Document VJE5KE62X29wxJvXeEKEgKnrN

Chemical Manufactures Association November 25,1997 Dear Vinyl Chloride Health Committee Members: Enclosed is the Unaudited Draft Final Report on the Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats. Please review it and make comments by COB December 12,1997. If you have any questions, please call Wendy K. Sherman at 703/741-5639. Thank you. Sincerely/ Cynthia Barrett Senior Admin Asst., Vinyl Chloride Health Committee BFG420I8 Innovation, Tfchnqlocy amj Re-.ponmkle Care* At Work I 300 WiiffiN Hi vo., AklinctOn, VA 22309 TeLtPHriM! 703 741 -3000 * Pax 7U.J-741 -6000 BFG 01532 Huntingdon STUDY NO. 96-4080 VINYL CHLORIDE COMBINED INHALATION TWO-GENERATION REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDY IN CD RATS Unaudited Draft Pinal Report Submitted to: Chemical Manufacturers Association Chemsar Department 1300 Wilton Boulevard Arlington, Virginia 33209 Ann: Hasmukh C. Shah. PhD. Date: 21 November 1997 Page l BFG42019 BFG 01533 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 STATEMENT OF COMPLIANCE Page 2 Praft final Rfpprt This study was designed to meet or exceed the guideline requirements ofthe EPA (Environmental Protection agency: TSCA Test Guidelines (EPA, 1985); Organisation for Economic Co-Operation and Development (OECD, Guidelines for testing of chemicals, Section 4: Health Effects, (OECD, 1981); and European Economic Community (EEC), Methods for the Determination of Toxicity (EEC, 1988)* This study was conducted in compliance with the FDA (Food and Drug Administration) Good Laboratory Practices (GLP) Regulations for Nonclinical Studies (FDA, 1988 * part 5 of21 CFR); EPA TSCA Good Laboratory Practice Standards (EPA, 1990 - Part 160 of 40 CFR); OECD Good Laboratory Practice Procedures (OECD, 1982 - Annex 2 C [81] 30 [FINAL]); and standard operating procedures ofHuntingdon Life Sciences. Raymond E Schroeder, M.S., DABT Study Director Date BFG42020 BFG 01534 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 3 Draft_EinaJ Report SIGNATURE PAGE SCIENTIST The following Scientist was responsible for the overall conduct ofthis study. Departmental supervisory personnel are listed on the personnel page ofthis report (Appendix P)* Raymond E. Schroeder, M.S., DABT Study Director Date SCIENTIFIC REVIEW The following Scientist has reviewed and approved this report Dean E. RodweU, M.S. Vice President, Toxicology Operations Date BFG42021 BFG 01535 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 QUALITY ASSURANCE STATEMENT Page 4 Draft Final Report Listed below are the dales that this study was inspected by the Quality Assurance Unit of Huntingdon Life Sciences, East Millstone, New Jersey, and the dates that finding? were reported to the Study Director and Management. Type of Inspection Date($) of Inspection Reported to Study Director and Management Quality Assurance Senior Auditor Date BFG42022 BFG 01536 Huntingdon Life Sciences Chemical Manufacturers Association 96*4080 ABSTRACT Page5 Draft Final Report This study conducted for Chemical Manufacturers Association, was designed to the potential toxicity and/or developmental toxicity of vinyl chloride. The test material was administered via whole body inhalation (six hours/day) to 100 mated rats (25 per group) at dose levels of 0,10, 100 and 1100 ppm during the Day 6-19 gestation interval. The exposures for these animals were performed concurrent with those of the on-going two-generation reproduction study. Both studies are performed under the same study number; however, only the developmental toxicity study is included in this report Animals were observed twice daily for mortality/morbidity and for obvious pharmacologic and/or toxicologic effects and each animal was given a detailed physical examination on Days 0 and daily on Days 6-20 of gestation. During the treatment period, these latter examinations were conducted approximately one-half hour after exposures were completed. Body weights were recorded on Days 0,6,9,12,15 and 20 of gestation and food consumption was recorded for over Days 0-6, 6-9, 9-12, 12-15 and 15-20. Animals were sacrificed on Day 20 of gestation and given a macroscopic postmortem evaluation which included weighing of the gravid uterus, kidneys and liver. The ovaries were evaluated for the presence and number of corpora lutes and uterine implantation data was recorded. Fetuses were removed from the uterus, weighted, sexed and evaluated for external abnormalities. Subsequently, one-half of the fetuses were processed for visceral examination (microdissection technique) and the remaining fetuses processed for staining of the skeletal structures with Alizarin Red S and examined for skeletal malformations and ossification variations. Mean exposure concentrations over the course of the study as determined by infrared spectrophotometry were close to the targeted concentration levels. The mean exposure concentration levels ( standard deviation) for the 10, 100 and 1100 ppm groups were 10.8 ( 1.1), 102 ( 11) and 1110(45) ppm, respectively. No maternal or developmental toxicity was seen at the 10 ppm exposure level. At the 100 ppm exposure level, the only maternal toxicity seen was an increase in the kidney weight relative to the Day 20 gestation weight At the 1100 ppm exposure level* the only maternal toxicity was an increase in kidney and liver weights relative to the Day 20 gestation weights. No developmental toxicity was seen at either the 100 or 1100 ppm exposure levels. Thus, the no-observed-effect level (NOEL) for maternal toxicity with vinyl chloride in the pregnant rat was 10 ppm and the NOEL for developmental toxicity was 1100 ppm. BFG42Q23 BFG 01537 Huntingdon Life Sciences Chemical Manufacture Aa<nri,,t,'TM, 96*4080 Page 6 Draft Final Rapnrt TABLE OF CONTENTS COVER PAGE.................................................................................................................................... 1 STATEMENT OF COMPLIANCE...................................................................................................2 SIGNATURE PAGE.......................................................................................................................... 3 QUALITY ASSURANCE STATEMENT........................................................................................ 4 ABSTRACT........................................................................................................................................5 TABLE OF CONTENTS................................................................................................................... 6 L INTRODUCTION.................................................................................................................9 1. MATERIAL AND METHODS 2.1. Regulatory Reference*...........iff***tir*i**(f*av4flf**tftMH**4H4*H44*t*t*i****'*******9 22. Study Management...................................................... 10 2.3. Experimental Outline................................. ..........................................................11 2.4. Study Dates............................................................................................................. 11 2.3. Test Material......................................................... 12 2.6. Test Animals.................................. 13 2.7. Selection/Group Alignment...... 14 2.8. Mating................................................................. -.................................................M 2.9. Animal Identification........................................................ 2.10. Veterinary Care.................... ..................................... ............ .........*.....................13 2.11. Husbandry During Non*Exposure Periods..... ...... ................................... 15 2.12. Test Material Administration.................................................................................16 2.13. Experimental Evaluations........................................... ................. . 18 2.14. Postmortem....................................................................................................-...... I9 2.15. Statistical Analysis...............................................-............*......................... -....... 21 2.16. Datastorage............................................ 23 2.17. Protocol Deviation................ BpG42024 BFG 01538 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 7 Dnft Final Report TABLE OF CONTENTS 3. RESULTS AND DISCUSSION 3.1. Chamber Monitoring Results................................................................. ,,,,25 3.2. Maternal Data................................................ .......................,............. --,,....,,...25 3.2.1. Mortality............................................................................ ..........TM.......25 3.22. Pregnancy Rates 26IM4tt*iil4tfiiiiiiiiaitii(iiiiMiaiiiiiMMaaaaafaai**t*ata a4***aa 32.3. Physical Observation Data.............. HI4l*4*a*a 26 3.2.4. Body Weight Data - Gestation Period................................... ........-.......26 32.5. Food Consumption Data - Gestation Period 2744I*M4I44444*4444444*4a44*M4v4aW44ff 3.2.6. Corpora Lutes and Uterine Implantation Data_____________ __________27 3.2.7. Macroscopic Postmortem Evaluations.......................... .............................27 32.8. Maternal Liver and Kidney Weight Ratios *-*+*******+#***********27 3.3. Fetal Data a4***iH*t**'f'*****'*>< ia(f'"**M4f**a*'tHfM4*HH4aH*4H4f*** MW4WW 28l44*4444*Mf444 3.3.1 Fetal Body Weight Data 28Him4mt<m*4Mt4*m4*>4*ft4H444*4*4l44444MIIIMMI4H444***4f 3.32 Fetal Sex Distribution Data.......................................................... 333 Fetal External Examination Data..... ............. 28 3.3.4 Fetal Visceral Examination Data.............................................................--29 33.5 Fetal Skeletal Examination Data............................................ ...,^.^..^.^..29 4. CONCLUSION.......................................................... ........................................................30 REFERENCES AND CALCULATIONS..................................... ............i TABLES 1. Summary of Survival and Pregnancy......... ...................... .......................... ....---------- .T1-1 2. Summary of Clinical Observations During Gestation....................2-1 3. Summary ofGestation Body Weights (grams).................... 4. Summary of Gestatfcm Body Weight Gain (grams) ......... .im>--B4< II I4444HM444H4444T 4-1 3. Summary ofGestation Food Consumption (grams/animal/day)....................................--T 5-1 6. Summary of Gestation Food Consumption (grams/kg/day)........... ................................... ...T 6*1 7. Summary ofCesarean Section Data.......... it44444**4l4M444+4*MMM*fiiiimiiiitiniini*ii*iirt*tMiw4T 7" 1 $. Summary of Gravid Uterine Weight and Net Body Weight Change (grama)..*....... T 8-1 9. Summary of Maternal Necropsy Observations........................... ....... -------------- -------- T 9-1 10. Summary of Absolute Organ Weights................................... ...........................T 10-1 Summary of Organ to Body Weight Ratio............... ............................... 10*2 11. Summary ofFetal Observations Malformations 4444M4444fH4fm#'MM*4**4M4#4H44444*MM*MTIM 12. Summary of Fetal Observations - Variations.-..........................--..................... ---------- T 12*1 BFG42025 BFG 01539 Huntingdon Life Sciences 96*4080 Page 8 Chemical Manufacturers AssociationDraft Final Report TABLE OF CONTENTS APPENDICES A. Individual Clinical Observations During Gestation..................... B. Individual Gestation Body Weights (grams)........................................... ......................____B*1 C. Individual Gestation Body Weight Change (grams)..................... ......................................,..C-I D. Individual Gestation Food Consumption (grams/animal/day) ********* D-I E. Individual Gestation Food Consumption (grams/kg/day).................. .--..............................E-l F. Individual Female Reproduction Data and Mean Fetal Weight Data................................ F-l G. Individual Gravid Uterine Weight and Net Body Weight Change (grams).... --........... G-I H. Individual Fetal Body Weights (grams) ....... ................. .--......--.......--... H-l I. Individual Maternal Necropsy Observations........................................................................... 1-1 J. Individual Organ and Final Body Weights............................................................... K. Individual Fetal External Observations................................................................. ............... K*1 L. Individual Fetal Visceral Observations.............. ....... ....................................... -...............L*1 M. Individual Fetal Skeletal Observations N. Inhalation Report ........... ...................................... ..................--..--N-I O. Huntingdon Life Sciences Historical Control Data................... ............................ ..............0*1 P. Testing Facility's Personnel................................................................. ..----P-1 BFG42026 BFG 01540 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 9 Draft Final Report 1. INTRODUCTION This study conducted for Chemical Manufacturers Association was designed to assess the potential maternal toxicity and/or developmental toxicity of vinyl chloride. The test material was administered via whole body inhalation (six hours/day) to 100 mated tats (25 per group) at dose levels of 0, 10, 100 and 1100 ppm during the Day 6*19 gestation interval. The exposures for these animals were performed concurrent with those of the on-going two-generation reproduction study. Both studies are performed under the same study number. This report only includes the methods and results of the developmental toxicity study. Species and strain of test method and route of test material administration and dose levels were determined by the Sponsor. 2. MATERIAL AND METHODS 2.1. REGULATORY REFERENCES 2.1.1. TEST GUIDELINES This study was designed to meet or exceed the guideline requirements of the following: EPA (Environmental Protection Agency): TSCA Test Guidelines (EPA, 1985); Organization for Economic Co-operation and Development (OECD, Guidelines for testing of chemicals. Section 4: Health Effects, (OECD, 1981); and European Economic Community (EEC), Methods for the Determination of Toxicity (EEC, 1988). 2.1.2. GOOD LABORATORY PRACTICES This study was conducted in compliance with FDA (Food and Drug Administration) Good Laboratory Practice (GLP) Regulations for Nonclinical Studies (FDA, 1988 - Part 58 of 21 CFR); EPA TSCA Good Laboratory Practice Standards (EPA, 1990 - Part 160 of 40 CFR); OECD Good Laboratory Practice Procedures (OECD, 1982 * Annex 2 C [81] 30 [FINAL]); and standard operating procedures of Huntingdon Life Sciences, Princeton Research Center. 2.1.3. ANIMAL WELFARE ACT COMPLIANCE This study complied with ail appropriate parts of the Animal Welfare Act regulations: 9 CFR Parts 1 and 2 Final Rules, Federal Register, Volume 54, No. 168, August 31, 1989, pp. 36112-36163 effective October 30, 1989 and 9 CFR Part 3 Animal Welfiua Standards; Final BFG42027 BFG 01541 Huntingdon Life Sciences Chemical Manufacturers Association 96-4030 Page 10 raft Final Report Rule, Federal Register, Volume 56, No. 32, February 15, 1991, pp. 6426*6505 effective March IS, 1991. 2.1.4. FACILITIES MANAGEMENT/ANIMAL HUSBANDRY Currently acceptable practices of good animal husbandry were followed '&* Guide for the Care and Use of Laboratory Animals. National Research Council, 1996. Huntingdon Life Sciences, East Millstone, New Jersey is folly accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC). 12, STUDY MANAGEMENT UL SPONSOR Chemical Manufacturers Association Chemstar Department 1300 Wilson Boulevard Arlington, Virginia 22209 222, SPONSOR REPRESENTATIVE Hasmukh C. Shah, Ph.D. 223, TESTING FACILITY Huntingdon Life Sciences P.O. Box 2360 Mcttlers Road East Millstone, New Jersey 08875-2360 2.2.4. STUDY DIRECTOR Raymond E. Schrocdcr, M.S., DABT BFG42028 BFG 01542 Huntingdon Lift Sciences Chemical Manufacturers Association 96-4080 Page II Draft Final Report 23, EXPERIMENTAL OUTLINE Developmental Toxicity Study: Group I (chamberhOuMd, ah*n air control m IV Expoav* Levels (ppm) 0 10 100 1100 Schedule 6 houra'day Gesarioc Days 6-19 Ocstnkn Days 6-19 Gesuttan Days 6-19 Gestadoa Days 6-19 Number ofAnimals Pnjponioo ofGestation Day 20 FfflHfVUtlT Mated Smifiad* U.lfanTutiiWV^M Evaluations ....... Day 20 Extosal Soft Tissue 25 25 AH 25 25 All A 25 25 All 'A A 25 25 All `A `Gross postmortem cummatioas performed end liver end kidneys were weighed *od preserved along wiih gross loiotis. 2*4. STUDY DATES 2.4.1. STUDY INITIATION 25 October 1996 (Date the Study Director signed the Protocol) 2.4.2. DATE OF ANIMAL RECEIPT 24 February 1997 2.43. INITIATION OF MATING 12 March 1997 2.4A, INITIATION OF EXPOSURES 19 March 1997 BFG42029 BFG 01543 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 12 Draft Final Report 2.4*5. TERMINATION OF EXPOSURES 10 April 1997 2.4.6. TERMINAL SACRIFICE 2-11 April 1997 2.4*7. STUDY TERMINATION Date Final Report is signed by the Study Director. 2,5. TEST MATERIAL Vinyl Chloride 2.5.1. SUPPLIER The GEON Company Pedricktown, NJ 08067 2.5.2. LOT NUMBER l 22tt* DATE RECEIVED 28 August 1996 2.5*4* DESCRIPTION Colorless gas L5J, PURITY >99.9% 2.5.6. STORAGE Room temperature BFG4203Q BFG 01544 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 13 Draft Final Report 2.5.7. ANALYSIS The purity of the lot of test material used on study was determined at the start of the program of studies, approximately 6-months into the program and at termination. These analyses were performed by the Analytical Laboratory of Huntingdon Life Sciences. Results of these analyses will be presented in the ensuing reproduction study. 2-5,8. ARCHIVAL SAMPLES A small sample (approximately 150 mU) from the lot of test material used for this study was taken and is being stored in the Archives of Huntingdon Life Sciences. 2.5.9. DISPOSITION At completion of the program of studies (reproductive study and developmental toxicity study), unused test material in the one ton pressurized cylinder was returned to the Supplier (The GEON Company, Pedricktown, NJ 08067). This lot of test material will be retained at GEON until issuance of the final reports. . .2 6 TEST ANIMALS Albino Rats (Outbred) VAF/Phli 2.6.1. STRAIN CD (Sprague-Diwlcy derived) [Crf: CD BR] 2.63. SUPPLIER Charles River Laboratories Portage, Michigan 49081 2.63. NUMBER OP ANIMALS Received; 160 females Placed on-test 100 females BpG4203l BFG 01545 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 14 Draft Final Report 2.6.4. AGE AT RECEIPT Females were 57 days in age at receipt 2.6^. WEIGHT AT GESTATION DAY 0 Mean: 213 grams Range: 172-252 grams 2.6.6. JUSTIFICATION FOR ANIMAL SELECTION The rat is a rodent animal model commonly utilized in reproduction/deveiopmental toxicity studies as recommended in the referenced guidelines. In addition, a historical data base is available at Huntingdon Life Sciences, East Millstone, New Jersey with this strain of rat for comparative evaluations. 2*6,7. ACCLIMATION PERIOD Approximately two weeks; all animali were observed for viability twice daily. Prior to mating, ail animals were by the rw-hnifjl staff to ascertain suitability for study. 2.7. SELECnON/GROUP ASSIGNMENT More females than required for the study were purchased and acclimated. Animals considered suitable for study on the basis of pretest physical examinations were included into the mating phase of the study. Females which mated were randomly assigned to groups daily in such a way as to most nearly equalize both the Day 0 gestatioa mean body weights between groups and the distribution of animals into groups. This was done by ranking the animals by body weight from lightest to heaviest and randomly assigning them to groups in blocks using a random numbers table. 1A MATING Females selected for mating were co-housed with male rats from an in-house breeding colony nightly in a 1:1 ratio. Vaginal smears were taken early in the morning following nightly intervals of cohousing. Hie females were considered to have mated if sperm was observed microscopically in the vaginal smear and/or a vaginal plug was observed. The day on which evidence of mating was observed was defined as Day 0 of gestation. BFG42032 BFG 01546 Huntingdon Life Sciences Chemical Manufacture Association 96-4080 Page 15 Draft Final Report 2.9. ANIMAL IDENTIFICATION Each female was assigned a temporary identification number upon receipt Mated females were ear-tagged with a number assigned by Huntington Life Sciences that was unique. This number plus the study number comprised a unique identification for each animal. Females were ear-lagged on Day 0 of gestation. 2.10. VETERINARY CARE Animals were monitored by the technical staff daily for any conditions requiring possible veterinary care. 2.11. HUSBANDRY DURING NON-EXPOSURE PERIODS* 2.11*1* HOUSING Animals were housed individually, except during mtfagi k suspended stainless steel cages with wire mesh floors. During mating, one male and one female were co-boused overnight until evidence of mating was seen. 11U* FOOD Certified Rodent Diet, No. 5002; (Meat) (PMI Feeds, Inc., St Louis, Missouri) without restriction, except during exposure 2.1U. FEED ANALYSES Analytical certification of batches of feed provided by the manufacturer were maintained on file at Huntingdon Life Sciences* 2*1L4. WATER Facility water (supplied by Elizabethtown Water Company, Westfield, New Jersey); without restriction, provided to individual animal cages via an automated watering system. 1 See Inhalation Report (Appendix N, page N-2) for husbandly during exposure period*. BFG42033 BFG 01547 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 16 Draft Final Repopt 2.11.5. MONTHLY WATER ANALYSES Monthly water analysis, provided by the supplier, are maintained on file at Huntingdon Life Sciences. 2.11*6. BIANNUAL WATER ANALYSES Biannual chemical and microbiological analyses of water samples collected from representative rooms in this facility were conducted to assure that water met standards specified under EPA National Primary Drinking Water Regulations (40 CFR Part 141). Results are maintained on file. 2.11.7. CONTAMINANTS There were no known contaminants in the feed or water which woe expected to interfere with the results of this Study. 2*11.8. ENVIRONMENTAL CONDITIONS Light/Dark Cycle Twelve hour light/daric cycle controlled via an automatic timer. Temperature Temperature was moottored and recorded twice daily. Owned: Actual: 20 to 24C 20 to 23*C Relative Humidity Relative humidity was monitored and recorded once daily. Desired: Actual; 40 to 70% 32 to 76% BpG42034 BFG 01548 Huntingdon Life Sciences Chemical Manufacturers Association 96*4080 Page 17 Draft Final Report 2.12. TEST MATERIAL ADMINISTRATION The test material was administered as a gas in the breathing air of tbe animals The test atmospheres were generated by an appropriate procedure developed at the Testing Facility. 2.12.L ROUTE OF ADMINISTRATION The test material was administered via whole-body 2.12*3. FREQUENCY OF TREATMENT Females were treated 6 hrs/day over the Day 6-19 g****1^ interval. 2.123. JUSTIFICATION FOR ROUTE OF ADMINISTRATION The inhalation route is one of the potential routes of hlwr?*n exposure Id this test material. 2.12.4. DOSE LEVELS Group 1*0 ppm Group H -10 ppm Group HI - 100 ppm Group IV-1100 ppm 2.12-5. INHALATION EXPOSURE GENERATION PROCEDURES Complete exposure procedures are presented in Appendix N (pages 4 and S). 2.12*6* CHAMBER MONITORING Chamber operation and monitoring procedures am presented in Appendix N (pages 3*6). 2.12,7* JUSTIFICATION FOR EXPOSURE CONCENTRATIONS The targeted exposure concentrations of vinyl chloride were 0,10,100 and 1100 ppm. These exposure levels correspond to oral equivalent doses of approximately 0, 92, 92 and 1012 mg/kgfday at ventilation rates of 1 L/min/kg, 100 percent absorption and a 6 hour/day exposure. The high concentration of vinyl chloride was selected baaed on die oral BFG42035 BFG 01549 Huntingdon Life Sciences Chemical Manufacturers Association 96-40S0 Page 1$ Draft Final Report equivalent of the limit dose of 1000 mg/kg body weightfday. The high exposure level of 1100 ppm was also expected to produce effects on the liver and other organ systems (ATSDR, 1993). The middle and low exposure levels were selected to provide a dose response for the observed effects and a noobserved effect level, respectively. 2.13. EXPERIMENTAL EVALUATIONS 2.13.1. VIABILITY CHECKS Animals were observed, at least twice daily in their cages, for mortality, general appearance and signs of severe toxic or pharmacologic effects. Animals in extremely poor health or in a possible monbund condition were identified for further monitoring and possible 2.13.2. PHYSICAL EXAMINATIONS Animals were removed from their cages and examined on Days Q and 620 of gestation. Examinations included observations of general condition, skin and for, eyes, nose, oral cavity, abdomen and external genitalia as well as evaluations of respiration. Unusual behavior and physical signs were recorded. During the test period, observations were performed postexpowre when animili were being ttantfpred to their home cages. 2.13A BODY WEIGHT Animals were removed from their cages and weighed using a Mettler Balance, Model FE4000 (Mettler Instrument Corporation, Hightstown, Hew Jersey). Body weights were recorded on Days 0,6,9,12, 13 and 20 of gestation. 2.13.4. FOOD CONSUMPTION Food was available, without restriction, 7 days/week, except during exposure periods. Animals were presented with weighed feeders on DaysO, 6,9, 12 and 13 of gestation. Feeders were removed on Days 6, 9,12,13 and 20 of gestation and a ``foeder-out" weight recorded using a Mettler Balance, Model PE4000 (Mettler Instrument Corporation, Hightstown, New Jersey). The resulting weight was subtracted from the BFG42036 BFG 01550 Huntingdon Life Sciences Chemical Manufacturer* Association 96-4080 Page 19 Draft Final Rennrt presentation weight of the feeder to obtain the grams consumed per animal per interval. Calculations grams offood consumed per interval + no. ofdays grams/animal/dsy grams offood consumed/kilogram ofbody weight/day (g/lcg/day) -- crams of feed consumed + no. ofdays previous body weight (kg) Measurement intervals (Le., die number of days over which food consumption waa measured) and the body weight Interval used to calculate grams of feed po* kilogram of body weight per day (g/lcg/day) m as follows; Day 0-6 - 6-day interval using Day 0 body weight Day 6-9 - 3-day interval using Day 6 body weight Day 9-12 " 3-day interval using Day 9 body weight Day 12-15 3 3-day interval wing Day 12 body weight Day 13*20 * 3-day interval using Day 13 body weight 2.14. POSTMORTEM 2.14,1. NECROPSY INFORMATION Method of Euthanasia Exsanguinadon following anesthesia with inhaled carbon dioxide 2*14*2. MACROSCOPIC EXAMINATIONS Complete macroscopic postmortem examinations were performed on all mated rats. Gross lesions were saved in 1094 neutral buffered formalin. During these examinations, the liver and kidneys were also weighed and preserved in 10% neutral buffered formalin for possible four* examination. Females were sacrificed on Day 20 of gestation and examined as follows; Reproductive System The intact uterus (ovaries attached) was removed from the abdominal cavity and weighed intact (with fetuses and placenta) using a Mettiers BFG42037 BFG 01551 Huntingdon Life Sciences Chemical Manufactufm Association 96U080 Page 20 Draft Final Bgwirf AK-160 balance (Mettier Instrument Corporation* HIghtstown, New Jersey), The uterus was then opened along the antimesometrial border and the number and location of the following were recorded for each uterine bom; live fetuses dead fetuses movement in response to touch. lack ofmovement in response to touch with no visible degeneration. late resorptions recognizable dead fetus degeneration regardless of size. undergoing early resorptions evidence of implantation but no recognizable fetus. implantation sites * total of resorptions and fetuses. Uteri without grossly visible implantations we? stained according to the procedure of Salcwski (1964) to idattUy the presence of sites of early resorption. If no stained sites were present* the female was considered not pregnant Ovaries The ovaries were dissected free from the uterus and evaluated for the presence and number ofcorpora lutea. 2.143. FETAL EVALUATIONS External Evaluations Each fetus was individually weighed using a Mettier Balance, Model PE4000, sexed externally (ano-genital distance) and examined for external malfonnations/variations to include observation for palatal defects. Skeletal Evaluations Approximately one-half of tike fetuses in each litter (alternating fetuses within the litter) were processed for Alizarin Red S staining of the skeletal structures. Prior to processing, the intact fetuses wen killed (overdose of inhaled carbon dioxide) and eviscerated (internal sex bFG42038 BFG 01551 Huntingdon Life Sciences Chemical Manufacture Atsmiitfap 96-4080 Page 2! Draft Final ftppon noted). Following staining, these fetuses were evaluated under a dissecting microscope for skeletal malformations and/or ossification variations. Soft Tiasne Evaluations The remaining fetuses in each litter were processed for soft tissue examination using a microdissection technique similar to the procedure of Staples (1974). The evaluations were performed on the fresh fetal specimens soon after removal from the uterus. The fetuses designated for soft tissue evaluation were decapitated (head placed in Bouin's solution for later evaluation). The fetal specimens were dissected so as to permit evaluation of tissues in the thoracic, abdominal and pelvic cavities. At completion of the examination, these fetuses were eviscerated and processed for Alizarin Rad S staining of the skeletal structures. The stained fetal specimens are being retained with the rest of the study specimens. Fetal heads were sectioned with a razor blade. The serial, transverse sections generated during this procedure were evaluated for malformations of the palate, eyes and brain. Fetal soft tissue evaluations (microdissection and head sections) were performed under a dissecting microscope. Resorptions Late resorptions were removed from the uterus, crown-rump distance recorded and examined for external malformations. Malformation data for late resorptions is reported but not included in the analyses of malformation data for live or dead fetuses recoveted on Day 20 of gestation. Only late resorptions with external malformations were saved (10% neutral buffered formalin). Early resorptions were noted and discarded without any further evaluation, 2.15. STATISTICAL ANALYSIS The following items were analyzed statistically in the final report: 2.15.1. CONTINUOUS DATA: Body weights (all recorded intervals)* Body weight change (between all recorded intervals to include Days 6-20 of gestation using the actual and corrected Day 20 gestation weights)* fiFG42039 BFG 01553 Huntingdon Life Sciences Chemical Manufacturers AasQftjfrtjon 96-4080 Page 22 Drift Final Report Food consumption values (all recorded intervals/ Organ weight data1 Number of corpora lutea* Uterine implantation data (fetuses1, resorptions*, implantations*) Pre-implantation loss* Post-implantation loss* Mean percent male and female fetuses per litter* Fetal weight distinguished by sex and as a composite for both sexes (litter as experimental unit/ 2.15,2, CONTINUOUS DATA-MULTIPLE GROUP ANALYSIS: Employed when data for more than one treated group is compared to control. All statistical tests were conducted at the 5% and 1%, two-sided risk levels. "Statistical evaluation of equality of means was made by the appropriate one way analysis of variance (ANOVA) technique, followed by a multiple comparison procedure, if needed. If ANOVA showed difference, no additional comparisons were made. If ANOVA was significant, Dunnett's test was used to determine which data, ifany, differed from the control. References for these techniques are as follows: Dunlap, W,P. and J.A. Duffy (1975) "Fortran TV functions for calculating exact probabilities associated with Z, Chi-square, T and F values." Behav. Res. Methods and Instrumentations, 7:59-60. Dunlap, W.P., M.S. Marx and G.J. Agamy (1981) "Fortran IV functions for calculating probabilities associated with Dunnetfs Test", Behav. Res. Methods and Instrumentations, 13:363-366. 'The Kruskal-Waliis test (2 X n) was used to test equality of means. If no differences were seen, no additional analyses were performed If differences were indicated, a 2 X 2 Kruskal-Waliis test was used to determine which treatment groups differed ftom control. BFG42040 BFG 01554 Huntingdon Life Sciences Chemical Manufacturers Association 964080 References for these techniques are as follows: Page 23 Dnft Final Report Dunlap* W.P, and J.A. Duffy (1975) "Fortran rv functions for calculating exact probabilities associated with Z, Chi-square, T and F values." Behav. Res. Methods and Instrumentations, 7:59-60. Siegel, S. (1956) Nonparametric Statistics for the Behavioral Sciences McGraw-Hill, New York. 2.154. INCIDENCE DATA: Mortality rate Pregnancy rates Incidence of litters containing fetuses with malformations (external, soft tissue and skeletal - total affected and by finding) 2.15.4. INCIDENCE DATA ANALYSIS: A Fisher Exact Test with Ekmferonm correction was performed to identify differences between the groups. References for these techniques are as follows; Hollander, M, and D. A. Wolf (1973) Nonparametric Ftatittiofi jyfethnds. Wiley, New York, NY, pp. 120-123. Siegel, $. (1956) Nonparametric Statistics for the Behavioral Sciences. MflGraw- Hill, pp. 98-99 and 104-106. 246, DATASTORAGE All data documenting experimental details and study procedures and observations will be recorded and maintained aa raw data. At the completion of the Study, all reports, raw data, preserved specimens, and retained samples pertaining to the portion* of the study performed at Huntingdon Life Sciences, as well as the original study protocol and the original final report will be maintained in the Archives of Huntingdon Life Sciences for e period of ten years after submission of the signed final report The Sponsor will be contacted in order to determine the final disposition of these material*. BFG42041 BFG 01555 Huntingdon Life Sciences Chemical Manufacturer* Association 96-4080 Page 24 Draft Pinal Repnrt 2.17. PROTOCOL DEVIATION The following protocol deviation occurred during the study but was not considered to have compromised the validity or integrity ofthe study: Relative humidity in the animal quarters was out of the protocol specified range on several occasions. BFG42042 BFG 01556 Huntingdon Life Sciences Chemical Manufacturers Association 96-4080 Page 25 Draft Final Report 3. RESULTS AND DISCUSSION 3.1, CHAMBER MONITORING RESULTS (Appendix N) The results of the Minn and gas chromatographic (GC) analyses ofthe exposure concentrations are summarized below, These data are presented in Appendix Nr pages N-10 to N-18 and demonstrate for each of the treated groups good correlation between the Miran and GC values and that these exposure levels were similar to the calculated nominal levels. Group Target Cone, (ppm) I0 n 10 m 100 IV 1100 Mean Miran Analytical Cone, (ppm) (SD) 0.0 (0.1) 10.8 (U) 102 (11) 1110 (45) MeaoGC Analytical Cone. CtSD) Mean Nominal Cone, (ppm) <SD) 0.5 ( 1.0) 10.9 (1.8) 105 (14) 1212 (120) 0 92 (0.6) 102 (9) 1110(143) Key: Cone." concentration; SD * Standard Deviation: GC gas chromatograph 3*2* MATERNAL DATA 3.2.1. MORTALITY (Table 1; Appendix A) No mortality occurred in the comrol or vinyl chloride treated groups. All animals survived to scheduled sacrifice. BFG42043 BEG 01557 Huntingdon Life Sciences Chemical Manufacture 96*4080 Page 26 Dttft Final Report 3JJ. PREGNANCY RATES CTtble 1; Appendix F) Pregnancy rales were comparable between the control and vinyl chloride-treated groups. Pregnancy mice for the control, 10, 1QQ and 1100 ppm treated groups were 92% ,96%, 38% and 96%, respectively. 3*2.3. PHYSICAL OBSERVATION DATA (Table 2; Appendix A) No adverse effect of treatment with vinyl chloride was indicated from clinical findings noted during the detailed physical examinations. There was a slight increase in tbe incidence of females with alopecia of the extremities and/or snout in the 100 ppm group but in the sbaence of a similar increase in the 1100 ppm group, this was not considered treatment-related. Other clinical findings seen in the treated groups occuned at low incidence or with similar frequency as control and were not considered treatment-related.. 3.2*4. BODY WEIGHT DATA-GESTATION PERIOD (Tables 3,4 and 8; Appendices B, C and G) Mean body weights for the treated groups were comparable to control data during the pretreatment period (Days 0-6) and early in the treatment period (Days 6-9,9-12,12*15). For Days 15-20 of gestation, mean body weights for all throe treated group* were significantly lower than control. Because these differences were slight (less than 10% in comparison to control data in tbe 100 and 1100 ppm groups and 12% in the 10 ppm group) and not dose-responsive, their toxicological significance, if any, is unclear. Tbe significant decrease in body weight gain seen for all three treated groups over the Day 6*20 gestation interval in comparison to control data was attributed to tbe reduction in body weight gain seen in these groups over the Day 15-20 gestation period* Mean body weight gains for all treated groups over tbe Day 6 to Day 20 gestation interval using the corrected Day 20 gestation weights (actual Day 20 gestatioo weight minus the weight of the gravid uterus) were comparable to control data. BFG42044 BFG 01558 Huntingdon Life Sciences Chemical Manufactory VttKiatiffll 96*4080 Page 27 Draft Final Rqwrt 32JL FOOD CONSUMPTION DATA - GESTATION PERIOD (Tables 5 and 6; Appendices D and fi) Mean food consumption data for the vinyl chloride-treated groups on both a grams/animal/day and grama/kg body weight/day basis were comparable to control during the prctreatment (Days 0-6) and treatment period (Days 6-9, 9-12, 12-15 and 15-20) were comparable to control and unaffected by treatment 3,2,6. CORPORA LUTEA AND UTERINE IMPLANTATION DATA (Table 7; Appendix F) No effect of treatment with vinyl chloride at an exposure level up to and inclusive of 1100 ppm was evident from corpora lutea or uterine implantation data. The mean corpora lutea and uterine implantation data (implants, fetuses, resorptions) for the treated groups were comparable to control data. Likewise, the mean pro* and post-implantation loss indices were comparable between these same groups, 3*2.7. MACROSCOPIC POSTMORTEM EVALUATIONS (Tabic 9; Appendix I) The few findings seen among the vinyl chloride*treated females during the maternal macroscopic postmortem examinations occurred as single occurrences and were not considered treatment-related. 3*2*8* MATERNAL LIVER AND KIDNEY WEIGHT RATIOS (Table 10; Appendix J) Liver weights, absolute and relative to Day 20 gestation weights, were comparable to control data is fee 10 and 100 ppm dose groups. In the 1100 ppm group, absolute liver weight was comparable to control data but the relative weight was significantly increased and this change was considered indicative of a treatment-related response. BpG42045 BFG 01559 Huntingdon Life Sciences Chemical Manufacturer* Association 96-4080 Page 28 Draft Final Report Kidney weights, absolute and relative to the Day 20 gestation weights, were comparable to control in the 10 ppm group. In the 100 and 1100 ppm groups, absolute kidney weights were comparable to control data but relative weights were slightly higher. These latter differences were statistically significant and considered indicative of a treatment-related response. 3J. FETAL DATA 3-3.1. FETAL BODY WEIGHT DATA (Table7;Appendices FtidH) No adverse effect of treatment with vinyl chloride at a dose level up to and inclusive of 1100 ppm was seen from fetal body weight data. Mean fetal body weights distinguished by sex and for both sexes combined were comparable between the control and treated groups. 3.3.2. FETAL SEX DISTRIBUTION DATA (Table 7; Appendix F) No adverse effect of treatment with vinyl chloride at a dose level up to and inclusive of 1100 ppm was seen from fetal sex distribution data. The mean percentage of male end female fetuses per litter was comparable between the control and treated groups. 3.3.3. FETAL EXTERNAL EXAMINATION DATA (Tables 11 aod 12; Appendix K) No malformations were seen in the external teminetii of the 318 control fetuses from 23 litters, 297 Group II (10 ppm) fetuses from 24 litters or 283 Group 111 (100 ppm) fetuses from 22 litters. In the 1100 ppm group, cnnionchischisis, a severe malformation involving the cranium and spinal cord, was seen in one fetus from the litter of female No. 4622. No other external malformations were seen in the remaining 304 fetuses examined in the 1100 ppm group from 24 litters. Though not seen in recent historical control data for this laboratory (Appendix 0, pages 0-7), a low incidence of cianiorachischisia has been noted in the recently published MARTA/MTA compilation of historical control data for the Crl:CD BR rat (average fetal and litter occurrences were BFG42046 BFG 01560 Huntingdon Life Science* Chemical Manufacture* 96-4080 Page 29 Draft Final Report 0.005% end 0.069, respectively.) The eraniorachiichisis seen in the high-dose group was considered to be an isolated occurrence and not treatment-related. One late resorption from the 10 ppm group had multiple facial malformations involving absence of snout, fleshy growth in the region of the snout and absence of the upper and lower jaw. This was the only late resorption seen in this study from the control and treated females. 3*3.4. FETAL VISCERAL EXAMINATION DATA (Tables 11 and 12; Appendix L) No visceral malformations were seen in the 167 control fetuses from 23 litters, 155 Group II (10 ppm) fetuses from 24 litters or the 158 Group IV (1100 ppm) fetuses from 24 litters. A low incidence of dissimilar visceral malformations was seen in the 147 Group HI (100 ppm) fetuses from 22 litters. In the absence of similar visceral malformations among the high-dose fetuses, the occurrence of these malformations in the mid dose group were considered spontaneous and not treatment-related. Other visceral findings such as distended ureter and/or distended renal pelvis are considered variations and these were seen with comparable frequency between the control and treated groups and no effect of treatment was evident from these data. 3,3.5. FETAL SKELETAL EXAMINATION DATA (Tables 11 And 12; Appendix M) No skeletal malformations were seen in the 151 control fetuses from 23 litters, 142 Group n (10 ppm) fetuses from 142 fetuses from 24 litters or 136 Group III (100 ppm) fetuses from 22 litters. In Group IV (1100 ppm), the only skeletal malformation involved the fetus noted during the external examination with craniorachischisis. No adverse effect of treatment was evident from fetal skeletal malformation data. BFG42047 BFG 01561 Huntingdon Life Sciences 96-4080 Chemical Manufacturers ArtriatinnDraft Final Report Page 30 No adverse effect of treatment was evident from fetal ossification variation data. The litter incidences for the various ossification variations seen during the study were generally comparable between the control and treated groups. In the high-dose group, the incidence of litters containing at least one fetus with reduced ossification of the cervical arches was significantly lower than control. This was not considered to represent an adverse effect oftreatment 4. CONCLUSION In this study, vinyl chloride was administered via whole body inhalation (6 hraJday) to pregnant rats at dose levels of 0,10,100 and 1100 ppm during Days 6-19 of gestation* No maternal or developmental toxicity was seen at the 10 ppm exposure level. At the 100 ppm exposure level, the only maternal toxicity seen was an increase in the kidney weight relative to the Day 20 gestation weight At the 1100 ppm exposure level, die only maternal toxicity was an increase in kidney and liver weights relative to the Day 20 gestation weights. No developmental toxicity was seen at either the 100 or 1100 ppm exposure levels. Thus, the no-obscrved-effect level (NOEL) for maternal toxicity with vinyl chloride in the pregnant rat was 10 ppm and the NOEL for developmental toxicity was 1100 ppm. BFG42048 BFG 01562 Huntingdon Life Sciences Chemical Manufacturers 96-4080 Page 31 Final ttepnrt REEEREHCE& REFERENCES AND CALCULATIONS ATSDR, (1993), Toxicology Profile for Vinyl Chloride. U.S. Department ofHealth and Human Services. Public Health Services- Agency for Toxic Substances end Disease Registry- EEC (1988). European Economic Community. Methods for the Determination of Toxicity. Official Journal of the European Communities, Vo]. 31, No. L133,30 May 1988. ISSN 03786978. EPA (1985). Environmental Protection Agency Toxic Substances Control Act Test Guidelines, Final Rule. 40 CFRPart 798,27 September 1985, pp. 39426-39433. EPA (1990). Environmental Protection Agency Toxic Substances Control Act; Good Laboratory Practice Standards. 40 CFR Part 792 (1 July 1990), FDA (1988). Food and Drug Administration Good Laboratory Practice for Nonclinical Studies. 21 CR Part 58(1 April 1988). MARTA/MTA Historical Control Data (1992-1994) for Developmental and Reproduction Toxicity Studies using CrlrCD BR Rat, Published and Distributed by Charles River Laboratories, December, 1995. OECD (1981). Organisation for Economic Co-Operation and Development Guidelines for Testing of Chemicals, Section 4 - Health Effects* Paris. OECD (1982). Organisation for Economic Co-Operation and Development, Principles of Good Laboratory Practice, ISBN 92-64-12367-9, Paris. Plowchalk, DJL, Smith, BJ. and Mattuon, DJL (1993). Assessment oftoxicity ofthe ovary using follicle quantitation and morphometries. In in Tmflmloyyt Vol. 3f PartB. Femala ftjpm^uetjye Toxicology. (]J. Heindel and RE. Eds.). Academic Press, Inc,, New York, NY. Salewski, E-1964. Parbcmcthode zum makroskopischen nachweii von implantations stellen am uterus der ratte. Archiv, Path, Exp. PharmakoL 247:367. Staples, RE. (1974), Detection ofVisceral Alterations in Mammalian Fetuses. Teratology, 9:37 (Abstract). BFG42049 BFG 01563 Huntingdon Life Science* Chemical Manufacturer* Ablation 9640*0 REFERENCES AND CALCULATIONS CALCULATIONS Preimplantatioii Lota: no, of corpora lutea * no, of implantation sitet/iko. of corpora lutea Postimplantation Loeat no. of implantation sites - no. of viable fetusea/no. of implantation sites Page n Final Rgpnrt BpG42050 BFG 01564 BFG^05, BFG 01565 Huntingdon Life Sciences 96-4060D Chemical Manufacturers Association TABLE 1 vinyl chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OP SURVIVAL AMD PREGNANCY Group Dose Level I 0 II III 10 100 No. of females mated N 25 25 25 Pregnant N 23 24 22 - Died/saerlfieed moribund N 0 00 - Elective sacrifice N 0 0 0 NOnpregnant N2 13 - Died/sacrificed moribund N 0 0 0 - Blective sacrifice N 0 0 0 Total no. of females died/ sacrificed moribund N t 0 Q.0 00 0.0 0.0 Examined at scheduled c-sect ion N 2S 25 25 BFG42052 - Nonpregnant N 2 13 - With total implant loss N \ 0 0.0 0 0.0 0 0.0 - with viable fetuses N t 23 92.0 24 96.0 22 Bfl .0 No statistically significant differences BFG42053 BFG 01S67 29-OCT-19 ,9:34 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association TABLE 2 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata SUWARY OP CLINICAL OBSERVATIONS DURING GESTATION (frequency/anima] Group Doae Level I II III 0 10 100 TERMINAL SACRIFICE Gen. Appearance RED EXUDATE FROM ANO GENITAL AREA Dermal-General ALOPECIA - EXTREMITIES/SNOUT ALOPECIA - GENERAL ocular OHROMODACRYORRHEA - UNILATERAL LACRIMATION - UNILATERAL Oral/Buccal INCISORS BROKEN/MISSING INCISORS MALOCCLUDED 25/25 0/ 0 10/ 2 4/ 1 / 1 3/ 1 0/ 0 9/ 1 35/25 1/ 1 11/ l 0/ 0 4/ 2 0/ 0 11/ 1 B/ 2 25/2! 0/ 1 45/ i 0/ i 0/ 0/ 0/ 0/ BFG42054 W 5 Ci * OCDv X BpG42055 BFG 01569 la-3E:l?-l$ 6:35 Huntingdon Life Sciences 96-4Q80D Chemical Manufacturers Association Group Dose Level OH TABLE 3 Vinyl Chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CP Rats SUM4ARY OP GESTATION BODY HEIGHTS (GRAMS) II III 10 100 DAY 0 MEAN S.D. N DAY 6 MEAN S.D, N DAY 9 MEAN SD N DAY 12 MEAN S.D N DAY 15 MEAN S.D. N DAY 20 MEAN S.D. N No statistically significant differences 214 13.7 23 243 14.8 23 2b* 16 0 23 2'IQ is. a 23 287 19.0 23 3S3 2S.3 23 214 12.3 24 240 13.3 24 2b0 13.8 24 266 16-7 24 282 IS. 8 24 340 19.2 24 210 12.9 22 240 13.7 22 251 13.2 22 266 33.2 22 282 14.5 22 341 23 .6 22 BFG42056 CO *n O LA 3 BFG42057 BFG 01571 H >M ooH (M0 Pi 0o4 CO k0 O lA dB rt* (N ^ o 04 4 ^ q1 H rt* N *O uj W -nf r- * OO'' oaH oM e Ok n o \d iM 40 Ok n k rt L <N H * N a o rt m* a rrt # o r** n m n .-< . rt m i-4o vao C* Ifl* M a r* o ve r- o rt u*i M H iflM vHd ao o Cl *mnor *eoHrt <on OW ii/tlfnN OH iO' nCl 'ie-On'n Cr4- n Cf"4 ' fl <H* wrtnf* s a4** -uu-f4l O' oa sa Oa tut. iprt Ok 31CWV4O4 <*3MJ ZSg ei tanrut jXiUi Q-H 3 <P t? BFG42058 BFG 01572 BpG42059 BFG 01573 Huntingdon Life Sciences 9<j-40B0D Chemical Manufacturers Association Group Dome Level TABLE 5 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata SUMMARY OP GESTATION POOD CONSUMPTION (GRAMS/ANIMAL/DAY) 1 11 III 0 10 100 BFG42060 DAYS 0 TO 6 MEAN S.D. N DAYS 6 TO 9 MEAN S.D. N DAYS 9 TO 12 MEAN S D. N DAYS 12 TO IS MEAN S.D. N DAYS IS TO 20 MEAN S.D. N No statistically significant differences 19 2.5 23 le 1.6 23 20 1.7 23 21 2.0 22 24 1.9 23 19 1.7 24 19 1.9 24 20 2.6 24 22 1.7 34 23 1.9 24 19 1,7 22 19 2.0 22 20 1.7 22 22 2.2 22 23 2.2 22 BFG42061 BFG 01575 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association Group Dose Level table 6 vinyl Chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CP Rate SUMMARY OP GESTATION POOD CONSUMPTION (GRAMS/KG/DAY) 1 II III 0 10 100 BFG42062 DAYS 0 TO 6 DAYS 6 TO 9 DAYS 9 TO 12 DAYS 12 TO IS MEAN S.D. U MEAN ' S.D. N MEAN S.D. N MEAN S.D N DAYS 15 TO 50 MEAN S.D. N No statistically significant differences 90 10.2 23 76 5.3 23 79 63 2i V9 4.8 22 84 4.2 23 89 B.5 24 77 6.7 24 81 B.O 24 81 5.3 24 83 5.9 24 93 10.7 22 77 8.0 22 81 5.6 22 81 7.3 22 82 4.7 22 BpG42063 BFG 01577 30-SEP-19 6 i38 BFG42064 Huntingdon Life Sciences 96-408QD Chemical Manufacturers Association Group Dose Level TABLE 7 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OF CESAREAN SECTION DATA I II III 0 10 100 pregnant N Dams with no Viable Fetusee N Dams with Viable Fetuses N Corpora Lutea No. per animal TOTAL MEAN S.D. implantation Sites No. per animal TOTAL MEAN S.D. Preimplantation Loss No. per animal TOTAL MEAN S.D. % par animal MEAN* S.D. Live Fetuses No. per animal TOTAL MEAN S.D. Males TOTAL MBANI S.D, Females total MEAN! QNo statistically significant differences 21 0 23 351 15.3 1.45 327 14.2 1.30 24 1.0 1.19 6.4 7.22 3 IS 13.0 1.64 149 46.7 14.39 169 S3.3 14.39 24 0 24 355 14.0 3.41 309 12.9 1.80 46 1.9 2.75 11.1 11.21 297 12.4 1.04 149 SO.7 16.50 148 49.3 16.50 22 0 22 337 15.3 4.31 289 13.1 2.55 40 2.2 3.02 11.8 12.68 283 12.9 2.57 133 46.5 12.41 150 53.5 12.41 2 m oo Huntingdon Life Sciences 96-4090D Chemical Manufacturers Association Group Dose Level TABLE 7 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate SUMMARY OP CESAREAN SECTION DATA 1 II III 0 10 100 Postimplantation Loss No. par animal TOTAL MEAN S.D. I impl. par animal Dead Fetuses No. per animal % of impl. per animal MEAN* S.D, TOTAL MEAN S.P* MEAN* S.D. Resorptions: Early No. per animal TOTAL MEAN S.D. % of impl* per animal NEAN% S.D. Resorptionst Late No. per animal % of iapl. per animal TOTAL MEAN S.D. MRAN% S.D. No statistically significant differences 9 0.4 0.58 2.9 4.26 0 0.0 0.00 0.0 0.00 9 0.4 0.58 2.9 4.26 0 Q.O 0.G0 0.0 0.00 12 0.5 0.78 3.8 5.66 0 0.0 0.00 0.0 0.00 11 o.s 0,72 3.5 S. 17 1 0.0 0.20 0.3 1.57 6 0.3 0.77 2.0 5.40 0 0.0 0.00 0.0 0.00 6 0,3 0.77 2.0 S.40 0 0.0 0.00 0.0 0,00 B FG 01579 tM oOH 1i1 if**il' NCMJ M V1*1- HNo M 1*1 Mio*l pi fi irt ^ rtN w(0 tM-i QQ 1*1`M M <*>* M k r*i O QO M MH *1 p* * *4 M rt O in 9i i-f <*> 9 t* t f-4 O ^ C- Kl HM rt in m *M O ms H m O vO J0 g T3 H S'" BFG42066 BFG 01580 fipC067 BFC 01581 a< > ao 30\\ O* (M (ji ta O- at p f-' pton eon non M O o.-i # r- n* n pi n n B) H O 040# 0> O * O -<i w >M H p> o HH Hrt# rt -n m S aaeOt ^*co4i v0e* uo0) av 3 SS 3s 4Sv4 3<ruMt 33 BFG42068 *j e 13 BFG 01582 BFG42069 BFG 01583 > 99 l/l ho a o o HO H HO o(ft IHH OO ir/t) a e oq o d oo d Ul o o H HO O a o O 9 9 H ft 9 0\ Jtil M JJ 3 l lM/> H Q 43 a 99 99 HO _l U Q(A H5o a* i0-i 49I1 *uO9H HnuucVu 5 91pVu4 VUri U99J =5 umc 'Hkue ia BFG4207I BFG 01585 ll-NOV-19 i.3 s 41 96-4G60D Group Dose Level TABLE 10 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata SUMMARY OF ABSOLUTE ORGAN HEIGHTS 1 II III 0 10 100 FINAL BODY HEIGHT g MEAN S.D. N 353 25.3 23 LIVER g MEAN S.D. N 14.418 0.9598 23 KIDNEYS g MEAN S.D. N 1.871 0.1256 23 MEAN INCLUDES ONLY DAMS WITH VIABLE FETUSES AT TERMINATION 340 19.2 24 14.022 1.O870 24 1.849 0.1388 24 341 23.6 22 14.267 1.4462 22 1.944 0.1322 22 96-4Q80D Group Dose Level TABLE 10 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata SUMMARY OF ORGAN TO BODY HEIGHT RATIO I II III 0 10 100 FINAL BODY WEIGHT 9 MEAN S.D. N 353 25.3 23 LIVER Ratio MEAN S.D. N 0.041 0.0023 23 KIDNEYS Ratio MEAN S.D. N 0.005 0.0004 23 Statistical key: - p<0.05 ** -> P<0.Q1 MEAN INCLUDES ONLY DAMS WITH VIABLE FETUSES AT TERMINATION 340 19.2 24 0.041 0.6017 24 o.oos 0.0005 24 341 23.6 22 0.042 0.0026 22 0.006** 0.0005 22 BpG42074 BFG 01588 21-NOV-19*. .3:20 BFG42075 Huntingdon Life Sciences Chemical Manufacturers Association Group Dose Level Litters Examined Externally Fetuses Examined CRANIORACHISCHIS1S Litter Incidence Petal Incidence TABLE 11 Vinyl Chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OP FETAL OBSERVATIONS - MALFORMATIONS I II HI 0 10 100 23 24 22 310 297 283 000 0 00 Litters Examined Viscerally Fetuses Examined LATERAL VENTRICLES - DISTENDED Litter Incidence Fetal incidence FOLDED RETINA Litter Incidence Petal Incidence 23 167 0 0 0 0 24 155 0 0 0 0 22 147 1 1 1 1 Litters Examined Skeletally Fetuses examined Number with findings 23 24 22 isi 142 136 000 TOTAL MALFORMATIONS NUMBER WITH EXTERNAL MALFORMATIONS Petal Incidence 0 00 Litter Incidence 0 00 NUMBER WITH VISCERAL MALFORMATIONS 2 Petal incidence 0 02 Litter Incidence 002 NUMBER WITH SKELETAL MALFORMATIONS * Fetal Incidence o00 Sta Litter Incidence 0 00 TOTAL NUMBER WITH MALFORMATIONS Fetal Incidence 0 02 Litter Incidence 0 02 No statistically significant differences bFG42076 BFG 01590 21-NOV-lb>. 13:21 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association Group Dose Level Littere Examined Externally Fetuses Examined Number with findings TABLE 12 Vinyl Chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OF FETAL OBSERVATIONS - VARIATIONS J II III 0 10 100 23 U> 0 24 297 0 22 283 0 Litters Examined viscerally Fetuses Examined URETER(S) DISTENDED Litter Incidence Fetal incidence RENAL PELVIS DISTENDED Litter Incidence Fetal Incidence 23 24 22 161 155 147 3 11 521 6 54 11 6 5 Litters Examined Skeletally Fetuses Examined 23 24 22 151 142 136 INTERPARIETAL REDUCED OSSIFICATION Litter Incidence 12 17 IS Fetal incidence 26 49 46 SUPRAOCCIFITAL REDUCED OSSIFICATION Litter Incidence 12 17 14 Fatal incidence 24 43 36 hyoid body unossxfxed Litter incidence Fatal Incidence IB 19 13 42 59 34 No statistically significant differences U O Z P O jg BFG 01591 Huntingdon Life Sciences 96-4060P Chemical Manufacturer* Association Group Dose Level TABLE 12 vinyl Chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Bats SUMMARY OP PETAL OBSERVATIONS - VARIATIONS I II III o 10 100 SQUAMOSAL(S) REDUCED OSSIFICATION Litter incidence 1 10 10 Petal Incidence 6 18 15 MAXILLA(B) REDUCED OSSIFICATION Litter Incidence Petal Incidence 2 4 MALAR(S) REDUCED OSSIFICATION Litter Incidence Petal Incidence 3 7 10 4 13 15 PARIETAL(s) REDUCED OSSIFICATION Litter Incidence 4 6 Fetal Incidence 7 11 FROOTAL(S) REDUCED OSSIFICATION Litter Incidence Fetal incidence l 3 PRESPHENOID REDUCED OSSIFICATION Litter incidence Fetal Incidence 1 l MALAR UNOSSIFIED Litter incidence Petal incidence 001 001 0UPRAOCCIPITAL UNOSSlFIBD Litter Incidence Fetal Incidence 001 001 statistically significant differences a O 8Z-0ZWMH 01592 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association Group Dose Level TABLE 12 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OF FETAL OBSERVATIONS - VARIATIONS I II HI 0 10 100 CERVICAL ARCH (US) REDUCED OSSIFICATION Litter Incidence Petal incidence CBRV1CAL RIB(S) PRESENT Litter Incidence Fetal Incidence THORACIC CENTRUM(A) REDUCED OSSIFICATION Litter Incidence Fetal Incidence THORACIC CENTRUM(A) BIPARTITE Litter incidence Fetal Incidence THORACIC CENTRUM (A) UNOSSIFlED Litter Incidence Fetal Incidence LUMBAR ARCH<ES| REDUCED OSSIFICATION Litter Incidence Fetal Incidence SACRAL ARCH(ES) REDUCED OSSIFICATION Litter Incidence Fetal Incidence SACRAL ARCH{ESI UNOSfilFlEO Litter Incidence Fetal incidence statistical Key 1 * - p<o,o$ 8 13 0 0 a 6 2 2 0 0 1 2 12 23 5 b 6 is 0 0 3 4 0 o 0 0 3 3 16 37 0 21 7 12 0 0 0 0 1 1 0 0 0 0 14 20 9 17 Huntingdon Life Sciences 96-4QBQD Chemical Manufacturers Association Group Dose Level TABLE 12 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OP PETAL OBSERVATIONS - VARIATIONS I II III 0 10 100 CAUDAL ARCH{BS) UNOSSIPIED Litter Incidence Petal Incidence 12 14 14 32 37 35 CAUDAL CENTRUM (A) UNOSSIPIED Litter Incidence Fetal Incidence 001 0 03 TBfcNBRA(B) S AND/OR 6 UNOSSIPIED Litter Incidence Petal Incidence 23 23 21 110 as 94 STBRNBBRA(B) 1,2,3 AND/OR 4 UNOSSIPIED Litter Incidence 2 34 Petal incidence 2 35 STBRNEBRA(B) 1,3 AND/OR 4 REDUCED OSSIFICATION Litter Incidence Petal incidence 023 026 RIB(S) 13TH RUDIMENTARY Litter incidence Petal Incidence 2 12 222 RIB(S) BENT Litter Incidence Petal Incidence 010 010 RIB(S) REDUCED OSSIFICATION Litter Incidence Petal incidence 110 2 10 No statistically significant differences OSOSfcOjg Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association Group Dose level TABLE 12 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats SUMMARY OF FETAL OBSERVATIONS - VARIATIONS I IZ lit o io loo BFG42081 METACARPAL(S) UNOSSIFI8D Litter Incidence Fetal Incidence 0 02 0 02 PUBIS(KS) UN0SSIF1BD Litter Incidence Petal Incidence l 24 125 ISCHIUM(A) UNOSSlFlED Litter Incidence Petal Incidence 003 0 03 PUBIS(ES) REDUCED OSSIFICATION Litter Incidence Fetal Incidence 2 54 2 S5 ISCHIUM(A) REDUCED OSSIFICATION Litter incidence i20 Fetal Incidence l30 Mo atatietically significant differences BFG42082 BFG 01596 29-OCT-19- 09:33 BFG42083 Huntingdon Life Sciences 96-4O0OD Chemical Manufacturers Association GROUP I FEMALE# 0 ppm OBSERVATIONS APPENDIX A vinyl chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OP GBSTATION 11111 012345678901234 1601 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1602 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1603 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1604 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1605 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1606 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1607 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1608 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1609 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1610 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1611 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1612 TERMINAL SACRIFICE WITHIN NORMAL LIMITS CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENT P PPPPPPPPP P PPFPPPPPP p PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP p PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP 86SI0 Orffl ba. eu a< iO o* eu a* sue* o*o* dddddddddddddd dddddddddddddd dddddddddddddd dddddddddddddd dddddddddddddd dddddddddddddd dddddddddddddd dddddd dddddddd zz dddd dd dddddddddddd zc dddddddd azzz ZZlzzzz d d d <3 XMHSHHd-d aSXUVH'C SXVtfl BXIHlT TYMtiON N 83IJITOYS TYU BXXHFl TWMON BDIdIMOYS Tfl SXIHIT TVHdON t SOIdldOYS TY) Siiwn TYM80M 1 HDIdIHOYS TY! SXINIT TYHHOH 1 S3I4IH3VB TY1 fcLIHIT TYWHOM i BdldlBSYe TV! SXIWIT TVWHQN I aOldlflDYS TVi enwn TVWHOM I aaamoDOTYN s TYdaxvriKn - noiiyi TvaaxvriNfl - vatnufOAUJYai a^IdlHOVS TYl SXIWIT TYMHON inoNS/samwaaxxa - vi SDIdldOYB TY SXIKIT TYHHON TYV8NSO - VI xnoHS/saiiiisHxxa - vi BOIdIHOYS TY o aa n 068L95*EZI0689S>f:ZT06eX9SCZIO ezzzzzzzzzztttttttttt NOIIVXgHD do aw SNOlXY z aOvd N0IIYXS39 DNIdna SNOIXYAdasaO TV3INIT3 TYftaiAIONI 0)6)1 u"f Aprils X)p^xax '[B^uauido'[BASa pus tmp3npoida)| uotivjouoo-omi. uot^IOX(UI pau^quioo T^ujA Y XIGNSddY uoT^eioosev e aoeo*-96 bbc Huntingdon Life Sciences 96-40B0D Chemical Manufacturers Association GROUP 1 FEMALE# 0 ppm OBSERVATIONS APPENDIX A Vinyl Chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OP GESTATION 1 111 : 0 U H 567890123- 1623 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1624 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 1625 TERMINAL SACRIFICE WITHIN NORMAL LIMITS CODE: 1-SLIGHT 2-MODERATE 1-MARKED P-PRESENT P PPPPPPPP1 P PPPPPPPP) P PPPPPPPP! Huntingdon Life Sciencea 96-40B0D Chemical Manufacturers Association GROUP II FEMALE# lOppm OBSERVATIONS APPENDIX A Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study In CD Rata INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAV OP GESTATION 11111 012345678901234 BFG42086 2601 TERMINAL SACRIFICE M1THIH NORMAL LIMITS 2602 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2603 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2604 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2603 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2606 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2607 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2608 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2609 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2610 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2611 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2612 TERMINAL SACRIFICE WITHIN NORMAL LIMITS COPE; 1-SLIGHT 2-MODERATE 3-MARKEP P-PRESBNT P PPPFPPPPE P PPPPPPPPC P PPPPPPPPI P PFPPPPPPI P PPPPPPPPI P PPPPPPPPI F PPPPPPPPI F PPPPPPPPI P PPPPPPPPI P PPPPPPPPI P PPPPPPPPI P PFPPPPPPI Huntingdon Life Sciences 96-4O0OD Chemical Manufacturers Association GROUP 11 FEMALE* lOppm OBSERVATIONS APPENDIX A Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OF GESTATION 11l11 Q1234567B901234 BFG42087 2612 TERMINAL SACRIFICE ALOPECIA - RXTRSMITIBS/8NOUT NITHIN NORMAL LIMITS 2614 terminal sacrifice WITHIN NORMAL LIMITS 2615 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2616 TERMINAL SACRIPICR RED EXUDATE PRUM ANOGENITAL AREA CHROMODACRYORRHBA - UNILATERAL INCISORS MALOCCLUDBD WITHIN NORMAL LIMITS 2617 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2618 TERMINAL SACRIFICE CHROMODACRYORRHRA - UNILATERAL INCISORS DROEBN/MISSING INCISORS MALOCCLUDBD NITHIN NORMAL LIMITS 2619 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2620 TERMINAL SACRIFICE MXTHIH NORMAL LIMITS 2621 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2622 TERMINAL SACRIFICE NITHIN NORMAL LIMITS CODE; 1'SLIGHT 2-MODBRATB 3-MARKED P-PRESENT 22222 P PPPP P PPPPPPPPl P PPPPPPPP! P P PPPPPPP I P PPPPPPPPl P PPPP 1 PPPP P PPPP P PPPPPPPPl P PPPPPPPP P PPPPPPPP P PPPPPPPP Huntingdon Life Sciences 96-4060D Chemical Manufacturers Association GROUP II FEMALE# lOppm OBSERVATIONS APPENDIX A vinyl chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OP GESTATION 11111 012345670901234 2623 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2624 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 2625 TERMINAL SACRIFICE WITHIN NORMAL LIMITS CODE: 1-SLIGHT 2-MODERATE 3-HARKED P-PRESENT P PPPPPPPPE P PPPPPPPPE P PPPPPPPPE td n O 4^ O oo 00 Huntingdon Life Science 96-4080D Chemical Manufacturers Association GROUP III 100 ppM FEMALE# OBSERVATIONS APPENDIX A Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OF GESTATION 11111 012345678901234 BFG42089 3601 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3602 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3603 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3604 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3605 TERMINAL SACRIFICE ALOPECIA - EXTREMITIES/SNOUT WITHIN NORMAL LIMITS 3606 TERMINAL SACRIFICE ALOPECIA - EXTREMITIES/SNOUT WITHIN NORMAL LIMITS 3607 TERMINAL SACRIFICE ALOPECIA - BXTREMIT1BS/SNOUT WITHIN NORMAL LIMITS 3600 Terminal sacrifice WITHIN NORMAL LIMITS 3609 TERMINAL SACRIFICE ALOPECIA - EXTREMITIES/SNOUT WITHIN NORMAL LIMITS 3610 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3611 TERMINAL SACRIFICE WITHIN NORMAL LIMITS CODEi I-SLIOHT 2-MODERATE 3-MARKED P-PRESENT P PPPPPPPPp P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP 22 P PPPPPPP 222222 P PPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP Huntingdon Life ScienciM 9S-4O0OD Chemical Manufacturers Association GROUP III 100 ppM FEMALES OBSERVATIONS APPENDIX A Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OF GESTATION 11111 012345678901234 BFG42090 3612 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3613 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3614 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3615 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3616 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3617 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3610 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3619 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3620 TERMINAL SACRIFICE ALOPECIA - BXTREHITIE8/SN0UT WITHIN NORMAL LIMITS 3031 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3623 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3623 TERMINAL SACRIFICE ALOPECIA - EXTREHITIEB/SNOUT WITHIN NORMAL LIMITS CODE: 1-SLIQHT 3-MODERATE 3-MARKED P-PRESENT P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP 22222 P PPPP P PPPPPPPPP P PPPPPPPPP 2233 P PPPH Bl Huntingdon Life Sciences 96-408QP Chemical Manufacturers Association GROUP III 100 ppM FEMALE# OBSERVATIONS APPENDIX A Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OF GESTATION 11111 012345678901234 3624 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 3625 TERMINAL SACRIFICE WITHIN NORMAL LIMITS CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENT P PPPPPPPPP P PPPPPPPPP 00 e K> O o Lmi -*a4 s >. SI < X Pi Jj "> o p* A IN B n r* Pi u N 1/1 NT <n n r* rt NH (N O pi 01 Pi tt *4 r* > J 1 1 i rl i rl in H* Pi ffl I 1 1 1 I pi Ct 1 I pi pi pi a 1 1 1 1 o* i i i in Oi a CM a a a at a* at o< at ft a a cw Bi a at At o< 0. a* at Ot at at a St ft ft St 0< ft ft ft Ot ft ft ft ft ft ft ft a< ft ft ft ft ft ft ft ft St ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft a. ft ft ft ft St ft ft ft ft ft & ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft a a. ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft a. ft ft ft ft ft ftft ft ft St ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ft ftft ft ft ft ft ft ft ft ft ft ft ft ft ft ft r> 04 pi o ft & 0* ft ft ft a* at Bi Bi Qi S* o o s g ca in tin g d o n L i f e S c ie n c e s 9 6 -4 0 8 OD te n ica l M anufacturers A sso cia tio n CODEr l - SLIGHT 2 -MODERATE 3 -HARKED P-PRESENT 8* 81 I OHFt 16 3 OS M VM XM a. j h a &** N i-t >0 BFG42092 Huntingdon Life Sciences 96-4QB0D Chemical Manufacturers Association GROUP IV FEMALES 1100 ppm OBSERVATIONS APPENDIX A Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats 1NDJVIPUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OF GESTATION 11111 012345678901234 4613 TERMINAL SACRIFICE WITHIN NORMAL LIMITS td 4614 33 a K1 4615 to O \0 4616 TERMINAL SACRIFICE WITHIN NORMAL LIMITS TERMINAL SACRIFICE WITHIN NORMAL LIMITS TERMINAL SACRIFICE WITHIN NORMAL LIMITS 4617 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 46lfi TERMINAL SACRIP1CB WITHIN NORMAL LIMITS 4619 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 4620 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 4621 TERMINAL SACRIFICE WITHIN NORMAL LIMITS 4622 TERMINAL SACRIFICE ALOPECIA - BXTRBMXTIB8/SN0UT WlTHZN NORMAL LIMITS 4623 terminal sacrifice WITHIN NORMAL LIMITS 4624 TERMINAL SACRIFICE ALOPECIA - RXTREMITIBS/SNOUT WITHIN NORMAL LIMITS CODEi 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENT P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPPPPPPPP P PPFPPPPPP P P PPPPPPPP 2 2222 2 2 P PP P PPPPPPPPP P PPPPPPPPP Huntingdon Life Sciences S6-4080D Chemical Manufacturers Association GROUP IV FEMALE# HOD ppm OBSERVATIONS APPENDIX A Vinyl Chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate INDIVIDUAL CLINICAL OBSERVATIONS DURING GESTATION DAY OF GESTATION 11111 0 1 1 H S fi U 0 1 2 3 4 4625 TERMINAL SACRIFICE ALOPECIA - EXTREMITIES/SNOUT CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENT 2 222322313 BFG42095 BFG 01609 30-SEP-19 .6:44 Huntingdon Life Sciences 96-4Q6QD Chemical Manufacturers Association GROUP I 0 ppm APPENDIX B Vinyl Chloride Combined Inhalation Two-Genaration Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL GESTATION BODY HEIGHTS (GRAMS) ANIMAL# DAY OP GESTATION 0 6 9 12 1601 200 242 237 250 1602 252 285 294 309 1603 189 223 237 254 1604 207 230 246 259 1605 208 235 255 271 1606 217 249 261 277 1607 2l3 235 246 259 1600 223 262 264 276 1609 227 260 260 290 1610 211 244 252 267 1611 212 237 240 253 1612 201 225 233 252 1613 207 237 244 256 1614 215 247 260 274 1615m. NP 217 250 261 267 1616 226 252 264 285 1617 227 250 264 280 l18x Nt> 20b 240 254 263 1619 207 24 0 246 266 1620 221 258 277 293 1621 222 248 253 275 1622 191 223 226 244 1623 202 219 238 261 1624 216 244 255 372 1625 227 256 271 383 MEAN 8.D. H 214 13.7 23 243 14.8 23 254 16.0 23 370 15.8 23 NP-NOT PREGNANT x-RXCLUDBp PROM MEAN 15 261 333 263 273 284 297 375 296 303 283 268 268 273 287 240 30B 298 256 285 314 297 257 278 290 309 287 19.0 23 20 323 415 321 333 347 368 324 364 395 344 335 332 344 352 276 379 376 244 347 381 366 316 339 355 370 353 25.3 33 BFG42096 Huntingdon Life Sciences 96-40B0D Chemical Manufacturers Association APPENDIX P Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats GROUP II lOppm INDIVIDUAL GESTATION BODY WEIGHTS {GRAMS) ANIMAL# DAY OP GESTATION 0 6 9 12 2501 2502 2603 3604 2605 2606 2607 26Q9 2609 2610 261lx 2612 2613 2614 2615 2616 2617 2619 2619 2620 2621 2622 2623 2624 2625 NP 221 226 196 206 210 317 211 22S 227 208 217 200 209 213 219 225 244 202 209 219 223 167 206 214 231 252 265 220 232 235 241 241 246 244 238 239 223 236 245 236 256 274 227 230 233 243 216 230 239 251 250 274 229 245 252 257 254 265 247 250 249 230 248 250 246 277 279 235 233 239 249 232 243 249 268 263 293 243 252 270 272 275 269 266 269 252 259 264 263 267 300 302 235 247 256 265 247 261 269 208 MEAN B.D. N 214 12.3 24 240 13.3 24 250 13.9 24 np-not pregnant X-BXCLUDBD PROM MEAN 266 16.7 24 15 279 312 259 272 291 267 290 281 277 279 243 274 280 281 276 315 314 257 269 273 273 262 291 282 300 282 15.8 24 20 326 364 312 338 359 341 348 335 336 325 251 349 334 336 345 397 373 303 333 332 331 313 349 333 357 340 19.2 24 BFG42097 Huntingdon Life Sciences 96-40000 Chemical Manufacturers Association APPENDIX B Vinyl Chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate GROUP III 100 ppM INDIVIDUAL GESTATION BODY HEIGHTS (GRAMS) ANIMAL# DAY OP GESTATION 0 6 9 12 3601 3602 3603 3604 HoS 3606 3607 3608x 3609 3610X 3611 3612 36X3 3614 3615 3616 3617 3610 3619 3620 3621 3622 3623 3G24X 3625 NP NP NP 224 319 199 203 2l3 216 218 220 172 208 220 195 210 213 218 224 195 200 210 217 223 226 209 213 199 256 239 227 233 241 238 245 240 212 239 252 221 236 232 242 260 220 235 237 249 257 257 237 227 262 265 250 239 233 251 247 260 248 228 247 265 230 249 239 258 271 236 244 24 7 262 254 267 248 226 272 201 262 253 251 269 264 270 245 237 237 278 250 268 253 279 286 251 261 271 274 275 280 26S 230 286 MEAN S.D. W 210 12.9 22 240 13.7 22 251 13.2 22 266 13.2 22 NP-NOT PREGNANT x-BXCLUDBD PROM MEAN 15 106 279 267 268 208 280 283 349 256 243 291 261 274 266 294 295 266 278 277 294 298 296 275 232 307 283 14.5 22 20 376 348 333 331 357 347 336 258 267 244 349 324 329 312 359 360 327 338 345 357 361 364 323 234 366 341 23.6 22 BFG42098 f Huntingdon Life Sciences 96-4080D chemical Manufacturers Association APPENDIX B Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CP Rata GROUP IV 1100 ppm INDIVIDUAL GESTATION BODY WEIGHTS (GRAMS) ANIMAL# DAY OP GESTATION 0 6 9 12 4601 4602 4603 4604 4605 4606 4607 4606 460?x 4610 4611 4612 4613 4614 4615 4616 4617 4610 4619 4620 4621 4622 4623 4624 4625 NP 204 211 201 201 215 2X5 217 219 193 199 226 233 211 212 220 222 199 199 312 215 223 224 212 312 238 224 240 224 228 244 241 2S1 246 233 235 247 260 251 238 249 2 46 227 238 237 250 261 253 253 246 227 232 251 235 235 251 248 265 254 232 241 266 261 254 245 263 256 234 247 244 260 261 265 256 252 239 247 259 2S3 250 265 263 280 270 229 248 264 270 276 266 277 277 250 367 266 272 280 281 282 263 250 MEAN 8.D. N 214 10*5 24 242 10.8 24 250 10.2 24 266 11.4 24 MP-NOT PREGNANT x-BXCLuOED PROM MEAN 15 26S 280 264 262 278 279 298 278 23? 264 288 293 295 28i 291 289 266 283 285 290 292 292 302 281 271 282 11-6 24 20 307 341 317 316 328 353 361 337 244 319 337 352 359 351 342 359 334 354 343 352 357 351 361 336 332 343 15.6 24 BFG42099 Bl BFG42100 BFG 01614 11-NOV-l* Q9j34 BFG42101 Huntingdon Life Sciences 96-4O0OD Chemical Manufacturers Association APPENDIX C Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats GROUP 1 0 ppm INDIVIDUAL GESTATION BODY HEIGHT GAIN (GRAMS) ANIMAL# DAY OP GESTATION 0 - 6 6-9 9-13 13 - 15 ISO). 41 -5 13 11 1602 33 9 IS 24 1601 34 14 17 10 1604 23 16 13 13 1606 36 20 17 13 1606 22 12 16 20 1607 22 11 13 16 160S 29 13 12 20 1600 33 0 22 14 1610 33 a 15 16 1611 25 j 13 15 1612 24 0 19 16 1612 30 6 11 16 1614 32 13 13 13 1G15K NP 33 11 6 -27 1616 26 12 21 24 1617 23 14 17 18 161BX NP 36 14 9 -6 1619 34 6 20 19 1620 37 19 16 21 1621 27 5 21 22 1622 31 3 10 14 1623 17 19 23 17 1624 26 U 17 17 162S 30 15 12 26 MEAN S.D. N 29 10 16 17 5.6 5.8 3.5 4.3 23 23 23 23 NP-NOT PREGNANT X-EXCWD&D FROM KEAN 15 - 20 62 82 58 61 63 71 49 68 91 6Q 67 64 71 65 36 70 79 -13 63 60 69 S9 61 66 61 66 6.7 23 6 - 20 82 130 96 103 112 110 89 112 13S 100 98 107 107 105 26 127 127 4 107 123 117 94 120 111 114 110 13.5 23 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association APPENDIX C Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats GROUP II lOppm INDIVIDUAL GESTATION BODY HEIGHT GAIN (GRAMS) DAY OF GESTATION ANIMALtf 0 - 6 6 - 9 9 - 12 ------------------- -------- --- - ------------ - - - _ - m m m 2601 31 -2 13 2602 39 9 19 2603 24 9 14 2604 25 13 0 2605 25 16 18 2606 24 16 IS 2607 29 12 23 2600 20 19 4 2609 10 2 19 2610 30 11 10 26UX NP 22 9 4 2612 2613 23 15 19 27 12 16 2614 32 5 14 2615 IS 10 21 2616 33 19 23 2617 30 4 23 2610 25 7 0 2619 22 2 15 2620 15 $ 17 2621 20 7 15 2622 31 14 IS 2623 32 5 19 2624 2$ 9 21 2625 19 18 19 12 - IS IS - 20 ______ 16 47 19 52 15 54 20 66 21 68 15 54 15 58 12 54 11 59 20 45 -9 9 16 74 16 54 IB 54 9 69 15 72 12 59 22 46 22 64 18 59 8 58 15 52 20 68 14 51 12 58 MEAN S.D. N CO 26 10 16 5.a 5.7 5.7 24 24 24 T) NPNOT PREGNANT o x-BXCWDBD FROM MEAN 16 4.0 24 58 8.2 24 6-20 74 99 92 107 124 100 107 89 91 87 13 125 97 91 109 130 99 75 103 99 88 96 111 94 107 100 13.8 24 Huntingdon Life Sciences Chemical Manufacturers Association APPENDIX C Vinyl chloride combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata GROUP 111 100 ppM INDIVIDUAL GESTATION BODY HEIGHT GAIN (GRAMS| ANIMAL# DAY OF GESTATION 0 - 6 6-9 9-12 12 - 15 15 - 20 6 - 20 1601 34 7 16 24 70 118 3602 22 11 11 17 70 109 3603 26 13 14 14 66 106 3604 30 0 18 17 62 96 3605 27 10 19 19 69 117 3606 22 9 17 16 66 109 3607 27 15 10 13 54 91 360flx NP 20 a -4 4 9 18 3609 40 16 9 19 11 55 3610x NP 31 8 -11 6 2 5 3611 32 13 13 14 58 98 3612 26 9 20 11 63 103 3613 26 13 19 6 55 93 3G14 19 7 14 13 46 81 3615 24 16 21 IS 65 117 3616 36 11 IS 10 65 100 3617 25 16 15 15 61 107 3618 34 9 17 17 60 103 3619 3620 27 10 25 6 67 108 33 13 12 20 63 107 3621 35 -3 21 23 63 104 3622 31 11 13 16 66 106 3623 28 11 17 10 49 66 3624x NP 14 -1 3 2 2 6 362S 63 10 14 21 59 104 MEAN S.D. N 30 10 16 15 6.9 4.6 3.9 4.6 22 23 22 22 CD Hn NP-NOT PREGNANT A-EXCLUDED FROM MEAN 60 12.7 22 101 14.0 22 Huntingdon Life Sciences 96-4080D Chemical Manufacturere Association APPENDIX C Vinyl Chloride Combined Inhalation Two-Generation Reproduction end Developmental Toxicity Study in CD Rata GROUP IV 1100 ppm INDIVIDUAL GESTATION BODY HEIGHT GAIN (GRAMS) ANIMAL* DAY OP GUSTATION 0 - 6 6-9 9 - 12 12 - 15 4601 30 8 14 18 4603 27 12 8 21 4603 22 12 18 12 4604 2B 7 15 12 4605 39 7 14 13 4606 27 7 15 17 4607 34 14 15 17 4608 27 9 15 9 4609X NP 30 10 -3 3 4610 35 7 7 16 4611 20 9 9 24 4612 27 1 9 23 4611 40 3 23 19 4614 26 8 21 15 4615 29 14 14 14 4616 23 10 21 12 4617 4618 26 7 16 16 39 10 20 16 4610 25 7 22 19 4620 34 10 12 18 4621 38 1 19 12 4622 29 12 15 12 4623 41 5 24 2D 4634 34 5 11 18 4625 -11 13 10 22 MEAN 8.D. N 28 8 IS 16 10.3 3.6 4.8 3.9 34 24 24 24 NP-NOT PREGNANT x-BXCLUDBD FROM MEAN 15 - 20 42 61 53 54 50 73 63 59 12 54 49 59 64 70 50 70 68 71 58 62 65 59 59 55 6l 60 7.8 34 6-20 83 102 94 80 04 111 110 92 21 84 91 93 108 113 92 113 108 H6 107 102 96 90 109 90 106 99 10.4 24 f iFG42I04 BFG42105 BFG 01619 30-SEP-li1 16;45 Huntingdon Life ficiencce 964080D Chemical Manufacturers Association APPENDIX D GROUP I 0 ppm vinyl Chloride combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL GESTATION POOD CONSUMPTION -- (GRAMS/ANIHAL/DAY) ANIMAL# DAY OP GESTATION 0-6 6-9 9-12 12 - IS 15 - 20 1601 21 16 19 19 22 1602 23 21 24 27 30 1603 19 19 16 19 34 1604 18 20 20 21 23 1605 Ifi 19 22 21 34 1606 20 20 19 23 23 1607 19 17 19 20 21 1608 20 20 19 22 25 1609 20 19 21 21 25 1610 21 19 21 22 24 1611 19 16 20 21 24 161 2 18 16 18 19 22 1613 18 19 18 20 25 1614 19 18 18 19 22 1615x NP 20 19 19 8 IB 1616 21 20 23 26 27 1617 28 20 20 21 24 161&X HP 23 20 22 18 16 1619 18 17 20 SPILL 24 1620 20 21 21 24 25 1621 20 19 21 24 27 1623 17 16 30 19 32 1623 18 17 21 21 24 1624 163$ 17 16 20 21 24 16 16 17 21 25 MEAN S.D, N 19 16 20 21 2.5 1.6 1,7 2.0 23 23 23 22 03 NP-NOT PREGNANT X-EXCLUDfiD PROM MEAN 24 1.9 23 o & Huntingdon Life Sciences 96-4O0OD Chemical Manufacturers Association APPENDIX P Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats GROUP II lOppm INDIVIDUAL GESTATION POOD CONSUMPTION -- (GRAMS/ANIMAL/DAYI ANIMAL|f DAY OF GESTATION 0-6 6-9 9-12 12-15 2601 20 16 21 23 2602 20 21 24 25 2603 lfl 17 18 20 2604 19 10 19 20 2605 21 19 22 23 2606 20 10 20 22 2607 20 10 21 23 2606 17 18 16 18 >609 20 16 19 20 2610 20 20 21 21 2611* NP 20 18 18 SPILL 2612 19 1H 19 24 2613 19 19 20 22 2614 Id 17 19 23 2615 10 19 10 20 2616 21 24 24 22 2617 23 22 24 24 261$ 10 18 14 2Q 2619 17 is 17 20 2620 10 10 19 20 2621 17 17 21 21 2622 21 19 21 22 2623 17 18 20 22 2624 17 20 22 22 2625 18 20 25 23 MEAN &.D. N 19 19 20 22 1.7 1*9 2.6 1.7 24 24 24 24 NF*NOT PREGNANT X-BXCLUDKD FROM MEAN 15 - 20 24 25 22 23 27 22 26 21 23 22 17 26 22 23 24 23 25 20 22 22 24 23 25 24 26 23 1.9 24 Huntingdon Life Sciences 96-408QD Chemical Manufacturers Association APPENDIX D vinyl chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD hats GROUP III 100 ppN INDIVIDUAL GESTATION FOOD CONSUMPTION -- {GRAMS/ANIMAL/DAY} ' ANIMALS DAY OP GESTATION 0 - 6 6-9 9-12 12-15 15 - 20 3601 20 18 20 23 25 3602 19 19 19 22 24 3603 10 17 21 20 23 3604 10 15 18 19 20 3605 3606 17 16 23 24 25 19 IB IB 22 23 3607 21 21 19 16 24 360Bx NP 19 17 17 19 18 3609 21 21 IB 22 18 3610* NP 20 20 16 14 16 3611 31 19 20 21 24 3612 17 16 18 19 21 3613 30 19 21 22 22 3614 17 17 19 20 21 361$ 19 21 21 23 25 3616 22 21 24 24 24 3617 22 18 20 21 22 3610 19 17 21 21 21 3619 IB 17 22 20 23 3620 22 22 19 26 27 3621 21 17 20 26 23 3622 19 IB 21 22 24 3623 17 19 20 31 21 3624x NP 15 14 16 16 17 362S 21 22 24 23 27 MEAN S.D. K 19 19 20 22 23 1.7 2.0 1.7 2.2 2.2 22 23 22 22 22 NP*N0T PREGNANT X-BXCLUDED PROM MEAN BFG42108 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association APPENDIX D Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats GROUP IV 1100 ppm INDIVIDUAL GESTATION POOD CONSUMPTION -- <GRAHS/ANIMAL/DAY) ANIMALS DAY OP GESTATION 0-6 6-9 9-12 12 - 15 4601 15 16 19 23 4602 17 19 20 22 4603 18 17 19 19 4604 17 18 20 21 4605 19 16 18 20 4606 19 15 19 21 460? 19 20 22 24 4608 18 18 20 20 4609x NP 20 19 15 18 4610 20 18 19 20 4611 19 19 2l 22 4612 21 19 19 23 4612 21 10 21 23 4614 18 16 20 21 4615 22 21 22 24 4617 19 18 19 21 4619 18 16 19 20 4620 22 18 21 21 4621 2Q 18 21 22 4622 19 19 21 24 4623 22 18 21 34 4624 19 19 19 32 4625 18 18 18 20 MEAN S.D. N 19 18 20 22 1.7 1.4 1.3 1.6 22 22 22 22 NP-NOT PREGNANT X-RXCLUDRD PROM HSAN 15 - 20 21 25 22 22 21 24 27 22 17 25 22 24 23 23 23 21 23 24 24 26 26 23 31 24 2.3 22 BFG42109 [/ BFG 01624 bFG42U 30-SEP-19 .6 s46 Huntingdon Lite Sciences 96-40B0D Chemical Manufacturers Association APPENDIX E vinyl chloride combined Inhalation Twp-Ceneration Reproduction and Developmental Toxicity Study in CD Rats GROUP I 0 ppm INDIVIDUAL GESTATION FOOD CONSUMPTION -- (GRAMS/KG/DAY) AMIHalR DAY OF GESTATION 0 - 6 6-9 9-12 12 - 15 15 - 20 1601 104 68 79 76 84 1602 08 75 81 87 89 1603 1604 99 84 77 76 90 88 85 80 80 81 1605 85 80 85 77 85 1606 91 80 71 78 79 1607 91 71 77 79 78 1608 90 80 73 80 85 1609 88 71 78 73 83 1610 1611 101 79 83 82 86 90 68 85 82 90 1612 88 73 78 76 82 1613 65 80 76 80 91 1614 86 72 6B 70 78 lfclbx NP 92 77 71 28 76 1616 95 79 87 90 86 1617 123 79 76 73 79 1610X NP 113 01 87 69 61 1619 aa 72 81 SPILL 84 1620 89 82 77 81 79 1621 89 75 B4 86 91 1622 1622 88 67 88 79 86 88 77 90 80 8? 1624 76 74 77 76 82 1625 68 69 64 73 80 MEAN S.D. N 90 76 79 79 84 10.2 5.3 6.3 4.8 4.2 23 33 23 aa 23 NP-NOT PRRgKaNT x-RxchUD&D FROM HBAN BFG42L11 Huntingdon Life Sciences 96-4oaoD Chemical Manufacturers Association APPENDIX B Vinyl chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats ___ .. GROUP II lOppm INDIVIDUAL GESTATION FOOD CONSUMPTION -- (GRAMS/KG/DAV) ANIMAL# DAY OF GESTATION 0 - 6 6 - 9 9-12 12 - IS 2601 90 65 86 87 2602 90 79 86 84 2609 92 76 79 81 2604 90 77 77 78 2605 99 81 87 85 2606 93 73 79 81 2607 94 75 84 85 2600 75 75 62 66 2609 87 66 78 76 2610 96 83 86 82 2611* NP 91 77 71 SPILL 2612 93 81 BO 91 2613 90 7? 01 03 2614 87 69 74 86 26lS 82 79 7 76 2616 95 94 87 74 2617 95 79 86 79 2618 89 80 60 84 2619 79 66 73 79 2620 84 79 80 78 2621 75 72 05 00 2622 113 87 92 89 2629 82 76 84 83 2624 80 82 89 82 2625 79 80 92 81 MEAN $.Z>, N 89 77 81 81 8.5 6.7 8.0 5.3 24 24 24 24 NP-NOT PREGNANT X-RXCLUDED FROM M&AN 15 - 20 87 80 84 84 92 77 90 73 83 78 71 97 00 83 86 72 80 76 82 81 89 89 89 84 87 83 5.9 24 Huntingdon Life Sciences 96-4060D Chemical Manufacturers Association APPENDIX E GROUP III 100 ppN Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study In CD Rats INDIVIDUAL GESTATION FOOD CONSUMPTION -- (GRAMS/KG/DAYI ANIMAL# DAY OP GESTATION 0 - 6 6 - 9 9-12 12-15 15 - 20 3601 89 70 76 81 82 3602 87 78 74 83 84 3603 90 76 86 80 85 3604 90 65 77 74 76 360S 3606 82 67 91 89 88 87 74 75 83 81 3607 96 86 74 61 84 360Sx NP 84 70 68 77 72 3609 124 97 81 91 71 3610x HP 97 86 66 60 66 3611 94 77 76 77 81 3612 87 74 80 74 82 3613 96 79 05 82 82 3614 82 74 78 79 78 3615 87 87 82 82 86 3616 98 80 87 82 80 3617 114 83 87 82 84 361B 93 73 87 62 76 3619 85 72 90 74 04 362Q 100 90 72 94 93 3621 95 66 7# 93 76 3622 84 72 BO 77 61 3623 83 79 82 78 77 3624X NP 71 61 69 72 71 362# 107 64 87 82 69 MEAN S.D. N 93 77 81 81 82 10,7 B.O 5.6 7.3 4.7 22 22 22 22 22 NP-NOT PREGNANT x-BXCLUDBD PROM MEAN BFG42113 Huntingdon Life Science^ 96-4060D Chemical Manufacturers Aeeociation GROUP IV 1100 ppm APPENDIX E Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata INDIVIDUAL GESTATION FOOD CONSUMPTION -- (GRAMS/KG/DAY) ANIMAL# PAY OF GESTATION 0-6 6-0 9-12 12 - 15 4601 72 69 82 94 4602 80 80 78 85 4603 88 74 79 75 4604 87 78 86 82 4605 87 64 70 75 4606 86 64 77 78 4607 90 78 85 85 4608 82 73 80 72 4609* NP 104 86 65 77 4610 103 77 78 80 4611 62 78 82 84 4612 86 72 74 84 4613 101 72 84 84 4614 83 69 80 79 4615 98 84 84 87 4617 96 78 83 84 4615 84 68 78 77 4620 101 71 80 78 4621 89 67 79 77 4622 85 75 79 86 4623 102 72 83 85 4624 92 76 75 85 4625 76 78 75 79 MEAN 8.D. N 89 73 79 82 8.4 S.3 3.9 4.9 22 22 22 22 NP-NOT PREGNANT x-BXCLUDRD FROM MEAN IS - 20 80 88 84 85 74 84 90 80 72 94 77 80 79 83 78 81 77 84 83 90 85 83 114 84 6.2 22 BFG42114 BFG42U5 BFG 01629 30-SEP-19 6:46 Huntingdon Life Science 96-40B0D Chemical Manufacturers Association APPENDIX F Vinyl Chloride combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL FEMALE REPRODUCTION DATA AND MEAN FETAL WEIGHT DATA CORPORA 4PREIMPL. IMPLANT ANIMAL# LUTEA LOSS SITES 1601 1602 1603 1604 1605 1606 1607 1603 1609 1610 1611 1612 1613 1614 1615 1616 1617 1610 161# 1620 1621 1622 1623 1624 1625 MEAN S.D. N 15 15 15 14 17 17 16 13 IB 14 15 14 16 15 NP 16 IS NP 14 15 15 12 16 16 15 15.3 1.45 23 HP-NOT PREGNANT 6.7 0.0 13.3 7.1 29.4 5.9 IS.8 0.0 5,6 0.0 13.3 0.0 6.3 6.7 12.5 S. 6 7.1 0.0 0.0 0.0 6.3 6.3 0.0 6.6 7.22 23 14 15 13 13 12 16 13 13 17 14 13 14 15 14 14 17 13 15 15 12 15 15 15 14.2 1.3B 23 FETUSES LIVE DEAD In) ft 13 0 0.0 15 0 0.0 12 0 0.0 13 0 0.0 11 0 0.0 16 0 0.0 12 0 0.0 13 0 0.0 17 0 0.0 13 0 0.0 1? 0 0.0 14 0 0.0 14 0 0.0 12 0 0.0 13 0 0.0 17 0 0.0 13 0 0.0 15 0 0.0 15 0 0.0 12 0 0.0 15 0 0,0 IS 0 0.0 IS 0 0.0 13. S o.o 1.64 0 .00 23 23 0.0 0.00 23 RESORPTIONS EARLY LATE TOTAL In) ft 1 0 1 7,1 0 0 0 0.0 1 0 1 7.7 0 0 0 0.0 1 0 1 8.3 0 0 0 00 1 0 1 77 0 0 0 0.0 0 0 0 0.0 1 0 1 7.1 0 0 0 0.0 0 0 0 0.0 1 0 1 6.7 2 0 2 14.3 1 0 1 7.1 0 0 0 0-0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0.4 0, SB 23 0.0 0.00 23 0.4 o.sa 23 2.9 4.26 23 SEX MALE FEMALE 94 4H 6 B 65 g 7 49 10 7 4$ 76 4 10 4 10 66 67 9a 7 a7 10 s 2 10 96 s 10 69 6.5 7.3 2.19 2.06 23 23 B! Huntingdon Life Science# 96-40B0D Chemical Manufacturers Association APPENDIX F Vinyl Chloride Combined Inhalation Two-Generation Reproduction end Developmental Toxicity Study in CP Rate GROUP II lOppm INDIVIDUAL FEMALE REPRODUCTION DATA AND MEAN FETAL HEIGHT DATA CORPORA iPfcBIMPL. IMPLANT ANIMAL# LUTEA LOSS SITES FETUSES LIVE DEAD (n) 1 RESORPTIONS EARLY LATE TOTAL (n) SEX MALE FEMALE 2601 8 12.5 7 7 0 0.0 0 0 0 0,0 34 2602 26 50.0 13 11 0 0.0 1 1 2 15.4 9a 2603 14 7,1 13 12 0 0.0 1 0 1 7.7 6 6 2604 17 23.5 13 13 0 0,0 0 0 0 0.0 5B 2605 IS 6.7 14 14 0 0.0 0 0 0 0.0 7 7 2606 15 13.3 13 13 0 0.0 0 0 0 0.0 67 2607 IS 0.0 IS 12 0 0.0 3 0 3 20.0 8 4 2600 13 15.4 11 11 0 0.0 0 0 0 0.0 47 2609 14 14.3 12 12 0 0.0 0 0 0 0.0 e4 2610 13 7.7 12 11 0 0.0 1 0 1 8.3 3 a 2611 NP 2612 IS 13.3 13 13 0 0.0 0 0 0 0.0 65 2613 13 7.7 12 12 0 0.0 0 0 0 0.0 9 3 2614 12 8.3 11 10 0 0.0 1 0 1 9.1 6 4 2615 15 0.0 IS 14 0 0.0 1 0 1 6.7 4 10 2616 22 27.3 16 16 0 0.0 0 0 0 0.0 5 11 2617 15 13.3 13 12 0 0.0 1 0 1 7.7 57 2618 14 7.1 13 13 0 0.0 0 0 0 0.0 4 9 2619 15 0.0 15 15 0 0.0 a 0 0 0.0 7 8 2620 13 0.0 13 13 0 0.0 0 0 0 0.0 9 4 2621 13 0.0 13 13 0 0.0 0 0 0 0.0 7 6 2622 12 0.0 12 11 0 0.0 i 0 1 9.3 9 2 2623 17 11.9 15 IS 0 0.0 0 0 0 0.0 7a 2624 14 7.1 13 12 0 0.0 i 0 1 7.7 6 6 2625 15 20.Q 12 12 0 0.0 0 0 0 0.0 40 MEAN S.D, 9 14. B 3.41 24 11.1 11.21 24 12.9 1.80 24 12-4 0.0 1.84 0.00 24 24 0.0 0.00 24 0.5 0.72 24 0.0 0.20 24 0.5 0.79 24 3.8 5.66 24 6.2 6.2 1.96 2.43 24 24 np-not pregnant BFG42U7 BF Huntingdon Life Science* 96-4O80D Chemical Manufacturers Association APPENDIX F vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Tonicity Study in CP Rats GROUP III 100 ppM INDIVIDUAL FEMALE REPRODUCTION DATA AND MEAN FETAL HEIGHT DATA CORPORA 8PRBIMPL. IMPLANT ANIMAL! LUTBA LOSS SITES FETUSES LIVE DEAD <n) 4 RESORPTIONS EARLY LATE TOTAL <n) 8 SEX MALE FEMALE 1601 3602 3603 3604 3605 3606 3607 3609 3609 3610 3611 3612 3613 3614 3615 3616 3617 3619 3610 3620 3621 3622 3623 3624 3625 MEAN fl.D. N 19 IB 13 17 28 17 13 NP 6 NP 14 20 13 9 14 14 14 14 14 30 16 15 16 NP 13 15.3 4.31 23 26.3 5.6 0.0 11.8 42.9 5.9 7.7 0.0 14.3 30.0 23.1 11-1 o.o 7,1 7.1 0.0 7.1 40.0 6.3 6.7 6.3 0.0 11. B 12.68 22 14 17 13 15 16 16 12 6 12 14 10 a 14 13 13 14 13 12 15 14 15 13 13.1 2.55 22 14 0 0.0 17 0 0.0 13 0 0.0 15 0 0.0 13 0 0.0 16 0 0.0 10 0 0.0 6 0 0.0 11 0 0.0 14 0 0.0 10 0 Q 0 0 0 0.0 14 0 o.o 13 0 0.0 13 0 0.D 14 0 0.0 13 0 0.0 12 0 0.0 15 0 0.0 14 0 0.0 15 0 o.o 13 0 0.0 12.9 0.0 2.57 0.00 22 22 0.0 0.00 22 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 3 0 3 18.8 0 0 0 0.0 2 0 2 16,7 0 0 Q 0.0 1 0 1 9.3 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 0.0 0 0 0 o.o 0 0 0 o.o 0 0 0 D.O 0 0 0 0.0 0 0 0 0.0 0 0 0 o.o 0 0 0 0.0 0 0 0 0.0 0 0 0 o.o 0.3 0.77 22 0.0 0.00 22 0.3 0.77 22 2.0 5.40 22 77 7 10 76 87 67 Ba 55 15 65 77 64 35 e6 3 10 58 S9 67 B4 5 10 95 69 76 6.0 6.8 1.91 1.92 22 22 NP-NOT PREGNANT bd n O tho- 00 Huntingdon Life Sciences 96-4060D Chemical Manufacturers Association APPENDIX F Vinyl Chloride Combined Inhalation Twi>-Generation Reproduction And Developmental Toxicity Study In CD Rats GROUP IV 1100 ppm INDIVIDUAL FEMALE REPRODUCTION DATA AND MEAN FETAL HEIGHT DATA CORPORA IPRBINPL. IMPLANT ANIMAL# LUTBA LOSS SITES FETUSES LIVE DEAD (n) % RESORPTIONS EARLY LATE TOTAL In) % SEX MALE FEMALE 4601 10 10 (o 9 9 0 0.0 0 0 0 0.0 S4 4602 17 17.6 14 12 0 0.0 2 0 2 14.3 84 4603 15 20.0 12 11 0 0.0 1 0 1 $.3 65 4604 12 0.0 12 12 0 0.0 0 0 0 0.0 $ 4 4605 13 7.7 12 11 0 0.0 1 0 1 $.3 6 5 4606 16 0.0 16 16 0 0.0 0 0 0 0.0 0 8 4607 IS 6.7 14 13 0 0.0 1 0 1 7.1 4 9 4608 15 26.7 11 11 0 0.0 0 0 0 0.0 $3 4609 HP 4610 10 40.0 6 6 0 0.0 0 0 0 0.0 33 4611 15 6,7 14 12 0 0.0 2 0 2 14.3 5 7 4612 14 0.0 14 14 0 0.0 0 0 0 0.0 6 6 4613 15 6.7 14 14 0 0.0 0 0 0 0,0 6 8 4614 22 27.3 16 16 0 0.0 0 0 0 0.0 6 10 4615 14 7.1 13 13 0 0.0 0 0 0 0.0 4 9 4616 16 6.3 IS IS 0 0,0 0 0 0 0.0 a 7 4617 15 6.7 14 14 0 0.0 0 0 0 0.0 6 $ 461$ 21 23.$ 16 14 0 0.0 2 0 2 12.5 77 4619 15 6.7 14 14 0 0.0 0 0 0 0.0 7 7 4620 17 11.8 15 15 0 o.o 0 0 0 0.0 7B 4621 15 6.7 14 13 0 0.0 1 0 1 7.1 6 7 4622 17 11.$ 15 11 0 0.0 4 0 4 26.7 65 4633 IS 13.3 13 12 0 0.0 1 0 1 7.7 75 4624 14 14.3 12 12 0 0.0 0 0 0 0.0 57 4625 15 0.0 15 IS 0 0.0 0 0 0 0.0 7 $ MEAN S.D. N 15.1 2 ,68 24 11.6 9.99 24 13,3 2.30 24 12.7 0.0 0.0 2.27 0.00 0.00 24 24 24 0.6 1.01 24 0.0 0.00 24 0.6 1.01 24 4.4 6.93 24 6.3 6.4 1.43 1.9$ 24 24 NP-NOT PREGNANT BFG 42U9 BFG 01634 2Q-NOV-1L 09:30 Huntingdon Life Sciences 96-4060D Chemical Manufacturers Association APPENDIX 0 Vinyl Chloride Combined Inhalation Two Generation Reproduction and Developmental Toxicity Study in CD Rats 0 ppm INDIVIDUAL GRAVID UTERINE HEIGHT AND NET BODY HEIGHT CHANGE (GRAMS) ANIMAL# UTERUS HEIGHT ADJUSTED HEIGHT NET HEIGHT CHANGE HEIGHT CHANGE FROM DAY 6 FROM DAY 6 1601 1602 1602 1604 1605 1606 1607 1608 1609 1610 1611 1612 1613 1614 161SX 1616 1617 1618X 1619 1620 1621 1622 1622 1624 1625 NE> NP MEAN S.D, N 67 91 64 66 61 63 62 73 96 69 72 63 73 63 1 76 90 3 73 60 87 67 79 61 70 75* 9,7 23 256 234 2S7 265 264 265 261 291 396 275 261 248 271 289 275 303 286 241 275 301 279 249 260 276 301 279. 19.5 23 15 62 29 130 34 98 35 103 49 112 26 lie 26 89 39 112 39 135 31 100 26 90 23 107 36 107 42 105 25 26 51 127 37 127 14 36 107 43 122 30 117 27 94 61 120 30 111 45 114 35. no. 8.5 12*5 23 23 ADJUSTED HEIGHT - TERMINAL BODY WEIGHT MINUS GRAVID UTERINE NBIGHT NET WEIGHT CHANGE FROM DAY 6 - TERMINAL CORRECTED BODY HEIGHT MINUS DAY 6 BODY HEIGHT NF-NOT pregnant x-BXCLUDBD PROM MEAN BFG42121 Huntingdon Life Sciences 96-40800 Choralcal Manufacturers Association appendix 0 Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata 10 ppm INDIVIDUAL GRAVID UTBRINS HEIGHT AMD MET BODY HEIGHT CHANGE (GRAMS) ANIMAL# UTERUS HEIGHT ADJUSTED HEIGHT NET HEIGHT CHANGE HEIGHT CHANGE PROM DAY 6 PROM DAY 6 2601 2602 2603 2604 260S 2606 2607 2608 2609 2610 26Hx 2612 2613 2614 261S 2616 2617 2618 2618 2620 2621 2622 2623 2624 2625 HP MEAN S.D. N 39 62 69 75 80 70 66 61 66 59 3 71 69 60 74 91 64 65 81 74 75 62 81 69 71 69. 10.0 24 287 302 243 263 279 271 282 274 270 266 249 277 365 276 271 296 309 238 253 258 256 2S1 268 264 287 271. 17.4 24 35 74 37 99 23 92 32 107 44 124 30 100 41 107 28 89 26 91 37 87 10 13 54 125 29 97 31 91 35 109 39 130 35 99 10 75 22 103 25 99 14 88 34 96 30 111 25 94 36 107 31. 100. 9.1 13*8 24 24 ADJUSTED HEIGHT - TERMINAL BODY HEIGHT MINUS GRAVID UTERINE HEIGHT NET HEIGHT CHANGE PROM DAY 6 - TERMINAL CORRECTED BODY HEIGHT MINUS DAY 6 BODY HEIGHT BFG42122 MP-NOT PREGNANT x-RXCLUDED PROM MEAN Huntingdon Life Sciences 96-408QD Chemical Manufacturer* Aaeociation APPENDIX G vinyl Chloride combined inhalation Tuo-Generation Reproduction and Developmental Toxicity Study in CD Rate 100 ppm INDIVIDUAL GRAVID UTERINE WRIGHT AND NET BODY WRIGHT CHANGE (GRAMS) ANIMAL# UTERUS WEIGHT ADJUSTED WEIGHT NET WRIGHT CHANGE WEIGHT CHANGE PROM DAY 6 PROM DAY 6 3601 3602 3603 3604 3605 3606 3607 3608x 3609 36l0x 3611 3612 3613 3614 3615 3616 3617 3615 3619 3630 3621 3622 3623 3624X 3625 NP NP NP 78 92 70 79 67 84 57 1 38 1 60 74 60 48 74 77 75 74 72 69 SO 78 72 1 72 298 256 363 252 290 263 279 257 229 243 269 250 369 265 285 284 251 264 273 288 281 286 251 233 294 40 118 17 109 37 106 19 98 50 117 25 109 34 91 17 18 17 55 45 37 98 29 103 33 93 33 81 43 117 24 100 32 107 29 103 36 108 38 107 23 104 30 108 14 86 56 32 104 MEAN SD. M 70. 12.0 22 271. 17.8 22 31. 9.0 22 101. 14.0 22 ADJUSTED WEIGHT - TERMINAL BODY WEIGHT MINUS GRAVID UTBRINK WEIGHT NBT WEIGHT CHANGE FROM MY 6 - TERMINAL CORRECTED BODY WEIGHT MINUS DAY 6 BODY WEIGHT W T1 NP-NOT PREGNANT x-BXCLUDBD FROM MEAN Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association APPENDIX G Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity study in CD Rate GROUP IV 1100 pym INDIVIDUAL GRAVID UTERINE HEIGHT AND NET BODY WEIGHT CHANGE (GRAMS) ANIMALS UTERUS WEIGHT ADJUSTED WEIGHT NBT WEIGHT CHANGE WEIGHT CHANGE PROM DAY 6 FROM DAY 6 4601 4602 4603 4604 4606 4606 4607 4600 4609x 4610 4611 4612 4613 4614 4615 4616 4617 4616 4619 4620 4621 4622 4623 4624 4625 NP 51 70 sa 61 62 63 77 69 12 39 65 81 71 80 67 70 83 72 70 74 75 66 69 64 79 257 271 259 255 266 270 284 269 232 280 273 271 287 271 275 202 252 282 273 278 202 205 292 272 253 33 03 31 102 3S 94 37 88 22 04 29 111 33 110 23 92 9 21 45 84 26 91 12 93 36 108 33 113 25 92 36 113 25 108 44 116 37 107 20 102 22 96 32 90 40 109 26 90 27 106 MEAN S.D. N 69, 10,4 24 272, 11.2 24 30. 7.6 24 99, 10.4 24 ADJUSTED WEIGHT - TERMINAL BODY HEIGHT MINUS GRAVID UTERINE HEIGHT NBT WEIGHT CHANGE FROM DAY 6 - TERMINAL CORRECTED BODY WEIGHT MINUS DAY $ BODY WEIGHT BFG42124 NP-NOT PREGNANT X-BXCLUDBD FROM MEAN BFG42125 BFG 01639 30-SBP-lSi 16;47 Huntingdon Life Sciences 96-4Q80D Chemical Manufacturers Association GROUP I ANIMAL# 1601 1602 1603 1604 1605 1606 1607 1600 1609 1610 1611 1612 1613 1614 1615 1616 1617 1618 1619 1620 1621 1622 1623 1624 1625 MEAN 8,D, M 0 ppm MEAN FETUS# 12 3.2 3.9 3-3 3.2 3.7 3.2 3.3 3.6 3 .4 3.3 3.4 3.5 3.4 3.0 UP 3.3 3.3 HP 3.3 3.3 3.4 3.3 3.4 3.4 3. S E 4.0 3.3 3.1 3.7 3.3 2.9 3.8 3.4 2.3 3.4 3.6 2.6 3 .4 3.4 3.3 3.0 3.3 3.6 a .6 2.8 3.2 3.0 3.1 3.7 3.0 3.3 3.7 l.S E 3.6 3.3 E 3.4 3.8 3.3 3.2 3.3 3.6 3.1 3,3 3.4 3.3 3.4 3.4 3.3 3.4 0.2 23 3 3.2 3.9 3.4 3.0 3.6 3.3 3.3 3.8 3.6 3.6 3.3 3.6 3,7 2.6 3.0 3.3 3.4 3.1 3.6 3.6 3.4 3.6 3.4 APPENDIX H Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate INDIVIDUAL FETAL BODY WEIGHTS (GRAMS) 4 3.3 4.0 3,3 2.7 E 3.0 3.5 3.7 3.3 3.4 3.6 3.7 E 2.4 3.6 3.3 3.6 3.1 3.5 3.6/ 3.5 3.5 3.9 5 3.3 3.6 3.3 3.4 3 .4 3.3 3.2/ 3.8 3.7 3.5 3.5 3.4/ 3.9 2.8 3.2 2.5 3.4 3.3 3.3 3.3 3.8 3.4 3.S 6 3-2 4.1 3.2/ 3.3 2.3 3.5/ 3.6 3.2 3.3 3.7 3,4 3.3 3.4 3.4 3.1 3.4 3.2/ 3,7 3-2/ 3.7 3.7/ 3,3 3.7 7 3.2/ 4.2/ 3.2 3.2/ 3.9 3.5 3,2 3.8 3.0 3.4 3.1 3.5 3.6 e 3.4/ 3.4 3.2 3.3 3.3 2,7 3.7 3.4/ 3.4 8 3.0 4,2 3.3 3.2 3.8 3.2 3.6 3.6 3.5 3.5 3 .4 3.6 4.0 2.5 3.6 3.6/ 3.4 3.2 3.5 3.4 3.4 3.4 3.5/ 9 3.3 3.6 3.3 3-0 3.9/ 33 3.3 3.3 3.4 3.5/ 3-5/ 3.6 3.3 3.4/ 3.2 3,4 3.3 3.2/ 3.2 3.3 3.3 3,2 3.6 10 3.1 3.8 3.6 3.1 3.7 3.3 3.3 3.3 3.4/ 3.5 3.7 3.4 3.3 E E 3.8 3.3 3.0 3.3 3.3 3.3 3.6 3.7 11 3.3 4.1 E 3.4 4.3 3.5 3.4 4.0/ 3.3 3.1 3.4 3.S 3.0/ 3.3 3.0 3-3 3.4 3.4 3.5 3.2 3.5 3.4 3.3 13 3.0 3.9 3.7 3,5 3.9 3.1 3.2 3.4 3.2 3.3 3.1 3.5 3.2 2.8 3.2 3.4 3.3 3.2 3.7 3-3 3.6 3.5 3.3 13 3.4 3.6 3.5 3.3 3.1 3.0 3.B 3.6 3.4 3.2 3.4 3.3 3,3 3.2 3.3 3.4 3.6 3.6 3.4 3.9 4.3 ) 3. 3, 3. 3, 3. 3. 3, 3, 3, 3. 3, 3. 3, 3, 3. B-Barly resorption L-bate resorption B-Abortion site I-Unplaiitatlon site /-Denotes position of cervix NP-NOT PREGNANT D-oead fetus p-Deiii BFG42126 Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association APPENDIX H Vinyl Chloride Combined Inhalation Two-Genaratiun Reproduction and Developmental Toxicity Study in CD Rats croup li loppm INDIVIDUAL PETAL BODY WBIGHTS (GRAMS) BFG42127 ANIMAL# MEAN 2601 2602 2603 2604 2606 3606 2607 2608 2609 2610 2611 2612 2613 2614 2615 2626 2617 2618 2619 2620 3621 3622 2623 3624 262$ MEAN S.D. N 3.5 3.3 3.0 3.5 3.3 3.3 3.6 3.6 3.5 3.4 NP 3-3 3.2 3.6 3.3 3-5 3.2 3.2 3.3 3.3 3.5 3.6 3.3 3.5 3.7 3.4 0.2 24 FETUS# 1 2 3 4 5 6 7 a 9 10 11 12 13 1 3.6 a.i 3.1 3.3 3.9 3.0 3.7/ 3.0 3.9 3 .4 3.6/ 3.1 3.6 3.2 L B 3.6 3.6 3.5 3.3 3.0 3.3 3.1 3.3 B 3,2/ 2.7 2.8 2.8 2.6 2.9 3 2 3.3 3.5 3.2 3.7 3.3 3.9 3.5 3.4 3. S 3.2 3.4 3.7 3.5 3.7/ 3.5 3.0 3.0 3.3/ 3.4 3.7 3.4 3.5 3.2 3,3 3 .6 3.8 3.3 3. 3.2 3.7 4.0 3.3 B 3.7 3-3 3.4 3.7 3.2 3.7 3.2 3-5 3.7 35 3.4 3.6 3-8 3.1 3.5 3.8/ 3.5/ 3.4/ 3.5 3.9 3.6 3.6 3.5 3.7 3.9 3.3 3.6 3.2 3.1 B 3.1 3.7 3. 3.4 3.5 3.6 3.1 3.5 3.8 3.3/ 3.5 3.9 3.4 3.7 3.6 3.4 3.2 3.4 3.3 3.4/ 3.6 3.0 3.6 E 3.6 3.6 3.5 2.8 3.1 3.2 3.3 3.3 3.5 3.3 3.4 3.5 3.5/ 3.2 3.4 3.5 3.0 3.2 3.2 3.0 3.1 3.0 3.4/ 3.3 3.3 3.5 3.4 3.2 3.3 3.4 3.3 3.6 3.3 3.8/ 3.6 E 3.8 4.0 3 ,6 2.6 3.5 3.1 3.7 3.1 3.2 3.2 3.6 3.4 3.4 3.7 3.3 3.6 3.2 3.6/ 3.5 3.3 3.7 3.4/ E 3.6 3.1 3.3 3.7 3.1 3.0 3. 3. 2.9 3.2 3.2 3.7 3.1 3.3 2.9/ 2.8 3.4 3.4 B 3.3 3.0 3.3 3.2 3.0 3.2 3.0 3.1/ 3.3 3.3 3.4 3-3 3.4 3.2 3.1 3.3 3.3 3.0 3.1 3.2 3.3 3.4 3.4/ 3.6 3.3 3.5 3.8 3.6 3. 3.3 3.3 3.2 3.7 3.6 3.3 3.4 3.5 3.6 3.3 3.6/ 3.3 3,0 3.4 3,4 3.7 3.6/ 3.3 3.5 3.7 3.2 4.0 3,1 3.5 3.4 3.3 3.5 3.5 4.0 3.7 B 3.6 3.3/ 3.9 3.4 3.7 3.6 3.7 3.2 3.5 3.6 3-4 3-3 3.3 3,0 3,2 3.4/ 3-2 3,1 3-3 3.5 3. 3.8 3.9 3.8 3.4 3.5 3.6 3.1 3.1 3.6/ B 3.7 3.3 3.5 3.7 3.6 3.6 3.8 3.6 3.7 3.6 3.9 3.7/ 4,0 3.7 3.9 E-Early resorption L-Late resorption B-Abortlon site I'lmplantation site D-oeed fetus P-Deliv /-Denotes position of cervix NP-NOT PREGNANT Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association APPENDIX H Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats GROUP III 100 ppM INDIVIDUAL PETAL BODY WEIGHTS (GRAMS) ANIMAL* MEAN 3601 3602 3603 3604 3605 3606 3607 3608 3609 3610 3611 3612 3613 3614 361$ 3616 3617 3610 3619 3620 3621 3622 3623 3624 3625 MEAN S.D, N 3.5 3.1 3,4 3.4 3.1 3.2 3.7 NP 3.5 NP 3.4 3.2 3,7 3.4 3.1 3.6 3.0 3 .4 3.3 3.S 3.5 3.7 3.0 NP 3.5 3.4 0.2 22 FETUS# 12 3.6 3.2 3.0 3.2 3 .6 3.5 3-0 3.2 B 2.7 3.0 3.1 3.6 3.5 3.6 3.8 2.6 3.5 2.6 3.2 3-6 3,7 3.4 3.6 33 3.1 3.6 3.6 3.9 4.0 3.5 3.6 3.6 3.5 3.7 3.6 3.3 3.4 3.4 3.7 2,7 2.0 3.6 3.5 34 3.6 3.3 3.1 3.4 3.4 3.5 3.6 3.4 B 3.2 3.0 3.3 3.4 3.7 3-2/ 3.3 B 3.7 3.0 3.7 3,5 3-5 3.4 3.2 2.0 3.3 3.0 3.9 3.6 3-9 3.6 3.5 3.1 3.3 3.6 3.4 3.6 3.6 3.0 3.3 2.7 3.0 3.2 3.1 5 3.0 3.3 3.4/ 3.5 3.2 3.2 B 3.6 6 3.8 3.6 3.6 3.1 2.9 3.0 8/ 3.6 7 3.8 3.0 3.0 3.0 3.3/ 3.1 3.6 e 3.2 3.0 2.8 3.3/ 3.1 3.4 3.7 9 3 .0 3.2/ 3,5 3.4 3.0 3.1/ 3.9 10 3.5/ 2.9 3.4 3.8 3.3 3.4 3.8 11 3.2 3.4 3.5 3.7 3.3 3.1 4.0 3.3 3.4 3.5 3.6 2.9 3.7 3,7 3.5/ 3.3 3.8 3.8 3.8 3.0 3.1 3.0 3-5 / 3.4 2.9 3.4 3.9 3.5 3.2 3.5 3.5 3.7/ 3.2 3-1/ 3.2/ 3.9 3.0/ 3.1 3.S 3-9/ 3.3 3.0/ 3.5/ 3.8 4.0 3.0 3.6 3.3 3.9 3.2 2.0/ 3.6/ 3-6 3.4 3 .4 3.5 3.5/ 3.8 3.2 3.5 3.1 4.0 3.0 3.6 3.9 3.3 3.3 3.6 3.5 3.6 2.7 3.3 3. B 3.4 3.3 3.0 3.3 3.0 4.0 3.1 3.5 3.0 3,7 3.6 3.0/ 3.0 3.6 4.1 3.5 3.2 3.4 3.5 3.9 2.9 3.7 3.9 3.3 3.6 3.3/ 3.9 3.5 12 3.8 3.1 3.4 3.3 3.2 32 3.4 3.7 3,5 3.2 3.4 3.6 3.6 3.1 2.8 3.5 3.7 3.2 3.7 13 3.6 3.3 3-5 3.3 3.2 3.2 3.2 3,0 3.2 3.5 3.4 3.3 3.4 3-8 3-0 3.4 B-Barly resorption L-Late resorption B-Abortion site I-Implantation site /-Denotes position of cervix WP-NOT PREGNANT D-Dead fetus P-Deli* B Huntingdon Life Science 96-408QD Chemical Manufacturers Association APPENDIX H vinyl chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate GROUP IV 1100 ppm INDIVIDUAL PETAL BODY HEIGHTS (GRAMS) / ANIMAL# MEAN 4601 4602 4603 4604 4605 4606 4607 4608 4609 4610 4611 4612 4613 4614 4615 4616 4617 46l6 4619 4620 4621 4622 4621 4624 4625 MEAN S.D. N 3.4 3.7 3.3 3.2 3.2 3.2 3.2 3.7 NP 3.7 3.2 3.7 3.3 3.2 3.1 3.3 3.4 3.3 3.1 3.1 3.4 3.3 3.7 3.1 3.3 3.3 0.3 34 FETUS# 5 6 7 8 9 10 11 12 13 1 3.3 3.5 3.2 3.6 3.6 3.0/ 4.0 3,6 2.9 B 3.1 B 3.3 3.7 B 3.6 3.3 3.4 3.2 3.7 3.1 3.7 3.6 3.5/ 3. S 4.0/ 3.9 3.5 2.9 4.2 3.0 4.0 3.4 3.7 3. 3.1 3.1 3.5 3.4 2.9 3.2 3.3 3,5/ 3.3 3,1 3.0 3,2 3-3 3-0 3.6 8 3.2/ 3.5 3.4 3,3 3.5 3.0 2,4 3.1 3.5 3.2 3.6 3,3 3.1 3.7 3,3 3.4 3.3 2.9 4.0 3.1 3.3 3.9 3.2 3.0 3.5 3.3/ 3.6 3.4 3.7 3.4 3.7/ 2.7 3.1/ 3.9 3.2 3.0 3.5 3.6 3.2 4.3 2.8 2.3 3.3 3.3 3. 3. 3.6/ 3.6 3.8 3.8 3.6 3.8 27 3.5 3.0 3-3 4.1 3.4 3,0 3.8 3.6 E 3.9 3.1 3-1 3.8 3.3 3-5 3.2 3.7 E/ 3.1 3.1 3.3 3.7 3.3/ 3.0 3.6 3.1 3-2 2,7 3.4/ 3.9 3.4 3.2 3.4 3-9 3.0 3.2 3.4 3.3 3, 3. 3. 3.2 2.7 3.1 3.5 3.5 3.3 3.1 2.9 3.1 3.6 3.3 2.6 3.3/ 3.3 3.0 3.0 3.1 3.0 2.9/ 3.1 3.3 3.2 3.1 3.2 3.2 3.3 3. 3.4 3.4 E 3,1 3.6 2.9 3.3 3.6 3.4 3-5 3.2 3.3 3-4 3 .4 3.3 3-3 3.6/ 3.7 3.3/ 3.0 3.0 3.3 3.2 3.3 3.3 3.7 3.6 3.6 3.3/ 3-0 3.4 3 .4 3.0 3.2 3,8 3.3 3.4 3.2 3.2 3 3. 3. 3.0 3.1 3.0 3.1 3.1 3,0/ 3.0 3.2 2.7 3,0 3.3 3.3 3.0 3 3.1 2.8 3.3 2.9 3-1 3.4 2.9/ 3.0 3-4 3.0 1,0 3.1 3.2 3 8 3.2 3.2 3.2 3.5 3.6 3.3 3.0 B 2.7 3.5 8 3.5/ 3.4 8/ B 3.2 3.8 3.6 3.4 3.8 3.8 3.2 3.2 3.6 3.5 3. 2. B 3.8 3.9 3.6 3.7 3.7 3.7/ 3.5 3.6 3.2 3.7 4.0 3.9 2.9 3.3 3.2 3.3/ 3.2 3.1 3.4 3.0 2.9 3.2 3,0 2.8 2.1 3.7 3.4 3.5 3.2 3.3 3.3 3.3/ 3.8 3.3 3.1 3.3 3.0 3. BFG42129 B-Early resorption L-Late resorption E-Abortion site J-implantation site /-Denotes position of cervix NP-NOT pregnant D-Dead fetus P-belli BFG42130 BFG 01644 ll-NOV-1^ 11:12 Huntingdon Life Sciences 96-4O0OD Chemical Manufacturers Association GROUP I ANIMAL# 0 ppm ORGAN APPENDIX I Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION 1601 1603 1603 1604 1606 1606 1607 1606 1609 1610 1611 1612 1613 1614 1615 1616 1617 GROSS EXAM NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO remarkable observations NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS ALOPECIA; MODERATE BOTH HINDPANS AND BOTH INGUINAL AREA NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS BFG42131 Huntingdon Life Sciences 96-4QB0D Chemical Manufacturers Association GROUP I ANIMAL# o ppm ORGAN APPENDIX 1 Vinyl chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION BFG42I32 1616 3-619 1620 1621 1622 1621 1624 1626 NO REMARKABLE OBSERVATIONS no remarkable observations NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS MO REMARKABLE OBSERVATIONS Huntingdon Life Sciences 96-4Q0OD Chemical Manufacturers Association GROUP II ANIMAL# lOppm ORGAN appendix i Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION 2601 2602 2603 2604 2605 2606 2607 2608 2609 2610 2611 2612 2613 2614 2615 2616 261? NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS BFG42133 Huntingdon Life Sciences 96~4080D Chemical Manufacturers Association GROUP II ANIMAL# loppm ORGAN APPENDIX I Vinyl Chloride Combined Inhalation TwO-OttnetAtion Reproduction and Developmental Toxicity Study in CD Rata INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION 261ft 3619 2620 2621 2622 2621 2624 262$ KIDNEY KIDNEY DISTENDED; EXTREME; LEFT NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association GROUP III 100 ppM ANIMAL# ORGAN APPENDIX I Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION 3601 3602 3603 3604 3605 3606 3607 360# 3609 3610 3611 3612 3613 3614 3615 3616 361? NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO RB4ARKABLB OBSERVATIONS NO RB4ARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS BFG42135 NP-NOT PREGNANT Huntingdon Life Sciences 96-*0$OD Chemical Manufacturers Association GROUP 111 100 ppM ANIMAL! ORGAN APPENDIX I Vinyl Chloride combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study In CD Rats INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION BFG42136 3616 3619 3620 3621 3622 3623 3624 3626 NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NPNOT PREGNANT Huntingdon Life Science* 96-4O0OD Chemical Manufacturers Association GROUP IV ANIMAL# 1100 ppm ORGAN APPENDIX I Vinyl Chloride Combined Inhalation Two-Generation Reproduction end Developmental Toxicity Study in CD Rets INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION 4601 4602 4603 4604 4605 4606 4607 4608 4609 4610 <611 4612 4613 4614 4615 4616 BLADDER UTERUS no remarkable observations NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS BLADDER HYPBRDISTRN&lQN; MODERATE FLUID PILLED (THICK WHITE) UTERUS DISTENDED; MODERATE FLUID FILLED (CLEAR) NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS BFG42137 Huntingdon Life Sciences 96-4Q0OD Chemical Manufacturers Association GROUP IV ANIMALS 1100 ppm ORGAN APPENDIX I vinyl chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in Cd Rats INDIVIDUAL MATERNAL NECROPSY OBSERVATIONS OBSERVATION 4617 4610 4619 4630 4631 4622 4623 4624 4625 GROSS EXAM NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS NO REMARKABLE OBSERVATIONS ALOPECIA; EXTREME SNOUT/EXTREMITIES (FORBPAMS BILATERAL) BFG42138 Bl BFG42139 BFG 01653 11-N0V-X9- 13i40 96-4QS0P FD4ALGS 0 ppm APPENDIX J Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rata ORGAN AND FINAL BODY WRIGHTS Animal Number 1601 1602 1603 1604 1605 1606 1607 1600 1609 1610 1611 1612 1611 1614 1615* 1616 1617 1610X 1619 1620 1621 1622 1623 1624 162$ FINAL BODY WEIGHT 9 323 41S 331 333 347 368 324 364 395 344 335 312 344 352 NP 276 379 376 NP 244 34 7 301 366 316 339 355 370 LIVRR weight Ratio 9 12.920 16.275 15.012 12.692 15.847 14.706 13.266 14.640 15.694 13.205 14.201 1 J 658 14 3 34 1 1 9*6 11 2 9`, 14 214 15.165 10.529 15.095 15.429 14.494 14.019 13.266 14.022 14.691 0.Q4O0 0.0392 Q.0460 0.0381 0.0456 0.0400 0.0410 0.0402 0.0398 0.0304 0 0424 0.0412 0 04 17 0 0)96 0 0409 0 0 J 7b 0.0403 0.0432 0-0435 0.0405 Q.0397 0.0443 0.0391 0.0417 0.0397 KIDNfiYS Weight Ratio 9 2.073 1.910 1.762 1.655 1.914 1.056 1.729 2.028 1.942 1.848 1.084 1 971 1 805 1 9?H 1 821 1 951 1 099 2.192 1.973 1.983 1.826 1.555 1.699 1.940 1.052 0.0064 0.0046 0.0055 0.0050 0.0055 0.0050 0,0053 0.0056 0.0049 0.0054 0 0056 0.0059 0.0053 0 0056 0 0066 0.0052 0 0050 0.0090 0.0057 0.0052 0.0050 0.0049 0.0050 0.0055 O.OOSO RATIO - ORGAN HBIGHT/BODY WRIGHT NP-NOT PREGNANT A-BXCLUDBD FROM MEAN % o ft * p 96 -4080D FEMALES 10 ppm APPENDIX J Vinyl Chloride Combined Inhalation TWo-Generation Reproduction and Developmental Toxicity study in CD Rats ORGAN AND PINAL BODY HEIGHTS Animal Number 2601 2602 2601 2604 2605 2606 2607 2609 2609 2610 2611x 2612 2613 2614 2615 2616 2617 26ia 2619 2620 2621 2622 2621 2624 2626 FINAL BODY WEIGHT 9 126 164 312 330 359 341 340 335 336 325 NP 251 346 374 336 345 307 373 303 333 332 331 313 349 333 357 LIVER Weight Ratio 9 14,235 15,410 13,064 13.317 14.056 13.602 14.670 14.655 12.664 12.670 0.954 15.006 13.201 U.223 74 766 16-425 16.199 12.200 13.599 14.081 12.052 12.952 14.S5S 13,441 14.044 O.0437 0.0424 0.0419 0.0394 0.0391 0.0399 0.0421 0.0439 0.0377 0,0397 0.0357 0.0431 0.0395 0.0424 0 0417 Q.0424 0.0435 0.0403 0.0408 0,0424 0.0309 0.0414 0.0417 0.0404 0.0416 KIDNEYS Neight Ratio 9 2.127 2.025 1.826 1,835 1.944 1.829 1.995 1.592 1.740 1.745 2.149 1.049 1.705 1.617 1.964 1.049 1.930 1.005 1.027 1.076 1.835 1.635 1.025 2.111 1.813 0.0065 0.0056 0.0059 0,OQ54 0.0054 0.0054 0.0057 0.004B 0,0052 0.0054 0.0006 0.0053 0.0051 0.0040 0.0057 0.0040 0.0052 0.0062 a.0055 0.0056 0.0055 0.0052 0.0052 0.0063 0.0051 RATIO * ORGAN WBIGHT/BODY WEIGHT NP-NOT PREGNANT k-RXCLUDBD FROM MEAN 96-4080D FEMALES 100 ppm APPENDIX J Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate ORGAN AND FINAL BODY HEIGHTS Animal iber FINAL BODY HEIGHT 9 3601 3602 3603 3604 3605 3606 3607 36O0X 3609 3610X 3611 3612 3613 3614 3615 3616 3617 3618 3619 3620 3621 3622 3623 3624X 3625 NP UP NP 376 348 333 331 3S7 347 336 258 267 244 349 324 329 312 359 360 327 338 345 357 361 364 323 234 366 LIVER Height Ratio 9 15.594 13.351 14.102 12.689 16.735 13.854 14.017 9.709 9,854 9.135 14.837 14.419 15.103 13.272 14.559 14,510 14.059 13.335 14.633 16 .464 14,733 15.151 12.900 9.663 15.710 0.041$ 0.0383 0.0424 0.0384 0.046B 0.0399 0.0417 0.0376 0.0369 0.0374 0.0425 0.0445 0.0460 0.0425 0.0405 0.0403 0.0430 0.0395 0,0424 0.0461 0.0408 0.0416 0.0399 0.0413 0.0429 KIDNEYS Height Ratio 9 2.022 1.683 2.079 1.749 2 .053 1.898 2.041 2.112 1-940 2.043 2.052 2.014 2.084 1.814 1.771 1.873 1.678 1.938 2.085 1.994 1.936 2.033 1.710 1.830 2.128 0.0054 0.0054 0.0062 0.0053 0.0057 0.0055 0.0061 0.0082 0.0073 0.0084 0.0059 0.0062 0.0063 0.0058 0.0049 0.0052 0.0051 0.0057 0.0060 0.0056 O.O054 0.0056 0.0053 0.0078 0.0058 RATIO - ORGAN NfilOHT/BODY WEIGHT NPN0T PREGNANT X-BXCLUDBD FROM MEAN 96-40B0D FEMALES GROUP IV 1100 ppm APPENDIX J Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate ORGAN AND FINAL BODY WEIGHTS Animal Number 4601 4602 4602 4604 4605 4606 4607 4600 4609x 4610 4611 4612 4613 4614 4615 4616 4617 461B 4610 4620 4621 4622 4623 4624 4625 FINAL BODY HEIGHT 9 307 241 317 316 32B 352 361 337 NP 244 319 337 352 359 351 342 359 334 354 342 252 357 351 361 236 332 LIVER Height Ratio 9 12.622 13.707 13.672 13.249 13.430 14.969 14.557 13.500 8.717 15.693 13.171 14.220 15.670 15.246 14.641 15.210 15.468 15.375 14.835 16.225 15.275 16.406 15.762 14.117 13.425 0.0411 0.0402 0.0431 0.0419 0.0410 0.0425 0.0404 0.0403 0.0350 0.0493 0.0390 0.0404 0.0437 0.0434 0.0429 0.0424 0.0463 0.0435 0.0432 0.0461 0.0426 0.0470 0.0436 0.0421 0.0404 KIDNEYS Haight Ratio 9 1.649 1.815 1.614 1.662 1.737 1.677 1.798 2.069 1.597 1.958 2.195 1.918 1.976 1.881 2.009 1.923 2.070 2.149 1.938 1.975 2.029 ' 2.013 1.866 2.115 1.742 0.0054 0.0053 0.0051 0.0059 0.0053 0.0053 0.0050 0.0061 0.0066 0.0061 0.0065 0.0054 O.OOSS 0.0054 0.0059 0.00S4 0.0062 0.0061 0.0056 0.0056 0.0057 0.0057 O.0O52 0.0063 0.0052 RATIO - ORGAN HEIGHT/BODY HEIGHT NP-NOT PREGNANT xEXCLUDED FROM MEAN BFG42143 CFG BFG^*4 BFG 01658 2l'HOV-l9 i3:22 BFG42I45 Huntingdon Life Science* 96-40B0D Chemical Manufacturers Association Q ppm FEMALE# PETUS# ORGAN APPENDIX R Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity study in CD Rate INDIVIDUAL PETAL EXTERNAL OBSERVATIONS CLASS OBSERVATION 1601 2P 3F 4M 5M 6M 7P aF 9M 10 H 11 M 12 H 11 M 14 H 1602 1M 2P 3V 4M 5F 6M 7F 8F 9F 10 F 11 N 12 P nf 14 P IS F 1603 1M 2F 3F 4F 5M 6M class CODES: H-MalformatIon v-variation WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS MXTHIM NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS bf<; BFG42146 Huntingdon Life Sciences 95-40800 Chemical Manufacturer* Association APPENDIX K Vinyl chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate 0 ppm INDIVIDUAL PETAL EXTERNAL OBSERVATIONS FEMALE# FETUS# ORGAN CLASS OBSERVATION 1603 (CONTINUED) 7P 8P 9M 10 M 13 P 13 M WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS 1604 1P 3M 3P 4P 5M 6M 7M 0? 9M 10 M 11 M 12 F 13 M WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS 1605 1P 3M 3M 5P 6M 7 It af 9F 10 F 11 M 13 M NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS 1606 1P 2K 3H 4P NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS CLASS CODES: MMalformatlon V-Varietion BFG ( BFG42147 Huntingdon Life Sciences 96*4080D Chemical Manufacturers Association APPENDIX K Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rate 0 ppm INDIVIDUAL PETAL EXTERNAL OBSERVATIONS FEMALE* FETUS* 1606 (CONTINUED) 5F 6M 7P ef 9F 10 M 11 N 12 M 13 P 14 H IS H 16 F 160? 1F 3P 4M 5F 6M 7M am 9N 10 F 11 H 12 F 13 M 1606 lM 2P 3F 4P 5F 6r 7M 8P 9P 10 P 11 M ORGAN CLASS OBSERVATION within normal LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS within NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS CLASS CODESt H-Halformation v-Varlation BFG PAGE APPENDIX K eeBEBB&SSggSSgBSSg M gggeesse 2SrriiSS5355c5ac3*S LjmmmmMmHH 1ZZZXIIX1 33333333333333333 3j3333333 zzzzz MM MM H sssssss EBsSEg 55*53 ****** K -K a lfo n o a tlo n v -V a ria tio n H untingdon L ife S ciences 96-40B0D C hem ical M a n u fa c tu re rs A s s o c ia tio n bX 1na * H rt XIISZEhhhbiZIlhhCh HMne>ini0^OHOHr;nintsr' mlCh********** Hmenmerm^oHcjr^* BFG42148 BFG42149 Huntingdon Life Science* 96-40BOD Chemical Manufacturers Association 0 ppm FEMALES FETUS# ORQAN APPENDIX K Vinyl Chloride combined inhalation Tvo^Generation Reproduction and Developmental Toxicity Study in CD Rata INDIVIDUAL FETAL EXTERNAL OBSERVATIONS CLASS OBSERVATION 1611 1M 2M 1H 4F 5M F 7F 8M 9F 10 H 11 M 12 P 11 F 1612 1F 2M 1F 4M SM 6N 7F 8F 9F 10 P 11 F 12 F 13 F 14 P 1613 1F 2F 1F 5M M 7N 8M CLASS CODES i lUMalfomatlon V-Varlation WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN MORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN MORMAL LIMITS WITHIN NORMAL LIMITS BFG Huntingdon Life Sciences 96~4060D Chemical Manufacturers Association APPENDIX K vinyl chloride Combined inhalation Twn-oeneratlen Reproduction and Developmental Tonicity Study in CD Rats o ppm INDIVIDUAL PETAL EXTERNAL OBSERVATIONS PBMALGR FETUS# ORGAN CLASS OBSERVATION 1613 (CONTINUED) 9F 10 P 11 F 13 P 13 F 14 P 15 P NITH1N NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS 1614 1616 1F 2F 3H 4N 5F 6M eh 9M 11 F 12 F 13 P 14 M 1P af 3M 4M 5P 6M 7F BF 9N 11 F 12 F 13 M 14 N WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS CLASS CODES; H-Halformation V-Variation BFG42150 BKG 01664 Huntingdon Lift sciences 96-40B0D Chemical Manufacturers Association 0 ppm FEMALE* PBTUS* ORGAN APPENDIX K vinyl Chloride Combined inhalation Two-Generation Reproduction and Developmental Tonicity study in CD Rats INDIVIDUAL FETAL EXTERNAL OBSERVATIONS CLASS OBSERVATION 1617 1M 2M 1P 4H 5P 6F 7F 6F 9M 10 M 11 N 12 H 13 F 14 P 15 H 16 P 17 H l6l9 1620 1P 2M 3M 4M SM 6P 7H ap 9P 10 P 11 M 12 P 13 N 1M 2M 3P 4F CLASS CODES t MpHalformation V*Variation HITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS HITHIN NORMAL LIMITS HITHIN NORMAL LIMITS HITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS BFG42151 Bbi Huntingdon Life Sciences 96-40&OD Chemical Manufacturers Association APPENDIX K Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats 0 ppm INDIVIDUAL PETAL EXTERNAL OBSERVATIONS FBNAUI# FETUS* ORGAN CIA8S OBSERVATION 1*20 (CONTINUED) 5F *M 7F ef 9F 10 M 11 M 12 F 12 M 14 M 15 M WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS 1*21 1F 2F 3M 4M 5M 6M 7M 8M 9F 10 F 11 M 12 N 13 M 14 F 15 H WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIM NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS 1*22 1F 2V 3F 4M 5P *P 7F am 8P WITHIM NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS 7LASS OODBSt K-MaUormation V-Variation b PG42152 BFC 16l BFG42153 H u n tin g d o n L d fe -S ciences 96-40BOD H -H alform atIon V -V a ria tio n PAGE Huntingdon Life Sciences 96-4080D Chemical Manufacturers Association o ppm FEMALE# FETUS# ORGAN appendix K vinyl chloride combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CD Rats INDIVIDUAL FETAL EXTERNAL OBSERVATIONS CLASS OBSERVATION 162S 1M 3F 3F 4M SM 6V 03 7 F -n 9 M o 9F 10 H to 11 F 13 F Lh 13 F 4^ 14 M IS F CLASS CODES; M-Malforauition V-Vurietion WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS me PAGE 11 888888 8 xizzzxx asaaaas 8888888 HH 4 HH M M HH l-H ZXIIIIX JJJJ ZgZWZHZhZHBHSH 88888 MMMHMMH ^88888 HujojggevL _ . . iMiiszi^qnklVi * * 'O w Cb ae APPENDIX K M-Halfo rm a tio n V *V a ria tio n CODES: L - la t e r e s o r p t io n H untingdon L ife S ciences 96-4060D C hem ical M a n u fa c tu re rs A s s o c ia tio n CODES: STATUS Xbb * a. x x X z CL X X X z Hrtrtf m*!* h r* <*i m 4 r* Zh hXhihbZBirhz Opt *-< nr-t nrf H BFG42155 CLASS FETAL Huntingdon Life Sciences 96-4080D chemical Manufacturer* Association APtfiNDiX K Vinyl Chloride Combined inhalation Two-generation Reproduction and Developmental Toxicity study in CD Rats BFG42156 10 ppm INDIVIDUAL PETAL EXTERNAL OBSERVATIONS FEMALE# 2601 FETUS# (CONTINUED) 13 H ORGAN CLASS OBSERVATION WITHIN NORMAL LIMITS 3604 1F 3P 3M 4P 5P 6N 7P 8F 9F 10 M 11 F 12 H 13 M 2605 1F 2P 3M 4M 5P 6M 7P 8F 9V 10 N 11 H 13 N 13 M 14 P 3606 1M 2H 3P 4P 5P 6N CLASS Codesi H*Malformation V-VarUtion WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WltHtN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS M1TMN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMIT'S M1THIN NORMAL LIMITS WITHIN normal limits WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS BFC BFG42157 Huntingdon Life sciences 96-408QD Chemical Manufacturers Association APPENDIX X Vinyl Chloride Combined Inhalation Two-Oeneretion Reproduction and Developmental Toxicity Study in CD Rate 10 ppm INDIVIDUAL PETAL EXTERNAL OBSERVATIONS PBMALB* PBTUSf ORGAN CLASS OBSERVATION 2606 (CONTINUED) 7F aH 9V 10 H 11 P 12 M 13 P MITHIN NORMAL LIMITS KITHIN NORMAL LIMITS MITHIN NORMAL LIMITS KITHIN NORMAL LIMITS MITHIN NORMAL LIMITS KITHIN NORMAL LIMITS KITHIN NORMAL LIMITS 2607 1M 3P 4M 5F 6H 7M aF 9H 10 M 11 P 13 H 14 M KITHIN NORMAL LIMITS WITHIN NORMAL LIMITS KITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS KITHIN NORMAL LIMITS MITHIN NORMAL LIMITS KITHIN NORMAL LIMITS WITHIN NORMAL LIMITS KITHIN normal limits 2608 1M 2P 3M 4P 5F 6P 7N a9 9M 10 F 11 9 KITHIN NORMAL LIMITS NITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS MITHIN NORMAL LIMITS MITHIN NORMAL LIMITS KITHIN NORMAL LIMITS MITHIN NORMAL LIMITS MITHIN NORMAL LIMITS MITHIN NORMAL LIMITS 3609 1P 3 PI 3M 4F MITHIN NORMAL LIMITS WITHIN NORMAL LIMITS MITHIN NORMAL LIMITS MITHIN NORMAL LIMITS CLASS CODES; HHalfoxmation ^Variation BFC; 01671 Huntingdon Life Sciences 96-4080D Chernies! Manufacturers Association APPENDIX K Vinyl Chloride Combined inhalation Two-Generation Reproduction and Developmental Toxicity Study in CP Rata 10 ppm INDIVIDUAL FETAL EXTERNAL OBSERVATIONS FEMALE# FETUS# ORGAN CLASS OBSERVATION 2609 (CONTINUED) 5M 6M 7P 8H 9H 10 F 11 M 12 M WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS 2610 1F 2F 3M 4F 5F 6F 7F 8F 10 M 11 F 12 M WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS 2612 1F 2F 3P 4F 5N 6M 7M 8M 8K 10 M 11 V 12 M 13 M WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS CLASS CODESi K-Halfonoation V-Variation SS'W0 4 8 BFG 0167: BFG42159 Huntingdon Life Sciences 96-4060D Chemical Manufacturer# Association 10 ppm FEMALE# FETUS# ORGAN APPENDIX X Vinyl Chloride Combined Inhalation Two-Generation Reproduction and Developmental Toxicity Study In CD Rate INDIVIDUAL FETAL EXTERNAL OBSERVATIONS CLASS OBSERVATION 3613 1M 2M 3H 4F 5H 6P 7M BM 9M 10 M 11 M 12 F 3614 1F 2F 3F 4M SP 6M 7H 9M 10 M 11 M 2615 1F 2F 3F 4F 5H 6F 7M P 9V 10 M 12 M 13 P class CODES t N-Malformatitm v-varlatiort WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS WITHIN NORMAL LIMITS BFG