)
0
2(2)
2(2)
0
7(6)
6(5)
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
5(2)
5(2)
0
1(0)
1(0)
0
0
0
0
0
• o
0
0
0
0
0
0
0
0
1(0)
0
1(0)
1(0)
0
1(0)
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 66 data sets of which <*0 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
«The "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-12*
-------
Table 2-58
SUMMARY OF ISONIAZID CARCINOGENIC BIOASSAY DATA
Species
Mouse
AKR
Male
Mouse
AKR
Female
Mouse
Swiss
Albino
Male
Mouse
Swiss
Albino
Female
Mouse
ASW/SN
Male
Mouse
ASW/SN
Female
Route of
Admin is- Nature of
tration Exposure
Oral-water 0 or 0.1* in drink-
ing water for 80
weeks; length of
experiment 80
weeks; 30 controls,
30/dose group.
Oral-water 0 or 0.1* in drink-
ing water for 80
weeks; length of
experiment 80
weeks; 30 controls,
30/dose group.
Oral-water 0, 0.15 or 0.05*
in drinking water
for 110 weeks;
length of experi-
ment 110 weeks; 110
controls,
-------
Table 2-58 (continued)
SUMMARY OF ISONIAZID CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Rat Oral-water 0 or 0.1* in drink- 0.14 Liver
MRC ing water for 170
Male weeks (length of
experiment); 100
controls. SO/dose
group.
Rat Oral-water 0 or 0.14 in drink- -- None
MRC ing water for 170
Female weeks (length of
experiment); 101
controls, SO/dose
group.
Mouse Oral-water 0 or 0.14 in drink- 0.14 Lung
Swiss ing water for 110
Albino weeks (length of
Male experiment); 110
controls, 55/dose
group.
Mouse Oral-water 0 or 0.14 in drink- 0.14 Lung
Swiss ing water for 110
Albino weeks (length of
Female experiment); 110
controls, 55/dose
group.
Mouse Oral-water 0 or 0.14 in drink- — None
C3H ing water for 90
Male weeks (length of
experiment); 30
controls, 30/dose
group.
Mouse Oral-water 0 or 0.14 in drink- — None
C3H ing water for 80
Female weeks (length of
experiment); 30
controls, 30/dose
group.
Toth and
Toth (138)
Toth and
Toth (138)
Toth and
Shubik
(139)
Toth and
Shubik
(139)
Toth and
Shubik
Toth and
Shubik
2-126
-------
Table 2-58 (continued)
SUMMARY OF ISONIAZIO CARCINOGENIC RIOASSAY DATA
Species
Hamster
Syrian
Golden
Male
Hamster
Syrian
Golden
Female
Mouse
A/J
Male
Mouse
BALB/C
Male
Mouse
BALB/C
Female
Mouse
C3Hf
Female
Route of
Adminis- Nature of
tration Exposure
Oral-water 0 or 0.1* in drink-
ing water for 140
weeks (length of
experiment); 100
controls, 50/dose
group.
Oral-water 0 or 0.1* in drink-
ing water for 120
weeks (length of
experiment); 100
controls, 50/dose
group.
Oral-water 0 or 0.1* in drink-
ing water for
-------
Table 2-58 (continued)
SUMMARY OF ISONIA210 CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orqan(s) Reference
Mouse Oral-water 0 or 0.10 in drink- 0.1* Lung
C3Hf ing water for 110
Male week* (length of
experiment); 26
controls, 36/dose
group.
Mouse Oral-water 0 or 0.1? in drink- -- None
BALB/C ing water for 94
Male weeks (length of
experiment); 9
controls, 15/dose
group.
Mouse Oral-water 0 or 0.1* in drink- — None
BALB/C ing water for 102
Female weeks (length of
experiment); 36
controls, 20/dose
group.
Mouse Subcutan- 0 or 2 mg every 2 mg Lung
8AL8/C eous other day for 18
Male weeks; length of
experiment 30
weeks; 102 con-
trols, 7*./dose
group.
Mouse Subcuton- 0 or 2 mg every 2 mg Lung
BALB/C eous other day for 18
Female weeks; length of
experiment 30
weeks; 90 con-
trols, 53/dose
group.
Peacock £
Peacock
Peacock
Peacock
Peacock
Peacock
Jones
•t al.
(U3)
Jones
• t al
(U3)
2-128
-------
Table 2-58 (continued)
SUMMARY OF ISONIAZID CARCINOGENIC BIOASSAY DATA
Species
Mouse
Strong-A
Male
Route of
Adminis-
tration
Subcutan-
eous
Nature of
Exposure
0, 2 or 4 mg every
other day for 18
weeks; length of
Lowest
Effective
Dose
2 mg
Highly
Affected
Oraan(s)
Lung
Reference
Jones
et al.
(143)
Mouse
Strong-A
Female
Subcutan-
eous
Hamster
Syrian
Golden
Male
Oral-water
Hamster
Syrian
Golden
Female
Oral-water
experiment 30
weeks; 210 con-
trols, 99 or 112/
dose group.
0, 2 or * mg every
other day for 18
weeks; length of
experiment 30
weeks; 209 con-
trols, 95 or 105/
dose group.
0, 0.1 or 0.2*
continuously for
length of experi-
ment, 0.3* for 42
weeks (given in
cycle of 6 weeks
on, 2 weeks off),
length of experi-
ment 140 weeks,
100 controls.
50/dose group (0.1
and 0.2*), 36
dosed (0.3*).
0. 0.1 or 0.2*
continuously for
length of experi-
ment, 0.3* for 42
weeks (given in
cycle of 6 weeks
on, 2 weeks off),
length of experi-
ment 120 weeks;
100 controls, 50/
dose group (0.1
and 0.2*), 35
dosed (0.3*).
2 mg
Lung
None
Jones
et al.
(143)
Toth and
Shubik
(144)
None
Toth and
Shubik
(144)
2-129
-------
Table 2-58 (continued)
SUMMARY OF ISONIAZID CARCINOGENIC BIOASSAY DATA
Route of
Adminis-
Species tration
Mouse Gavage
CBA/CB/Se
male
Mouse Gavage
CBA/C8/S0
Female
Mouse Gavage
BALB/c/
Cb/Se
Male
Mouse Gavage
BALB/c/
Cb/Se
Female
Mouse Gavage
CBA/CB/Se
Male
Mouse Gavage
CBA/CB/Se
Female
Nature of
Exposure
0 or 1 . 99 mg/day
for 36 weeks.
length of exper-
iment 105 weeks;
37 controls, 18/
dose group.
0 or 1 .99 mg/day
for 36 weeks,
length of exper-
iment 99 weeks; 47
controls, 17/dose
group.
0 or 2 mg/day for
4 weeks, length
of experiment 99
weeks; 22 con-
trols, 10/dose
group.
0 or 2 mg/day for
4 weeks, length
of experiment 99
weeks; 23 con-
trols, 10/dose
group.
0 or 2 mg/day for
36 weeks, length
of experiment 148
weeks; 37 controls,
18/dose group.
0 or 2 mg/day for
36 weeks, length
of experiment 99
Lowest Highly
Effective Affected
Cose Orqan(s) Reference
1.99 Lung Biancifiori
mg/day et al .
(151)
1.99 Lung Biancifiori
mg/day et al .
(131)
None Biancifiori
et al.
(131)
None Biancifiori
et al .
(131)
2 mg/day Lung Severi and
Biancifiori
(134)
2 mg/day Lung Severi and
Biancifiori
(Hit)
weeks; 47 controls,
17/dose group.
2-130
-------
Table 2-58 (continued)
SUMMARY OF ISONIAZID CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ Cs) Reference
Sever! and
Bioncifiori
(134)
Sever! and
Bioncifiori
(134)
Bhide
et al.
(145)
Rat Oral-water 0 or 0.35* continu- — None
Cb/Se ously for 48 weeks,
Male length of experi-
ment 109 weeks; 28
controls. 49/dose
group.
Rat Oral-water 0 or 0.35* continu- 0.35* Breast
Cb/Se ously for 48 weeks,
Female length of experi-
ment 109 weeks; 22 con-
trols, 40/dose group.
Mouse Gavage 0, 0.55. 1.1 or 2.2 0.55 Lung
Swiss mg/day 6 days/week mg/day
Male for 104 weeks, or
2.2 mg/day, 6 days/week
for 17 weeks. 50 con-
trols, 30/dose group
(0.55 and 1.1), 24 in
group getting 2.2 mg/
day for 104 weeks, 6 in
group 2.2 getting mg/
day for 17 weeks.
Length of experiment
104 weeks.
Mouse Gavage 0 or 1.1 mg/day, 6 1.1 Lung Bhide
Swiss days/week for mg/day et al.
Female length of experi- (145)
ment, observed 104
weeks; 60 con-
trols, 44/dose
group.
Mouse Gavage 0, 1.1 or 2.2 mg/ 1.1 Lung Bhide
Strain A kg, 6 days/week mg/day et al.
Male for length of ex- (145)
periment, observed
91 weeks; 20 con-
trols, 20/dose
group.
2-131
-------
Table 2-58 (continued)
SUMMARY OF ISONZAZIO CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
trotion
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s) Reference
Mouse Oral-food 0 or 35 mg/day 35/26.3 Lung Jones
Strong-A for 6 weeks, then mg/day et al.
Male 26.3 mg/day for (143)
12 weeks. Length
of experiment 30
30 weeks; 106 con-
trols, 139/dose
group.
Mouse Oral-food 0 mg/day; or 35 mg/ 35/26.3 Lung Jones
Strong-A day for 6 weeks, mg/day et ol
Female then 26.3 mg/day (1»3)
for 12 weeks.
Length of experi-
ment 30 weeks; 108
controls, 145/dose
group.
2-132
-------
Animal *odel
Table 2-59
SUMMARY OF CARCINOGENIC DATA SETS FOR LEAD0
Route of Administration
Species Sex Orol Gavoqe Inhalation
Subcu- Skin Instil-
Igneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
KDb
KD
1(0)
11(5)
3(2)
3(2)
2(1)
KD
0
0
0
0
KO)
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
1(1)
2(0)
2(0)
1(0)
0
0
0
0
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
°There were a total of 33 data sets of which 15 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-133
-------
Table 2-60
SUMMARY OF LEAD CARCINOGENIC BIOASSAY DATA
Species
Rat
Fischer
344
Male
Rat
Long-
Evans
Male
Rat
Wistar
Male
Rat
Wistar
Female
Rat
Wistar
Male
Rat
Wistar
Female
Rot
Wistar
Male
Route of Lowest Highly
Adminis- Nature of Effective Affected
tration Exposure Dose Orqan(s)
Oral-food 0 or 1* continuously — None
for length of exper-
iment (52 weeks);
150 controls, 150
dosed.
Oral-water 0 or 25 ppm contin- — None
uously for length
of experiment {180
weeks); 52 con-
trols. 52 dosed.
Oral-food 0 or 0.1* continu- 0.1* Kidney
ously for length of
experiment (12k
weeks); 14 con-
trols. 16 dosed.
Oral-food 0 or 0.1* continu- 0.1* Kidney
ously for length of
experiment (12*
weeks); 15 con-
trols. 18 dosed.
Oral-food 0 or 1* continu- 1* Kidney
ously for length of
experiment (104
weeks); 13 con-
trols, 13 dosed.
Oral-food 0 or 1* continu- 1* Kidney
ously for length of
experiment (104
weeks); 13 con-
trols, 11 dosed.
Oral-food 0 or 1* continu- 1* Kidney
ously for length
of experiment (99
Reference
Hinton
et al.
(1*6)
Schroeder
et al.
-------
Table 2-60 (continued)
SUMMARY OF LEAD CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon(s)
Reference
Rat Oral-food 0 or 369 pg/kg/day
Long- for length of exper-
Evons intent (167 weeks);
Male A 34 controls, 32
Female dosed.
Mouse Oral-food 0 or 0.1* continu-
Swiss ously for length of
Male experiment or 1*
continuously for 13
weeks, then 0.5)1
for 91 weeks; ob-
served 104 weeks,
25 controls,
25/dose group.
Mouse Oral-food 0 or 0.1* continu-
Swits ously for length of
Female experiment or 1*
continuously for 13
weeks, then 0.5*
for 91 weeks; ob-
served 104 weeks,
25 controls.
25/dose group.
Hamster Oral-food 0, 0.1 or 0.5* con-
Golden tinuously for length
Male of experiment (104
weeks); 22 controls,
22/dose group.
Hamster Oral-food 0, 0.1 or 0.5*
Golden continuously for
Female length of experi-
ment (104 weeks);
23 controls,
24/dose group.
Noni
Non«
Kanisawa and
Schroeder
(35)
Van Esch and
Xroes (150)
None
Van Esch and
Kroes (150)
None
Van Esch and
Kroes (150)
None
Van Esch and
Kroes (150)
2-135
-------
Table 2-60 (continued)
SUMMARY OF LEAD CARCINOGENIC BIOASSAY DATA
Species
Mouse
Strong/A
Male i
Female
Route of
Adminis-
tration
IP Injec-
tion
Nature of
Exposure
0, 2. 5 and 10 mg/
kg 3 times/week
for 5 we^ks (15
injections);
observed 30 weeks.
20 controls, 20/
dose group.
Lowest
Effective
Dose
2 mg/kg
Highly
Affected
Orqan(s)
Lung
Reference
Stoner
et ol.
(21)
Hamster
Syrian
Golden
Male i
Female
Rat
Wistar
Male «
Female
Intratro-
cheal in-
stillation
Oral-food
0 or 1 mg/week for
10 weeks; observed
60 weeks, 30 con-
trols, 30 dosed.
0 or 3 mg/day in
diet, length of
dosing varied from
9 weeks to 11*
weeks (length of
experiment); B-26/
dose group; 9* con-
trols.
None
3 mg/day
Hypo-
physis
brain;
Lung
Kobayashi
and Okamoto
(63)
Zawirska
(151)
2-136
-------
Animal Model
Table 2-61
SUMMARY OF CARCINOGENIC DATA SETS FOR M£LPHALANa
Route of Administration
Specie* Sex Oral Govoge Inhalation
Subcu- Skin Instil-
toneous Painting Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)0
2(0)
2(1)
1(0)
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 7 data sets of which 1 was considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-137
-------
Table 2-62
SUMMARY OF MELPHALAN CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Oose
Highly
Affected
Orgon(s)
Reference
Mouse Introperi- 0, 0.02. 0.09, 0.39
A/J toneal or 1.6 mg/kg, 3 times
Male i injection a week for * weeks.
Female Observed 39 weeks.
330 controls, SO/
dose group.
0.02
mg/kg
Lung
Shimkin
et ol.
(22)
2-138
-------
Animol Modal
Toble 2-63
SUMMARY OF CARCINOGENIC DATA SETS FOR METHOTREXATE°
Route ef Administrotion
Species Sex Orol Govoge Inholotion
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rot
Rot
Other
Other
Other
Male
Female
Mixed6
Mai*
Female
Mixed
Male
Female
Mixed
KDb
KD
0
0
0
0
KD
KD
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2(0)
0
1(0)
0
0
0
0
0
0
0
1(0)
2(0)
0
2(1)
3(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a -total of 16 data sets of which 6 were considered suitable for risk
assessment.
''The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-139
-------
Table 2-64
SUMMARY OF METHOTREXATE CARCINOGENIC BIOASSAY DATA
Specie*
Mice
Swiss
Mala
Route of
Admin is- Nature of
tration Exposure
Oral-food 0, 3. 5, 8 or 10
ppm in diet daily
on alternate week*
for length of ex-
periment (120
week*). 70 con-
trols, 36 in 3
ppm, 36 in 5 ppm,
42 in 8 ppm, and
48 in 10 ppm dose
groups.
Lowest Highly
Effective Affected
Oose Orqan(s) Reference
None Rustic and
Shubik
(152)
Mice Oral-food 0, 3, 5, 8 or 10
Swiss ppm in diet daily
Female on alternate weeks
for length of ex-
periment (120
week*). 70 con-
trols, 36 in 3
ppm, 36 in 5 ppm,
42 in 8 ppm, and
48 in 10 ppm dose
groups.
Hamsters Oral-food 0, 5, 10 or 20 ppm
Syrian in diet daily on ol-
Colden ternate weeks for
Male length of experi-
ment (120 weeks).
49 controls. 42 in
5 ppm 42 in 10
ppm, and 40 in 20
ppm dose groups.
Hamsters Oral-food 0. 5, 10 or 20 ppm
Syrian in diet daily on ol-
Golden ternote weeks for
Female length of experi-
ment (120 weeks).
49 controls, 42 in
5 ppm. 42 in 10
ppm, and 99 in 20
ppm dose groups.
None
Rustic and
Shubik
(152)
None
Rustia and
Shubik
(152)
None
Rustia and
Shubik
2-140
-------
Table 2-64 (continued)
SUWARY OF METHOTREXATE CARCINOGENIC BIOASSAY DATA
Specie*
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqon(s)
Reference
Rats Intraperi- 0 or 0.625 mg/kg once
Sprague- toneol in- a week for length
Oawley jection of experiment (130
Male weeks). 36 con-
trols, 30 dosed.
Rats Intraperi- 0 or 0.625 mg/kg once
Sprague- toneal in- a week for length
Oawley jection of experiment (130
Female weeks). 33 con-
trols, 31 dosed.
None
None
Schmahl
and Hobs
(153)
Schmahl
and Hobs
(153)
2-1*1
-------
Toble 2-6S
SUMMARY OF CARCINOGENIC DATA SETS FOR MUSTARD GAS
Animal
Species
MOUSe
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Model
Sex
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
Route of Administration
Oral
0
0
0
0
0
0
0
0
0
Gavoqe
0
0
0
0
0
0
0
0
0
Ir.halotion
0
0
0
0
0
0
0
0
0
Subcu-
taneous
0
0
J(3)*>
0
0
0
0
0
0
Shin
Pointing
0
0
0
0
0
0
0
0
0
Injection
0
0
KD
0
0
0
0
0
0
Instil-
lation
0
0
0
0
0
0
0
0
0
TP
0
0
)
0
0
0
0
0
0
°There were a total of *» iJoto sets all of which were considered suitable for risk
assessment.
''The "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
cThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
-------
Table 2-66
SUMMARY OF MUSTARD GAS CARCINOGENIC BIOASSAY DATA
Specie1;
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Qrqgn(s)
Reference
Mouse Intravenous
A Strain
Male *
Female
Mouse
C3H
Male «
Female
Mouse
C3Hf
Mole ft
female
Subcutan-
eous in-
jection
Subcutan-
eous in-
jection
Mouse Subcutan-
A Strain eous in-
Male * jection
Female
0 or 0.16 M9 every
other day for a
total of 4 injec-
tions, 48/dose
group. Length of
experiment 16 weeks.
0 or 0.1 mg in a
single injection
or 0.025 mg weekly
for 6 weeks; 16
controls, 16-24/
dose group; ob-
served until
natural death (104
weeks).
i»0 untreated con-
trols; 50 animals
received 0.025 mg
weekly for 6
weeks; observed
until natural
death (104 weeks).
0 or 0.25 mg weekly
for 5 weeks; ob-
served until
natural death (104
weeks); SO animals/
group.
0.16 >tg
Lungs
(only
organ
examined)
None
Heston
(154)
Heston
(155)
None
Heston
(155)
None
Heston
(155)
2-U3
-------
Animal Model
Table 2-67
SUMMARY OF CARCINOGENIC DATA SETS FOR 2-NAPHTHYLAMIN£a
Route of Administration
Species Sex __Qrql Govoqe Inhalation
Subcu- Skin Instil-
taneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
K0>°
2(1)
0
0
0
1(1)
1(0)
6(1)
8(8)
2(2)
2(2)
0
1(0)
2(1)
0
2(0)
2(1)
0
0
0
0
0
0
0
0
0
0
1(1)
1(1)
3(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
°There were a total of 37 data «et« of which 21 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in. the data
base and subsequent analyses.
°The "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
-------
Table 2-68
SUMMARY OF 2-NAPHTHYLAMINE CARCINOGENIC BIOASSAY DATA
Species
Mouse
A/J
Male «
Female
*
Rat
Wistar
Female
Mouse
Swiss
Male
Mouse
Swiss
Female
Mouse
Swiss
Male A
Female
Combined
Dog
Beagle
Female
Route of
Adminis-
tration
Intraperi-
toneal in-
jection
Gavage
S.C. in-
jection
S.C. in-
jection
S.C. in-
jection
Oral
(capsule)
Lowest Highly
Nature of Effective Affected
Exposure Dose Orqan(s)
0, 6.25 25, 100 6.25 Lung
or 400 mg/kg 3 mg/kg
times/week for k
weeks; 330 con-
trols, 30/dose
group. Length of
experiment 39 weeks.
0 or 300 mg/kg one — None
day/week for 57
weeks, observed
100 weeks; 20 con-
trols, 20 dosed.
0 or 100 pg injec- — None
ted 3 times/week
for one week; ob-
served 52 weeks;
2% controls, 28
dosed.
0 or 100 pg injec- — None
ted 3 times/week
for one week; ob-
served 52 weeks;
30 controls, 23
dosed.
Single injection -- None
of 0 or 30 «.g; ob-
served 43 weeks;
58 controls; 68
dosed.
0 or 5 mg/kg daily — None
for k weeks; ob-
served 156 weeks;
Reference
Shimkin
et al .
Hicks
et al.
(156)
Rodomski
et al .
(157)
Radomski
ee al.
(JlZ)
Radomsk i
et al .
(157)
Radomsk i
ee al .
(158)
<» controls, 4
dosed.
2-145
-------
Table 2-68 (continued)
SUMMARY OF 2-NAPHTHYLAMINE CARCINOGENIC BIOASSAY DATA
Species
Mouse
IF
Male
Mouse
IF
Female
Mouse
CBA
Male
Mouse
CBA
Female
Monkey
Rhesus
Female
Route of Lowest Highly
Adminis- Nature of Effective Affected
tration Exposure Dose Qrqon(s)
Gavage 0 or 5 mg in orach is 5 mg Liver
oil twice/week for
length of experi-
ment (72 weeks); 6
controls, 13
dosed .
Gavage 0 or 5 mg in arachis 5 mg Liver
oil twice/week for
length of experi-
ment (72 weeks); 5
controls, 12
dosed.
Gavage 0 or 5 mg in arachis 5 mg Liver
oil twice/week for
length of experi-
ment (89 weeks); 7
controls, 9 dosed.
Gavage 0 or 5 mg in arachis 5 mg Liver
oil twice/week for
length of experi-
ment (89 weeks); 7
controls, 1%
dosed.
Gavage 13 dose groups with 6.25/ Bladder
variable doses and 12.5
dosing schedules nig /kg
Reference
Bonser
ft ol.
(159)
Bonser
et ol.
(159)
Bonser
et ol.
(159)
Bonser
et al.
(159)
Conzelman
et al .
(160)
Dog
Beagle
Mole i
Female
Oral, p.o.
received 0 or from
6.25 to UOO mg/kg
for up to 257
weeks, 6 times/
week; length of
experiment 257
weeks; 1 to 3
animals/dose
group.
0, 6.25 or 12.5 mg/kg
6 days/week for length
of experiment (26 weeks);
1 animal/group.
None Conzelman
and Moulton
(161)
2-146
-------
Toble 2-68 (continued)
SUMMARY OF 2-NAPHTHYLAMINE CARCINOGENIC BIOASSAY DATA
Species
Dog
Beagle
Male ft
Female
Dog
Beagle
Male ft
Female
Dog
Beagle
Male ft
Female
Dog
Beagle
Male ft
Female
Dog
Beagle
Male ft
Female
Dog
Beagle
Male ft
Female
Dog
Beagle
Male ft
Female
Route of Lowest Highly
Adminis- Nature of Effective Affected
tration Exposure Dose Orqan(s)
Oral, p.o. 0. 6.25, 12.5, 25 — None
or 50 mg/kg 6 days/
week for length of
experiment (39 weeks);
1/dose group.
Oral, p.o. 0, 6.25, 12.5 or 25 mg/kg Bladder
25 mg/kg 6 days/
week for length of
experiment (52 weeks);
I/dose group.
Oral, p.o. 0. 6.25, 12.5 or 25 mg/kg Bladder
25 mg/kg 6 days/
week for 65 weeks
(length of experiment);
I/dose group.
Oral, p.o. 0, 6.25, 12.5 or — None
25 mg/kg 6 days/
week for 78 weeks
(length of experiment);
I/ dose group.
Oral, p.o. 0, 6.25, 12.5 or 6.25 Bladder
25 mg/kg 6 days/ mg/kg
week for 10t weeks
(length of experiment);
I/dose group.
Oral, p.o. 0, 6.25, 12.5, 25 or 25 mg/kg Bladder
50 mg/kg 6 days/
week for length
of experiment (95
weeks); 1-3 ani-
mals/group.
Oral, p.o. 0, 6.25. 12.5 or 6.25 Bladder
25 mg/kg 6 days/ mg/kg
week for length
of experiment (130
Reference
Conzelman
and Moult on
(161)
Conzelman
and Moult on
(161)
Conzelmon
and Moult on
(161)
Conzelman
and Moult on
(161)
Conzelman
and Moult on
(161)
Conzelman
and Moult on
(1.61)
Conzelman
and Moulton
(161)
weeks); 1-3 ani-
mals/group.
2-H7
-------
Table 2-68 (continued)
SUMMARY OF 2-NAPHTHYLAMINE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exoosure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Mouse Oral-food 0 or 2,000 ppm con- 2,000 Liver Yoshida
BALB/c tinuously for tO ppm et al.
Female weeks; length of (162)
experiment 55
weeks; 20/group.
Rat Oral-food 0 or *3 mg/kg/doy, — None Bonser
Albino 7 days/week for 90 et al.
Male * weeks; length of (159)
Female experiment 90
weeks; %9 con-
trols, 50 dosed.
2-1*8
-------
Animp1 Model
Table 2-69
SUMMARY OF CARCINOGENIC DATA SETS FOR NICKEL0
Route of Administrotion
Species Sex Oral Govoge
Mouse
MOUSe
Mouse
Rat
Rot
Rat
Other
Other
Other
Male
Female
Mixedc
Mai*
Female
Mixed
Male
Female
Mixed
0
0
1(0)
0
0
0
KD
0
0
0
0
0
0
0
0
0
0
0
Inhalation
0
1(0)
0
3(3)
2(1)
2(1)
0
0
KO)
Subcu-
taneous
0
1(0)
0
0
0
0
0
0
0
Skin
Pointing
0
0
0
1(0)
0
0
0
0
0
Injection
2(0)»>
0
7(1)
22(15)
1*(3>
7(1)
KD
0
1(0)
Instil-
lacion
0
0
0
1(0)
2(0)
*O)
0
0
1(0)
TP
0
0
0
1(0)
KO)
0
0
0
0
°Th«re were a total of 77 data set* of which 28 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-1*9
-------
Table 2 /J
SUMMARY OF »«tCKEL CARCINOGENIC BIOASSAY DATA
Species
Rat
Fischer
344
Male
Route of
Adminis-
tration
Intra-
renal in-
jection
Nature of
Exposure
0, 0.6, 1.2. 2.5,
5.0 or 10.0 ing/rat
nickel subsulfide
administered in a
Lowest
Effective
Dose
5.0 mg
Highly
Affected
Orqan(s)
Kidney
Reference "
Sunderman
et al.
(163)
single injection;
length of experiment
104 weeks, 35 con-
trols, 11-24/dose
group.
Rat Intro- 0, 5.0, and 10.0
Fischer renal in- mg/rat nickel sul-
344 jection fide administered
Female in a single injec-
tion; length of
experiment 104
weeks, 17 controls,
14/dose group.
Rat Inhalation 0 or 40 ppm nickel
Wistar carbonyl for one
Male hour. Length of
experiment 171
weeks; .19 controls,
285 dosed.
Rat Inhalation 0 or 2 ppm nickel
Wistar carbonyl 3 days/
Male week, 1 hr/doy for
154 weeks (length of
experiment); 32 con-
trols, 64 dosed.
Rat Intro- 0, 0.6, 1.2, 2.5
Fischer muscular or 5.0 mg nickel
344 injection subsulfide in a
Albino single injec-
Male tion; length of
experiment 111
weeks; 60 con-
trols, 30/dose
group.
5.0 mg Kidney
None
None
0.6 mg
Hind
leg
(injec-
tion
site)
Sunderman
et ol.
(163)
Sunderman I
Donnelly
(164)
Sunderman It
Donnelly
(164)
Sunderman
et ol,
(89)
2-150
-------
Toble 2-70 (continued)
SUMMARY OF NICKEL CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat
Wistar
Male «
Female
Rat
Fischer
Male
Rat
Fischer
Intro-
femoral
instilla-
tion
Inhalation
Inhalation
Female
0 or 5 mg nickel
injected at weeks
1 and 78; length
of experiment 120
weeks; 23 controls,
100 dosed.
0 and 0.97 mg/m^
nickel tubsulfide
5 days/week, 6
hrs/day for 80
weeks; length of
experiment 11*
weeks; 120 controls,
122 dosed.
0 and 0.97 mg/m5
nickel subsulfide
5 days/week, 6
hrs/doy for 80
weeks; length of
experiment 11*
weeks, 121 controls,
10* dosed.
5 mg Thigh Heuper
(injec- (165)
tion site)
None
None
Ottolenghi
et al.
(166)
Ottolenghi
et ol.
(166)
Mouse
A/Strong
Male 4
Female
Xntraperi-
toneal in-
jection
Rat
Fischer
Male
IM injec-
tion
0, 3, 7.5 and 15
mg/kg nickel ace-
tote 3 times/week.
length of experi-
ment 30 weeks, 20
controls. 20/dose
group.
0 or 20 mg nickel
sulfide injected
once into thighs
(1/2 of dose in
each thigh);
length of experi-
ment 10*-, 30 con-
trols. 30 dosed.
None
20 mg
Thigh
(injec-
tion
site)
Stoner
ee al.
(72)
Maenzo
et al.
<§£>
2-151
-------
Table 2-70 (continued)
SUMMARY OF NICKEL CARCINOGENIC 8IOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Rat
Unknown
Rat
Fischer
Mole
Hamster
Syrian
Male
Inhalation
Intra-
muscular
injection
0. 0.015 or 0.03 ppm
nickel corbonyl
5 times/week for
one hr or single one
hr exposure to 0.125
ppm; length of ex-
periment 103 weeks;
*1 controls, 32-
80/dose group.
0 or 10 mg nickel
subsulfide in a
single injection,
length of experi-
ment 10* weeks; 20
controls, 23 dosed.
Hamster IM injec- 0, 5 or 10 mg nickel
Syrian tion subsulfide in o
Mole single injection,
observed 10«»
weeks; 1% controls.
15-17/dose group.
Rat Intra- 0 or 5 mg nickel
Fischer hepatic in a single injec-
3<»
-------
Table 2-70 (continued)
SUWIARY OF NICKEL CARCINOGENIC BIOASSAY DATA
Species
Rot
Wistor
mala
Route of
Adminis-
tration
IW injec-
tion
Nature of
Exposure
7 mg nickel sub-
•ulfide in a tin-
gle injection or
Lowest
Effective
Dose
7 mg
Highly
Affected
Organ(s)
Thigh
muscle
Reference
KasprzaK
et ol.
(169)
control vehicle
every 2 days for
weeks, 20/dose
group, length of
experiment 104
weeks.
Rat
Wistar
Male
Rat
Fischer
Male
IM injec-
tion
Intro-
testiculor
0 or 258 Mg nickel
sulfate in a sin-
gle injection,
every 2 days for 4
weeks, 20/dose
group, length of
experiment 104
weeks.
0 or 10 mg nickel
subsulfid* in a
single injection;
length of experi-
ment 87 weeks; 18
controls, 19
dosed.
None
10 mg
Testis
Kasprzak
•t ol.
(169)
Oomjanov
• C al.
(170)
Rat
Sprague-
Dnwley
Male
Rat
Fischer
Int-roreool
injection
Wale i
Female
Intraocular
injection
0 or 10 mq nickel 10 mg Kidney
subsulf ide in a
single injection,
observed 52 weeks,
16 controls. 16
dosed.
0 or 0.5 mg nickel 0.5 mg Eye
subsulf ide in a
single injection,
observed k2 weeks,
11 controls, 15
dosed.
Jasmin and
Riopelle
( 171 )
Albert
ee oj .
2-153
-------
Table 2-70 (continued)
SUMMARY OF NICKEL CARCINOGENIC BIOASSAY DATA
Species
Rot
Fischer
Albino
Mole
Rot
Fischer
Albino
Mole
Rot
Sprogue-
Dowley
Male
Route of
Adminis-
tration
IM injec-
tion
IM injec-
tion
IV injec-
tion
Lowest
Nature of Effective
Exposure Dose
0 or 2.5 mg nickel 2.5 mg
subsulfide injected
into muscle of right
thigh at start of
experiment, ob-
served 100 weeks; 2k
controls, 24 dosed.
0 or 1.2 mg nickel 1.2 mg
subsulfide injected
into muscle of right
thigh at start of
experiment, ob-
served 100 weeks, 49
controls, 27 dosed.
0 or 22 mg/kg nickel
carbonyl injected at
start of experiment
or 9 mg/kg every 3
Highly
Affected
Orgon(s)
Thigh
(injec-
tion
site)
Thigh
(injec-
tion
site)
None
Reference
Sunderman
and McCully
(173)
Sunderman
and McCully
(173)
Lou et al .
(174)
weeks for 18 weeks,
length of experiment
130 weeks; IS con-
trols. 26 or 61/
dose group.
Rat IV injec- 0 or 22 mg/kg nickel
Sprague- tion corbonyl injected at
Dowley start of experiment
Female or 9 mg/kg every 3
weeks for 18 weeks.
length of experiment
161 weeks; 32 con-
trols, 46 or 60/
dose group.
Rat IM injec- Single injection of
Fischer tion 0. 3.6 or 14.4 mg
Albino nickel observed 104
Male weeks; 20 controls.
10/dose group.
22 mg/kg
Total
malignant
TBAs
Lou ee al
(174)
None
Sunderman
and Maenza
<§§>
2-154
-------
Species
Table 2-70 (continued)
SUMMARY OF NICKEL CARCINOGENIC BIOASSAY DATA
Rout* Of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(sl
Reference
Rat IM injec- Single injection of
Fischer tion 0, 5.6 or 22.4 mg
Albino nickel monosulfide,
Male observed 104 weeks;
20 controls, 10/dos*
group.
Rat IM injec- Single injection of
Fischer tion 0, 5 or 20 rug nic-
Albino kel subsulfide.
Male observed 104 weeks;
20 controls, 9 or
10/dose group.
None
5 mg
Thigh
{injec-
tion
site)
Sunderman
and Maenza
(89)
Sunderman
and Maenza
(89)
Rat
Fischer
Albino
Mole
IM injec- Single injection of
tion 0, 9.2 or 36. 8 mg
nickel iron-sulfide
matte, observed 104
weeks; 20 controls,
10/dose group.
36.8 mg Thigh
(injec-
tion
site)
Sunderman
and Maenza
(§§)
2-155
-------
Anjmol Modal
Table 2-71
SUMMARY OF CARCINOGENIC DATA SETS FOR NITRILOTRIACETIC ACIDa
Route of Administration
Species S«x Oral Govoge Inhalation
Subcu- Skin
toneous Painting
Instil-
Injection lotion
TP
Mouse
Mouse
Mouse
Rot
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Mole
Female
Mixed
Mole
Female
Mixed
3(3)0
3(3)
0
6(5)
5(«O
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
KO)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of IB data sets of which 15 were considered suitable for risk
assessment.
''The number in parenthesis indicates the number of data sets that *•.*? considered
suitable for risk assessment, and were further abstracted for inclusion in the au«.u
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-156
-------
Table 2-72
SUMMARY OF NITRILOTRIACETIC ACID CARCINOGENIC BIOASSAY DATA
Soecies
Rot
Fischer
344
Mole
Rat
Fischer
344
Female
Rat
Fischer
344
Mole
Rat
Fischer
344
Female
Mouse
B6C3F-I
Male
Moute
B6C3F-I
Female
Route of
Adminis- Nature of
tration Exoosure
Oral-food 0, 0.02, 0.2 or 2%
continuously for
length of experi-
ment (104 weeks);
24 controls. 24/
dose group.
Oral-food 0, 0.02, 0.2 or 2%
continuously for
length of experi-
ment (104 weeks);
24 controls, 24/
dose group.
Oral-food 0, 0.75 and 1.5*
for 77 weeks;
length of experi-
ment 104 weeks; 20
controls, 50/dose
group .
Oral-food 0, 0.75 and 1.5*
for 77 weeks;
length of experi-
ment 104 weeks;
20 controls, 50/
dose group.
Oral -food 0. 0.25 and 0.5*
for 77 weeks;
length of experi-
ment 90 weeks; 20
controls, 50/dose
group .
Oral-food 0, 0.25 and 0.5*
for 77 weeks;
length of experi-
Lowest Highly
Effective Affected
Dose Oraan(s)
0.2* Urinary
system
0.02* Respira-
tory
system
None
None
0.25* Hemopoie-
tie sys-
tem
None
Reference
NCI (175)
NCI (175)
NCI (175)
NCI (175)
NCI (175)
NCI (175)
ment 90 weeks; 20
controls, 50/dose
group.
2-157
-------
Table 2-72 (continued)
SUMMARY OF NITRILOTRIACETIC ACID CARCINOGENIC BIOASSAY DATA
Species
Mouse
B6C3F-,
Male
Route of
Adminis-
tration
Oral-food
Nature of
Exposure
0, 0.75 and 1.5*
for 77 weeks;
length of experi-
ment 90 weeks; 20
controls, 50/dose
group.
Lowest
Effective
Dose
0.75*
Highly
Affected
Organ(s)
Urinary
system
Reference
NCI (175)
Mouse
B6C3F-,
Female
Rat
Fischer
Male
Rat
Fischer
Oral-food
Oral-food
Oral-food
Female
Mouse
Swiss
Male
Oral-water
Mouse
Swiss
Female
Oral-water
0. 0.75 and 1.5*
for 77 weeks;
length of experi-
ment 90 weeks; 20
controls, 50/dose
group.
0, 0.75 and 1.5*
for 77 weeks;
length of experi-
ment 10<» weeks; 20
controls. 50/dose
group.
0. 0.75 and 1.5*
for 77 weeks;
length of experi-
ment 10% weeks; 20
controls. 50/dose
group.
0 or 25 fiwg/day.
5 days/week for 26
weeks; length of
experiment 38
weeks; "+0 con-
controls, kO
dosed.
0 or 25 mg/day.
5 days/week for
26 weeks; length
of experiment 38
weeks; kO con-
trols, 40 dosed.
None
NCI (175)
0.75*
Endocrine NCI (175)
glands
0.75*
Liver;
Digestive
system.
NCI (175)
None
Greenblatt
and
Lijinsky
(176)
None
Greenblatt
and
Lijinsky
(176)
2-158
-------
Tab10 2-72 (continued)
SUMMARY OF NITRILOTRIACETIC ACID CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest. Highly
Effective Affected
Dose Or gem (s)
Reference
Rat
MRC
Male
Rat
MRC
Female
Oral-water
Oral-water
Rat
Sprogue-
Dawley
Male
Oral-water
0 or 100 mg/day
5 days/week for
84 week*; length
of experiment
weeks; 15 con-
trols, 15 dosed.
0 or 100 mg/day
5 days/week for
84 weeks; length
of experiment. 104
weeks; 15 con-
trols, 15 dosed.
0 or 1,000 ppm
continuously for
length of experi-
ment (104 weeks);
192 controls, 196
dosed.
None
Lijinsky
«t al.
(177)
None
Lijinsky
• t al.
(177)
1000 ppm Kidney
Goyer
•t al.
(1Z§)
2-159
-------
Animal Model
Table 2-73
SUMMARY OF CARCINOGENIC DATA SETS FOR PHENACETINa
Route of. Administration
Species Sex Oral Govaqe Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Mole
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
3(3)0
3(3)
0
7(3)
5(2)
KO)
0
0
1(0)
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 21 data sets of which 12 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyse*.
eThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-160
-------
Tobl* 2-7%
SUMMARY OF PHENACETIN CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Do«»
Hignly
Affected
Organ(s)
Reference
Rat
Sprogue-
Dawley
Mai*
Oral-food
Rat
Sprogue-
Dawley
Female
Rot
SPF
Sprague-
Dowley
Mai*
Mous*
B6C3F1
Mai*
Oral-food
Oral-food
Oral-food
Mous*
B6C3F-J
Female
Oral-food
Mous*
C57BL/6
Mai*
Oral-food
0. 1.25* or 2.5*
for 77 weeks; ob-
served for 104
weeks. 65 con-
trols, 50/dose
group.
0. 1.25* or 2.5*
for 77 weeks; ob-
served for 10%
weeks. 65 con-
trols, 50/dos*
group.
0 or 0.535* contin-
uously for l*ngth
of experiment (117
weeks); 30 con-
trols, 30 dosed.
0. 0.6 and 1.25*
continuously for
96 weeks; length
of experiment 104
weeks; 50 con-
trols. 52/dose
group.
0, 0.6 and 1.2S*
continuously for
96 weeks; length
of experiment 10%
weeks; 50 con-
trols, 52/dose
group.
0. 268 and 75% ma,/
kg/day for length
of experiment (80
weeks); %0 con-
trols, %0/dose
group.
1.25*
1.25*
0.6*
Nasal Isaka
cavity; et al.
Urinary (179)
passages;
Hemopoietic
systems
Nasal Isaka
cavity, et al
Urinary (V79)
passages;
Hemopoietic
systems
Non*
Johansson
(180)
Kidney
Nakonishi
•t al.
(181)
Non*
Nakanishi
• t al.
(181)
Non*
Macklin and
Szot (182)
2-161
-------
Table 2-7% (continued)
SUMMARY OF PHENACFTIN CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Mouse Oral-food 0, 268 and 75* mg/
CS7BL/6 kg/day for length
Female of experiment (80
weeks); 40 con-
trols. 40 (268
*g/Kg/doy). 41
(754 mg/kg/doy).
Rat Gavage 0 or 1000 mg/kg 3
Wittar times/week for one
Female week; observed 104
weeks; SO con-
trols, 60 dosed.
Rat Oral-food 0. 0.322 and 0.644*
Fischer continuously for
344 79 weeks; observed
Male weeks;- 50 con-
trols. 50/dose
group.
Rat Oral-food 0. 0.322 and 0.644*
Fischer continuously for 79
344 weeks; observed
Female 113 weeks; 50 con-
trols, 50/dose
group.
Mouse Oral-food 0, 0.322 and 0.64411
B6C3Ff continuously for
Male 79 weeks; observed
94 weeks; 50 con-
trols. SO/dose
group.
Mouse Oral-food 0. 0.322 and 0.644*
B6C3F-) continuously for
Female 79 weeks; observed
94 weeks; 50 con-
trols. 50/dose
group.
None
Macklin and
Szot (182)
None
Kunze
et ol.
(183)
0.322
Adrenal NCI (184)
None
NCI (184)
Non«
NCI (184)
None
NCI (184)
2-162
-------
Table 2-75
SUMMARY OF CARCINOGENIC DATA SETS FOR POLYCHLORINATED BIPHENYLS°
Animol Model Route of Administration
Species Sax Orol Govoge Inholotion
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rot
Rat
Other
Other
Otner
Mole
Female
Mixedc
Male
Female
Mixed
Male
Female
Mixed
%<3>»
0
0
*<0
*(2)
0
0
0
0
0
0
0
0
0
0
0
0
ft'
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
0
0
°There were a total of 12 data «et» of which 6 were considered suitable for risk
assessment.
°The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were 'i-*ner abstracted far inclusion in the data
base and subsequent analyses.
eThe "nixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-
-------
Toble 2-76
SUMMARY OF POLYCHLORINATED BIPHENYLS CARCINOGENIC BIOASSAY DATA
Species
Adminis-
tration
Nature of
Exposure
Effective Affected
Dose Orgon(s) Reference
Rat Oral-food 0, 25, 50 or 100
Fischer ppm for length of
344 experiment (105
Male weeks); 2* con-
trols, 24/dose
group.
Rot Oral-food 0, 25, 50 or 100
Fischer ppm for length of
344 experiment (105
Female weeks); 24 con-
trols, 24/dose
group.
Mouse Oral-food 0, 100. 250 or SOO
DO pp«n continuously
Mole for length of ex-
periment (32
weeks); 12 con-
trols. 36/dose
group.
Mouse Oral-food 0 or 300 ppm con-
BALB/CJ tinuously for length
Male • of experiment (47
Female weeks); 100 con-
trols. 50/dose
group.
Rat Oral-food 0 or 100 ppm con-
Sherman tinuously for length
Female of experiment (99
weeks); 200 con-
trols, 200/dose
group.
Mouse Oral-food 0 or 250 ppm con-
00 tinuously for length
Mole of experiment (24
weeks): 20 con-
trols, 20/dose
group.
None
NCI (185)
None
NCI (185)
None
Ito
et oi.
(186)
300 ppm Liver
100 ppm Liver
Kimbrough
• Linder
Kimbrough
et o2.
(188)
None
Ito
ee ol.
(186)
2-184
-------
Animp1 Model
Toble 2-77
SUMMARY OF CARCINOGENIC DATA SETS FOR RESERPINE0
Route of Administrotion
Species Sex Orol Govoqa Inholotion
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rot
Rot
Rot
Other
Other
Other
Mole
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
KDb
KD
0
2(1)
2(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 6 data sett of which * were considered suitable for risk
assessment.
°The number in parenthesis indicates the number of doto sets thot were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
eThe 'mixed* sex indicates thot either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-165
-------
Table 2-78
SUMMARY OF RESERPINE CARCINOGENIC BIOASSAY DATA
Species
Rat
Fischer
344
Male
Route of
Adminis-
tration
Oral -food
Nature of
Exposure
0, 5 or 10 ppm con-
tinuously for 103
weeks; length of
experiment 106
weeks; SO controls,
50/dose group.
Lowest Highly
Effective Affected
Dose Organ(s)
5 *»~«n Adrenal
gland
Reference
NCI (189)
Rat Oral-food 0. 5 or 10 ppm con- 5 ppm Pituitary NCI (189)
Fischer tinuously for 103 gland
344 weeks; length of
Female experiment 106
weeks; 50 controls,
50/dose group.
Mouse Oral-food 0, 5 or 10 ppm con- 5 ppm Seminal NCZ (189)
B6C3Fi tinuously for 103 vesicle
Male weeks; length of
experiment 106
weeks; 50 controls.
50/dose group.
Mouse Oral-food 0, 5 or 10 ppm con- 5 ppm Mammary NCI (189)
B6C3F1 tinuously for 103 gland
Female weeks; length of
experiment 106
weeks; 50 controls,
50/dose group.
2-166
-------
Animal Modal
Toble 2-79
SUMMARY OF CARCINOGENIC DATA SETS FOR SACCHARIN0
Route of Admjnistrotion
Species Sax Oral Govoge Inhalation
Subcu- Skin Instil-
tonaous Pointing Injection lotion
Mouse
Mouse
Mouse
Rot
Rat
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
K0)«>
2(1)
KO)
11(9)
7(5)
0
0
0
2(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 27 data sets of which 18 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-187
-------
Tool* 2-80
SUMMARY OF SACCHARIN CARCINOGENIC BIOASSAY DATA
Rout* of
Adminis-
Sp0ci«» trotion
Mica Oral -food
Swiss
Female
Rot Oral-food
Charles
River CO
Sprague-
Dowley
Mai*
Rat Oral -food
Char1**
River CD
'•proiue-
Dnwl jy
Female
Mous* Intraperi-
A/He toneol in-
Female jection
Rot Oral-food
Charles
River CO
Mole
Nature of
Exposure
0 or 5* in diet for
length of experi-
ment (77 weeks);
100 controls, SO
dosed.
0 or 5£ sodium
saccharin in
diet continuously
for length of ex-
periment (112
weeks); 50 con-
trols, 50 dosed.
0 or 5* sodium
saccharin in diet
diet continuously
for length of ex-
periment (142
weeks): 50 con-
trols, 50 dosed.
0. 650 or 3250
mg/kg 5 times/
week for 8 weeks;
length of experi-
ment 2<» weeks; SO
controls. 20/dos*
group .
0. 90. 270. 810
or 2<»30 mg/kg/day
for length of ex-
periment (111
Lowest Highly
Effective Affected
Dose Organ(s) Reference
Non* Ro*
et ol.
(69)
SJt Para- Arnold
thyroid; et ol .
Bladder (190)
Non* Arnold
et ol .
(190)
Non* Stoner
*e ol .
(191)
None Munro
et al .
(192)
weeks); 60 con-
trols. 60/dose
group.
2-168
-------
Table 2-80 (continued)
SUMMARY OF SACCHARIN CARCINOGENIC BIOASSAY DATA
Specie*
Route of
Adminis-
trotion
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Qrqon(s) ffeferen c e
Rat
Charles
River CD
Female
Oral-food
Rat
Wistor
Male
Oral-food
0. 90, 270. 810
or 2430 mg/kg/day
for length of ex-
periment (111
weeks): 60 con-
trols . 60/dose
group.
0 or 5K continu-
uously for 92
week* from week
5 to week 36;
length of experi-
ment 36 weeks; 18
controls. 32
dosed.
Not:
None
Munro
•t ol
(192)
Nakanishi
et ol.
(193)
Rat
Vistar
Male
Rat
Wistar
dale
Oral-food
Oral-food
Rat
Wintor
SPF
Male
Oral-food
0 or 5* continu-
ously for length
of experiment (40
weeks); 18 con-
trols, 2k dosed.
0 or 5* continu-
uously for 32
weeks from week
? to week 83;
length ef experi-
ment 10<» weeks;
42 control*. 20
dosed.
0 or 4000 mg/kg/
day for length of
experiment (105
weeks); 55 con-
trols, 7% dosed.
None
None
Nakanishi
• t al .
Cohen
• t ol.
(194)
None
Cnowaniec
and NICKS
2-109
-------
Table 2-80 (continued)
SUMMARY OF SACCHARIN CARCINOGENIC BIOASSAY DATA
Species
Rat
Wistor
i-PF
Female
Route of
Adminis-
tration
Oral-food
Nature of
Exposure
0 or 4000 mg/kg/
day for length of
experiment (105
week*); 50 con-
trols, 75 dosed.
Lowest
Effective
Dose
„
Highly
Affected
Orqan(s)^
None
Reference
Cnowaniec
and Hicks
(195)
Rot
Wistor
Male
Rot
Wistor
Female
Rot
Fischer
Oral-voter
Oral-water
Oral-food
male
Monkey
Rhesus
Male 1
Female
Oral-per os
0 or 2000 mg/kg/
day for length of
experiment (105
weeks; 50 con-
trols. 70 dosed.
0 o- 2000 mg/kg/
day for length of
experiment (105
weeks; 50 con-
trols. 50 dosed.
0 or 50 continu-
ously for length
of experiment or
5* continuously
for 102 weeks.
length of experi-
ment 104 weeks:
37 controls,
21/dose group.
0, 20. 100 or 500
mg/Kg/day. 6 days/
week for length of
experiment (359
weeks); 6 con-
trols. 4-5/dose
group.
None
None
None
Chowoniec
and Hicks
(195)
Chovariiec
and Hicks
(II5.)
Cohen
et ol.
M&6)
None
ec ol
(197)
2-170
-------
Table 2-80 (continued)
SUMMARY OF SACCHARIN CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orgon(s)
Reference
Mouse
Swiss
Female
Rat
Fischer
344
Male
Pellet
implant
Oral-food
Rat
Fischer
344
Female
Oral-food
22 mg pellet con-
taining 0 or 20*
(0 or 4.4 mg) sac-
charin implanted
at start of
study, length of
experiment 57
weeks; 200 con-
trols, 200 dosed,
0, 400, 2000,
10,000 or 50,000
ppm in food (ad
libitum) from
week 4 to end of
experiment (36
weeks); 30-31/
dose group.
0. 400. 2000,
10,000 or SO,000
pom in food (ad
libitum) from
week 4 to end of
experiment (36
weeks); 30-31/
dose group.
4.4 mg Bladder
Bryan
et al.
(198)
Non«
Nakanishi
et al.
(199)
None
Nakanishi
et al.
(199)
2-171
-------
Toble 2-81
SUMMARY OP CARCINOGENIC DATA SETS FOR
2,3,7,8-TETRACHLORODIBEN20-P-OIOXIN (TCDD)
Animal Model
Route of Administration
Species Sex Oral Gavoge Inhalation
Subcu- Skin Xnstil-
tuneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
0
0
0
2(2)
KD
0
0
0
0
2(2)*>
KD
0
KD
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2(0)
0
1(0)
0
0
0
0
2(1)
*(1)
0
0
0
0
0
0
0
0
0
2(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 19 data sets of which 10 were considered suitable for risk
assessment.
°The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-172
-------
Table 2-82
SUMMARY OF 2,3,7.8-TETRACHLOROOIBENZO-P-DIOXjN CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Oraan(s)
Reference
Mouse Skin 0 or 0.001 pg — None NTP (200)
Swiss painting TCDD applied 3
Webster times/week for 99
Male weeks. Length of
experiment 10*
weeks; *5 controls;
30 dosed.
Mouse Skin 0 or 0.005 ng 0.005 Skin NTP (200)
Swiss painting TCDD applied 3
Webster times/week for
Female 10* weeks (length
of experiment);
*5 controls; 30
dosed.
Rat Oral-food 0, 1, 5, 50 or 5 ppt Liver Van Miller
Sprogue- 500 parts per et al.
Dowley trillion or 1, 5, (201)
Male 50, 500 or 1000
parts per billion
in feed for 78
weeks; length of
experiment 95
weeks-, 10/dose
group.
Rat Gavoge 0, 0.005. 0.025 0.005 Thyroid; NTP (200)
Osborne- . or 0.25 ?g/kg ad- M9/kg Subeu-
Mendel ministered 2 taneous
Male times/week for tissue
10* weeks; length
of experiment 107
weeks; 75 con-
trols, 50/dose
group.
2-173
-------
Toble 2-82 (continued)
SUMMARY OF 2,3,7,8-TETRACNLOROOIBENZO-P-DIOXIN CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Oraan(s)
Reference
Rat Gavag* 0, 0.005, 0.025
Osborne- or 0.25 pg/kg ad-
Mendel ministered 2
Female times/week for
104 weeks; length
of experiment
107 weeks; 75
controls. 50/dose
group.
Mouse Gavage 0, 0.005, 0.025
B6C3F-J or 0.25 fig/kg ad-
Male ministered 2
times week for
104 weeks; length
of experiment
107 weeks; 75
controls, SO/
dose group.
Mouse Gavage 0, 0.02, 0.1 or
B6C3F- 1.0 Mg/kg admin-
Female istered 2 times/
week for 104
weeks; length of
experiment 107
weeks; 75 con-
trols, 50/dose
group.
Mouse Gavage 0, 0.007, 0.7 or
Swiss/ 7.0 *.g/kg TCDD
H/Riop once a week for
Male 52 weeks; length
of experiment 100
weeks; 45/dose
group.
0.005
Liver;
Adrenal
gland
NTP (200)
0.25
Liver
NTP (200)
1.0
kg
Hemato-
poietic
system;
Liver
NTP (200)
0.007
Mg/kg
Lung;
Hemato-
poietic
system
Toth
•t al
(IP.?)
2-174
-------
Table 2-82 (continued)
SUMMARY OF 2,3,7,8-TETRACHLORODIBEN20-P-OIOXIN CARCINOGENIC BICASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Rat
Sprague-
Dawley
Male
Rat
Sprogue-
Dawley
Female
Oral-food
Oral-food
0, 0.001. 0.01 or
0.1 MQ/kg/day TCOO
for length of ex-
periment (10*
weeks); 86 con-
trols, 50/dose
group.
0, 0.001, 0.01 or
0.1 pg/kg/doy TCDO
for length of ex-
periment (104
weeks); 86 con-
trols, 50/dose
group.
0.1
Oral
cavity;
Adrenal
gland
Kociba
•t ol.
(203)
0.1
Liver;
Lung
Kociba
et ol.
(203)
2-175
-------
Table 2-83
SUMMARY OF CARCINOGENIC DATA SETS FOR TETRACHLOROETHYLENE°
Animal
Specie*
Mouse
Mouee
Mous«
Rot
Rat
Rat
Other
Other
Other
Model
Sex
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
Route of Administration
Oral
0
0
0
0
0
0
0
0
0
Govoqe
2(1 )*
2(1)
0
2(1)
2(1)
0
0
0
0
Inhalation
KD
KD
0
1(1)
KD
0
0
0
0
Subcu-
taneous
0
0
0
0
0
0
0
0
0
Skin
Painting
0
1(0)
0
0
0
0
0
0
0
Injection
1(0)
0
0
0
0
0
0
0
0
Instil-
lation
0
0
0
0
0
0
0
0
0
TP
0
0
0
0
0
0
0
0
0
°There were a total of
assessment.
data sets of which 8 were considered suitable for risk
"The number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-176
-------
Table 2-84
SUMMARY OF TETRACHLOROETHYLENE CARCINOGENIC BIOASSAY DATA
Species
Mouse
B6C3F-,
Male
Route of
Adminis-
tration
Gavage
Nature of
Exposure
Dosage administered
5 days/week as fol-
lows: 0 mg/kg for 78
Lowest
Effective
Dose
450/500
mg/kg
Highly
Affected
Orqan(s)
Liver
Heference
NCI (204)
weeks, or 450 mg/kg
for 11 weeks, then
550 mg/kg for 67
weeks; or 900 mg/kg
for 11 weeks, then
1100 mg/kg for 67
weeks; length of
experiment 90 weeko,
20 controls, SO/
dose group.
Mouse Gavage Dosage administered 300/400 Liver NCI (204)
B6C3F-I 5 days/week as fol- mg/kg
Female lows: 0 mg/kg for 78
weeks, or 300 mg/kg
for 11 weeks, then
400 mg/kg for 67
weeks; or 600 mg/kg
for 11 weeks, then 800
mg/kg for 67 weeks;
length of experiment
90 weeks; 20 controls,
SO/dote group.
Rat Inhalation 0, 200 or 400 ppm 5 200 ppm Memo- NTP (205)
F333/N days/week, 6 hrs/day poietic
Male for 104 weeks. system
Length of experiment
104 weeks; 50/dose
group.
Rat Inhalation 0, 200 or 400 ppm 5 200 ppm Memo- NTP (205)
F333/N days/week, 8 hrs/day poietic
Female for 104 weeks. system
Length of experiment
104 weeks; 50/dose
group.
2-177
-------
Table 2-84 (continued)
SUMMARY OF TETRACHLOROETHYLENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Oraan(s)
Reference
Mouse Inhalation 0, 100 or 200 ppm 5
B6C3Fi days/week, 6 hrs/day
Male for 104 weeks.
Length of experiment
104 weeks; 49 or SO/
dose group.
Mouse Inhalation 0, 100 or 200 ppm 5
B6C3F"| days/week, 6 hrs/dcy
Female for 104 weeks.
Length of experiment
104 weeks; 49 or SO/
dose group.
Rat Gavage Dosage administered
Osborne- 5 days/week as fol-
Mendel lows: 0 mg/kg for 78
Male weeks, or 500 mg/kg
for 26 weeks, then 700
mg/kg for 6 weeks, or
1000 mg/kg for 26
weeks, then 1400 for 6
weeks; length of
experiment 110 weeks;
20 controls, S(./dose
group.
Rat Gavage Dosage administered
Osborne- 5 days/week as follows:
Mendel 0 mg/kg for 78 weeks,
Female or 500 mg/kg for 56
weeks, then 600 mg/kg
for 3 weeks, then 700
mg/kg for 6 weeks, or
1000 mg/kg for 56
weeks, then 1200 mg/kg
for 3 weeks, then 1400
mg/kg for 6 weeks; length
of experiment 110
weeks; 20 controls,
50/dose group.
100 ppm Liver
NTP (205)
100 ppm Liver
NTP (205)
None
NCI (204)
None
NCI (204)
2-178
-------
Animal Model
Table 2-85
SUMMARY OF CARCINOGENIC DATA SETS FOR TOXAPHENEa
Route of Administration
Species Sax Oral Govoqa Inholotion
Subcu- Skin Instil-
toneous Painting Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixed6
Male
Female
Mixed
Male
Female
Mixed
1(1)"
KD
0
1(1)
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of
-------
Table 2-86
SUMMARY OF TOXAPHENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(s) Reference
Rat Oral-food Dosage administered
Osborne- daily in the diet
Mendel according to the
Mole following schedule:
0 ppm for 109 weeks;
1280 ppm for 2
week*, then 640 ppm
for 53 weeks, then
320 ppm for 25
weeks, or 2560 ppm
for 2 weeks, then
1280 ppm for 53
weeks, then 640 ppm
for 25 weeks; length
of experiment 109
weeks; 10 controls,
50/dose group.
Rat Oral-food Dosage administered
Osborne- daily in the diet
Mendel according to the
Female following schedule:
0 ppm for 109 weeks;
or 640 ppm for 25
weeks, then 32C ppm
for 25 weektt, or
1280 ppm for 55
weeks, or 640 ppm
for 25 weeks; length
of experiment 109
weeks; 10 controls,
50/dose group.
None
NCI (206)
None
NCI (206)
2-180
-------
Table 2-86 (continued)
SUMMARY OF TOXAPHENE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orgon( s ) Reference
Mouse Oral-food Dosage administered 80/160 Liver NCI (20§)
B6C3F-) daily in the diet ppm
Male according to the
following schedule:
0 ppm for 91 weeks;
160 ppm for 19
weeks, then 80 ppm
for 61 weeks; or 320
ppm for 19 weeks.
then 160 ppm for 61
weeks; length of
experiment 91 weeks;
10 controls, 50/dose
group.
Mouse Oral-food Dosage administered 80/160 Liver NCI (206)
B6C3F-I daily in the diet ppm
Female according to the
following schedule:
0 ppm for 91 weeks;
160 ppm for 19
weeks, then 80 ppm
for 61 weeks; or 320
ppm for 19 weeks,
then 160 ppm for 61
weeks; length of
experiment 91 weeks;
10 controls, SO/dose
group.
2-181
-------
Animal Model
Table 2-87
SUMMARY OF CARCINOGENIC DATA SETS FOR TRICHLOROETHYLENE°
Route of Administration
Species Sex Oral Gavoge Inhalation
Subcu- Skin Instil-
toneous Painting Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rot
Rat
Other
Other
Other
Male
Female
Mixed0
Male
Female
Mixed
Male
Female
Mixed
0
0
0
0
0
0
0
C
0
8(ob
5(4)
0
7(2)
7(2)
0
0
1 0
0
KD
2(2)
0
KD
2(2)
0
KD
KD
0
0
1(1)
0
0
0
0
0
0
0
0
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 34 data sets of which 22 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that wer« considered
suitable for risk assessment, and were further abstracted for inclusi i in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-182
-------
Toble 2-68
SUWIARY OF TRICHLOROETHYLENE CARCINOGENIC BIOASSAY DATA
Specie*
Route of
Admini's-
trotion
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Oroon(s) Reference
louse
B6C3F-I
Male
Gavage
Mouse
B6C3F-)
Female
Gavage
R-'t
Osborne-
Mendel
Male
Gavage
Rat Gavog«
"nborne-
-halation
0, 1,200 or 2.400
mg/kg 5 days/week
for 77 weeks;
length of experiment
90 weeks; 20/con-
trols, 50/dose
group.
0. 900 or 1,800
mg/kg 5 days/week
for 77 weeks; length
of experiment 90
weeks; 20/controls,
50/group.
0, 500 or 1,000
mg/kg/5 days/week
for 78 weeks;
every 4th week, no
doae, length of
experiment 110
weeks; 20 controls,
SO/dose group.
0, 500 or 1,000
mg/kg 5 days/week
for 78 weeks;
every <»th week, no
dose; length
of experiment 110
weeks; 20 controls,
50/dose group.
0, 100 or 500 ppm
air 5 days/week,
6 hr/day for 77
weeks; length of
experiment 128
weeks; 50/dose
group.
1200
mg/kg
Liver
NCI (76)
1800
mg/kg
Liver
NCI (76)
None
NCI (76)
None
NCI (76)
None
Henschler
et ol.
(207)
2-185
-------
Toble 2*88 (continued)
SUMMARY OF TRICHLOROETHYLENE CARCINOGENIC 8IOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Mouse
NMRI
Female
Inhalation
Rat
Wistar
Mcle
Inhalation
Rat
Wistar
Female
Inhalation
Hamster
Syrian
Male
Inhalation
Hamster
Syrian
Female
Inhalation
0, 100 or 500 ppm
air 5 days/week,
6 hr/day for 77
weeks; length of
experiment 128
weeks; 30/dose
group.
0, 100 or 500 ppm
air 5 days/week,
6 hr/doy for 77
weeks; length
of experiment 156
'weeks; 30/dose
group.
0, 100 or 500 ppm
air 5 days/week,
6 hr/day for 77
weeks; length of
experiment 156
weeks; 30/dose
group.
0, 100 or 500 ppit
oir 5 days/week,
6 hr/doy for 77
weeks; length of
experiment 128
weeks, 30/dose
group.
0, 100 or 500 ppm
air 5 days/week,
6 hr/day for 77
weeks; ler.gth of
experiment 128
weeks, 30/dose
group.
500 ppm
Hemoto-
poietic
Henschler
et ol.
(207)
None
Henschler
et ol.
(207)
None
Henschler
et ol.
(207)
None
Henschler
et al.
(207)
None
Henschler
et al.
(207)
2-184
-------
Table 2-88 (continued)
SUMMARY OF TRICHLOROETHYLENE CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
trotion
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(g) Reference
Mouse
ICR/Ha
Female
Mouse
B6C3F-I
Male
Mouse
B6C3F-J
Female
Rot
F3
Male
Skin
painting
Gavage
Govoge
Gavage
Rot Gavag<
Female
Rat
Sprague-
Dawley
Male
Inhalation
0 or 1 mg, 3
times/week for 83
week* (length of
experiment ) ;
30/dose group.
0 or 1000
5 days week for
103 weeks (length
of experiment);
50/dose group.
0 or 1000 mg/kg,
5 days week for
103 weeks (length
of experiment);
50/dose group.
0, 500 or 1,000
mg/kg, 5 days/
week for 103
weeks (length of
experiment); SO/
dose group.
0. 500 or 1000
mg/kg, 5 day*/
week for 103
weeks (length of
experiment);
50/dose group.
0, 50, 150 or 450
ppm, 5 days/week,
hr/day for 10*
weeks (length of
experiment ); SO/
dose group.
None
1000
mg/kg
Liver
Van Ouuren
et al.
(208)
NTP (209)
1000. Liver
mg/kg
NTP (209)
None
NTP (209)
None
NTP (209)
None
Fukuda
et al.
(210)
2-185
-------
Table 2-68 (continued)
SUMMARY OF TRICHLOROETHYLENE CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Organ(s)
Reference
Mouse
CO-1
Female
Inhalation
Mouse
ICC/Ha
Male
Gavage
Mouse
ICR/Ha
Female
Gavoge
Mouse
ICR/Ha
Male
Mouse
ICR/Ha
Female
Gavage
Gavaga
0, 50, ISO or 450
ppm, 5 days/week,
7 hr/day for 104
weeks (length of
exper iment); SO/
dose a.roup.
0 or 2.% g/kg for
34 weeks, then
1.2 g/kg for 28
weeks; length of
expf • iment 128
weeks; SO/dose
group.
0 or 1.8 g/kg for
5% weeks, then 0.9
g/kg for 28 weeks;
length of experi-
ment 128 weeks;
SO/dose group.
0 or 0.5 mg, 1 time/
week for 90 weeks
(length of experiment);
30/dose group.
0 or 0.5 mg, 1 time/
week for 90 weeks
(length of experiment);
50/dose group.
150 ppm Lung
None
None
None
None
Fukuda
et ol.
(210)
Henschler
ee ol.
(211)
Henschler
et 01.
(211)
Van Duuren
et ol.
(208)
Van Duuren
•t ol.
(208)
Mouse
ICR/Ha
Female
Subcutaneous
injection
0 or 0.5 mg, 1 time/
week for 90 weeks
(length of experiment);
SO/dose group.
None
Van Duuren
•t al.
(208)
2-186
-------
Tobl- 2-89
SUMMARY OF CARCINOGENIC DATA SETS FOR 2,4,6-TRICHLOROPHENOL°
Animal Model
Route of Administration
Species Sex Oral Gavoge Inhalation
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
nous*
Mouse
Rat
Rat
Rat
Other
Other
Other
Male 1(1)b
Female 1(1)
Mixed* 0
Male 1(1)
Female 1(1)
Mixed 0
Male 0
Female 0
Mixed 0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of * data sets all of which were considered suitable for risk
assessment.
DThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed* sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-187
-------
Toble 2-90
SUMMARY OF 2,4,6-TRICHLOROPHENOL CARCINOGENIC BTOASSAY DATA
Species
Rot
Fischer
Route of
Adminis-
tration
Oral-water
Nature of
Exposure
0, 5,000 or 10,000
ppm in water for
106 weeks (length
Lowest
Effective
Dose
5,000
ppm
Highly
Affected
Organ(s)
Hemato-
poietic
system
Reference
NCI (212)
Male
Rat
Fischer
344
Female
Mouse
B6C3F-,
Male
Oral-water
Oral-water
Mouse
B6C3F<|
Female
Oral-water
of experiment);
20 controls, 50/
dose group.
0, 5,000 or 10,000
ppm in water for
106 weeks (length
of experiment);
20 controls, SO/
dose group.
0, 5,000 or 10,000
ppm in water for
105 weeks (length
of experiment);
20 controls, SO/
dose group.
0 or 10,000 ppm for
98 weeks, then re-
duced to 2,500 ppm
for bV weeks; or
20,000 ppm for 38
weeks, then reduced
to 5,000 ppm for 67
weeks; length of
experiment 105
weeks; 20 controls,
SO/dose group.
None
NCI (212)
5,000
ppm
Liver NCI (212)
20.000/
5,000
ppm
Liver
NCI (212)
2-188
-------
Animal Model
Toble 2-91
SUMMARY OF CARCINOGENIC DATA SETS FOR VINYL CHLORIDE0
Route of Administration
Specie* Sex Orol Govooe Inhalation
Subcu- Skin Instil*
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rot
Rot
Rot
Othjr
Other
Other
Mole
Female
Mixed6
Male
Female
Mixed
Mole
Female
Mixed
0
0
0
2(2)
2(2)
0
0
0
0
0
0
0
2(2)
2(2)
0
0
0
0
12(11)*
9(8)
KD
15(12)
14(10)
1(1)
KD
0
0
0
0
0
KD
KD
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1(1)
1(1)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
°There were a total of 65 data sets of which 56 were considered suitable for risk
assessment.
bThe number in parenthesis indicates the number of data sets that were considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe "mixed" sex indicates that either both sexes were tested, but results were not
reported separately, or sex of test animal was unknown.
2-189
-------
Toble 2-92
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSA* DATA
Su«cies
Mouse
Charles
River
CD1
Mole
MOUS9
Charles
River
C01
Kale
Mouse
Charles
River
CD1
Male
Rot
Wistar
Male
Rot
Wistor
Female
Route of
Adminis- Nature of
tration Exposure
Inhalation 0, 2,500 or 6,000
ppm $ hrs/day, 5
days/week for 21
weeks; length of ex-
periment 22 weeks; 4
controls, 3/dose
group.
Inhalation 0, 2,500 or 6.000
ppm 5 Mrs/day, 5
days/week for 26
weeks; length of ex-
periment 26 weeks;
4 controls, 7/2,500
ppm group, 6/6,000
ppm group.
Inhalation 0, 2,500 or 6,000
ppm 5 hrs/day, 5
days /week for 26
weeks; length of ex-
periment 31 weeks;
3 controls. 7/2,500
ppm group, 1/6,000
ppm group.
Oral-food 0, 1.7, 5.0 or
14.1 mg/kg body
weight/day for 148
weeks (length of
experiment); 60/dose
group .
Oral-food 0, i.7, 5.0 or
14.1 mg/kg body
weight/day for 135
Lowest Highly
Effective Affected
Dose Orqan(s)
2500 Lung
ppm
2500 Lung
ppm
2500 Lung;
ppm Liver
1.7 mg/ Pitui-
kg/day tary.
Liver
1.7 mg/ Liver
kg/day
Reference
Suzuki
(213)
Suzuki
<22!>
Suzuki
(213)
Feron
et al.
(214)
r., -n
et ol.
(214)
weeks (length of
experiment); 60/dose
group.
2-190
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Speciet
Flouts of
Adminis-
tration
Nature of
Exoosur*
Lowest
Eff*ctiv*
Dos*
Highly
Aff*ct*d
Orqan(s)
R*f*r*nc*
Rat
Wittar
Male
Oral-food
Rat
Wittar
Femol*
Oral-food
Rat
CO-1
Albino
Mol*
Inhalation
Rat
CO-1
Albino
Female
Inhalation
0, 0.017, 0.17 or
1.7 mg/kg body
weight/day for 146
w**k* (length of
•xp*rim*nt); 100/
dot* group at 0,
0.017, 0.17 dot*t;
50/dot* group at 1.7
mg/kg dot*.
0, 0.017, 0.17 or
1.7 mg/kg body
w*ignt/day for 148
w**kt (length of
•xp*rim*nt); 100/
dot* group at 0,
0.017. 0.17 dot*t;
50/dot* group at 1.7
mg/kg dot*.
0, SO, 250 or
1,000 pptR 8 hrt/
day, 9 dayt/week
for up to 26 weekt;0
obt*rv*d for addi-
tional 52 w**kt;
l*ngth of *xp*rim*nt
78 ««**kt; 20/dot*
group.
0, 50, 250 or
10,000 pom 6 hrt/
day. 5 dayt/w**k
for up to 26 w**kt;a
obt*rv*d for addi-
tional 52 w**kt;
length of experiment
78 weeks; 20/dot*
group.
None
Til «t d
(215)
Non*
Til *t ol
(215)
Non*
Hong
•e ol.
50 ppm
Mammary
gland
Hong
et ol
(216)
2-191
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Admin is-
trotion
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Mouse Inhalation 0, 5( 250 or 1000
CO-1 ppm 6 hours/day, 5
Male days/week for up to
26 weeks;0 observed
for additional 52
weeks; length of ex-
periment 65-78 weeks.
8-28/dose group.
Mouse Inhalation 0, 50. 250 or 1000
CO-1 ppm 6 hours/day, 5
Female days a week for up to
26 weeks;0 observed
for additional 52
weeks; length of ex-
periment 65-78 weeks.
8-28/dose group.
Rot Intraperi- 0 or 4.25 mg once;
Sprague- toneal 4.25 twice at two
Dowley injection month intervals
Mole and 4.25 three times
at two month inter-
vals; length of ex-
periment 144 weeks;
30/dose group.
Rat Intraperi- 0 or 4.25 mg once;
Sprague- toneal 4.25 twice at two
Dawiey injection month intervals,
Female and 4.25 three times
at two month inter-
vals; length of ex-
periment 144 weens;
30/dose group.
Rat Subcutan- 0 or 4.25 mg once;
Sprague- eous in- length of experi-
Dawley Jection ment 145 weeks;
Male 35/dose group.
50 ppm
Lung;
Liver
Hong
et al.
(216)
50 ppm
Mammary
gland;
Lung
Hong
et ol.
(216)
None
Maltoni
et al.
Nont
Moltoni
et al.
(2)
None
Maltoni
et al.
(2)
2-192
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Rot
Sprogue-
Dowley
Female
Rat
Sprague-
Oawley
Female
Route of
Adminis-
tration
Subcutan-
eous in-
jection
Inhalation
Nature of
Exposure
0 or 4.25 mg once;
length of experi-
ment 145 weeks;
35 / dose group.
0 or 2500 ppm 5
days /week, 4 hr/
day for 7 weeks;
then 7 hr/doy for
69 weeks; length of
experiment 90 weeks;
60/dose group.
Lowest Highly
Effective Affected
Dose Organ(s)
None
2500 ppm Brain;
Liver
Reference
Moltoni
et ol.
(7)
Maltoni
et ol.
(7)
Rat
Sprague-
Dawley
Male
Rat
Sprague-
Oawley
Female
Rat
Wistor
Male
Inhclotion
Inhalation
Inhalation
0, 1, 5. 10 or 25
ppm 5 days/week,
4 hr/day for 52
weeks; length of
experiment 147
weeks; 60/dose
group.
0, 1. 5. 10 or 25
ppm 5 days/week.
4 hr/day for 52
weeks; length of
experiment 147
weeks; 60/dose
group.
0 or 1 ppm 5 days/
week, 4 hr/day for
52 weeks; length
of experiment 134
weeks; 120/dose
group.
None
Maltoni
et ol.
5 ppm
Mammary
gland
Maltoni
et ol.
(I)
None
Maltoni
•t ol.
2-193
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Rat
Sprague-
Dawley
Male
Rat
Sprague-
Dawley
Female
Rat
Charles
River CD
Male ft
Female
Mouse
CO-1
Male *
Female
Mouse
CD-1
Male
Route of
Adminis- Nature of
tration Exposure
Gavage 0, 0.03, 0.3 or
1 .0 mg/kg/day, 5
day s /week for 59
weeks; length of
experiment 136
weeks; 75/dose
group.
Gavage 0 , 0.03, 0 . 3 or
1 .0 mg/kg/day, 5
days /week for 59
weeks; length of
experiment 136
weeks; 75/dose
group.
Inhalation 0, 50, 250 or
1 , 000 ppm 5 days/
week, * hr/doy
for 52 weeks
length of experi-
ment); 32/dose
group.
Inhalation 0, 50, 250 or
1.000 ppm 5 days/
week, 4 hr/day
for 52 weeks
(length of
experiment);
32/dose group.
Inhalation 0, 50, 250 or
1,000 ppm 5 days/
week for *>, 13 or
Lowest Highly
Effective Affected
Dose Organ(s) Reference
— None Mai ton i
et al.
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC ..IOASSAY DATA
Species
Route of
Adminis-
trotion
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqon(s)
Reference
Mouee Inhalation 0, 50, 250 or 250 ppm Lung; Hong
CD-1 1,000 ppm 5 days/ Liver et al.
Female week for k, 13 or (216)
26 weeks; length
of experiment 78
weeks; 16/dose
group.
Rat Inhalation 0, 50, 250 or — None Hong
Charles 1,000 ppm 5 days/ et ol.
River CO week, 6 hr/day for (216)
Male 26 or 42 weeks;
length of experi-
ment 92 weeks;
10-20/dose group.
Rat Inhalation 0, 50, 250 or — None Hong
Charles 1,000 ppm 5 days/ et al.
River CO week, 6 hr/day for (216)
Female 26 or <»2 weeks;
length of experi-
ment 92 weeks;
10-20/dose group.
Mouse Inhalation 0, SO. 250 or 1,000 Lung Lee et al.
CD-1 1,000 ppm 5 days/ ppm (218)
Male week, 6 hre/day
for 26 weeks
(length of exper-
iment); 6-18/dose
group.
Mouse Inhalation 0, 50 or 250 ppm — None Lee et ol
CD-1 5 days/week, 6 hr/ (218)
Male day for 52 weeks
(length of experi-
ment); 2-5/dose
group.
2-195
-------
Table 2-92 {continued}
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Orqan(s)
Reference
Mouse Inhalation 0, SO, 250 or — None
CD-I 1,000 pom 5 days/
Female week, 6 hr/doy for
13 weeks (length of
experiment); 12/
dose group.
Mouse Inhalation 0, 50, 250 or 250 ppm Lung;
CD-I 1,000 ppm 5 days/ Liver
Female week, 6 hr/day
for 39 weeks (length
of experiment); k/
controls, 15-19/dose
group.
Mouse Inhalation 0 or 50 ppm, 5 — None
CD-I days/week, 6 hr/
Female day for 52 weeks
(length of ex-
periment); 16/
controls, 3/dose
group.
Rat Inhalation 0 or 5000 ppm, 5 — None
Wistar days/week, 7 hr/
Male day for 52 weeks
(length of exper-
iment); 10/dose
group.
Rat Inhalation 0 or 5000 ppm, 5 5000 Liver;
Wistar * days/week, 7 hr/ ppm Nasal
Female day for 52 weeks cavity
(length of experi-
ment); 10/dose
group.
Lee et al.
(218)
Lee et al
(218)
Lee et al
(218)
Feron et al
(219)
Feron et al
(219)
2-196
-------
'-92 (continued)
IDE CARCINOGENIC BIOASSAY DATA
of
posure
Lowest Highly
Effective Affected
Dose Qrgon(s)
Reference
Rot
Sprogue-
Dowley
Mole
50. 250 or 250 Liver; Lee et ol.
,000 5 day*/week, pom Lung (218)
or 38 week*
(length of ex-
piriment); 6-
15/doce group.
0, 50, 250 or — None Lee et ol.
1,000 5 days/week, (218)
6 hrc/doy for 25
week* (length of
experiment); 16-
19/do«e group.
,on 0, 50, 250 or — None Lee et al
1,000 5 days/week, (218)
6 hrs/doy for 13
weeks (length of
experiment); 12-
17/3o*e group.
Inhalation 0 or 30 ppthou, 5 30 Zymbol's Viola
days/week, 4 hr/ ppthou gland et al.
day for 52 weeks; (220)
length of exper-
iment 5
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Organ(s)
Reference
Rat
Sprague-
Dawley
Female
Inhalation
Rat
Sprague
Dawley
Male
Inhalation
Rat
Sprague
Dawley
Female
Inhalation
Rat
Sprague
Oawley
Male
Inhalation
0, 50, 250, 500,
2,500, 6,000 or
10,000 ppm 5 days/
week, * hr/doy
for 52 weeks,
length of experi-
ment 135 weeks;
30/dose group,
0, 100, 150 or
200 ppm, S day*/
week for 52 week*;
length of experi-
ment 1^3 weeks ;
85 contra1.*,
60 /dose
0, 100, 150 or
200 ppm, 5 days/
week for 52 weeks;
length of experiment
1
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Ncture of
Exposure
Lowest
Effective
Dose
Highly
Affected
Ofa.an(s)
Reference
Rat inhalation 0, 50, 250. 500, 250 Zymbal's Maltoni
Sprague- 2,aOO, 8,000 or ppffl gland; et ol.
Dawley 10.000 ppm, 5 day*/ Mammary (7)
Female week, *• hr/doy for glond
17 weeks; length of
experiment 156
weeks; 30/dose
group.
Mouse Inhalation 0, 50, 250, 500. 250 Lung; Maltoni
Swiss 2.500. 6,000 or ppm Liver et ol.
Male 10.000 ppm. 5 (7)
days/week. % hr/day
for 30 weeks; length
of experiment 81
weeks; 80 controls,
30/dose group.
Mouse
Swiss
Female
Inhalation
0. 50. 250. 500,
2,500, 6.000 or
10,000 ppm. 5
days/week, * hr/day
for 50 weeks; length
of experiment 81
weeks; 70 controls,
30/dose group.
50
ppm
Lung;
Liver
Maltoni
et al.
Rat
Wistar
Male
Inhalation
0. 50. 250, 500.
2.500, 6,000 or
10,000 ppm, 5
days/week, t hr/day
for 52 weeks, length
of experiment 165
weeks; 30/dose
group.
10.000
ppm
Liver
Maltoni
ee ol.
2-199
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Hamster Inhalation 0, 50, 250, 500, 2,500 Stomach Maltoni
Golden 2,500, 6,000 or ppm et ol.
Male 10,000 ppm, 5 (7)
days/week, % hr/day
for SO weeks; length
of experiment 109
weeks; 62 controls,
SO/dose group.
Rat Inhalation 0 or SO ppm 5 — None Maltoni
Sprogue- days/week, % hr/ et ol.
Dawley day for 52 weeks; (7)
Male length of experi-
ment 142 weeks; 50
controls, 150/dose
group.
Rat Inhalation 0 or 50 ppm 5 50 ppm Mammary Maltoni
Sprogue- days/week, % hr/ gland et al.
Dawley day for 52 week*; (7)
Female length of experi-
ment 142 weeks; SO
controls, 150/dose
group.
Rat Inhalation 0 or 6,000 ppm (1. — None Maltoni
Sprague- * or 5 times/week), et ol.
Dawley 10,000 ppm (1,4 or (7)
Male 5 times/week), 1
hr/day for 25
weeks; length of
experiment 15%
weeks; 109 con-
trols. 60/dote
group.
2-200
-------
Table 2-92 (continued)
SUMMARY OF VINYL CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
trotion
Nature of
Exposure
Lowest Highly
Effective Affected
Dot* OrQon(s)
Reference
Rot
Sprogue-
Dowley
Female
Inholotion
Rat
Sprague-
Dowley
Mole
Rot
Spragu*-
Dawl*v
FwnaU
Govog*
Gavag*
0 or 6,000 ppm (1.
% or S tim*«/w»«h),
10.000 pom (1.4 or
S tim««/w»«k), 1
hr/doy for 25
%MMk«; length of
•xpvrinwnt 154
w««Kt; 120 con-
trol*. 60/do*«
group.
0, 3.S3, 16.8 or 50
mg/kg. 5 dayt/w««k
for 52 w««k»;
length of experiment
136 weeks; 40/dote
group.
0, 3.33. 16.6 or 50
mg/kg. 5 days/week
for 52 week*;
length of experiment
136 weeks; «0/do*e
group.
None
Moltoni
et ol.
50
mg/kg
Liver
Moltoni
et al.
16.6
mg/kg
Liver
Moltoni
et al.
°Ab»tracted as two data sets; one dosing for 13 weeks, the other for 26 weeks.
2-201
-------
Table 2-93
SUWARY OF CARCINOGENIC DATA SETS FOR VINYLIDENE CHLORIDE0
AnimolModel
Rout* of Admjnistrotion
Species Sex Orol Govoge Inholotion
Subcu- Skin Instil-
toneous Pointing Injection lotion
TP
Mouse
Mouse
Mouse
Rat
Rat
Rat
Other
Other
Other
Male
Female
Mixede
Male
Female
Mixed
Male
Female
Mixed
0
0
0
3(1)
3(1)
0
0
0
0
1(1>»
KD
0
2(1)
3(2)
0
0
0
0
7(7)
7(7)
KD
7(5)
7(5)
2(0)
0
0
0
0
HO)
0
0
0
0
0
0
0
0
1(0)
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
QTh»r« w*r* a total of <»6 data m*t* of which 32 wor» con«id*r*d «uitabl* for risk
bTh« numb«r in par«nth«»it indicate* th« number of data »«t« that w«r« considered
suitable for risk assessment, and were further abstracted for inclusion in the data
base and subsequent analyses.
cThe 'mixed" sex indicates that either both sexes were tested, but results were not
reported veparotely. or sex of test animal was unknown.
2-202
-------
Toble 2-94
SUMMARY OF VINYLID£NE CHLORIDE CARCINOGENIC 8IOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
£ose
Highly
Affected
OrQon(s)
Reference
Rot
Wistar
Albino
Male
Inhalation
9 or 200 ppfli, 5
days/week, 4 hr»/
day for 26 weeks;
0 or 100 ppm 5
days/week, * hrs/
day for an addi-
tional 28 weeks (52
weeks total expo-
sure); observed 10%
weeks, SO controls,
51 dosed.
None
Viola and
Caputo
(221)
Rat
Wistor
Albino
Female
Inhalation
Rat
BOIV
Female
Mouse
Albino
CO-1
Male 4
Female
Gavoge
Inhalation
0 or 200 ppm, 5
days/week, 4 hrs/
day for 28 weeks;
0 or 100 ppm 5
daya/week, 4 hrs/
day for on addi-
tional 26 weeks (52
weeks total expo-
sure); observed 104
weeks, 30 controls,
23 dosed.
0 or ISO mg/kg in
•ingle dose; ob-
served 120 weeks.
14 controls; 24
dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (52
week*}; 38 controls,
36 dosed.
None
Non«
Viola and
Caputo
(22D
None
Ponomarkcv
* TomotiS
(222)
Lee et al.
(217)
2-203
-------
Toble 2-94 (continued)
SUMMARY OF VINYLIDENE CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Rout* of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dot*
Highly
Aff«ct«d
Orqan(s)
Reference
Rat
Charles
River CO
Mole
Rat
Charles
River CO
Female
Mouse
CO-1
Male
Mouse
CO-1
Female
Rat
Charles
River CO
Male
Rat
Charles
River CO
Female
Inhalation
Inhalation
Inhalation
Inhalation
Inhalation
Inhalation
0 or 55 ppm, 5
days/week, 6 hrs/
day for 43 weeks;
length of experiment
84 weeks; 16 con-
trols, 1% dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for 49 weeks;
length of experiment
94 weeks; 16 con-
trols, 16 dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for 4 weeks;
observed for 56
weeks; 16 controls,
8 dosed.
0 or 55 pom, 5
days/week, 6 hrs/
day for 4 weeks:
observed for 56
weeks; 18 controls,
8 dosed.
0 or 55 ppm. 5
days/week, 6 hrs/
day for 26 weeks;
length of of experi-
ment 77 weeks; 20
controls, 20 dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for 26 weeks;
length of experiment
77 v«eks; 20 con-
trc?a. 20 dosed.
None
Hong et ol.
(216)
None
Hong et ol.
(216)
None
Hong et al
(2J6)
None
Hong ee ol
(216)
None
Hong et al
(216)
None
Hong et ol
2-204
-------
Toble 2-9* (continued)
SUMMARY OF VINYLIDENE CHLORIDE CARCINOGENIC BIOASSAY DATA
Sp*Ci*«
Rout* Of
Adminis-
tration
Notur* of
Expo«ur*
Low**t Highly
Effective Aff*ct*d
Do«« Oraanf*.) Reference
Mouse
CO-1
Mol*
Inhalation
Mou**
CO-1
Female
Inhalation
Mouse
CO-1
Male
Inhalation
0 or 55 ppm, 5
day*/week, 6 hr«/
day for 12 w*ek*;
ob**rved for 64
week*; 16 control*,
8 do«*a.
0 or 55 ppm, 5
day*/week, 6 hr*/
day for 12 week*;
ob**rv*d for 64
w**k*; 16 control*.
8 do«*d.
0 or 55 ppm, 5
doy*/w««k, 6 hr*/
day for 26 w««k*;
ob*«rv*d for 77
M*«ks; 28 control*.
12 do««d.
Non*
Hong »t ol
(216)
Non*
Hong »t ol
(216)
Non*
Hong *t ol
(216)
Mou**
CO-1
F*mal*
Inhalation
Mou«*
Albino
CO-1
Mai*
Inhalation
0 or 55 ppm, 5
day*/w**k, 6 hr*/
day for 26 w**k»;
ob**rv*d fo" 77
w**k*; 28 control*,
12 do**d.
0 or 55 ppm, 5
day*/w**k, 6 hr*/
day for length of
experiment (52
week*); 1% control*,
14 doted.
Non*
Hong et ol
(216)
Non*
Lee et ol
(21B)
Mou**
Albino
CO-1
Female
Inhalation
0 or 55 ppm, 5
(Joy*/week, 6 hr*/
day for length of
experiment (52
week*); 16 control*.
16 do**d.
Non*
Lee et ol
(218)
2-205
-------
Table 2-9* (continued)
SUMMARY OF VINYLIDENE CHLORIDE CARCINOGENIC BIOASSAY DATA
Specie*
Route of
Adminis-
tration
Nature of
Exposure
Lowest
Effective
Dose
Highly
Affected
Orqan(s)
Reference
Rat
Charles
River CD
Male
Rat
Churles
River CD
Female
Mouse
Albino
CD-1
Male
Mouse
Albino
CO-1
Female
Mouse
Albino
CD-1
Male
Mouse
Albino
CO-1
Female
Inhalation
Inhalation
Inhalation
Inhalation
Inhalation
Inhalation
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (52
weeks); 36 controls,
36 dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (52
weeks); 36 controls,
36 dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (39
weeks); 20 con-
trols, 20 dosed.
0 or 55 ppm, 5
days/week, 6 hr«/
day for length of
experiment (39
wweks); 20 controls.
20 dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (26
weeks); 2% controls,
2t dosed.
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (26
weeks); 2t controls,
2% dosed.
Lee et ol
(218)
None
Lee et al.
(218)
None
Lee et al
(218)
None
Lee et ol
(218)
None
Lee et al
(218)
None
Lee et ol
(218)
2-206
-------
Table 2-94 (continued)
SUMMARY OF VINYLIDENE CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowest Highly
Effective Affected
Dose Oraonfs)
Reference
Mouse
Albino
CD-I
Male
Mouse
Albino
CO-1
Female
Rat
Sprague-
Dawlay
Mole
Inhalation
Inhalation
Inhalation
Rat
Sprague-
Dowley
Female
Inhalation
0 or 55 ppm, 5
days/week, 6 hrs/
day for length of
experiment (13
weeks); 36 control*.
36 dosed.
0 or 55 ppm. 5
days/week, 6 hrs/
day for length of
experiment (13
weeks); 36 controls.
36 dosed.
0. 10. 25. 50.
100 and 150 ppm,
5 days/week, *
hrs/day for 52
weeks, length of
experiment 130
weeks; 100 controls.
30/dose group (10,
25, 50 and 100 ppm}.
60 dosed (150 ppm).
0. 10. 25, 50.
100 and 150 ppm.
5 days/week, k
hrs/day for 52
weeks, length of
experiment 130
weeks; 100 controls,
30/dose group (10,
25, 50 and 100 ppm).
60 dosed (150 ppm).
None
Lee et ol
(218)
None
Lee et ol
(218)
None
Maltoni
et ol.
<§)
None
Maltoni
•t a2.
2-207
-------
Table 2~9
-------
Table 2-94 (continued)
SUMMARY OF VINYLIDENE CHLORIDE CARCINOGENIC BIOASSAY DATA
Species
Route of
Adminis-
tration
Nature of
Exposure
Lowast Highly
Effective Affected
Qrqan(s) Reference
Mouse Gavage 3, 2 or 10 rag/kg, 2 mg/kg
B6C3F-, 5 days/week for
Female length of experi-
ment (104 week*); 50
controls, 50.'dose
group.
Hemato-
poietic
system
NTP (225)
2-209
-------
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