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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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. ------- 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 ------- 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. ------- 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 ------- organization of toxicological data for exchange of data and information within the regulated industries. ------- 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. ------- 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. ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 ------- 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 (%). 45 ------- 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 46 ------- 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 ------- 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 48 ------- 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 ------- 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 50 ------- 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. 51 ------- 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. 52 ------- 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. 53 ------- APPENDIX A List of Tissues and Tissue Codes 54 ------- 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 55 ------- APPENDIX B List for SNOP Codes for Pathology 56 ------- |