1、STDmAPIIPETRO TR 412-ENGL 1778 0732270 Ob06823 710 H . 4-5 FETAL DATA . 4-9 CONCLUSION . 4- 1 1 5 . REFERENCES . 5-1 6 . LOCATION OF SPECIMENS, RAW DATA AND FINAL REPORT 6-1 7 . FIGURES Mean Maternal Body Weights During Gestation - Rats 7-1 Mean Maternal Food Consumption During Gestation - Rats . 7-
2、2 Mean Maternal Body Weights During Gestation - Mice . 7-3 Mean Maternal Food Consumption During Gestation - Mice 7-4 . li1 STD-API/PETRO TR 412-ENGL 1998 m 0732290 0606832 723 m Italicized sections in the Table of Contents have been omitted from this publication. These sections are on file at API a
3、nd may be obtained by contacting the APT Information Specialist, 1220 L St.,Washington, D.C., 20005. LIST OF TABLES Table Page 1. Summary of Concentrations . 4-2 2. Summary of GC Syringe Sample Fingerprints of Exposure Atmosphere Results . 4-3 3. Charcoal Tube Samples - Summary of Daily Mean Ratios
4、4-4 4. Summary of Particle Size Distribution Measurements 4-5 5. Pregnancy Rates . 4-6 LIST OF APPENDICES Appendix A ANIMAL TERMINATION HISTORY- RATS. A-I Appendix B MEAN MATERNAL BODY WEIGHTS DURING GESTATION - RATS . B-l INDIVIDUAL MATERNAL BODY WEIGHTS DURING GESTATION - RATS B-2 Appendix C MEAN
5、MATERNAL BODY WEIGHT CHANGE DURING GESTA TION - RA TS C- I INDIVIDUAL MATERNAL BODY WEIGHT CHANGE DURING GESTATION - RATS C-2 Appendix D PREFACE . D-I MEAN GRA VID UTERINE WEIGHT AND NET MATERNAL BODY WEIGHT ChYNGE - RATS . 0-2 INDIVIDUAL GRA VID UTERINE WEIGHT AND NET MATERNAL BODY WEIGHT CHANGE -
6、RATS . 0-3 Appendix E MEAN MATERNAL FOOD CONSUMPTION DURING GESTATION - RATS . E-1 INDIVIDUAL MATERNAL FOOD CONSUMPTION DURING GESTATION - RATS E-2 iV STD.API/PETRO TR 4L2-ENGL 1998 = O732290 ObOb833 bbT ItaEicized sections in the Table of Contents have been omitted from this publication. These sect
7、ions are on file at API and may be obtained by contacting the API Information Specialist, 1220 L St.,Washington, D.C., 20005. Appendix F PREFACE F-1 SUMMARY INCIDENCE OF DETAILED PRE-EXPOSURE PHYSICAL OBSERVATIONSDURING GESTATION - RATS . F-2 INDIVIDUAL DETAILED PRE-EXPOSURE PHYSICAL OBSERVATIONS DU
8、RING GESTATION - RATS . F-3 SUMMARY INCIDENCE OF DETAILED POST-EXPOSURE PHYSICAL OBSERVATIONS D URI” GESTA TION - RA TS . F-8 INDIVIDUAL DETAILED POST-EXPOSURE PHYSICAL OBSERVATIONS DURING GESTATION - RATS . F-1 O Appendix G SUMMARY OF REPRODUCTION DATA AND MEAN FETAL WIGHT DATA - RATS . G-1 INDIVID
9、UAL FEMALE REPRODUCTION DATA AND MEAN FETAL WEIGHT DATA - RATS . G-2 Appendix H INDIVIDUAL FETAL STATUS AND UTERDJE LOCATION DATA - RATS . H-1 Appendix I PATHOLOGY - MACROSCOPIC POSTMORTEM OBSERVATIONS - RATS . i . 1-1 Appendix J SUMMARY OF FETAL EXTERNAL MALFORMATIONS - RATS . J-1 INDIVIDUAL FETAL
10、EXTERNAL EXAMINATION DATA - RATS . .J-2 Appendix K ANIMAL TERMINATION HISTOR Y - MICE K- I Appendix L MEAN MATERNAL BODY WEIGHTS DURING GESTATION - MICE . L-I INDIVIDUAL MATERNAL BODY WEIGHTS DURING GESTA TION - MICE . L -2 V STD-APIIPETRO TR 412-ENGL 1998 m 0732290 0606834 5Tb m Italicized sections
11、 in the Table of Contents have been omitted from this publication. These sections are on file at API and may be obtained by contacting the API Information Specialist, 1220 L St.,Washington, D.C., 20005. Appendix M MEAN MATERNAL BODY WEIGHT CHANGE DURING GESTATION - MICE M-1 INDIVIDUAL MATERNAL BODY
12、WEIGHT CHANGE DURING GESTATION - MICE M-2 Appendix N PREFA CE N- I MEAN GRA VID UTERINE WEIGHT AND NET MATERNAL BODY WEIGHT CHANGE - MICE . N-2 INDIVIDUAL GRA VID UTERINE WEIGHT AND NET MATERNAL BODY WEIGHT CHANGE - MICE . N-3 Appendix O MEAN MATERNAL FOOD CONSUMPTION DURING GESTATION - MICE . 0-1 I
13、NDIVIDUAL MATERNAL FOOD CONSUMPTION DURING GESTATION - MICE 0-2 Appendix P PREFACE P-1 SUMMARY INCIDENCE OF DETAILED PRE-EXPOSURE PHYSICAL OBSERVATIONS DURING GESTATION - MICE . P-2 INDIVIDUAL DETAILED PRE-EXPOSURE PHYSICAL OBSERVATIONS DURING GESTATION - MICE P-3 SUMMARY INCIDENCE OF DETAILED POST-
14、EXPOSURE PHYSICAL OBSERVATIONS DURING GESTATION - MICE . P-8 INDIVIDUAL DE TAIL ED POST-EXPOSURE PHYSICAL OBSERVATIONS DURING GESTATION - MICE P-9 Appendix Q SUMMARY OF REPRODUCTION DATA AND . MEAN FETAL WEIGHT DATA - MICE Q- 1 4-2 INDIVIDUAL FEMALE REPRODUCTION DATA . AND MEAN FETAL WEIGHT DATA -MI
15、CE vi . Italicized sections in the Table of Contents have been omitted from this publication . These sections are on file at API and may be obtained by contacting the MI Information Specialist. 1220 L St.,Washington, D.C., 20005 . Appendix R INDIVIDUAL FETAL STATUS AND UTERINE LOCATION DATA . MICE R
16、-1 Appendix S PATHOLOGY . MACROSCOPIC POSTMORTEM OBSERVATIONS . MICE S- 1 Appendix T SUMMARY OF FETAL EXTERNAL MALFORMATIONS . MICE T-1 INDIVIDUAL FETAL EXTERNAL EXAMINATION DATA . MICE T-2 Appendix U TABLE OF CONTENTS U-1 INTRODUCTION . U-2 EXPOSURE CHAMBER SYSTEM U-3 EXPOSURE ATMOSPHERE GENERA TIO
17、N SYSTEM . U-6 EXPOSURE A TMOSPHERE MONITORING SYSTEMS . U-12 CHAMBER MONITORING RESULTS . U-22 Appendix V TABLE OF CONTENTS V-1 AN ANALYTICAL METHOD FOR THE DETERIMINATION OF UNLEADED GASOLINE VAPOR CONDENSATE (API 94-02) V-2 Appendix W TABLE OF CONTENTS W-1 HISTORICAL CONTROL DATA - RATS W-2 HISTO
18、RICAL CONTROL DATA - MICE . W-8 Appendix X PROTOCOL AND PROTOCOL AMENDMENTS . X-1 vii LABORATORY TITLE PAGE STUDY NO. 95-6082 API STUDY NO. 08200-0601-SH9343 A RANGE-FINDING DEVELOPMENTAL INHALATION TOXICITY STUDY OF UNLEADED GASOLINE VAPOR CONDENSATE (API 94-02) IN RATS AND MICE VIA WHOLE-BODY EXPO
19、SURE LABORATORY Huntingdon Life Sciences Mettlers Road P.O. Box 2360 East Millstone, N.J. 08875-2360 SPONSOR American Petroleum Institute Health and Environmental Sciences Department 1220 L Street, N.W. Washington, D.C. 20005 FINAL REPORT date final report is produced . vl11 STD-APIIPETRO TR 412-ENG
20、L 1998 0732290 0606837 205 LABORATORY SIGNATURE PAGE This report constitutes a true and faithfiil account of the procedures adopted and the results obtained in the performance of this study. Raymodd E. Schroeder, M.S., D.AB .T. Study Director Date ,/ ,cud .-f A.LL J-T reduced weight gain over the Da
21、y 6-20 gestation interval using the actual Day 20 gestation weight; and reduced food consumption over the Day 6-9 gestation interval. No developmental toxicity was seen in the rat at the 9000 ppm exposure level. 1-2 STD.API/PETRO TR YL2-ENGL L998 0732290 Obob844 445 Section 2 INTRODUCTION The proced
22、ures and results obtained fiom a range-finding inhalation toxicity study of Unleaded Gasoline Vapor Condensate (MI 94-02) in rats and mice via whole body exposure are presented in this report. This study was conducted at Huntingdon Life Sciences, Mettlers Road, P.O. Box 2360, East Millstone, New Jer
23、sey 08875-2360. This inhalation study was pedormed to provide range-finding information on the maternal and developmental toxicity of Unleaded Gasoline Vapor Condensate (MI 94-02) in rats and mice. Data fiom this study will be used to identi the appropriate rodent species and exposure levels to use
24、in a definitive inhalation developmental toxicity study. Unieaded Gasoline Vapor Condensate (MI 94-02) was administered as a vapor, via inhalation (whole-body) exposure, 6 howdday to 40 mated rats (1 Ogroup) during Days 6-19 of gestation and to 40 mated mice (I Olgroup) during Days 6- 17 of gestatio
25、n. Exposure levels were 300, 1000,3000, and 9000 ppm. Ten mated rats and ten mated mice which served as controls, were chamber-housed and received filtered room air only, 6 hodday over the same treatment intervals. Procedures used during the study are presented in the Materiais and Methodfleferences
26、 section of the report. Maternal and developmental toxicity data for the rat are presented in Appendices A through J and similar data for the mouse are presented in Appendices K through T. Data regarding the inhalation exposures are presented in Appendix U. Results, as well as methods used, for the
27、chamber analyses performed by the Testing Facilitys Metabolism and Analytical Department are presented in Appendix V. Historical control data for both rats and mice are presented in Appendix W. A copy of the study protocol and protocol amendments are presented in Appendix X. 2- 1 - STD=API/PETRO TR
28、4L2-ENGL L998 0732290 ObObBY5 381 m Section 3 MATERIALS AND METHODSREFERENCES REGULATORY REFERENCES Good Laboratory P ractices This study was conducted in compliance with Part 792 of 40 CFR (EPA Good Laboratory Practices - TSCA). Animal Welfare Act Comdian ce This study complied with all appropriate
29、 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. 361 12- 36163 effective October 30,1989 and 9 CFR Part 3 Animal Welfare Standards; Final Rule, Federal Register, Volume 56, No. 32, February 15, 1991, pp. 6426-65
30、05 effective March 18,1991. Facilities Man aPement/Animal Husbandry Currently acceptable practices of good animal husbandry were followed, e.g., Guide for the Care and Use of Laboratory Animals; DHHS Publication No. (NIH) 86-23, Revised 1985. Huntingdon Life Sciences, East Millstone, New Jersey is f
31、ully accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC). STUDY MANAGEMENT SDonsor American Petroleum Institute Health and Environmental Sciences Department 1220 L Street, N.W. Washington, D.C. 20005 SDonsor Remesen tative Richard A. Rhoden, Ph.D. 3-1 STD=API/
32、PETRO TR 412-ENGL 1998 M 0732290 O606846 218 M Testing Facility Huntingdon Life Sciences Mettlers Road P.O. Box 2360 East Millstone, New Jersey 08875-2360 Study Director Raymond E. Schroeder, M.S., D.A.B.T. EXPERIMENTAL DESIGN Number of Animals Proportion of Fetuseaitter Treatment Mated Sacrificedb
33、Evaluated for Schedulea External Exposure Malformations Level Rats Mice Rats Mice andlor Group Test Material pm) (GD) (GD) Rats Mice (GD20) (GD 18) Variations I Control O 6-19 II Unleaded Gasoline 300 6-19 Vapor Condensate (API 94-02) III Unleaded Gasoline 1000 6-19 Vapor Condensate (API 94-02) IV U
34、nleaded Gasoline 3000 6-19 Vapor Condensate (API 94-02) V Unleaded Gasoline goooc 6-19 Vapor Condensate 6-17 10 10 10 10 Ali 6-17 10 10 10 10 All 6-17 10 10 10 10 All 6-17 10 10 10 10 All 6-17 10 10 10 10 All (A61 94-02) aExposures were 6 houdday. bComplete gross postmortem evaluations were performe
35、d on all animals. GD = gestation day “The Lower Explosive Limit (LEL) for Unleaded Gasoline Vapor Condensate (NI 94-02) as reported in the American Petroleum Institute DTI Report 2509 was 1.25% (12,500 ppm). The high-exposure level of 9000 ppm represents approximately 75% of the LEL. 3-2 STD.API/PET
36、RO TR 412-ENGL 1998 0732290 Ob06847 154 STUDY DATES Study Initiation (Date Study Director signed the Protocol) 14 June 1995 Initiation of Mating (Experimental Start Date) Rats: 19 June 1995 Mice: 21 June 1995 Initiation of Exposure Rats: 26 June 1995 Mice: 28 June 1995 Termination of Exposure Rats:
37、19 July 1995 Mice: 13 July 1995 Terminal Sacrifice Rats: 10-20 July 1995 Mice: 10-14 July 1995 Experimental Termination (Date of Last Data Collection) Rats: 20 July 1995 Mice: 14 July 1995 Study Termination 29 September 1997 3-3 STD-API/PETRO TR 4L2-ENGL 1778 D 0732290 OhOb848 090 m MATERIAL Unleade
38、d Gasoline Vapor Condensate (API 94-02) TEST MATERIAL INFORMATION LOT NO. PURITY DESCRIPTION RECEIVED DATE API 94-02 Considered Clear liquid 6 March 1995 December 1999 100% I TEST I I I I DATE I EXPIRATION 1 Supplier Chevron Research and Technology Company 100 Chevron Way Richmond, California 94802-
39、0627 Analysis Documentation of the identity, strength, purity, composition; and synthesis, fabrication, and/or derivation of the test material was the responsibility of the Sponsor. Stabil (Meal) (PMI Feeds, Inc., St Louis, MO) was available without restriction. Each animals cage was fitted to retai
40、n a glass feeder jar with a stainless steel lid. During the acclimation period, fresh feed was provided weekly to the rats while the mice received fresh feed every three to four days. During gestation, fresh food was presented to the rats on Days O, 6 and 12. The mice were provided with fresh food o
41、n Days O, 3,6,10 and 14 of gestation. (Note: For the mice, one animai each from the control, 300,1000 and 3000 ppm groups and two animals fiom the 9000 ppm groups were not provided with fresh feeders on Day 3 of gestation due to an oversight. This oversight was not considered to have compromised the validity or integrity of the study as the feeders contained suffkient feed for the animals to Day 6.) 3-8
