United Stales
Environrrtntal Protection
Agency
of Pesticides Programs
Washington. DC 20*60
PB90-213885
EPA 540/09-90-092
May 1990
vvEPA Studies/Chronic
Data Formats for
Chronic/Oncogenicity Rodent
Bioassays
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June 1989
STUDIES Format for Toxicological Data
from Chronic Rodent Bioassays
prepared under
EPA Contract No. 68-08-0056
to Dynamac Corporation
EPA Task Manager
Richard A. Levy
Dynamac Project Manager
Brion T. Cook
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TABLE OF CONTENTS
i. Disclaimer iii
ii. Interagency Electronic Data Transfer Workgroup iv
iii. Acknowledgements v
I. Introduction 1
n. Background 2
m. Philosophy 4
IV. Data File Naming Conventions 6
V. STUDIES Format Data File Descriptions 7
A. Outline of File Descriptions
1. INDEX.CHR 8
2. ANIMAL.CHR 12
3. PATH.CHR 14
4. BODYWT.CHR 16
5. FOODCS.CHR 17
6. ORGANWT.CHR 18
7. CLINOBS.CHR 19
8. HEMATO.CHR 20
9. CLINCHEM.CHR 22
10. URINAL.CHR 24
11. PATHGLOS.CHR . 27
12. TISSUE.CHR 28
13. TEXT.CHR 29
B. Detailed File Descriptions 30
1. INDEX.CHR 31
2. ANIMAL.CHR 35
3. PATH.CHR 38
4. BODYWT.CHR 40
5. FOODCS.CHR 41
6. ORGANWT.CHR 42
7. CLINOBS.CHR 43
8. HEMATO.CHR 45
9. CLINCHEM.CHR 47
10. URINAL.CHR 49
11. PATHGLOS.CHR 51
12. TISSUE.CHR 52
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VI. Data Submission Specifications 53
Vn. Appendix A List of Tissues and Tissues Codes 54
. Appendix B List of SNOP Codes for Pathology 56
u
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DISCLAIMER
This report was prepared under contract to an agency of the United States government.
Neither the United States government nor any of its employees, contractors,
subcontractors, or their employees makes any warranty, expressed or implied, or assumes
any legal liability or responsibility for any third party's use or the results of such use of
any information, product, or process disclosed in this report, or represents that its use
by such third party would not infringe on privately owned rights.
Publication of this data in this document does not reflect the joint or separate views and
policies of each sponsoring agency. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
1U
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Interacencv Electronic Data Transfer Workerouo
Richard A, Levy, M.P.H. Chairman
Senior Scientist, Biostatistics
Science Analysis and Coordination Branch
Health Effects Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
Reto Engler, Ph.D.
lexicologist
Chief, Science Analysis and Coordination
Branch
Health Effects Branch
Office of Pesticide Programs
U.S. Environmental Protection Agency
Herbert 'Pepi' Lacayo, Ph.D.
Statistician
Statistical Policy Branch
Office of Policy, Planning, and Evaluation
U.S. Environmental Protection Agency
Marion Copley, D.V.M.
Pathologist
Section Head, Toxicology Branch I -
Insecticides /Rodenticides
Health Effects Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
Roger Gardner, M.S.
Toxicologist
Toxicology Branch I - Insecticides/
Rodenticides
Health Effects Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
William R. Fairweather, Ph.D.
Statistician
Chief, Statistical Application Branch
Center for Drugs and Biologies
Food and Drug Administration
Janet Springer, M.S.
Statistician
Director, Division of Mathematics
Center for Food Safety and Applied Nutrition
Food and Drug Administration
James J. Colaianne, Ph.D.
Statistician
Chief, Biometrics Branch
Center for Veterinary Medicine
Food and Drug Administration
Robert J. Condon, Ph.D
Mathematical Statistician
Biometrics Branch
Center for Veterinary Medicine
Food and Drug Administration
Michael W. O'Donnell, Ph.D.
Statistician
ChiefV Environmental Design and Evaluation Branch
Division of Mathematics
Center for Food Safety and Applied Nutrition
Food and Drug Administration
Judy S. Chen, Ph.D.
Statistician
Center for Medical Devices and Radiologic Health
Food and Drug Administration
Fred A. Hines, D.V.M
Pathologist
Diagnostic Pathology Branch
Division of Pathology
Center for Food Safety and Applied Nutrition
Food and Drug Administration
Prem Dua, D.V.M.
Pathologist
Diagnostic Pathology Branch
Division of Pathology
Center for Food Safety and Applied Nutrition
Food and Drug Administration
IV
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Murray S. Conn, Ph.D. Ralph L. Kodell, Ph.D.
Toxicologist Mathematical Statistician
Chief, Division of Health Effects Biometry Staff
Consumer Product Safety Commission National Center for lexicological Research
Food and Drug Administration
James J. Chen, Ph.D.
Mathematical Statistician
Biometry Staff
National Center for Toxicological Research
Food and Drug Administration
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ACKNOWLEDGMENTS
The authors, Richard A. Levy of the Environmental Protection Agency's Office of
Pesticide Programs and Brion T. Cook of Dynamac Corporation, wish to thank the
members of the interagency Electronic Data Transfer Workgroup for their
dedication and effort in the development of the formats described in this
document The authors also wish to acknowledge the support, encouragement, and
counsel provided by Reto Engler of the Environmental Protection Agency and the
willingness of Dave Gaylor of the National Center of Toricological Research in
providing support and comments to these documents. In addition, the authors wish
to acknowledge the efforts of Roy Sjoblad and Mike loannou of the Environmental
Protection Agency and Todd Holderman, Karen Maher, Kevin Junghans, Tom
England and Lori Brunsman of Dynamac Corporation for their technical support.
This document was reviewed by:
Reto Engler, Ph.D.
Toxicologist
Chief, Science Analysis and Coordination Branch
Health Effects Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
Philip Ross, Ph.D.
Statistician
Chief, Statistical Policy Branch
Office of Policy, Planning, and Evaluation
U.S. Environmental Protection Agency
James Skaptason,
Computer Scientist
FIFRA '88 Implementation Task Force
Office of Pesticide Programs
U.S. Environmental Protection Agency
Murray S. Conn, Ph.D.
Toxicologist
Chief, Division of Health Effects
Consumer Product Safety Commission
Ralph L. Kodell, Ph.D.
Mathematical Statistician
Biometry Staff
National Center for Toxicological Research
Food and Drug Administration
VI
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Fred A. Hines, D.V.M.
Pathologist
Diagnostic Pathology Branch
Division of Pathology
Center for Food Safety and Applied Nutrition
Food and Drug Administration
vu
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I. Introduction
The purpose of this document is to present file formats for the electronic transfer of
individual animal toxicological data generated from long-term rodent chronic/oncogenicity
studies. Through cooperation and discussions between the US Environmental Protection
Agency (EPA), the Department of Health and Human Services' Food and Drug
Administration (FDA), the National Center for Toxicological Research (NCTR), and the
Consumer Product Safety Commission (CPSC) these formats have been developed to
meet the electronic data submission requirements of these agencies. It is intended that
these formats be available for all electronic transfer of toxicological data between the
chemical industry and the government, within the chemical industry itself and between
government agencies.
This document presents the electronic data submission formats for parameters in a
chronic/oncogenicity bioassay. The categories of parameters which are described include:
pathology data - gross and microscopic
body weight
1 o
food consumption
organ weight
clinical chemistry
hematology
urinalysis
Users of this document should read the data submission specifications found in Section
VII on page 53 before using these formats.
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n. Background
Both the EPA and the FDA are responsible for the evaluation of data generated from
long-term rodent oncogenicity studies to fulfill regulatory mandates. These studies,
conducted by the chemical industry, are routinely submitted to the responsible agency
only in a hard copy format Since a great amount of data are generated during these
studies the evaluation process can be very complex and time consuming. Discussions
between these two agencies and other agencies including CPSC and NCTR have
considered developing a format by which the chemical industry could submit data to the
agency on some electronic media. It is acknowledged by everyone concerned that this
would greatly enhance the review process by permitting the amount of time to evaluate
the study to decrease and the effort given to the analysis to increase. Data provided in
electronic form would allow for customized tabulation and summarization, and more
efficient use of computers for statistical analysis since hand counts and data transcription
would no longer be necessary, thus reducing human error. These ideas were first
realized by the FDA in 1986 with the first description of such a format prepared by the
Statistical Application and Research Branch of the Center for Drug Evaluation and
Biologies. The EPA envisioned a more global approach and an expanded format that
could be constructed for all categories measured in a chronic bioassay and coined the
acronym, STUDIES, Submitters Toxicological Uniform Data Information Exchange
Standard, as the name of this standard format. Categories evaluated in a chronic
bioassay and hence could be included in the STUDIES format are:
o tumor incidence data
o body weight
o food consumption
o organ weights
o clinical chemistry
o hematology
o urinalysis
In addition, the STUDIES format could be applied to other types of studies submitted
to these agencies for lexicological review. These studies include:
o acute toxicity studies
o subchronic studies
o teratology
o reproduction
While all lexicological studies described above could be encompassed by the STUDIES
format, one study type must be chosen to use as a pilot effort. Because
chronic/oncogenicity studies serve as a large portion of the overall weight-of-evidence in
judging the lexicological potential of a chemical it was chosen as the study type to use
in developing the first STUDIES format.
The STUDIES chronic rodent bioassay format was designed, recognizing that the needs
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of the various agencies involved may differ in content but that the goals of the format
are the same. This document contains: 1) descriptions of computer file structures, and
2) the parameters necessary for data evaluation, and 3) a description of how these
various files relate to each other.
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ffl. Philosophy
The STUDIES format provides a modular approach to the evaluation of lexicological
data submitted to regulatory agencies. While the different types of lexicological studies
may require data that are unique to that type of study, there are parameters that are the
same from study type to study type. The STUDIES format allows for similar data from
different lexicological studies to be submitted in similar file formats, while also providing
for those parameters that are unique to a specific study type. This modular approach
gives a system that is easily adapted or modified as the data requirements change. These
formats as designed offer portability for use in a mainframe environment or
minicomputer as well as a personal computer since they follow the ASCII standard for
data representation.
The data from a lexicological study is submitted as a set of computer files. There is one
file which contains background information concerning the study which has the same
format for each different study type. This provides consistency from study type to sludy
type. Other files contain daia regarding specific lexicological parameters. For example,
all daia concerning animal body weights resides on one daia file. The structure of this
file is ihe same for every sludy type for which animal body weights are to be submitted,
whether ii be a chronic rodenl bioassay, leralology, or reproduction sludy. Daia which
is unique lo a specific sludy type, such as tumor incidence from a chronic rodenl
bioassay, would have a formal unique lo that type of study. A subset of the background
information has been identified as information lo be included as a 'header* record for
every other data file to be submitted with thai study. This provides a logical connection
between files and insures easy identification of files that correspond to a specific study.
The format of the data files have been designed to be as flexible as possible. As
described in this document, Ihe formal allows for daia lo be submitted in either fixed
length fields or variable length fields. For the fixed length field approach a definitive
number of characters are allowed for each parameter. The variable length field approach
allows for a specific character lo be used as ihe delimiter between fields.
It is envisioned that a library of glossaries will be established lo provide descriptions of
lexicological events that are more easily provided in coded form on the daia files. For
example, pathological observation codes presented in a daia file would be linked lo a file
containing the set of all possible codes and its associated description of the pathological
observation. A defaull glossary (codes and descriptions) has been established for
pathological observations for Ihe chronic rodenl bioassay formal based on ihe National
Toxicology Program's Standard Nomenclature of Palhology (SNOP). Additional glossaries
for pathological observations and other lexicological evenls could be provided by ihe daia
submitters to describe their data. These would be kept on file and used on future data
submissions. These glossaries would also be used by more than one agency or by more
than one data submitter.
The STUDIES format approach allows for ihe consistent and accurate tracking of data
submitted lo various agencies. These formats also could be used as a standard for ihe
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organization of toxicological data for exchange of data and information within the
regulated industries.
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IV. Data File Naming Conventions
All data for a given lexicological study have the same data file extensions as shown
below:
.CHR - chronic/oncogenicity rodent bioassay
.ACU - acute studies
.SCR - subchronic rodent studies
.TER - teratology rodent studies
.REP - reproduction rodent studies
STUDIES formats for non-rodent species (i.e.,dog, primate, guinea pig) will be addressed
at some time in the future. This document will focus only on the STUDIES for
chronic/oncogenicity rodent bioassays.
All data files for a specific category of parameters have the same name as shown below:
INDEX - study background information
ANIMAL - individual animal background
information concerning tissues,
hematology, clinical chemistry,
and urinalysis parameters examined.
PATH - pathology observations
BODYWT - body weight data
FOODCS - food consumption data
ORGANWT - organ weight data
CLINOBS - clinical observations
HEMATO - hematology data
CLINCHEM - clinical chemistry data
URINAL - urinalysis data
PATHGLOS - pathology observations code glossary file
TISSUE - tissue code glossary file
TEXT - additional information as necessary
For example, the clinical chemistry data submitted for a chronic/oncogenicity study would
be named, CLJNCHEM.CHR and the organ weight data submitted for a teratology study
would be named, ORGANWT.TER. The specific contents and structure of these data
files are described in detail in Section V.
Thirteen different types of files could be submitted under the chronic/oncogenicity
STUDIES format. A separate set of files would be submitted for each sex.
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V. STUDIES Format Data File Descriptions
A. Outline of File Descriptions
The STUDIES format for chronic/oncogenicity rodent bioassay data consists of up to
twelve files which contain data describing the toxicological effects for individual animals
generated from a chronic/oncogenicity bioassay.
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1. FORMAT FOR INDEX.CHR
This file contains background information about the chronic/oncogenicity study. This file
exists as one single record.
Item Field Length
1 1
2 200
3 100
4 100
5 100
6 8
7 8
8 100
9 50
10 50
11 100
12 15
13 15
14 15
15 50
16 1
Description
Record Type
F = fixed
V = variable
Chemical Name 1
Chemical Name 2
Study Type Description
Study Sponsor
Study beginning date (in the
form MMDDYYYY)
Study ending date (MMDDYYYY)
Conducting Laboratory
Animal Species
Animal Strain
Source, of Animal
Study Identification Code 1 -
conducting laboratory study identification
Study Identification Code 2 -
sponsor study identification
Study Identification Code 3 -
internal Agency identification
Pathologist
External Peer Review
1 = no external peer review
2 = external peer review
8
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FORMAT FOR INDEX.CHR (continued')
Item Field Length Description
17 50 Route of Administration (dermal,
oral, dietary, etc.)
18 2 Days of Dosing
19 2 Dose Unit Code
1 = ppm
2 = mg/kg
Additional codes are to be
explained in TEXT.CHR.
20 240 Dosing Regimen (i.e., two times per
week by dermal injection, etc.)
21 2 Number of Dose Groups
22 3 Number of Animals per Dose
Group by Study Design - there are as
many values as indicated in Item 21.
Each value is treated as a separate
field.
23 2 Number of Satellite Groups
24 3 Number of Animals in each Satellite
Group - there are as many values as
indicated in Item 23. Each value is
treated as a separate field.
25 2 Number of Animals per Cage
26 1 Sex
M = male
F = female
27 6 PATHGLOS.CHR File Code-will include
an agency designation code, version
designation code and a company glossary
code. Default is the NTP SNOP codes.
28 8 File Version Date (MMDDYYYY)
29 2 Number of Tissues Examined
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FORMAT FOR INDEX.CHR (continued^
Item _ Field Length
30 6 TISSUE.CHR File Code - structure same
as the glossary file code. Default is the
NTP tissue codes.
31 1 Body Weight Measurement Unit
M = milligrams (mg)
G = grams (g)
K = kilograms (kg)
32 1 Food Consumption Measurement Unit
M «• milligrams (mg)
G = grams (g)
K - kilograms (kg)
33 1 Organ Weight Measurement Unit
M = milligrams (mg)
G = grams (g)
K = kilograms (kg)
10
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FORMAT FOR INDEX.CHR (continued^
The following Items from the INDEX.CHR file would also be included as the first record
in every additional file submitted for the study. This will be referred to as the 'header
record' and will be referenced in each additional file. The 'header record' is not a
separate record in INDEX.CHR as it is a subfile of INDEX.CHR. The 'HEADER
RECORD' is used to link files common to a single study.
Item Field Length Description
1 200 Chemical Name 1
2 15 Study Identification Code 1 -
conducting laboratory study identification
3 15 Study Identification Code 2 -
sponsor study identification
4 "15 Study Identification Code 3 -
internal Agency identification
5 8 File Version Date (MMDDYYYY)
6 1 Sex
M = Males
F = Females
11
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FORMAT FOR ANIMAL.CHR
This file contains information about the individual animal tissues examined for gross and
microscopic pathology, the dosing regime, and the animals scheduled for hematology,
clinical chemistry, and/or urinalysis evaluation.
Item Field Length Description
1-6 Header record (see page 11)
7 8 Animal Number
8 12 Animal Necropsy Accession Number
9 10 Dose value for treated or control animals
10 1 Dose Code
1 = untreated controls
2 = vehicle controls
3 = positive controls
4-8 = optional groups
9 = animal was treated
11 1 Hematology Evaluation Code - Animal
included in hematology evaluation
1 = yes
2 = no
12 1 Clinical Chemistry Evaluation Code -
Animal included in clinical chemistry
evaluation
1 = yes
2 = no
13 1 Urinalysis Evaluation Code -Animal
included in urinalysis evaluation
1 = yes
2 = no
14 8 Date dosing started (MMDDYYYY)
15 - 8 Date dosing ended (MMDDYYYY)
16 8 Date of death (MMDDYYYY)
17 4 Interval between date dosing
started and date dosing ended in days
12
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FORMAT FOR ANIMAL.CHR (continued^
Item Field Length Description
18 4 Interval between date dosing
started and date of death in days
19 2 Animal Disposition
1 = Death on Study
2 = Interim Sacrifice # 1
3 - Interim Sacrifice # 2
4 = Interim Sacrifice # 3
5 = Terminal Sacrifice
6 — Missing animal
7 = Accidental kill animal
8 = Moribund sacrifice
9 or greater = optional, use
TEXT.CHR file to explain
20 10 Cage Identification
21 1 Ever Examined Code
1 s at least one tissue was examined
2 = no tissues were examined
22 1 Tissue Examination Code
1 = tissue examined, suitable
specimen
2 = tissue examined, unsuitable
specimen
3 = tissue not examined
23 2 Number of Tissue Sections
24 2 Number of Slides Prepared
25 1 Autolysis Code
1 = tissue was at least partially
autolyzed
2 = tissue was not autolyzed
3 = not applicable (tissue not examined)
Thus, there are as many sets of Tissue Examination Codes, Number of Tissue Sections,
Number of Slides Prepared, and Autolysis Codes as there are number of tissues examined
in Item 29 of INDEX.CHR.
13
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FORMAT FOR PATH.CHR
This file contains the individual animal pathology incidence data.
_ Item Field Length _ Description _ _
1-6 Header record (see page 11)
7 8 Animal Number
8 3 Field Count - the number of distinct
pathology descriptions given for this
9 16 Pathology Code
Up to 16 characters for lesions code from
the PATHGLOS.CHR file. Dependent
upon specific glossary. Only codes for
observed lesions are to be recorded.
Default is the NTP SNOP codes.
10 2 Tissue code
The tissue code from the TISSUE.CHR
file for the observed pathology.
11 1 Lesion Distribution Code
1 = focal
2 = multifocal
3 = diffuse
4 = segmental
5 = diffuse, multifocal
6 = other
7 = not applicable, neoplastic lesion
12 2 Multiplicity code
The number of lesions described in Item
9 above for this tissue
13 1 Severity Code
As defined by the company and explained
in TEXT.CHR
14 1 Lesion Disposition Code
1 = Lesion present, primary cause of
death
. 2 = lesion present, contributory cause
of death
14
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FORMAT FOR PATH.CHR (continued')
Item Field Length Description
3 = Lesion present, could not be
determined if cause of death
4 = Lesion present, not cause of death
5 = Lesion present, cause of death
determination not attempted
6 = Not a lesion
Items 9-14 would be repeated for as many distinct pathology observations in Item 10
Field Count. For example, if the value if Item 8 was 5, indicating 5 pathology
observations were to be described, there would be 5 sets of Items 9-14 to describe these
5 observations.
15
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FORMAT FOR BODYWT.CHR Body Weight Data
This file contains individual animal body weight information.
Item Fieli Length Description
1-6
7
8
9
10
11
Header record (see page 11)
8
10
3
3
10
Animal number
Dose value
Number of Distinct
Observations
Time of observation
Body weight - body
Time Periods
in Days
weight for time
of
in
Item 10.
Items 10 and 11 would be repeated for every time period in Item 9. Example, body
weight data for one year collected once a month would result in 12 pairs of time and
body weight data. The value of Item 9 would be 12.
16
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FORMAT FOR FQQDCS.CHR Food Consumption Data
This file contains individual animal food consumption information.
Item Field Length Pescription
1-6 Header record (see page 11)
7 8 Animal number
8 10 Dose value
9 1 Multiple Caged Animals code for food
consumption based on individual animal
values or cage averages.
1 = values are individual animal food
consumptions.
2 = values are cage averages.
10 3 Number of Distinct Time Periods of
Observation
11 3 Time of observation in Days
12 10 Food Consumption - food consumption for
time in Item 11.
Items 11 and 12 would be repeated for every time of food consumption data. Example,
food consumption data for one year collected once a month would result in 12 pairs of
time and food consumption data. The value of Item would be 12.
17
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FORMAT FOR ORGANWT.CHR Organ Weight Data
This file contains individual animal organ weight information.
Item Field Length Description
1-6
7 8
8 10
9 10
10 3
11 2
Header record (see page 11)
Animal number
Dose value for treatment groups
Final Body Weight - for calculation
organ-to-body weight ratios.
Time of observation in Days
Organ Code - use the same codes
of
as
defined in the TISSUE.CHR file
12 10 Organ Weight - organ weight for organ
coded in Item 11 and determined at time
in Item 10.
13 1 Bilateral Organ Code
1 = organ is not bilateral or weight is
for only one of the two bilateral
organs
2 = organ is bilateral and weight is
expressed as combined weight of
each organ
Items 11-13 would be repeated for each organ with one record per animal. If 10 organ
weight values are to reported, there would 10 combinations of time, organ code and
organ weight values.
18
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FORMAT F QT? CJJNOBS.CHR Clinical Observations
This file contains individual animal clinical observations with one animal per record.
This file contains information such as animal appearance, animal activity, and palpable
masses.
Item Field Length Description
1-6 Header Record (see page 11)
7 8 Animal Number
8 10 Dose value
9 3 Clinical Observation Field Count - the
number of different distinct clinical
observations for this animal by study end.
10 80 Clinical Observation Description
11 1 Palpable/Not Palpable Mass Designation
1 = if description described in Item 10
above is a palpable mass
2 = if description in Item 10 above is
not a palpable mass
12 2 Description Field Count - the number of
times the description in Item 10 above is
recorded for this animal.
13 8 First Date Observed - date observation in
Item 10 above was first observed
(MMDDYYYY)
14 8 Last Date Observed - date observation in
Item 10 above was last observed
(MMDDYYYY)
The dates in Items 13 and 14 above are used to describe a continuous time period
during which a specific clinical observation was observed. If the observation was observed
for only one week then only the date the observation was first observed (Item 13 above)
would be completed with the date last observed (Item 16) remaining blank. There are
as many pairs of Items 13 and 14 as there are field counts in Item 12. Items 10-14 would
be repeated for as many distinct pathology observations in Item 11, Clinical Observation.
Field Count. For example, if the value if Item 11 was 5, indicating 5 pathology
observations were to be described, there would be 5 combinations of Items 12-16 to
describe these 5 distinct types of clinical observations.
19
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FORMAT FOR HEMATO.CHR Hematology Data
This file contains individual animal hematology data with one record per animal.
Item Field Length Description
1-6 Header Record (see page 11)
7 8 Animal number
8 10 Dose value
9 2 Number of Measurements - maximum
number of hematology parameters
measured in each animal. This value
describes the number of measurements
beginning with Item 12. Certain
parameters listed below are required while
others are optional. Other parameters
not listed below may also be included.
Additional parameters are to be described
in TEXT.CHR. A default value of 6
should be used when the six required
measurements below are reported.
10 3 Number of Distinct Time Periods of
Observations
11 3 Time of observation in Days
•
12 10 Hematocrit (%)
13 10 Hemoglobin (g/d)
14 10 Leukocyte count (xlO3)
15 10 Erythrocyte count (xlO6)
16 10 Platelet count (xlO3)
17 10 Leukocyte differential count (%)
18 10 *Plateletcrit (%)
19 10 *Mean corpuscular Hb (pg)
20 10 . "Mean corpuscular Hb concentration (g/d)
20
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FORMAT FOR HEMATO.CHR ^continued')
Item Field Length Description
21 10 "Mean corpuscular volume (MM3)
22 10 'Reticulocyte count (%RBC)
23 10 •Thromboplastin time (seconds)
24 10 'Clotting time (seconds)
25 10 *Prothrombin time (seconds)
Items 11 through 25 would be repeated for every time period of hematology data
collection Example, hematology values measured at 3,6, and 9 months would result in 3
sets of items 11 through 25 as one record. The value of Item 10 would be 3.
* not generally required for chronic studies
21
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FORMAT FOR CLINCHEM.CHR Clinical Chemistry
This file contains individual animal clinical chemistry data with one record per animal.
Item Field Length Description
1-6 Header record (see page 11)
7 8 Animal number
8 10 Dose value
9 2 Number of Measurements - maximum
number of clinical chemistry parameters
measured in each animal. This value
describes the number of measurements
beginning with Item 12. Certain
parameters listed below are required
while others are optional. Other
parameters not listed below may also be
included. Additional parameters are to
be described in TEXT.CHR. A default
value of 14 should be used when only
the 14 required measurements below are
reported.
10 3 Number of Distinct Time Periods of
Observations
11 3 Time of observation in Days
12 10 Calcium (mg/d)
13 10 Chloride (mg/d)
14 10 Phosphorous (mg/d)
15 10 Potassium (mg/d)
16 10 Sodium (mg/d)
17 10 Albumin (g/d)
18 10 Blood urea nitrogen (mg/d)
19 10 Glucose (mg/d)
22
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FORMAT FOR CLINCHEM.CHR (continued)
Item
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
Field Length
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
Description
Blood creatinine (mg/d)
Cholesterol (mg/d)
Total serum protein (g/d)
Creatine phosphokinase
(u/d)
Serum alanine aminotransferase (SGPT)
(u/d)
Serum aspartate
aminotransferase SCOT) (u/d)
•Magnesium (mg/d)
•Triglyceride (mg/d)
•Total bilirubin (mg/d)
•Alkaline phosphatase (u/d)
•Cholinesterase (u/d)
•Lactic acid dehydrogenase (u/d)
•gamma glutamyl transferase (u/d)
•Glutamate dehydrogenase (u/d)
*alpha-l-globulin (g/d)
•alpha-2-globuUn (g/d)
•beta-globulin (g/d)
•gamma-globulin (g/d)
Items 11-37 would be repeated for every time of clinical chemistry data collection.
Example, clinical chemistry values measured at 3,6, and 9 months would result in 3 sets
of items 12-37 as one record. The value of Item 10 would be 3.
• not generally required for chronic studies.
23
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FORMAT FOR URINAL.CHR Urinalysis Data
This file contains individual animal urinalysis data with one animal per record.
Item Field Length Description
1-6 10 Header record (see page 11)
7 8 Animal number
8 10 Dose value
9 2 Number of Measurements - maximum
number of urinalysis parameters
measured in each animal. This value
describes the number of measurements
beginning with Item 12. Certain
parameters listed below are required
while others are optional. Other
parameters not listed below may also be
included. Additional parameters are to
be described in TEXT.CHR. A default
value of nine should be used when only
the nine required measurements below
are reported.
10 3 Number of Distinct Time Periods of
Observations
11 3 Time of observation in Days
12 10 Volume (ml)
13 10 Specific gravity
14 1 Protein
0 = measurement performed, not
present
1-8 = values for possible grading scale.
Scale to be described in
TEXT.CHR
9 = measurement not performed
15 1 Glucose
0 = measurement performed, not
present
1-8 = values for possible grading scale.
24
-------
FORMAT FOR URINAL.CHR (continued*!
Jtem Field Length Description
Scale to be described in
TEXT.CHR
9 = measurement not performed
16
17
18
19
20
21
22
25
25
10
10
Ketones
0 = measurement performed, not
present
1-8 = values for possible grading scale.
Scale to be described in
TEXT.CHR
9 = measurement not performed
Bilirubin
0 = measurement performed, not
present
1-8 = values for possible grading scale.
Scale to be described in
TEXT.CHR
9 = measurement not performed
Blood
0 = measurement performed, not
present
1-8 = values for possible grading scale.
Scale to be described in
TEXT.CHR
9 = measurement not performed
Sediment (microscopic) - description of
finding
Appearance - description of finding
*PH
•Nitrate
0 = measurement performed, not
present
1-8 = values for possible grading scale.
Scale to be described in
TEXT.CHR
9 = measurement not performed
25
-------
FORMAT FOR URINAL.CHR (continued^
Item Field Length Description
23 10 'Urobilogen
0 = measurement performed, not
present
1-8 = values for possible grading scale.
Scale to be described in
TEXT.CHR
9 = measurement not performed
Items 11-23 would be repeated for every time of urinalysis data collection. Example,
urinalysis values measured at 3, 6 , and 9 months would result in 3 sets of item 11-23
as one record. The value of Item 10 would be 3.
* not generally required for chronic studies
26
-------
FORMAT FOR PATHGLOS.CHR
Optionally, this file can be provided by the company if they do not wish to use the
default NTP SNOP codes, which exist as a file with this format. Each Pathology Code,
Pathology Description and Tissue Code occur as one record.
Item Field Length Description
1-6 Header record (see page 11)
7 16 Pathology Code
8 100 Pathology description corresponding to
the pathology code
9 2 Tissue Code - from the list provided by
the submitter in TISSUE.CHR as default
NTP codes.
27
-------
FORMAT FOR TISSUE.CHR
Optionally, this file can be submitted by the company if they do not wish to use the
default NTP tissue codes, which exist as a file with this format. Each Tissue Code and
Tissue Description occur as one record.
Item
1-6
7
8
Field Length
2
100
Description
Header record (see page
Tissue Code
Tissue Description
10)
If a company submits its own list of Tissue Codes, a PATHGLOS.CHR file must also
be submitted with the correct tissue codes. This is true even if the company uses the
NTP SHOP Codes for pathology .
28
-------
FORMAT FOR TEXT.CHR
This file would contain any optional individual animal data that the company wished to
provide on an individual animal basis. The format for this file would be structured but
can vary in format and would have to be submitted by the company. This file could
contain a variety of different information. It would contain any additional data that the
company wished to submit to support their position that is not provided for in these
formats, including any codes used to qualify the data. This file would also be used to
explain any optional codes for data in these formats, i.e., additional codes for animal
dispositions as described in ANIMAL.CHR Items 21. This file would also be used to
describe in narrative form any peculiarities in the study as well as descriptions of gross
pathology observations. It is to be used by each respective Agency as needed. It is also
possible to have multiple TEXT.CHR files with names such as TEXT1.CHR,
TEXT2.CHR, etc.
This file must also contain a list of the files being submitted with this package, i.e, the
ten files containing data from the chronic/oncogenicity study, the two optional files
containing the NTP Tissue codes and the NTP SNOP codes, and any TEXT.CHR files.
This file must begin with the 'header record'. In addition, this file must also contain a
description of the experimental design of the study including any satellite groups.
29
-------
DETAILED FIELD DESCRIPTIONS
This section provides the detailed descriptions of the data files described above. A
definition of each field is provided. When using these descriptions it should be kept in
mind that each file is made of a number of data records with one record per animal,
with the exception of the 'header record', one record at the beginning of each file
(except INDEX.CHR) that contains background information from the study and is used
as the logical link between all data files for a study.
30
-------
INDEX.CHR
1. Record Type - This is a one character field used to denote if the data in this
file is in fixed or variable format. A fixed record format is designated with an
'F. A variable record format is designated with a 'V. For variable length
records a '#' is used to indicate the end of a field. For files submitted in
variable length formats, the field length in characters described below would not
be used. Instead the field would contain as many characters as needed to
display the value of the field, with the '#' symbol denoting the end of the field.
The next field would then begin with the next position. Under the variable
length format, a field that is not used is represented by '##' to indicate that the
field is empty. A '$' would be used to indicate the end of a record. An '$$'
would be used to indicate the end of a file. Under the fixed format, the
required number of columns must remain vacant to describe a field that is
empty.
2. Chemical Name 1 - A 200 character field for the chemical name.
3. Chemical Name 2 - A 100 character field for the chemical name. This field is
used for synonyms or alternative names to the chemical in Item 2 above.
4. Study Type Description - A 100 character field for a description of the study
type (i.e., chronic/oncogenicity bioassay).
5. Study Sponsor - A 100 character field for the name of the company sponsoring
the study.
6. Study Beginning Date - The date on which the study began (i.e., dosing began)
in the form MMDDYYYY in which MM is a two-digit number for .the month,
DD is a two-digit number for the day, and YYYY is a four-digit number for the
year. The date January 15, 1989, would be represented as 01151989.
7. Study Ending Date - The date on which the study ended (i.e., the last animal
was sacrificed) in the form MMDDYYYY. The date December 20, 1991, would
be represented as 12201991.
8. Conducting Laboratory - A 100 character field for the name of the laboratory
at which the study was conducted.
9. Animal Species - A 50 character field for the species of animal used in the
study.
10. Animal Strain - A 50 character field for the strain of animal used in the study.
11. Source of Animal - A 100 character field for the source of
the animals for the study including address and location.
31
-------
INDEX.CHR (continued')
12. Study Identification Code 1 - A fifteen character code used for a study code
provided by the laboratory conducting the study.
13. Study Identification Code 2 - A fifteen character code used for a study code
provided by the study sponsor. This may be a different number than Study
Identification Code 1 if the study was not performed at the sponsor's laboratory.
14. Study Identification Code 3 • A fifteen character code used as a code by the
Agency reviewing the data. This code will be added to the file by the reviewing
Agency and should be submitted blank.
15. Pathologist - A 50 character field for the study pathologist.
16. External Peer Review - A one character field indicating if an outside peer
review has been performed on the study. A T indicates no external peer review
has been conducted. A '2' indicates that a peer review has been conducted.
17. Route of Administration - A 50 character field to describe the how the
chemical was administered to the animals in the study, i.e., dermal, oral, dietary.
18. Days of Dosing - A two character field for the number of days per week the
animals were dosed. A feeding in which animals were administered the chemical
in their diet would be indicated by a value of '7', indicating the animals were
dosed each day of the week. A dermal injection in which animals were dosed
twice a week by injection would be indicated by a value of '2'.
19. Dose Unit Code - A two digit field used to describe the dosing units. For A
value of T is used to indicate dosing in ppm, a value of '2' is used to indicate
dosing in mg/kg. Other dosing unit codes can be used and should be described
in TEXT.CHR.
20. Dosing Regimen - A 240 character field for the description of the dosing
regimen and provides the doses used for the study. This field is also used to
describe changes in the dosing pattern or peculiarities in the dosing regimen. For
example, a study with a vehicle control, a positive control, and two treated
groups may be described as 'VEHICLE CONTROL, POSITIVE CONTROL, 100
PPM, and 1000 PPM DOSE GROUPS OF 50 ANIMALS'.
21. Number of Dose Groups - a two digit field used to indicate the number of dose
groups in the study.
22. Number of Animals per Dose Group by Study Design - a three digit, field used
to indicate the number animals in each dose group. Each value is treated as a
separate field with as many fields as the value of Item 21 above.
32
-------
INDEX.CHR (continued*)
23. Number of Satellite Groups - a two digit field used to indicate the number of
satellite groups used in the study.
24. Number of Animals in each Satellite Group - a three digit field used to indicate
the number gui'm^k in each satellite group. Each value is treated as a separate
field with as many fields as the value of Item 23 above.
25. Number of Animals per Cage - a two digit field used to indicate the number of
animals to each cage by study design.
26. Sex - A one character field indicating the sex of the animals under study. A
value of 'M' is used to designate males; an 'F is used to designate females.
Each sex will have a separate set of STUDIES files.
27. PATHGLOS.CHR File Code - A six character field to indicate which pathology
glossary file is being used for pathology descriptions. This field is assigned by
the Agency after approval of the pathology glossary, and includes a two-digit
code identifying the Agency, a two-digit code identifying the company submitting
the glossary, and a two-digit code identifying the version of the code. For
example, a pathology glossary file code of 010203 may indicate a glossary
approved by the US EPA (01) by Company X (02) as the third glossary (03)
approved for that company. Specific glossary file codes are the responsibility of
the Agency to which the data are submitted. The default PATHGLOS.CHR
Code File is the NTP SHOP codes.
28. File Version Date - An eight character field in the form MMDDYYYY (see
description in 6 above) used to indicate the date the current file of data is being
submitted.
29. Number of Tissues Examined - A three character field used to indicate the
number of tissues examined for pathology observations. The value of this field
is the same as the number of pairs of Tissue Examination Codes and Autolysis
Codes in ANIMAL.CHR.
30. TISSUE.CHR File Co4g - A six character field used to designate the tissue code
file which provides the codes for each tissue examined in the study. The
structure of this field is the same as the PATHGLOS.CHR File Code. The
default file is the NTP Tissue Codes in Appendix A. If a company submits its
own list of Tissue Codes, a PATHGLOS.CHR file must also be submitted with
the associated tissue codes. This is true even if the company uses the NTP
SNOP Codes for pathology .
31. Body Weight Unit Measurement - the unit of measurement of the body weight
data where, M = milligrams (mg), G = grams (g), and K = kilograms (kg).
33
-------
INDEX.CHR (continued)
32. Food Consumption Unit Measurement - the unit of measurement of the food
consumption data where, M = milligrams (mg), G = grams (g), and K =
kilograms (kg).
33. Organ Weight Measurement Unit - the unit of measurement of the food organ
weight data where, M = milligrams (mg), G = grams (g), and K = kilograms
(kg).
34
-------
ANIMAL.CHR
1-6. " Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMAL.CHR file and the information is unique to
that study, the information in the header record is used to identify a study
and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal T
8. Animal Necropsy Number - A twelve character field for the unique identifier of
each animal used in the necropsy process. This field would be used in a
situation when the necropsy number is different from the animal number;
otherwise it would remain blank.
9. Dose Value - A ten character field for the dose value administered to the
animal. Control groups should also be coded.
10. Dose Treatment - A one character field containing a code for dose treatment.
The codes are as follows:
1 = untreated controls
2 = vehicle controls
3 - positive controls
4-8 = optional groups
9 = animal was treated
Codes 1-3 are used to identify the type of control used in the study. Values of
4-8 are used to identify other types of controls. A value of 9 is used when the
animal is a treated animal.
11. Hematology Evaluation Code - A one character field to indicate if the animal
was part of the hematology evaluation. A value of 1 is used to indicate 'Yes',
and a value of 2 is used to indicate 'No'.
12. Clinical Chemistry Evaluation Code - A one character field to indicate if the
animal was part of the clinical chemistry evaluation. A value of 1 is used to
indicate 'Yes', and a value of 2 is used to indicate 'No'.
13. Urinalysis Evaluation Code - A one character field to indicate whether the
animal was part of the urinalysis evaluation. A value of 1 is used to indicate
35
-------
ANIMAL.CHR (continued^
'Yes', and a value of 2 is used to indicate 'No'.
14. Date Dosing Started - The date dosing began in each animal in the format
MMDDYYYY (see Item 6 in the INDEX.CHR detailed field description for
format).
15. Date Dosing Ended - The date dosing ended for each animal in the format
MMDDYYYY (see Item 6 in the INDEX.CHR detailed descriptions for format).
16. Date of Death - The date each animal died in the format MMDDYYYY (see
Item 6 in the INDEX.CHR detailed instructions).
17. Interval between date dosing started and date dosing ended -The time interval in
days that has elapsed between the date dosing started for each animal and the
date that dosing ended.
18. Interval between date dosing started and date animal died - The time interval in
days that has elapsed between the date dosing started for each animal and the
date each animal died.
19. Animal Disposition - A one character value for a code describing the type of
death or final condition of each animal. The codes to be used are as follows:
1 = Death on Study
2 = Interim Sacrifice # 1
3 = Interim Sacrifice # 2
4 = Interim Sacrifice # 3
5 - Terminal Sacrifice
6 = Missing Animal
7 = Accidental kill animal
8 = Moribund sacrifice
9 or greater = optional disposition
A value of 1 is used to describe animals that are found dead during the course
of the study apparently of natural causes and no intervention. A value of 2-4 is
used to indicate animals that were sacrificed as part of a scheduled kill other
than a terminal sacrifice. These codes allow up to 3 such sacrifices. If greater
than three interim sacrifices are scheduled a value of 9 or greater is used. A
value of 5 is used to indicate animals that are sacrificed as part of a scheduled
sacrifice at the termination of the study. A value of 6 is used to indicate
animals that become missing during the course of the study. A value of 7 is
used for animals that are accidentally killed during the study. A value of 8
is used for animals that are sacrificed in a moribund condition or in extremis.
Values of 9 and greater are use for animals that die from conditions other than
those described by codes 1 through 8. (If these values of 9 or greater are used,
the descriptions associated with each code is to be submitted in TEXT.CHR.
36
-------
ANIMAL.CHR (continued')
20. Cage Identification - A ten character field for an animal cage identification.
21. Ever Examined Code - A one character field used to indicate if any tissues from
an animal were ever examined for pathological events. A value of 1 is used to
indicate that at least one tissue was examined. A value of 2 is used to indicate
that no tissues were examined.
22. Tissue Examination Code - A one character field used to indicate if a particular
tissue was examined for pathological events. A value of 1 is used to indicate the
tissue was examined and was suitable for evaluation, a value of 2 is used to
indicate the tissue was examined but was unsuitable for evaluation, or a value of
3 is used to indicate that the tissue was not analyzed.
23. Number of Tissue Sections - A two digit field for the number of sections
examined for that tissue.
24. Number of Slides Prepared - A two digit field for the number of slides that
were prepared for examination. It is assumed that all prepared slides will be
examined.
25. Autolvsis Code - A one character fields used to indicate the autolysis condition
of the tissue being examined. A value of 1 is used to indicate that the tissue
was at least partially autolyzed. A value of 2 is used to indicate that the tissue
was not autolyzed. A value of 3 is used to indicate that the tissue is designated
not applicable because it was not examined. In this situation the Tissue
Examination Code in 22 above must have a value of 3.
There are as many combinations of Items 22 through 25 as there are number of
tissues to be examined as reflected in Item 29 of INDEX.CHR.
37
-------
PATH.CHR
1-6. Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMALCHR file and the information is unique to the
study, the information in the header record is used to identify the study
and all files submitted with it
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Field Count - A 3 character field for indicating the distinct number of
pathological observations for the animal. For example, if 15 different lesions are
coded and described, this value would be 15. It will vary between animals as
the number of pathological observations varies.
9. Pathology Code - A 16 character code for the pathological condition observed in
the animal These are described in the PATHGLOS.CHR file which is
identified by Item 27, PATHGLOS.CHR File Code, in the INDEX.CHR file.
10. Tissue Code - A two character field for the tissue in which the pathology
observation coded in Item 9 above is found. These are described in the
TISSUE.CHR file which is identified by Item 30, TISSUE.CHR File Code in the
INDEX.CHR file.
11. Lesion Distribution Code - A one digit field to describe the distribution of the
pathology observation coded in Item 9 above. The codes are as follows:
1 = focal
2 = multifocal
3 = diffuse
4 = segmental
5 = diffuse, multifocal
6 = other
7 = not applicable, observation is a neoplastic lesion
If a code of '6' is used to indicate the lesion distribution is different from the
available codes, the additional codes should be described in TEXT.CHR.
12. Multiplicity Code - A two digit field to describe the occurrence of multiple
lesions. It is the number of the same type of lesion found in the tissue.
38
-------
PATH.CHR fcnntimied'l
13. Severity Code - A one character field to describe the severity of the pathological
observation. If used, the codes for this field are to be described in the
TEXT.CHR file.
14. Lesion Disposition Code - A one character field to describe the condition of
the observed lesion. The codes are as follows:
1 = Lesion present and the lesion is the primary cause of death
of the animal
2 = Lesion present and the lesion is a contributory cause of
death of the animal
3 = Lesion present, but the relationship of the lesion to the
cause of death while attempted
could not be determined
4 = Lesion present, but it did not cause the death of the animal
5 = Lesion present, but the cause of death of the animal is not
attempted
6 = The pathological observation is not a lesion.
There are as many combinations of Items 9-14 as there are values of Item 8,
Field Count.
39
-------
BODYWT.CHR
This file contains the individual body weights of the animals in the study.
1-6. Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMAL.CHR file and the information is unique to the
study, the information in the header record is used to identify the study
and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value for Treatment Groups - A ten character field for the dose value
administered to the
9. Number of Distinct Time Periods of Observations - A three digit field for the
number of different time periods for which body weight values are to be
reported.
10. Time of Observation - A three character field for the time for which the body
weight value in Item 11 below is associated. This value must be in days.
11. Body Weight Value - A ten character field for the body weight of the animal for
the time in Item 10 above.
Items 10 and 11 are repeated for every time for which body weight data are
presented. If the value of Item 9 is 12 indicating that 12 sets of body weight
values are to be reported, there would be 12 sets of Items 10 and 11.
40
-------
FOODCS.CHR
This file contains the individual food consumption of the animals in the study.
1-6. Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMAL.CHR file and the information is unique to the
study, the information in the header record is used to identify the study
and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value for' Treatment Groups - A ten character field for the dose value
administered to the animal.
9. Multiple Caged Animal - A one digit code to indicate if the food consumption
values are based on individual animal measurements or on cage averages. A
value of T indicates food consumption values are for individual animals, a value
of '2' indicates that values are based an cage averages.
10. Number of Distinct Time Periods of Observations - A three digit field for the
number of different time periods for which food consumption values are to be
reported.
11. Time of Observation - A three character field for the time for which the food
consumption value in Item 12 below is associated. This value must be in days.
12. Food Consumption Value - A ten character field for the food consumption value
for the animal for the time in 11 above.
Items 11 and 12 are repeated for every time for which food consumption data
are presented. If the value of Item 10 is 12 indicating that 12 sets of food
consumption values are to be reported, there would be 12 sets of Items 11 and
12.
41
-------
ORGANWT.CHR
This file contains the individual organ weight values of the animus in the study.
1-6. Deader Record - The first record of the file is the header record which contains
6 fields from the INDEX.CHR file. This record is the first record of all
subsequent files associated with this study. It serves as the method of
identification of all files associated with this study. Since every study contains an
ANIMAL.CHR file and the information is unique to the study, the information
in the header record is used to identify the study and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value for Treatment Groups - A ten character field for the dose value
Administered to the animal.
9. Final Body Weight - A ten digit field used for the final body weight of the
animal to be used in calculating organ-to-body weight ratios.
10. Time of Observation in Days - A three character field for the time for which the
organ weight value in Item 12 below is associated. This value must be in Days.
11. Organ Code - A two character code for the organ. This code must coincide
with the tissue codes presented in the TISSUE.GHR file.
12. Organ Weight - A ten character value for the organ weight for the animal for
the time in Item 10 and the organ in Item 11 above.
13. Bilateral Organ Code - A one character code indicating if the condition of the
organ weight for bilateral organs. Thie code is used to distinguish between
weights for bilateral organs where the weight reported for one of the bilateral
organs from where the weight reported is the sum of both bilateral organs. A
code of T is used if the organ is not a bilateral organ or if one of a pair of
bilateral organ weights is being reported. A code of '2' is used if the organ
weight being reported is bilateral and the combined weight of both organs is
being reported.
Items 10-13 are repeated for every time for which organ weight data are
presented.
42
-------
dJNOBS.CHR
This file contains information on the clinical observations made for each animal during
the course of the study.
1-6. Header Record - The first record of the file is the header record which contains
6 fields from the INDEX.CHR file. This record is the first record of all
subsequent files associated with this study. It serves as the method of
identification of all files associated with this study. Since every study contains an
ANIMAL.CHR file and the information is unique to the study, the information
in the header record is used to identify the study and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value ...for....Treatment Groups - A ten character field for the dose value
administered to the animal.
9. Clinical Observation Field Count - A 3 character field for indicating the distinct
number of clinical observations for the animal. For example, if IS different
clinical observations are coded and described, this value would be 15. It will
vary between animals as the number of clinical observations varies.
10. C]jnigaJiObservation Description - An 80 character field use for the description
of the clinical observation.
11. Palpable Mass/Not Palpable Mass Designation - A one character field used to
indicate if the description described in 12 is or is not a palpable mass. This is
used to indicate palpable masses. A value of T is used to indicate that the
observation is a palpable mass. A value of '2' is used to indicate that the
observation is not a palpable mass.
12. Observation Field Count - A two digit number to indicate if how many
observation periods described in Item 10 are to be recorded for this animal.
13. First Date Observed - the date the clinical observation in 15 above was first
observed in the MMDDYYYY format
14. Last Date Observed - the date the clinical observation in 15 above was last
observed. The dates in Items 13 and 14 are used to describe a continuous time
period during which a specific clinical observation was observed. If the
observation was observed for only one week then only the date the observation
43
-------
CLINOBS.CHR (continued^
was first observed (Item 13 above) would be completed with the date last
observed (Item 14) remaining blank. There are as many pairs of Items 13 and
14 as there are field counts in Item 12.
Items 11-14 would be repeated for as many distinct pathology observations in
Item 9 Clinical Observation Field Count. For example, if the value if Item 13
was 5, indicating 5 pathology observations were to be described, there would be
5 combinations of Items 11-14 to describe these 5 observations.
44
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HEMATO.CHR
This file contains information on hematology parameters.
1-6. Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMAL.CHR file and the information is unique to the
study, the information in the header record is used to identify the study
and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value for Treatment Groups - A ten character field for the dose value
administered to the animal.
9. Number of Measurements - A two digit field used for the maximum number of
hematology parameters per animal being reported in this file. Fourteen
parameters are listed below in Items 13-26. If all of these parameters were
measured in each animal the value of his field would be 14. A default value of
8 should be used for the 8 required measurements. Certain of the parameters
below may be optional for chronic studies (indicated by an asterisk).
10. Number of Distinct Time Periods of Observations - A three digit field for the
number of different time periods for which hematology values are to be
reported.
11. Time of Observation - A three character field for the time for which the
hematology parameters items below is associated. This value must be in days.
12. Hematocrit - the value is expressed as a percentage (%).
13. Hemoglobin - the value is expressed in g/dl.
14. Leukocyte Count - the value is expressed in xlO3.
15. Ervthrocvte Count -the value is expressed in xlO6.
16. Platelet - the value is expressed in xlO3.
17. Leukocyte Count - the value is expressed in percentage (%).
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18. Plateletcrit - the value is expressed in percentage (%).
19. Mean Corpuscular Hb - this value is expressed in picograms
(Pg).
20. *Mean corpuscular Hb concentration - this value is expressed in g/d.
21. *Mean Corpuscular Volume - this value is expressed in MM3.
22. *Reticulocyte Count - this value is expressed as percent red blood cells.
23. *Thromboplastin Time - this value is expressed in seconds.
24. *Clotting Time - this value is expressed in seconds.
25. *Prothrombin Time this value is expressed in seconds.
Items 11 through 25 would be repeated for every time period of hematology data
collection with one record per animal.
* not generally required for chronic studies
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CLINCHEM.CHR
This file contains information on clinical chemistry parameters.
1-6. Header Record - The first record of the file is the header record which contains
6 fields from the INDEX.CHR file. This record is the first record of all
subsequent files associated with this study. It serves as the method of
identification of all files associated with this study. Since every study contains an
ANIMAL.CHR file and the information is unique to the study, the information
in the header record is used to identify the study and all files submitted with it.
The remaining records the file contain specific lexicological data with one record per
Animal. Thus a file for an animal study with 240 animals would have 241 records
including the header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value for Treatment Groups - A ten character field for the dose value
administered to the animal.
9. Number of Measurements - A two digit field used for the maximum number of
clinical chemistry parameters per animal being reported in this file. Twenty-six
parameters are listed below in Items 12-37. If all of these parameters were
measured in each animal the value of his field would be 26. A default value of
14 should be used for the 14 required measurements. Certain of the parameters
below may be optional for chronic studies (indicated by an asterisk).
10. Number of Distinct Time Periods of Observations - A three digit field for the
number of different time periods for which clinical chemistry values are to be
reported.
11. Time of Observation in Days - A three character field for the time for which the
clinical chemistry parameters items below is associated. This value must be in
days.
12. Calcium - this value is expressed in mg/d.
13. Chloride - this value is expressed in mg/d.
14. Phosphorous - this value is expressed in mg/d.
15. Potassium - this value is expressed in mg/d.
16. Sodium - this value is expressed in mg/d.
17. Albumin - this value is expressed in g/d.
47
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CLINCHEM rHR fcontinued^
18. Blood Urea Nitrogen - this value is expressed in mg/d.
19. Glucose - this value is expressed in mg/d.
20. Blood Creatinine - this value is expressed in mg/d.
21. Cholesterol - this value is expressed in mg/d.
22. Total Serum Protein - this value is expressed in g/d.
23. Creatinine phosphokinase - this value is expressed in u/d.
24. Serum Alanine Aminotransferase (SGPT) - this value is expressed in u/d.
25. Serum Aspartate Aminptransferase (SGOT) - this value is expressed in u/d.
26. "Magnesium - this value is expressed in mg/d.
27. *Triglyceride - this value is expressed in mg/d.
28. 'Total Bilirubin - this value is expressed in mg/d.
29. 'Alkaline phosphatase - this value is expressed in u/d.
30. * Cholinesterase - this value is expressed in u/d.
31. ^Lactic Acid Dehydrogenase - this value is expressed in u/d.
32. 'gamma - Glutamyl Transferase - this value is expressed in u/d.
33. "Glutamate dehydrogenase - this value is expressed in u/d.
34. *alpha-l-globulin - this value is expressed in g/d.
35. * alpha-2-globulin - this value is expressed in g/d.
36. *beta-globulin - this value is expressed in g/d.
37. * gamma-globulin - this value is expressed in g/d.
Items 11 through 37 would be repeated for every time of clinical chemistry data
collection with one record per animal.
* not generally required for chronic studies
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URINAL.CHR
This file contains information on urinalysis parameters.
1-6. Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMAL.CHR file and the information is unique to the
study, the information in the header record is used to identify the study
and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Animal Number - An eight character field for the unique identifier of each
animal.
8. Dose Value for Treatment Groups - A ten character field for the dose value
administered to the animal,
9. Number of Measurements - A two digit field used for the maximum number of
urinalysis parameters per animal being reported in this file. Twelve parameters
are listed below in Items 12-23. If all of these parameters were measured in
each animal the value of his field would be 12. This value should be used as
the default value since these 12 measurements are required. A default value of
9 should be used for the 9 required measurements. Certain of the parameters
below may be optional for chronic studies (indicated by an asterisk).
10. Number of Distinct Time Periods of Observations - A three digit field for the
number of different time periods for which hematology values are to be
reported.
11. Time of Observation - A three character field for the time for which the
urinalysis parameters below is associated. This value must be in days.
12. Volume - the volume of the urine is expressed in milliliters (ml).
13. Specific Gravity - the value is expressed in g/g.
14. Protein - A scaled coding system is used for this parameter depending on the
magnitude or the severity of the response. A value of '0* is used to indicate that
while the measurement was performed, the parameter was not observed. Values
of T through '8' are used to indicate the magnitude or the severity of the
response. A value of '9' is used to indicate that the measurement was not
performed for that animal. A description of the scale used is to be provided in
49
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URINAL.CHR (continued")
TEXT.CHR.
15. Glucose - A scaled coding system is used for this measurement See 14 above
for codes.
16. Ketones - A scaled coding system is used for this measurement See 14 above
for codes.
17. Bilirubin - A scaled coding system is used for this measurement See 14 above
for codes.
18. Blood - A scaled coding system is used for this measurement See 14 above for
codes.
19. Sediment - a 25 character field used to describe the microscopic sediment
findings in urine.
20. Appearance - a 25 character fields used to describe the appearance of the urine.
21. *pH - a ten character field for the pH of the urine.
22. 'Nitrate - A scaled coding system is used for this measurement See 14 above
for codes.
23. *Urobilogen - A scaled coding system is used for this measurement See 14
above for codes.
Items 12-23 would be repeated for every time of urinalysis data collection with one
record per animal.
* not generally required for chronic studies
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PATHGLOS.CHR
This file contains codes and descriptions for each code for pathological observations. A
default PATHGLOS.CHR has been established for submitters that do not provide their
own pathology file. The default code is the National Toxicology Program's Standard
Nomenclature of Pathology (SNOP). Copies of these programs are included.
Alternatively, this file can be provided by the company if they do not wish to use the
default NTP SNOP codes. However, the submitted PATHGLOS.CHR file must be in
the format described below and must be approved by the agency to which the data are
being submitted. It is envisioned that a file approved by one agency would be
acceptable to all other agencies using these formats. This would provide consistency
between agencies and eliminate the need for submitters to supply each agency with a
different pathology coding scheme. Once a file is approved, it will be assigned a
PATHGLOS.CHR File Code which is to submitted with the data in Item 24 of
INDEX.CHR.
1-6. Header Record - The first record of the file is the header record which
contains 6 fields from the INDEX.CHR file. This record is the first
record of all subsequent files associated with this study. It serves as the
method of identification of all files associated with this study. Since every
study contains an ANIMAL.CHR file and the information is unique to the
study, the information in the header record is used to identify the study
and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Pathology Code - A 16 character field used for the pathology observation code.
8. Pathology Description - A 100 character field used for the pathology description
associated with the Pathology Code in 7 above.
9. Tissue Code - A two character field for the tissue code associated with the
Pathology Code and Pathology Description in 7 and 8 above. These codes must
correspond with the code submitted in TISSUE.CHR or the default NTP Tissue
Codes.
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TISSUE.CHR
This file contains codes and descriptions for each tissue examined in the study. A
default TISSUE.CHR has been established for submitters that do have or do not wish
to provide their own tissue file. The default code is the National Toxicology Program's
tissue list. Copies of the file can be obtained from each responsible agency.
1-6. Header Record - The first record of the file is the header record which contains
6 fields from the INDEX.CHR file. This record is the first record of all
subsequent files associated with this study. It serves as the method of
identification of all files associated with this study. Since every study contains an
ANIMAL.CHR file and the information is unique to the study, the information
in the header record is used to identify the study and all files submitted with it.
The remaining records contain specific lexicological data with one record per animal.
Thus a file for an animal study with 240 animals would have 241 records including the
header record.
7. Tissue Code - A two character field for the tissue code.
8. Tissue Description - A 100 character field for the tissue description associated
with the tissue code in 7 above.
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VII. Data Submission Specifications
For the U.S. EPA, data is to be submitted only on 5.25 inch high density diskettes in
ASCII file format. EPA would also prefer the use of the FIXED format data files.
Other Agencies involved in this effort may allow a variety of electronic media for
electronic data submission. Each agency should be contacted concerning its own media
specifications.
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APPENDIX A
List of Tissues and Tissue Codes
54
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Code Tissue
26 Regional Lymph Node
27 Blood Smear
28 Skin
29 Mandibular Lymph Node
30 Mammary Gland
31 Salivary Gland
32 Thigh Muscle
33 Sciatic Nerve
34 Bone Marrow
35 Costochondral Junction Rib
36 Thymus
37 Larynx
38 Trachea
39 Lungs and Bronchi
40 Heart
41 Thyroid
42 Parathyroids
43 Esophagus
44 Stomach
45 Duodenum
46 Jejunum
47 Heum
48 Colon
49 Rectum
50 Mesenteric Lymph Nodes
51 Liver
52 Gall Bladder
53 Pancreas
54 Spleen
55 Kidneys
56 Adrenals
57 Bladder
58 . Seminal Vesicles
59 Prostate
60 Testes
61 Ovaries
62 Uterus
63 Nasal Cavity
64 Brain
65 Pituitary
66 Eyes
67 External and Middle Ear
68 Spinal Cord
69 Other
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APPENDIX B
List for SNOP Codes for Pathology
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