ABSTRACT

The developmental toxicity of gasoline with MTBE vapor condensate was evaluated in 25 confirmed-mated female Crl:CD®(SD)IGSBR rats/exposure group at target concentrations of 0, 2000, 10,000, and 20,000 mg/m3 in air.  The animals were exposed daily for six hours from Gestation Day (GD) 5 through GD 20.  There was evidence of slight maternal toxicity as indicated by  statistically significant decreases from control in the 20,000 mg/m3 target exposure level for body weight change and food consumption at the GD 8 - GD 11 interval.  No other statistically significant differences were noted between the control and treated groups for the maternal parameters.  There were no statistically significant differences for uterine implantation data, external, and visceral observations in the fetuses.  The incidence of dumbbell vertebral centra was statistically significantly increased in the 10,000 mg/m3 target group. This increase was not considered treatment related due to the lack of a dose response.  Therefore, the No Observable Adverse Effect Level for maternal toxicity was established at the 10,000 mg/m3 target exposure level and the No Observable Adverse Effect Level for developmental toxicity was established at 20,000 mg/m3 target exposure level.

i

	TABLE OF CONTENTS

   ABSTRACT		i

   TABLE OF CONTENTS		ii

   TITLE PAGE		vi

   APPROVAL SIGNATURES		vii

   PERSONNEL		viii

   QUALITY ASSURANCE STATEMENT 		ix

Section			Page

1.   SUMMARY		1-1

2.   INTRODUCTION		2-1

	STUDY INITIATION		2-1

	EXPERIMENTAL START DATE		2-1

	EXPERIMENTAL TERMINATION DATE		2-1

	INLIFE TEST PERIOD		2-1

	JUSTIFICATION FOR SELECTION OF TEST SYSTEM		2-1

	JUSTIFICATION OF DOSING ROUTE		2-1

	JUSTIFICATION OF DOSE SELECTION		2-2

	COMPLIANCE		2-2

3.   MATERIALS AND METHODS		3-1

	TEST SUBSTANCE		3-1

		Substance Identification		3-1

			Characterization of the Test Substance		3-1

			Analysis of Mixtures		3-2

			Sample Retention		3-2

			Carrier		3-2

		TEST SYSTEM		3-3

			Test Animal		3-3

			Animal Receipt Information		3-3

			Quarantine and Acclimation Period		3-3

			Number and Sex		3-3

			Age at Initiation of Gestation		3-3

			Weight at Initiation of Gestation		3-3

			Animal Identification		3-4

			Selection		3-4

			Feed		3-4

			Water		3-4

			Housing		3-5

			Environmental Conditions		3-5

ii

	TABLE OF CONTENTS (CONT’D)

		EXPERIMENTAL DESIGN		3-7

			Mating		3-7

			Experimental Groups		3-7

			Administration of Test Substance and Exposure Schedule		3-7

			The Chamber		3-7

			The Test Atmosphere		3-8

			Experimental Evaluation		3-8

			Euthanasia and Cesarean Section		3-8

			Examination of fetuses		3-9

			Tissue Preservation		3-9

			Records		3-9

			Statistical Analysis		3-9

4.   RESULTS AND CONCLUSION/DISCUSSION		4-1

		CLINICAL INLIFE OBSERVATIONS AND SURVIVAL		4-1

		GESTATION BODY WEIGHT		4-1

		GESTATION FOOD CONSUMPTION		4-1

		GROSS POSTMORTEM OBSERVATIONS		4-2

		UTERINE IMPLANTATION DATA		4-2

		FETAL BODY WEIGHT		4-2

		FETAL OBSERVATIONS		4-2

			External Observations		4-2

			Visceral Observations		4-3

			Skeletal Observations		4-3

		EXPOSURE AND CHAMBER CONDITIONS		4-3

		DISCUSSION		4-5

		PROTOCOL EXCEPTIONS		4-6

5.   LIST OF ABBREVIATIONS		5-1

		STATISTICAL SYMBOLS AND ABBREVIATIONS		5-1

		UTERINE IMPLANTATION DATA ABBREVIATIONS		5-2

		FETAL EXTERNAL AND VISCERAL EXAMINATION

		ABBREVIATIONS		5-2

6.   REFERENCES		6-1

LIST OF TABLES

Table			Page

4-1.   Mean exposure concentrations		4-3

4-2.   Summary of chamber uniformity		4-4

iii

	TABLE OF CONTENTS (CONT’D)

APPENDIX A

SURVIVAL BAR GRAPH		A-1

APPENDIX B

GESTATION OBSERVATIONS		B-1

APPENDIX C

GESTATION BODY WEIGHT		C-1

APPENDIX D

GESTATION FOOD CONSUMPTION		D-1

APPENDIX E

GROSS POSTMORTEM OBSERVATIONS		E-1

APPENDIX F

UTERINE IMPLANTATION DATA		F-1

APPENDIX G

FETAL BODY WEIGHT		G-1

APPENDIX H

FETAL OBSERVATIONS		H-1

APPENDIX I

SUMMARY OF EXPOSURE DATA		I-1

APPENDIX J

ANALYTICAL CHEMISTRY REPORT		J-1

iv

TABLE OF CONTENTS (CONT’D)

APPENDIX K

STATISTICIANS REPORT		K-1

APPENDIX L

HISTORICAL CONTROL DATA		L-1

APPENDIX M

FEED AND WATER ANALYSES		M-1

v

FINAL REPORT

PROJECT NUMBER:  171334

Test Substance: Gasoline WITH MTBE Vapor Condensate

(MRD-00-713)

Whole-Body Inhalation Developmental Toxicity Study in Rats

with Baseline Gasoline Vapor Condensate (MRD-00-713)

PERFORMED FOR:

AMERICAN PETROLEUM INSTITUTE

1220 L Street Northwest

Washington, D.C. 20005-4070

PERFORMED AT:

EXXONMOBIL BIOMEDICAL SCIENCES, INC.

Laboratory Operations, Mammalian Toxicology Laboratory

1545 Route 22 East, P.O. Box 971

Annandale, New Jersey 08801-0971

STUDY COMPLETION DATE:  TBD

vi

	APPROVAL SIGNATURES

D. J. Devlin, Ph.D.						Date

Director, Toxicology and Environmental Sciences

I hereby accept responsibility for the validity of these data and declare that to the best of my knowledge, the study contained herein was performed under my supervision in compliance with the EPA, United States Environmental Protection Agency, Good Laboratory Practices (GLP) Standards for Inhalation Exposure Health Effects Testing, 40 CFR, Part 79.60, 1994 with the following exception.

The storage of the sorbent tubes collected for the detailed capillary/GC analysis was not documented.  The tubes were stored in the necropsy freezer after sample collection until they were transferred to the Analytical Chemistry Group for analysis.

Water and feed analyses were not performed in a GLP compliant laboratory.

These minor deviations from the EPA Good Laboratory Practice Standards had no adverse effect on the integrity or results of the study.

G. W. Trimmer, B.A.						Date

Study Director

T.M. Gray, M.S. D.A.B.T.					Date

Sponsor

vii

	PERSONNEL

Study Director:						G. W. Trimmer, B.A.

Sponsor:							American Petroleum Institute

								1220 L Street Northwest

								Washington, D.C. 20005-4070

Sponsor Representative:					T. M. Gray, M.S., D.A.B.T.

Director, Laboratory Operations

(Study Initiation through October 31, 2004)			J. J. Freeman, Ph.D., D.A.B.T.

Laboratory Coordinator (effective November 1, 2004):	G. W. Trimmer, B. A.

Toxicology and Animal Care Supervisor:			R. C. Forgash, B.S.

Compound Preparation Supervisor:				E. J. Febbo, M.S.

Analytical Chemistry Supervisor:				D. J. Letinski, M.S.

Quality Assurance/Archives Section Head

(Study Initiation through February 28, 2005)			W. J. Bover, Ph.D.

Quality Assurance/Archives Supervisor

(effective March 1, 2005)		:			R. Pristas, M.S.

Veterinarian:							R. L. Harris, D.V.M.

Reproductive Toxicology Consultant:				S. B. Harris, Ph.D.

Statistician:							M. J. Nicolich, Ph.D

Statistician Consultant:					G. Bukhbinder, Ph.D.

viii

QUALITY ASSURANCE STATEMENT  PRIVATE

STUDY NUMBER:	171334

TEST SUBSTANCE:	MRD-00-713

STUDY SPONSOR:	American Petroleum Institute

Listed below are the inspections performed by the Quality Assurance Unit of ExxonMobil Biomedical Sciences, Inc., the date(s) of inspection, and the date(s) findings were reported to the Study Director and Management.

Study Phase 			Date(s) of			Reported to		Reported to

Inspected			Inspection			Study Director		Management

Protocol			01,02 Aug 01		02 Aug 01		02,07,14 Aug 01

Animal Receipt/		01 Aug 01			09 Aug 01		14,16 Aug 01

Uncrating

Gestation Day 8 		28 Aug 01  		28 Aug 01		30 Aug 01,

Body Weights										12,17 Sep 01

Gestation Day 8		29 Aug 01			30 Aug 01		25,31 Oct 01

Consumption Weights

Uterus Removal 		11,12 Sep 01		13 Sep 01		17,18,21 Sep 01

and Weighing

PM Viability			14 Sep 01			18 Sep 01		21 Sep 01

Final Report			04-08 Mar 02,  		04 Apr 02		05 Apr 02,

				11 Mar-02-04 Apr 02				18,23 Oct 06

Second Review of		11-13, 16 Oct 06		16 Oct 06		18,23 Oct 06

Final Report

Third Review of		26 Mar 08			26 Mar 08		26 Mar 08

Final Report

The final report accurately reflects the methods, procedures and observations documented in the raw data.

			Robert Pristas, M.S.				Date

			Quality Assurance Unit Coordinator

ix

SUMMARY

This study was conducted to evaluate the potential developmental toxicity of the test substance, Gasoline with MTBE Vapor Condensate (GMVC).  GMVC was administered via whole-body inhalation exposure to pregnant rats during the period of major organogenesis and fetal growth.  GMVC was administered by whole-body inhalation exposure to 25 confirmed-mated Crl:CD®(SD)IGSBR female rats at target doses of 0 (air control), 2000, 10,000, and 20,000 mg/m3 for six hours (plus the theoretical equilibration time) daily from Gestation Day (GD) 5 through GD 20. The Sponsor selected the exposure levels based upon safety considerations and previously conducted mammalian toxicity studies.

Clinical observations were made daily during gestation.  Body weight and food consumption measurements were made on GD 0, 5, 8, 11, 14, 17, 20, and 21.  On GD 21, animals were sacrificed by CO2 asphyxiation followed by exsanguination.  The reproductive organs and the abdominal and thoracic cavities were examined grossly.  Uterine weights with ovaries attached were recorded.  Uterine contents were examined, and the numbers of live, dead and resorbed fetuses were recorded.  All fetuses were weighed, sexed externally, and examined externally for gross malformations.  Apparent non-gravid uteri were placed in 10% ammonium sulfide solution for confirmation of non-pregnancy status.

The viscera of approximately one-half of the fetuses of each litter were examined by fresh dissection.  After these fetuses were examined, they were decapitated.  The heads were preserved in Bouin's solution for at least two weeks, rinsed, and subsequently stored in 70% ethanol.  The fetal heads were sectioned and examined with a dissecting microscope for the presence of abnormalities.  The remaining fetuses judged to be alive at the C-section were eviscerated, processed for skeletal staining, stained for bone and cartilage, and examined for the presence of skeletal malformations and variations.

There was evidence of maternal toxicity in the 20,000 mg/m3 target exposure group as indicated by statistically significant decreases in body weight gain and food consumption for the GD 8-11 interval.  All dams survived to scheduled terminal sacrifice on GD 21.  At the GD 21 cesarean section one animal in each group was found to be not pregnant (i.e. no evidence of implantation sites).  All animals were free of clinical or postmortem effects attributable to treatment with GMVC.

1-1

SUMMARY   (CONT'D)

There were no statistically significant differences between the control and the GMVC treated groups for uterine implantation data, fetal body weights, and external, and visceral observations.  The incidence of dumbbell-shaped vertebral centra was statistically significantly increased in the 10,000 mg/m3 target group and the incidence was slightly greater than observed in the historical control data.  However, this increase was not considered treatment related due to the lack of a dose response.

In conclusion, administration of the test substance to rats by whole-body inhalation exposure during the period of organogenesis and fetal growth resulted in a transient statistically significant decrease in food consumption and body weight change at the GD 8 - GD 11 interval.  No other treatment-related observations were evident in the treated groups that were statistically or biologically significantly different from the observations in the control group.

Therefore, the No Observable Adverse Effect Level for maternal toxicity was established at the 10,000 mg/m3 target exposure level and the No Adverse Effect level for developmental toxicity was established at 20,000 mg/m3 target exposure level for this study.

1-2

INTRODUCTION

This study was conducted to evaluate the developmental toxicity of Gasoline with MTBE Vapor Condensate (MRD-00-713) administered via whole-body inhalation exposure to pregnant rats during the period of major organogenesis and fetal growth.

This study was conducted for the American Petroleum Institute, 1220 L Street Northwest, Washington, D.C. 20005-4070 (subsequently referred to as the Sponsor).

The study was conducted by ExxonMobil Biomedical Sciences, Inc. (EMBSI) Laboratory Operations, Mammalian Toxicology Laboratory, 1545 Route 22 East, P.O. Box 971, Annandale, New Jersey 08801-0971.  The EMBSI Mammalian Toxicology Laboratory is accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC International).

STUDY INITIATION (PROTOCOL SIGNATURE DATE)

August 17, 2001

EXPERIMENTAL START DATE

August 25, 2001

EXPERIMENTAL TERMINATION DATE

March 27, 2002

Inlife Test Period

August 19, 2001 to September 18, 2001

Justification for Selection of Test System

The rat is one of the species required by the EPA for the developmental toxicity testing requirement of Section 211b of the Clean Air Act (EPA, 1994).

Justification of Dosing Route

Exposure by inhalation is a likely route of human exposure.

2-1

Justification of Dose Selection

The high dose of 20,000 mg/m3 was selected based on safety concerns as one-half of the Lower Explosive Limit.  The low dose (2000 mg/m3) was expected to produce a No Adverse Effect Level based on the results of previous subchronic and developmental studies conducted on this material, related materials, or some combination thereof.  The mid dose (10,000 mg/m3) was selected as the approximate mid point between the low and high doses to produce a dose response relationship, if one existed in this treatment range.

Compliance

This study was conducted to meet/exceed compliance with the following standards and requirements:

EPA, United States Environmental Protection Agency, Good Laboratory Practices (GLP) Standards for Inhalation Exposure Health Effects Testing. 40 CFR, Part 79.60, 1994.

EPA, United States Environmental Protection Agency, Vehicle Emissions Inhalation Exposure Guideline. 40 CFR, Part 79.61, 1994.

Animal Welfare Act of 1966 (P.L. 89-544), as amended in 1970, 1976, and 1985.  Code of Federal Regulations, Title 9 [Animals and Animal Products], Subchapter A - Animal Welfare Parts 1, 2, and 3.

This study was conducted in accord with the following guidelines and standards:

EPA, United States Environmental Protection Agency, Health Effects Test Guidelines OPPTS 870.3600 Inhalation Developmental Toxicity Study, Public Draft, June 1996.

EPA, United States Environmental Protection Agency, Health Effects Test Guidelines, OPPTS 870.3700, August 1998.

OECD, Organization for Economic Cooperation and Development, Guidelines for the Testing Chemicals, Proposal for Updating Guideline 414, January 2001.

Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C., 1996.

2-2

MATERIALS AND METHODS

TEST SUBSTANCE

Substance Identification

EMBSI Identification:  	MRD-00-713

Sponsor Identification:	Gasoline with MTBE Vapor Condensate

Supplier:			Chevron Research and Technology Company

Lot #:				API 00-02

Description:			Clear colorless liquid

Storage Condition:		Ambient outdoor conditions (blanketed with nitrogen)

Date Received:		Tank numbers: 		Expiration Date:

December 11, 2000		1, 3 , 6, 7		December 2005

April 9, 2001			10, 11 - 14, 16		April 2005

Characterization of the Test Substance

The stability, identity, strength, purity, and composition or other characteristics that appropriately identified the test substance was performed by the testing laboratory (EMBSI).  Documentation is maintained at ExxonMobil Biomedical Sciences, Inc., Annandale, New Jersey.  Characterization will be reported as part of EMBSI Study 167490.  Additionally, Appendix J shows the stability of the test substance over the course of the exposure interval.

The documentation of methods of synthesis, fabrication, and/or derivation of the test fuel were the responsibility of the Sponsor.  This was not completed when the study initiated, but is currently maintained by the Sponsor.

3-1

TEST SUBSTANCE   (CONT'D)

Analysis of Mixtures

Nominal Concentration.  A nominal exposure concentration was calculated on a daily basis.  The net weight of test substance used was determined and was divided by the total volume of air passing through the chamber to give the nominal concentration.

Analytical Concentration.  The concentration of the test atmosphere in each chamber and the chamber room was determined approximately hourly during each exposure by on-line gas chromatography.  The chamber concentrations were measured in the breathing zone of the rats.  A backup analytical device (calibrated infrared vapor monitor) was also available.  The hourly chromatographic analyses showed five major components of the test atmosphere and was used to assess the stability of the test substance over the duration of the study.

Additionally, a sorbent tube sample of the test atmosphere was collected by drawing a known volume of the test atmosphere from each chamber  through a calibrated critical orifice once during each week of the study.  These samples were stored in a freezer and analyzed by the detailed capillary/GC method used for the initial characterization analysis of the liquid test substance.This analysis was done to determine component proportions of the test material atmosphere compared to the liquid test material.

Chamber Homogeneity.  Distribution samples were drawn from twelve different points within the chamber at each exposure level during the validation of the exposure system for this study.

Particle Size Analysis.  A particle size determination of the aerosol portion of the test atmosphere was conducted at least once during the chamber trials for Study 171334 from the 0 mg/m3 and 20,000 mg/m3 concentrations.  The particle size determination was repeated for the 20,000 mg/m3 concentration due to a problem with the original determination.  The samples were taken using a multistage cascade impactor.  Preweighed glass fiber filters were used to collect aerosol on each stage, which were associated with specific cutoff diameters for aerodynamic particle size in microns.  Since minimal aerosol was present, no further calculations were performed.

Sample Retention

No retention samples were taken due to the practical and safety considerations of storing a mixed gas/liquid phase substance under pressure.

Carrier

Air

3-2

TEST SYSTEM

Test Animal

Species:		Rat

Strain/stock:		Crl:CD®(SD)IGSBR

Supplier:		Charles River Laboratories, Inc.

			Raleigh, North Carolina

Animal Receipt Information (Females)

Receipt Date:			August 9, 2001

Purchase Order Number:	1AM08020

Quarantine and Acclimation Period

10 days; animals were checked for viability at least once daily.

Number and Sex

150 sexually mature virgin females

100 females were allocated to study groups after confirmation of mating; the additional 50 females were ordered to assure there would be 100 mated females and to make the mating as efficient as possible without exceeding the necropsy capacity of the laboratory.

50 sexually mature males (22-23 weeks old at the initiation of mating) were received for mating purposes from a different colony than the females to assure they were not siblings.  These rats were also used for mating with at least one other study.  The males were received on November 6, 2001.

Age at Initiation of Gestation (Designated GD 0)

Females:	Approximately 12-13 weeks

Weight at Initiation of Gestation (Designated GD 0)

Females:	236 to 305 grams

3-3

TEST SYSTEM   (CONT'D)

Animal Identification

Individual ear tags and corresponding cage identification.

Selection

More animals than required for the conduct of the study were purchased and acclimated.  Animals determined to be unsuitable for inclusion on this study because of poor health, outlying body weights, or other abnormalities were excluded from selection by the Study Director, and/or technical staff.

Feed

Certified Rodent Diet Meal 5002, ad libitum

Manufacturer:		PMI Feeds Inc.

			Richmond, Indiana

Analysis:		Performed by PMI Feeds Inc.  Copies of the feed analyses are maintained in the EMBSI Toxicology Laboratory and included in this report (Appendix M).  These analyses were not performed in a GLP-compliant laboratory.

Contaminants:	There were no known contaminants in the feed believed to have been present at levels that may have interfered with this study.

The availability of feed was checked daily for all animals.  Animals were without food while in the exposure chambers.

Water

Automatic watering system, ad libitum

Supplier:		ExxonMobil Research and Engineering Clinton Facility deionized water system.

Analysis:		Periodic analysis is the responsibility of the testing laboratory.  A copy of the results is maintained at the testing laboratory and included in this report (Appendix M).  This analysis was not performed in a GLP-compliant laboratory.

Contaminants:	There were no known contaminants in the water believed to have been present at levels that may have interfered with this study.

The availability of water was checked daily for all animals.  Animals were without water while in the exposure chambers.

3-4

TEST SYSTEM (CONT'D)

Housing

Room Number:	PE103

Chamber rooms:	PE102, PE110

Housing:		Single housed during the study period, except during mating.

Caging:		Suspended stainless steel and wire mesh with absorbent paper below cages.

Environmental Conditions

Animal Room

Temperature:		64 to 72 degrees Fahrenheit

Humidity:		30 to 78.9 percent relative humidity (see Protocol Exceptions)

Lighting:		Approximately 12 hours light (0600 to 1800 hours) and 12 hours dark (1800 to 0600 hours) by automatic timer.

Temperature was monitored at least twice daily and humidity was monitored at least once daily.  Additionally, a non-validated computerized system monitored the temperature, humidity, and lighting continuously for alarm purposes.

Chambers

Temperature:		64 to 78 degrees Fahrenheit (see Protocol Exceptions and Appendix I)

Humidity:		38 to 95 percent relative humidity (see Protocol Exceptions and Appendix I)

Temperature and humidity were monitored continuously and recorded approximately every 30 minutes during the exposure.

Light Intensity

Animal Room Light Intensity:	7.8 to 43.6 foot-candles

Chamber Room Light Intensity:	38.0 to 44.3 foot-candles

Light intensity was measured four times (see protocol exceptions) during the study (the first day of exposures, during the second week and third week of exposures and the last day of exposures) in both the animal room and the chamber room.  Light intensity was measured in the animal room in a cage approximately three feet above the floor level.  In the chamber room the light intensity was measured three feet above floor level in the approximate center of each generation room.

3-5

TEST SYSTEM (CONT'D)

Environmental Conditions (cont’d)

Chamber Noise Levels and Oxygen Levels

Noise Level:		72.8 to 81.2 db

Oxygen Level:	20.7 to 20.9%

The oxygen level and the noise level were measured in each exposure chamber on the first day of exposures, during the second week and third weeks of exposures and on the last day of exposures (see protocol exceptions).

3-6

EXPERIMENTAL DESIGN

Mating

On the initial scheduled mating day, females were placed in males' cages in a 1:1 (male:female) ratio.  Males and females were paired based on sequential Physical Identification Numbers.  A sufficient number of animals were co-housed in an attempt to produce an acceptable number of mated animals to accommodate lab scheduling.  Mating was confirmed on the following morning by observation of a copulatory plug (vaginal).  The day on which mating was confirmed was considered Day 0 of gestation (GD 0).  After confirmation of mating, each mated female was returned to its own cage.  New females then were placed in the males' cages until the required number of mated females was obtained by continuous cohabitation in consideration of lab scheduling.  Mated females subsequently were assigned to dose groups by a computer generated body weight sorting program (WEIGHT) using the GD 0 body weights to ensure mean body weight was similar between all groups on GD 0.

Experimental Groups

 PRIVATE  Group

 Number	Number of Females per Group	Target Dose

(mg/m3)

1. 	(Carrier Control)	25	 0

2. 	Low 	25	2000

3	. Intermediate 	25	10,000

4	. High	25	20,000

Administration of Test Substance and Exposure Schedule

The experimental and control animals were placed (whole body) into 1.0 M3inhalation chambers that were operated under dynamic conditions. The exposure period was at least 6 hours per day. The test substance atmosphere generation system was started after the last animal was placed in the exposure chambers and the generation system was stopped six hours later.  The animals remained in the chambers for at least an additional 23 minutes (theoretical cequilibration time) while the test atmosphere cleared.  The animals were exposed from GD 5 through GD 20.

The Chamber

The chambers used for exposure are stainless steel and glass and have a total volume of approximately 1.0 M3.  They operated at a flow rate (approximately 12-15 air changes/hour) sufficient to ensure timely equilibration.  The flow of air through each chamber was monitored continuously using a calibrated flow measuring device and recorded approximately every 30 minutes.  All chambers were maintained at a slight negative pressure.  The pressure was monitored continuously and recorded approximately every 30 minutes.

3-7

EXPERIMENTAL DESIGN   (CONT'D)

The Test Atmosphere

The control group was exposed to clean filtered air under conditions identical to those used for groups exposed to the test substance.  The test substance was administered fully vaporized in the breathing air of the animals.  The test atmosphere composition and concentration remained constant at each exposure level over the daily six-hour period. The daily mean exposure concentrations were within ± 10% of the target exposure levels with the exceptions listed in the Protocol Exceptions section.

Experimental Evaluation

Animals were examined for viability at least twice daily during the study.  Body weights were taken prior to selection, and on GD 0, 5, 8, 11, 14, 17, 20, and 21.  Food consumption was measured for mated females on GD 5, 8, 11, 14, 17, 20, and 21.  A clinical examination was given to each female prior to selection, and daily during gestation.  Additionally, group observations of the animals for mortality and obvious toxic signs while in the chambers were recorded at 15, 30, 45, and 60 minutes after initiation of the exposure and then hourly during each exposure.

Euthanasia and Cesarean Section

Euthanasia of the dams was by CO2 asphyxiation followed by exsanguination.  A gross necropsy was performed on all confirmed-mated females.

The fetuses were placed in a refrigerator to slow down and eventually terminate vital signs after the external examination and weighing.

Mated females were euthanized on GD 21.  Body weights were recorded on the day of necropsy. Uterine weights with ovaries attached were recorded at the time of necropsy.  Uterine contents were examined and the numbers and locations of implantation sites, early and late resorptions, live and dead (alive or dead in utero) fetuses were counted.  Corpora lutea also were counted.  The uteri of all apparently non-pregnant females were stained with 10% ammonium sulfide to confirm pregnancy status.

Evaluations of dams during cesarean section and subsequent fetal evaluations were conducted without knowledge of treatment group in order to minimize bias.

3-8

EXPERIMENTAL DESIGN   (CONT'D)

Examination of Fetuses

Each fetus was weighed and examined externally for gross malformations.  Fetal sex was determined by external examination and confirmed internally only on those fetuses receiving visceral examinations.

The viscera of approximately one-half of the fetuses of each litter were examined by fresh dissection (Staples, 1974; Stuckhardt and Poppe, 1984).  After these fetuses were examined, they were decapitated.  The heads were preserved in Bouin's solution for at least two weeks, then rinsed and subsequently stored in 70% ethanol.  Free-hand razor blade sections of the Bouin's-fixed fetal heads were examined for the presence of abnormalities.  The remaining live fetuses (alive in utero) were eviscerated, processed by double staining with Alizarin red and Alcian blue, and examined for the presence of bone and cartilage malformations and ossification variations.

Fetal evaluations were conducted without knowledge of treatment group in order to minimize bias.

Tissue Preservation

Fetal heads were fixed in Bouin's solution and then preserved in 70% ethanol.  The fetal skeletons were preserved in glycerine with thymol after they were processed and stained.

Records

A copy of the protocol, final report, raw data, computer generated listings of raw data, supporting documentation, and tissue specimens are maintained in the EMBSI Toxicology Laboratory Archives.

Statistical Analysis

Statistical evaluation of equality of means was done by an appropriate one way analysis of variance and a test for ordered response in the dose groups.  First, Bartlett's Test was performed to determine if the dose groups had equal variance (Snedecor and Cochran, 1989).  If the variances were equivalent, the hypothesis that there was no difference in response between the groups was tested using a standard one-way analysis of variance (Snedecor and Cochran, 1989).  If the variances were equal, the testing was done using parametric methods, otherwise nonparametric techniques were used.

Continuous data were tested for statistical significance as follows:  Where applicable, percentages were calculated and transformed by Cochran's transformation, followed by the arc sine transformation (Snedecor and Cochran, 1989).  The raw percentages and the transformed percentages both were tested for statistical significance.

3-9

EXPERIMENTAL DESIGN (CONT'D)

Statistical Analysis (Cont'd)

For the parametric procedures, a standard one way ANOVA using the F distribution to assess significance was used (Snedecor and Cochran, 1989).  If significant differences among the means were indicated, Dunnett's Test was used to determine which treatment groups differed significantly from control (Dunnett, 1964).  In addition to the ANOVA, a standard regression analysis for linear response in the dose groups was performed.  The regression also tested for linear lack of fit in the model.

For the nonparametric procedures, the test of equality of means was performed using the Kruskal-Wallis Test (Hollander and Wolfe, 1973).  If significant differences among the means were indicated, Dunn's Summed Rank Test was used to determine which treatment groups differed significantly from the control (Hollander and Wolfe, 1973).  In addition to the Kruskal-Wallis Test, Jonckheere's Test for monotonic trend in the dose response was performed.

Bartlett's Test for equal variance was conducted at the 1% level of significance.  All other tests were conducted at the 5% and 1% level of significance.  However, the 5% level of significance was considered statistically significant for these analyses.  The 1% level of significance was reported as additional information.

The following data were not included in the statistical analyses:

Gestation body weight and body weight change data for females that were not pregnant

Gestation food consumption for females that were not pregnant

Means and standard deviations were calculated for animal, exposure and chamber environmental data.  The coefficient of variation also was calculated when considered relevant for the exposure  data.

3-10

EXPERIMENTAL DESIGN (CONT'D)

Statistical Analysis (Cont'd)

Fetal body weight was analyzed by a mixed model analysis of variance that provided an accurate statistical model of the biology.  The analysis used the litter as the basis for analysis and effectively used the litter size as a covariate.  The model considered dose group, litter size, and fetal sex as explanatory variables.  If the overall effect of dose, or the dose by sex effect, was statistically significant the dose groups means were tested pairwise vs. the control group using least squares means.  The least squares means allowed comparisons that accounted for differences in litter size and sex.  The mathematical model was based on a paper by Chen, et al (1996).  The analysis was run using SAS with code suggested in Little, et al (1997).

The analysis of anomalies (malformations or variations) was based on a Generalized Estimating Equation (GEE) application of the linearized model, Ryan (1992).  The model used the litter as the basis for analysis and considered correlation among littermates by incorporating an estimated constant correlation and the litter size as a covariate.  If the overall effect of dose, or the dose by sex effect, was statistically significant the dose groups were tested pairwise vs. the control group using least squares means.  The least squares means allowed comparisons that accounted for differences in litter size.  Three categories of anomalies were tested, and within each category specific anomalies also were tested.  In addition to the category specific anomalies a series of combined analyses were performed within each category as applicable:

Combined Malformations and Variations for All Fetuses

Combined Malformations and Variations for Alive Fetuses

Malformations for All Fetuses

Malformations for Alive Fetuses

Variations for All Fetuses

Variations for Alive Fetuses

3-11

RESULTS AND CONCLUSIONS/DISCUSSION

CLINICAL INLIFE OBSERVATIONS AND SURVIVAL

Survival Bar Graph:  Appendix A

Incidence of Gestation Observations:  Appendix B

Individual Gestation Observations:  Appendix B

All maternal animals survived to scheduled study termination on GD 21.  One female in each group was not pregnant.

There were no clinical signs indicative of maternal toxicity.  The majority of dams in all dose groups were free of observable abnormalities during the entire gestation period.  Clinical signs were limited to alopecia of the trunk for one control and one 2000 mg/m3 target female and dried ocular discharge for one 20,000 mg/m3 target female.  Clinical signs were not evident in the 10,000 mg/m3 target dams.

GESTATION BODY WEIGHT

Mean Gestation Body Weight and Body Weight Change:  Appendix C

Individual Gestation Body Weight and Body Weight Change:  Appendix C

There were no statistically significant differences in the mean gestation body weight between treated and control dams at any interval during the gestation period.  There also were no statistically significant differences in mean uterine weight between treated and control dams.  There was a statistically significant decrease in mean body weight change in the dams of the 20,000 mg/m3 target concentration at the GD 8-11 interval versus control.  Additionally, there was a statistically significant linear decrease in body weight change in the treated groups for this interval and for GD 0-21 corrected for uterine weight.

GESTATION FOOD CONSUMPTION

Mean Gestation Food Consumption:  Appendix D

Individual Gestation Food Consumption:  Appendix D

There was a statistically significant decrease in mean food consumption in the 20,000 mg/m3 target dams at the GD 8-11 interval versus control.  There also was a statistically significant linear decrease in food consumption in the treated groups for this interval and the GD 5-8 interval.  However, the food consumption in the treated groups was not statistically significantly different from the control at the GD 5-8 interval, but there was a statistically significant difference between the treated groups.  There were no other statistically significant differences in mean gestation food consumption between treated and control dams during the remainder of the gestation period.

4-1

RESULTS AND CONCLUSIONS/DISCUSSION (CONT’D)

GROSS POSTMORTEM OBSERVATIONS

Incidence of Gross Postmortem Observations:  Appendix E

Individual Gross Postmortem Observations:  Appendix E

The gross postmortem examination of the dams revealed alopecia for one 2000 mg/m3 target dam.  All other dams were free of grossly observable abnormalities.

UTERINE IMPLANTATION DATA

Mean Uterine Implantation Data:  Appendix F

Individual Uterine Implantation Data:  Appendix F

There were no statistically significant differences in the uterine implantation parameters between the control and the treated groups.  However, there were statistically significant linear decreases in the number of resorptions, resorptions/implantation, transformed resorptions/implantation % postimplantation loss, and the total number of affected fetuses in the treated groups.  Inversely, there were statistically significant linear increases in the fetuses/implantation and the transformed fetus/implantation.  These trends were not indicative of toxicity.  Additionally, there were no dead fetuses in any group.

FETAL BODY WEIGHT

Mean Fetal Body Weight:  Appendix G

Individual Fetal Body Weight:  Appendix G

Statistician’s Report:  Appendix K

There were no statistically significant differences in mean fetal body weight between the control and treated groups based on a mixed model analysis of variance that considered dose group, litter size, and fetal sex as explanatory values.

FETAL OBSERVATIONS

Incidence of Fetal Observations:  Appendix H

Individual Fetal Observations:  Appendix H

Statistician’s Report:  Appendix K

There were no statistically significant differences between the control and the treated groups for external variations and malformations, visceral variations and malformations, or skeletal malformations.

4-2

RESULTS AND CONCLUSIONS/DISCUSSION (CONT’D)

FETAL OBSERVATIONS (CONT’D)

External Observations

There were no statistically significant differences from the control group in the treated groups for the incidence of fetal external observations.  External observations were limited to stunted, fetus discolored red, malrotated hindpaw, filamentous tail, microstomia, and cleft palate.

Visceral Observations

There were no statistically significant differences from the control group in the treated groups for the incidence of fetal visceral observations.  Visceral observations were minimal and were limited to low incidences of anophthalmia, hydroureter, hydronephrosis, dilated cerebral ventricle, malpositioned nasal septum, retinal fold, and hydrocephaly.

Skeletal Observations

Skeletal observations are listed in Appendix H.  The most frequently noted observations during fetal examinations were bifid centra of the thoracic vertebrae, rudimentary lumbar ribs, and hypoplastic anlage of the thoracic vertebral centra.  The incidence of dumbbell-shaped vertebral centra was statistically significantly increased in the 10,000 mg/m3 target group and the incidence was slightly greater than observed in the historical control data.  There was also an increased incidence of dumbbell-shaped vertebral centra anlage at 2,000 mg/m3. These increases were not considered biologically significant or treatment related due to the lack of a dose response.

Several related skeletal observations, such as unossified and hypoplastic vertebral centra, were combined for statistical analysis (Appendix K).  There were no statistically significant differences from the control group in the treated groups for combined related skeletal observations.

 EXPOSURE DATA AND CHAMBER CONDITIONS

Summary of Exposure Data:  Appendix I

The range of chamber concentrations for the exposure period as represented by the daily mean analytical data and nominal data of each day are listed in Table 4-1:

Table 4-1 - Mean Daily Exposure Concentrations (Analytical and Nominal)

Target	2000 mg/m3	10,000 mg/m3	20,000 mg/m3

	Analytical	Nominal	Analytical	Nominal	Analytical	Nominal

Mean	2101	1762	10725	9512	20409	17599

S.D.	96.6	76.4	541.2	305.4	1037.6	509.7

Minimum	1956	1657	10104	8631	16100	16597

Maximum	2455	1940	12790	10321	21567	18944

S.D. - Standard deviation

4-3

RESULTS AND CONCLUSIONS/DISCUSSION (CONT’D)

EXPOSURE DATA AND CHAMBER CONDITIONS (CONT’D)

Satisfactory chamber uniformity was observed for the 12 points in the chamber that were analyzed.  The range of  concentrations for each chamber are listed in Table 4-2.

Table 4-2 - Summary of Chamber Uniformity

Target	2000 mg/m3	10,000 mg/m3	20,000 mg/m3

Mean	2108	10776	20341

S.D.	62.8	330.6	813.7

CV (%)	3.0	3.1	4.0

Minimum	2022	10397	19226

Maximum	2200	11714	21646

S.D. - Standard deviation

CV - Coefficient of variation

The particle size determination was performed once for the control chamber and twice for the 20,000 mg/m3 target chambers.  The initial particle size determination for the 20,000 mg/m3 target chamber collected 7200 ug of particles while the control chamber had no particles.  The particles collected from the 20,000 mg/m3 target chamber were considered to be due to dander and fur in the make-up air and no particles were detected in the 20,000 mg/m3 target chamber during the repeat of the particle size determination.  Therefore, there was no aerosol component to the chamber concentrations.

The oxygen levels in the chambers ranged from 20.7 to 20.9% at the intervals when they were monitored.  The noise level in the chambers ranged from 72.8 to 81.2 db.  The light intensity in the chamber rooms ranged from 38.0 foot-candles to 44.3 foot candles.

4-4

DISCUSSION

There was evidence of maternal toxicity in this study at the 20,000 mg/m3 target exposure group as indicated by  statistically significant decreases in mean body weight change and mean food consumption at the GD 8-11 interval.  However, the decrease in these parameters did not result in a statistically significant decrease in body weight at GD 11 or statistically significant differences in the GD 5-21 or GD 0-21 body weight change intervals..

There were no treatment-related statistically significant differences between the control and the GMVC treated groups for uterine implantation data, fetal body weights, and external, visceral, and skeletal observations.  The incidence of dumbbell-shaped vertebral centra was statistically significantly increased in the 10,000 mg/m3 target group and the incidence was slightly greater than observed in the historical control data. The incidence of dumbbell-shaped vertebral centra anlage (cartilaginous structure) was also statistically increased in the 2,000 mg/m3 target goup compared to the control group.  However, these observations were not considered related to treatment due to the lack of a dose response.

In conclusion, administration of the test substance to rats by whole-body inhalation exposure during the period of organogenesis and fetal growth resulted in signs of slight maternal toxicity and no developmental toxicity.

Therefore, the No Observable Adverse Effect Level for maternal toxicity was established at the 10,000 mg/m3 target exposure level and the No Observable Adverse Effect Level for developmental toxicity was established at 20,000 mg/m3 target exposure level for this study.

4-5

PROTOCOL EXCEPTIONS

ANIMALS OUT OF WEIGHT RANGE:  Three animals were over the protocol-specified 200-300 gram body weight range at Gestation Day 0.  These animals were in the 2,000 mg/m3 target group (#ICK386F, 305 g; and #IGK452F, 301 g) and the 20,000 mg/m3 target group (#IGK429F, 303 g).

This deviation had no adverse effect on the study results or integrity.

MEAN CHAMBER CONCENTRATION:  The mean chamber concentrations for treatment group chambers were outside the acceptable range (( 10%) in seven instances.  The following is a list of the dates and the extent of the deviation:

Date			Required Concentration (mg/m3)	Mean Concentration (mg/m3)

August 27, 2001			10,000				11180

September 3, 2001			10,000				11161

September 4, 2001			2000				2236

September 4, 2001			10,000				11075

September 5, 2001			2000				2455a

September 7, 2001			10,000				12790

September 7, 2001			20,000				16100

a – This deviation was caused by a very high value (3897 mg/m3) at the fifth hour of the exposure.  The cause of this high value was unknown.

These deviations had no adverse effect on the study results or integrity.

CHAMBER TEMPERATURE AND HUMIDITY:  Due to the method used to generate the test substance atmospheres, the chamber-room air was kept as cool as possible to keep the temperature in the 10,000 mg/m3 and the 20,000 mg/m3 target concentration chambers from exceeding the protocol-defined range. The cooler room air resulted in numerous instances of the mean temperature and humidity in the control chamber being below the protocol defined range.  The decreased temperature also caused the humidity in the chambers to be above the protocol-defined range on numerous occasions.  Additionally, the mean temperatures were above the protocol required range on several occasions.  The individual temperature and humidity deviations are noted in Appendix I as bold italicized values.

These deviations had no adverse effect on the study results or integrity.

CHAMBER CONCENTRATION OF SEPTEMBER 15, 2001:  At the 1-hour sampling for the chamber concentration on September 15, 2001 the gas chromatography system did not initiate.  The system was restarted and it worked normally for the rest of the sampling intervals on September 15, 2001.

These deviations had no adverse effect on the study results or integrity.

4-6

PROTOCOL EXCEPTIONS (CONT'D)

ANIMAL ROOM TEMPERATURE AND HUMIDITY:  The temperature and humidity were out of range in the animal room on the following days:

Date				Deviation

August 25, 2001		Humidity of 73.3% RH

August 26, 2001		Humidity of 78.9% RH

August 26, 2001		Temperature of 67.8(F

These deviations had no adverse effect on the study results or integrity.

LIGHT INTENSITY, NOISE LEVEL AND OXYGEN LEVEL:  The protocol specified that the light intensity, noise level and oxygen level be measured three times during the study (the first day of exposures, during the second week of exposures and the last day of exposures).  These parameters were measured four times during the study, the extra measurements were taken during week three of exposures.

These deviations had no adverse effect on the study results or integrity

No other circumstances occurred that would have affected the quality or integrity of the data.

4-7

LIST OF ABBREVIATIONS

STATISTICAL SYMBOLS AND ABBREVIATIONS

No difference		p(0.05		p(0.01		Statistical Statement

(PARAMETRIC)

A-						No statistical difference among the means

			     A		     A+		Significant difference among the means

L-						No linear response to the dose levels

			      L		     L+		Response is linearly related to dose

			      Q		     Q+		Linear response shows lack of fit

(NONPARAMETRIC)

		K-						No statistical difference among the means

				      K		      K+		Means differ significantly

		J-						No ordered response to the dose levels

				       J		       J+		An ordered response to the dose levels

			       *		      **		Mean significantly different from control

								mean

	NT						Data not tested

5-1

LIST OF ABBREVIATIONS (CONT'D)

UTERINE IMPLANTATION DATA ABBREVIATIONS

ABBREVIATION			PARAMETER

Resorp					Resorptions (early and late)

Implants				Implantation sites

CL					Corpora Lutea

Preimplant	Pre implantation loss = (corpora lutea - implantation sites)/corpora lutea x 100

Postimplant	Post implantation loss = (implantation sites - total live)/implantation sites x 100

Mal					Fetuses with malformations

Var					Fetuses with variations

Affected				Resorptions + dead + malformations

FETAL EXTERNAL AND VISCERAL EXAMINATIONS

+ = No observable abnormalities

Stunted = Any fetus weighing less than 4.00 grams

Organs and tissues examined

External:  	General body size, contour, and integrity (e.g. head,spine,abdomen); limbs;

digits; pinnae; eye bulges; palate/lip; tongue; snout/jaw; anogenital region; tail

Viseral:	Urogenital system; adrenals; stomach; spleen; pancreas; thymus; large/small

			Intestines; liver; lungs; heart and associated major vessels; thyroid; trachea;

			Esophagus; brain ventricles (single free-hand razor section)

Malformations are indicated by a capitalized footnote (e.g. "A").  Developmental variations are indicated by a lower case footnote (e.g. "a").  Observations which are not considered malformations or variations are indicated by an asterisk (e.g. "*").

5-2

REFERENCES

Animal Welfare Act of 1966 (P.L. 89-544), as amended in 1970, 1976, and 1985.  Code of Federal Regulations, Title 9 [Animals and Animal Products], Subchapter A -Animal Welfare Parts 1, 2, and 3.

Bevan, C., Tyl, R. W., Neeper-Bradley, T. L., Fischer, L. C., Panson, R. D., Douglas, J. F., and Andrews, L. S, 1997.  Developmental Toxicity Evaluation of Methyl Tertiary-butyl Ether (MTBE) by Inhalation in Mice and Rabbits.  Journal of Applied Toxicology 17(S1): 521-529.

Bradley, J.V., Distribution Free Statistical Tests.  Prentice Hall, Englewood Cliffs, N.J., 1968, pp. 195-203.

Chen, J.J., Gaylor, J.B. and Laborde, D.W. “Dose-response modeling of growth for developmental toxicity”, Environmetrics, vol 7, pg 135-144, 1996.

Dunnett, C., New Tables for Multiple Comparisons with a Control, Biometrics 20, 1964, pp. 482-491.

EMBSI, Draft Lab Report for Study 169534M:  Whole-Body Inhalation Developmental Toxicity Study in Mice with Baseline Gasoline Vapor Condensate, 2002.

EPA, United States Environmental Protection Agency, Good Laboratory Practices (GLP) Standards for Inhalation Exposure Health Effects Testing. 79.60 CFR Vol. 59, No. 122, 27 June1994.

EPA, United States Environmental Protection Agency, Vehicle Emissions Inhalation Exposure Guideline. 79.61 CFR Vol. 59, No. 122, 27-June 1994.

EPA, United States Environmental Protection Agency, Health Effects Test Guidelines OPPTS 870.3600 Inhalation Developmental Toxicity Study, Public Draft, June 1996.

EPA, United States Environmental Protection Agency, Health Effects Test Guidelines, OPPTS 870.3700, August 1998.

Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, National Academy Press, Washington, D.C., 1996.

6-1

REFERENCES (CONT'D)

Hollander, M. and Wolfe, D.A. Nonparametric Statistical Methods, John Wiley and Sons, New York, 1973.

Khera, K.S., 1981.  Common Fetal Aberrations and Their Teratologic Significance:  a Review.  Fundam. Appl. Toxicol. 1: 13-18.

Little, Milliken, Stroup, and Wolfinger, “SAS System for Mixed Models“, SAS Institute, Cary, NC, 1997, section 5.6.2, pg 203.

OECD, Organization for Economic Cooperation and Development, Guidelines for the Testing of Chemicals, Test Guideline 414, 2001.

Ryan, L., “The use of generalized estimating equations for risk assessment in developmental toxicity”, Risk Analysis, 12(3), pg 439-447, 1992.

SAS/STAT, V8.02, copyright © 1999-2001, SAS Institute, Inc., Cary, NC.

Snedecor, G.W., and Cochran, W.G., Statistical Methods, 8th ed., Iowa State University Press, Ames, Iowa, 1989.

Staples, R.E., Detection of Visceral Alterations in Mammalian Fetus, Teratology, 9:A-37, 1974.

Stuckhardt, J.L. and Poppe, S.M., Fresh Visceral Examination of Rat and Rabbit Fetuses Used in Teratogenicity Testing, Terato. Carcino. Mutagen., 4, 1984, pp. 181-188.

6-2

APPENDIX A - SURVIVAL BAR GRAPH

TARGET DOSE: 0 MG/M3

ANIMAL

GESTATION DAY

NUMBER

0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK329F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK327F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK332F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK337F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK331F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK351F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK360F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK334F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK370F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK343F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK373F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK346F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK379F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK342F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK378F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK402F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK419F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK388F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK417F 	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGK439F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK431F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK433F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK435F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK446F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK447F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

A-1

APPENDIX A - SURVIVAL BAR GRAPH (CONT'D)

TARGET DOSE: 2000 MG/M3

ANIMAL

GESTATION DAY:

NUMBER

0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK328F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK338F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK330F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK341F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK362F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK364F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK358F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK412F 	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGK416F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK359F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK347F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK335F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK418F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK413F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK425F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK422F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK384F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK386F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK442F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK466F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK430F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK445F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK452F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK471F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK458F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

A-2

APPENDIX A - SURVIVAL BAR GRAPH (CONT'D)

TARGET DOSE: 10,000 MG/M3

ANIMAL

GESTATION DAY:

NUMBER

0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK369F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK339F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK361F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK356F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK355F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK357F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK348F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK368F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK393F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK336F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK409F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK394F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGK371F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK381F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK401F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK414F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK398F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK377F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK454F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK455F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK434F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK437F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK443F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK444F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK449F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

A-3

APPENDIX A - SURVIVAL BAR GRAPH (CONT'D)

TARGET DOSE: 20,000 MG/M3

ANIMAL

GESTATION DAY:

NUMBER

0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK366F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK365F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK344F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK349F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK352F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK375F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK333F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK350F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK383F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK363F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK340F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK354F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK380F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK382F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK423F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK389F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK385F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK424F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK429F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK436F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK441F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK432F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK453F 	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGK459F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGK460F	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

NOTE:  	GD  - GESTATION DAY

N    -  NOT PREGNANT

	P     -  PREGNANT

	=     -  24 HOURS

A-4

APPENDIX B - GESTATION OBSERVATIONS

(INCIDENCE OF GESTATION OBSERVATIONS BY TARGET DOSE)

	GESTATION DAY

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

SURVIVORS (A)

	0 MG/M3	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24 24

2000 MG/M3	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24 24	24

10,000 MG/M3	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24 24	24

20,000 MG/M3	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24 24	24

NO OBSERVABLE ABNORMALITIES

0 MG/M3	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	23 24

2000 MG/M3	24	24	24	24	24	24	24	24	24	24	23	23	23	23	23	23	23	23	23	23 23	23

10,000 MG/M3	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24	24 24	24

20,000 MG/M3	24	24	24	24	24	24	23	23	24	24	24	24	24	24	24	24	24	24	24	24 24	24

ALOPECIA TRUNK

	0 MG/M3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0

2000 MG/M3	0	0	0	0	0	0	0	0	0	0	1	1	1	1	1	1	1	1	1	1	1	1

10,000 MG/M3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

20,000 MG/M3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

DRIED OCULAR DISCHARGE

	0 MG/M3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

2000 MG/M3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

10,000 MG/M3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

20,000 MG/M3	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0

NOTE:  (A) -  TOTALS DO NOT INCLUDE NON-PREGNANT ANIMALS

B-1

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 0 MG/M3

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK329F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK327F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK332F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK337F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK331F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK351F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK360F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK334F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK370F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK343F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK373F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK346F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK379F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-2

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 0 MG/M3 (CONT'D)

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK342F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK378F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK402F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK419F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK388F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK417F

	ANIMAL NOT PREGNANT

	IGK439F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK431F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK433F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK435F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK446F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	-	+

	ALOPECIA TRUNK

	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	+	-

IGK447F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-3

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 2000 MG/M3

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK328F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK338F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK330F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK341F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK362F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK364F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK358F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK412F

	ANIMAL NOT PREGNANT

	IGK416F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK359F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	-	-	-	-	-	-	-	-	-	-	-	-

	ALOPECIA TRUNK

	-	-	-	-	-	-	-	-	-	-	+	+	+	+	+	+	+	+	+	+	+	+

IGK347F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK335F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-4

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 2000 MG/M3 (CONT'D)

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK418F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK413F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK425F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK422F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK384F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK386F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK442F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK466F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK430F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK445F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK452F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK471F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK458F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-5

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 10,000 MG/M3

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK369F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK339F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK361F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK356F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK355F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK357F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK348F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK368F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK393F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK336F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK409F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK394F

	ANIMAL NOT PREGNANT

	IGK371F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-6

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 10,000 MG/M3 (CONT'D)

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK381F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK401F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK414F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK398F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK377F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK454F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK455F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK434F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK437F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK443F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK444F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK449F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-7

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 20,000 MG/M3

ANIMAL

	GESTATION DAY

NUMBER	OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK366F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK365F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK344F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK349F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK352F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK375F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK333F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK350F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK383F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK363F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK340F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK354F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK380F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-8

APPENDIX B - GESTATION OBSERVATIONS (CONT'D)

(INDIVIDUAL GESTATION OBSERVATIONS)

TARGET DOSE: 20,000 MG/M3 (CONT'D)

ANIMAL

	GESTATION DAY

NUMBER	 OBSERVATION

	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21

IGK382F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK423F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK389F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK385F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK424F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK429F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK436F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK441F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	-	-	+	+	+	+	+	+	+	+	+	+	+	+	+	+

	DRIED DISHARGE RIGHT EYE	-	-	-	-	-	-	+	+	-	-	-	-	-	-	-	-	-	-	-	-	-	-

IGK432F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK453F

	ANIMAL NOT PREGNANT

	IGK459F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

IGK460F

	NO OBSERVABLE ABNORMALITIES	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+	+

B-9

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(MEAN GESTATION BODY WEIGHT BY TARGET DOSE)

(SEE LIST OF ABBREVIATIONS FOR STATISTICAL SYMBOLS ON PAGES 5-1 AND 5-2)

(GRAMS)

	GD 0	GD 5	GD 8	GD 11	GD 14	GD 17	GD 20	GD 21	UTERUS	GD 21C

FEMALE	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-

0 MG/M3

MEAN	265.9	297.8	305.4	320.1	334.3	363.3	410.4	430.3	111.6	318.7

STD.DEV.	13	12.7	12.2	12.6	14.8	16.9	20.3	22.1	12.7	16.1

(N)	24	24	24	24	24	24	24	24	24	24

2000 MG/M3

MEAN	267.0	301.8	308.8	323.5	335.3	367.0	417.5	436.5	115.3	321.1

STD.DEV.	16.6	19.5	21.7	22.1	24.4	28.7	35.6	38.0	15.7	26.2

(N)	24	24	24	24	24	24	24	24	24	24

10000 MG/M3

MEAN	267.2	299.7	304.1	318.8	330.6	361.8	412.0	430.6	113.6	317

STD.DEV.	17.0	18.9	17.0	20.1	21.1	24.3	28.4	31.8	14.6	21.9

(N)	24	24	22	24	24	24	24	24	24	24

20000 MG/M3

MEAN	266.5	291.8	303.5	312.9	325.7	358.1	409.1	427.3	114.4	312.9

STD.DEV.	14.8	24.3	17.2	16.4	18.0	22.4	28.8	29.0	14.8	18.3

(N)	24	24	24	24	24	24	24	24	24	24

C-1

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(MEAN GESTATION BODY WEIGHT CHANGE BY TARGET DOSE)

(SEE LIST OF ABBREVIATIONS FOR STATISTICAL SYMBOLS ON PAGES 5-1 AND 5-2)

(GRAMS)

	GD 0-5	GD 5-8	GD 8-11	GD 11-14	GD 14-17	GD 17-20	GD 20-21	GD 5-21	GD 0-21	GD 0-21C

FEMALE	K-J-	K-J-	A+L+	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-	A-L

0 MG/M3

MEAN	31.9	7.6	14.8	14.2	29.0	47.1	19.9	132.5	164.4	52.8

STD.DEV.	8.5	5.7	4.6	5.4	5.5	8.7	8.6	17.5	18.1	13.0

(N)	24	24	24	24	24	24	24	24	24	24

2000 MG/M3

MEAN	34.8	7.0	14.7	11.8	31.7	50.5	19.0	134.6	169.4	54.1

STD.DEV.	6.3	6.2	7.0	6.6	7.1	8.6	5.2	23.7	25.4	14.4

(N)	24	24	24	24	24	24	24	24	24	24

10000 MG/M3

MEAN	32.5	5.7	13.3	11.8	31.1	50.3	18.6	131.0	163.4	49.8

STD.DEV.	6.2	4.8	5.8	7.7	9.3	5.9	6.5	18.7	19.4	12.2

(N)	24	22	22	24	24	24	24	24	24	24

20000 MG/M3

	    *

	MEAN	25.3	11.7	9.4	12.8	32.4	51.0	18.1	135.5	160.8	46.4

STD.DEV.	18.9	14.7	6.7	4.4	6.3	8.0	4.6	21.0	21.4	13.5

(N)	24	24	24	24	24	24	24	24	24	24

NOTE:

GD  - GESTATION DAY

	21C (DAY 21 CORRECTED) = DAY 21 BODY WEIGHT - UTERINE WEIGHT

C-2

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT)

(GRAMS)

TARGET DOSE:  0 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	UTERINE

NUMBER	0	5	8	11	14	17	20	21	21C	WEIGHT

IGK329F	244	285	292	308	326	357	410	434	317	117

IGK327F	250	285	288	312	321	344	392	408	295	113

IGK332F	251	288	299	306	325	354	400	429	338	91

IGK337F	252	277	284	293	299	323	369	381	282	99

IGK331F	257	296	304	321	336	373	424	441	321	120

IGK351F	259	299	316	332	347	381	426	434	317	117

IGK360F	259	298	303	315	335	367	417	435	318	117

IGK334F	262	298	307	317	337	360	409	422	307	115

IGK370F	254	280	277	293	301	324	371	390	296	94

IGK343F	273	300	306	322	335	359	396	415	318	97

IGK373F	278	292	314	332	357	387	433	462	348	114

IGK346F	281	305	311	321	347	388	451	471	331	140

IGK379F	251	289	296	313	328	354	407	411	294	117

IGK342F	263	284	300	321	329	366	412	439	322	117

IGK378F	265	283	295	308	319	353	399	414	301	113

IGK402F	269	299	310	333	346	372	407	432	335	97

IGK419F	272	312	312	329	339	367	424	452	327	125

IGK388F	278	313	318	333	347	369	419	440	327	113

IGK417F NP

	IGK439F	292	328	328	340	358	382	430	450	337	113

IGK431F	275	304	309	314	330	351	390	404	315	89

IGK433F	278	307	312	328	338	373	436	450	324	126

IGK435F	291	314	320	334	349	382	436	454	336	118

IGK446F	266	299	312	327	334	364	397	418	323	95

IGK447F	262	312	316	331	341	369	395	442	320	122

C-3

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT)

(GRAMS)

TARGET DOSE: 2000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	UTERINE

NUMBER	0	5	8	11	14	17	20	21	21C	WEIGHT

IGK328F	240	273	279	297	313	338	382	389	284	105

IGK338F	249	279	279	294	310	344	389	406	281	125

IGK330F	262	294	313	340	349	389	439	460	337	123

IGK341F	246	280	283	292	302	322	364	382	294	88

IGK362F	249	283	281	314	302	333	375	386	291	95

IGK364F	259	295	306	324	335	375	432	464	339	125

IGK358F	264	298	313	321	326	361	411	429	310	119

IGK412F NP

	IGK416F	259	304	308	322	335	360	398	417	328	89

IGK359F	270	292	300	315	328	357	411	436	315	121

IGK347F	274	303	306	322	333	361	402	424	320	104

IGK335F	277	319	330	350	362	409	462	483	358	125

IGK418F	253	286	295	304	316	337	382	399	299	100

IGK413F	257	289	304	319	327	363	422	446	312	134

IGK425F	263	295	299	307	325	359	420	441	315	126

IGK422F	272	313	313	316	328	353	403	420	305	115

IGK384F	280	310	323	336	353	385	439	456	336	120

IGK386F	305	341	356	369	390	429	491	509	374	135

IGK442F	259	285	279	290	303	326	363	376	291	85

IGK466F	289	331	339	348	364	404	472	488	354	134

IGK430F	277	323	324	337	343	382	435	453	335	118

IGK445F	282	312	314	342	355	378	428	455	339	116

IGK452F	301	347	355	371	389	421	487	511	370	141

IGK471F	252	292	301	316	323	355	396	413	308	105

IGK458F	270	300	311	317	336	367	416	432	312	120

C-4

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT)

(GRAMS)

TARGET DOSE: 10,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	UTERINE

NUMBER	0	5	8	11	14	17	20	21	21C	WEIGHT

IGK369F	251	280	286	299	334	339	395	403	280	123

IGK339F	260	302	306	319	311	366	411	427	309	118

IGK361F	272	305	313	321	331	354	396	406	311	95

IGK356F	236	270	274	292	293	322	367	386	287	99

IGK355F	253	288	287	304	322	354	410	434	307	127

IGK357F	266	302	304	323	325	360	412	429	328	101

IGK348F	267	304	308	322	332	369	419	448	325	123

IGK368F	286	319	320	337	348	375	424	447	337	110

IGK393F	251	280	281	290	308	332	373	384	287	97

IGK336F	251	274	274	284	296	323	373	387	279	108

IGK409F	274	303	309	323	336	367	421	455	331	124

IGK394F NP

	IGK371F	269	298	308	320	332	373	432	454	329	125

IGK381F	299	325	328	348	362	402	465	488	351	137

IGK401F	254	278	288	295	309	333	375	389	288	101

IGK414F	257	297	309	312	325	349	396	407	292	115

IGK398F	262	296	303	302	315	338	381	395	307	88

IGK377F	264	294	310	322	336	364	408	429	323	106

IGK454F	292	329	331	344	353	386	438	452	333	119

IGK455F	244	278	294	311	321	348	395	409	320	89

IGK434F	295	338	  291$	357	376	411	466	482	347	135

IGK437F	263	289	  339$	312	319	360	410	436	329	107

IGK443F	279	298	306	328	337	372	427	446	327	119

IGK444F	274	313	318	331	344	382	436	462	337	125

IGK449F	294	332	333	355	370	403	459	480	344	136

C-5

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT)

(GRAMS)

TARGET DOSE: 20,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	UTERINE

NUMBER	0	5	8	11	14	17	20	21	21C	WEIGHT

IGK366F	242	279	288	294	301	328	368	385	305	80

IGK365F	266	296	302	307	323	354	407	428	312	116

IGK344F	273	305	309	325	344	380	441	455	317	138

IGK349F	279	320	335	356	370	414	478	494	353	141

IGK352F	258	279	294	306	313	343	391	403	296	107

IGK375F	262	302	309	320	337	368	417	443	326	117

IGK333F	265	231	284	296	310	335	385	407	302	105

IGK350F	269	238	292	303	316	342	392	411	308	103

IGK383F	261	285	290	302	316	345	385	403	299	104

IGK363F	263	289	287	300	307	341	372	385	292	93

IGK340F	268	306	316	325	345	391	447	463	329	134

IGK354F	271	301	310	321	329	357	400	425	307	118

IGK380F	244	266	277	290	305	330	378	396	282	114

IGK382F	255	281	293	299	311	345	391	400	290	110

IGK423F	258	288	289	306	317	357	417	427	302	125

IGK389F	261	295	303	313	324	359	413	433	310	123

IGK385F	261	284	302	305	318	337	382	402	300	102

IGK424F	278	296	316	327	331	365	424	447	319	128

IGK429F	303	328	318	324	344	384	438	454	333	121

IGK436F	281	314	323	328	338	369	428	452	341	111

IGK441F	288	322	342	327	338	367	418	432	323	109

IGK432F	242	277	286	296	311	342	392	413	318	95

IGK453F NP

	IGK459F	258	292	292	299	309	344	394	417	298	119

IGK460F	289	329	327	341	360	397	461	479	347	132

C-6

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT CHANGE)

(GRAMS)

TARGET DOSE:  0 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-21	0-21	0-21C

IGK329F	41	7	16	18	31	53	24	149	190	73

IGK327F	35	3	24	9	23	48	16	123	158	45

IGK332F	37	11	7	19	29	46	29	141	178	87

IGK337F	25	7	9	6	24	46	12	104	129	30

IGK331F	39	8	17	15	37	51	17	145	184	64

IGK351F	40	17	16	15	34	45	8	135	175	58

IGK360F	39	5	12	20	32	50	18	137	176	59

IGK334F	36	9	10	20	23	49	13	124	160	45

IGK370F	26	-3	16	8	23	47	19	110	136	42

IGK343F	27	6	16	13	24	37	19	115	142	45

IGK373F	14	22	18	25	30	46	29	170	184	70

IGK346F	24	6	10	26	41	63	20	166	190	50

IGK379F	38	7	17	15	26	53	4	122	160	43

IGK342F	21	16	21	8	37	46	27	155	176	59

IGK378F	18	12	13	11	34	46	15	131	149	36

IGK402F	30	11	23	13	26	35	25	133	163	66

IGK419F	40	0	17	10	28	57	28	140	180	55

IGK388F	35	5	15	14	22	50	21	127	162	49

IGK417F NP

IGK439F	36	0	12	18	24	48	20	122	158	45

IGK431F	29	5	5	16	21	39	14	100	129	40

IGK433F	29	5	16	10	35	63	14	143	172	46

IGK435F	23	6	14	15	33	54	18	140	163	45

IGK446F	33	13	15	7	30	33	21	119	152	57

IGK447F	50	4	15	10	28	26	47	130	180	58

C-7

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT CHANGE)

(GRAMS)

TARGET DOSE:  2000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	0-5	0-21	0-21C

IGK328F	33	6	18	16	25	44	7	116	149	44

IGK338F	30	0	15	16	34	45	17	127	157	32

IGK330F	32	19	27	9	40	50	21	166	198	75

IGK341F	34	3	9	10	20	42	18	102	136	48

IGK362F	34	-2	33	-12	31	42	11	103	137	42

IGK364F	36	11	18	11	40	57	32	169	205	80

IGK358F	34	15	8	5	35	50	18	131	165	46

IGK412F NP

IGK416F	45	4	14	13	25	38	19	113	158	69

IGK359F	22	8	15	13	29	54	25	144	166	45

IGK347F	29	3	16	11	28	41	22	121	150	46

IGK335F	42	11	20	12	47	53	21	164	206	81

IGK418F	33	9	9	12	21	45	17	113	146	46

IGK413F	32	15	15	8	36	59	24	157	189	55

IGK425F	32	4	8	18	34	61	21	146	178	52

IGK422F	41	0	3	12	25	50	17	107	148	33

IGK384F	30	13	13	17	32	54	17	146	176	56

IGK386F	36	15	13	21	39	62	18	168	204	69

IGK442F	26	-6	11	13	23	37	13	91	117	32

IGK466F	42	8	9	16	40	68	16	157	199	65

IGK430F	46	1	13	6	39	53	18	130	176	58

IGK445F	30	2	28	13	23	50	27	143	173	57

IGK452F	46	8	16	18	32	66	24	164	210	69

IGK471F	40	9	15	7	32	41	17	121	161	56

IGK458F	30	11	6	19	31	49	16	132	162	42

C-8

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT CHANGE)

(GRAMS)

TARGET DOSE:  10,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-21	0-21	0-21C

IGK369F	29	6	13	35	5	56	8	123	152	29

IGK339F	42	4	13	-8	55	45	16	125	167	49

IGK361F	33	8	8	10	23	42	10	101	134	39

IGK356F	34	4	18	1	29	45	19	116	150	51

IGK355F	35	-1	17	18	32	56	24	146	181	54

IGK357F	36	2	19	2	35	52	17	127	163	62

IGK348F	37	4	14	10	37	50	29	144	181	58

IGK368F	33	1	17	11	27	49	23	128	161	51

IGK393F	29	1	9	18	24	41	11	104	133	36

IGK336F	23	0	10	12	27	50	14	113	136	28

IGK409F	29	6	14	13	31	54	34	152	181	57

IGK394F NP

IGK371F	29	10	12	12	41	59	22	156	185	60

IGK381F	26	3	20	14	40	63	23	163	189	52

IGK401F	24	10	7	14	24	42	14	111	135	34

IGK414F	40	12	3	13	24	47	11	110	150	35

IGK398F	34	7	-1	13	23	43	14	99	133	45

IGK377F	30	16	12	14	28	44	21	135	165	59

IGK454F	37	2	13	9	33	52	14	123	160	41

IGK455F	34	16	17	10	27	47	14	131	165	76

IGK434F	43	-47a	66	19	35	55	16	144	187	52

IGK437F	26	50 a	-27	7	41	50	26	147	173	66

IGK443F	19	8	22	9	35	55	19	148	167	48

IGK444F	39	5	13	13	38	54	26	149	188	63

IGK449F	38	1	22	15	33	56	21	148	186	50

Values were considered spurious and were not used in the statistical analyses

C-9

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(INDIVIDUAL GESTATION BODY WEIGHT CHANGE)

(GRAMS)

TARGET DOSE:  20,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-21	0-21	0-21C

IGK366F	37	9	6	7	27	40	17	106	143	63

IGK365F	30	6	5	16	31	53	21	132	162	46

IGK344F	32	4	16	19	36	61	14	150	182	44

IGK349F	41	15	21	14	44	64	16	174	215	74

IGK352F	21	15	12	7	30	48	12	124	145	38

IGK375F	40	7	11	17	31	49	26	141	181	64

IGK333F	-34	53	12	14	25	50	22	176	142	37

IGK350F	-31	54	11	13	26	50	19	173	142	39

IGK383F	24	5	12	14	29	40	18	118	142	38

IGK363F	26	-2	13	7	34	31	13	96	122	29

IGK340F	38	10	9	20	46	56	16	157	195	61

IGK354F	30	9	11	8	28	43	25	124	154	36

IGK380F	22	11	13	15	25	48	18	130	152	38

IGK382F	26	12	6	12	34	46	9	119	145	35

IGK423F	30	1	17	11	40	60	10	139	169	44

IGK389F	34	8	10	11	35	54	20	138	172	49

IGK385F	23	18	3	13	19	45	20	118	141	39

IGK424F	18	20	11	4	34	59	23	151	169	41

IGK429F	25	-10	6	20	40	54	16	126	151	30

IGK436F	33	9	5	10	31	59	24	138	171	60

IGK441F	34	20	-15	11	29	51	14	110	144	35

IGK432F	35	9	10	15	31	50	21	136	171	76

IGK453F NP

IGK459F	34	0	7	10	35	50	23	125	159	40

IGK460F	40	-2	14	19	37	64	18	150	190	58

NOTE:  NP - ANIMAL NOT PREGNANT    GD  - GESTATION DAY      $ - APPARENT BAD VALUE, EXCLUDED FROM CALCULATIONS

              21C (DAY 21 CORRECTED) = DAY 21 BODY WEIGHT - UTERINE WEIGHT

C-10

APPENDIX D - GESTATION FOOD CONSUMPTION

(MEAN GESTATION FOOD CONSUMPTION BY TARGET DOSE)

(SEE LIST OF ABBREVIATIONS FOR STATISTICAL SYMBOLS ON PAGES 5-1 AND 5-2)

(GRAMS)

GD 0-5	GD 5-8	GD 8-11	GD 11-14	GD 14-17	GD 17-20	GD 20-21	GD 5-20	GD 0-21

FEMALE	A-L-	AL+	AL+	A-L-	A-L-	A-L-	A-L-	A-L-	A-L-

0 MG/M3

	MEAN	121.3	72.1	71.9	74.1	77.0	80.2	24.3	375.3	520.8

STD.DEV.	12.6	8.8	6.6	8.5	6.3	5.8	5.8	29.7	38.8

(N)	24	24	24	24	24	24	24	24	24

	2000 MG/M3

	MEAN	125.5	74.5	71.9	73.8	78.5	83.5	26.1	383.2	534.7

STD.DEV.	16.9	8.3	7.3	10.4	8.9	10.0	4.0	40.8	58.1

(N)	24	24	24	23	24	23	24	22	22

	10000 MG/M3

MEAN	123.0	71.3	71.0	71.7	75.8	81.1	25.1	368.6	516.6

STD.DEV.	12.9	6.3	6.8	6.7	7.3	9.1	3.7	26.1	37.3

(N)	23	24	24	23	24	24	24	23	23

	20000 MG/M3

     *

MEAN	118.8	67.9	66.5	72.1	77.0	82.6	26.9	366.0	513.2

STD.DEV.	16.2	7.6	7.0	6.3	6.9	8.0	5.5	29.1	40.4

(N)	24	24	23	23	24	24	24	23	23

	NOTE:  GD - GESTATION DAY

D-1

APPENDIX D - GESTATION FOOD CONSUMPTION

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  0 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-20	0-21

IGK329F	117	76	73	74	78	80	29	381	527

IGK327F	109	68	67	68	73	79	23	355	487

IGK332F	107	72	65	75	78	84	33	374	514

IGK337F	102	65	60	61	67	68	23	321	446

IGK331F	117	76	71	70	76	85	26	378	521

IGK351F	129	83	79	84	89	85	23	420	572

IGK360F	116	43	70	48	76	81	27	318	461

IGK334F	129	80	72	76	71	73	22	372	523

IGK370F	99	58	57	63	64	73	22	315	436

IGK343F	119	71	70	70	70	72	23	353	495

IGK373F	100	74	74	80	83	90	32	401	533

IGK346F	139	79	75	88	89	93	27	424	590

IGK379F	116	68	68	70	74	76	15	356	487

IGK342F	118	68	69	73	76	75	26	361	505

IGK378F	113	65	67	71	82	79	22	364	499

IGK402F	123	77	83	86	83	82	26	411	560

IGK419F	134	72	73	74	73	81	29	373	536

IGK388F	136	76	77	77	72	79	25	381	542

IGK417F NP

	IGK439F	136	76	76	80	80	79	30	391	557

IGK431F	126	71	70	80	74	80	22	375	523

IGK433F	119	72	71	76	79	84	21	382	522

IGK435F	125	74	72	79	84	87	28	396	549

IGK446F	139	85	86	78	82	81	4	412	555

IGK447F	142	82	80	77	76	78	24	393	559

D-2

APPENDIX D - GESTATION FOOD CONSUMPTION (CONT’D)

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  2000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-20	0-21

IGK328F	98	65	65	67	73	71	20	341	459

IGK338F	107	66	67	43	73	71	22	320	449

IGK330F	100	78	77	75	95	89	27	414	541

IGK341F	117	70	70	S	65	74	22

IGK362F	112	63	66	68	68	75	22	340	474

IGK364F	134	75	76	77	80	S	33

IGK358F	122	75	71	66	76	84	25	372	519

IGK412F NP

	IGK416F	135	72	73	74	76	82	28	377	540

IGK359F	107	64	64	67	74	81	26	350	483

IGK347F	124	74	74	77	79	80	27	384	535

IGK335F	142	81	82	87	90	99	29	439	610

IGK418F	124	76	79	70	65	71	22	361	507

IGK413F	119	72	73	70	78	85	28	378	525

IGK425F	115	64	61	66	74	80	31	345	491

IGK422F	133	73	57	67	75	79	22	351	506

IGK384F	130	84	79	80	87	88	25	418	573

IGK386F	138	84	76	92	94	98	28	444	610

IGK442F	110	66	62	68	69	72	24	337	471

IGK466F	155	88	80	87	92	106	32	453	640

IGK430F	143	77	73	77	85	92	30	404	577

IGK445F	129	72	76	80	79	89	30	396	555

IGK452F	170	97	87	90	90	98	32	462	664

IGK471F	126	77	70	71	71	77	21	366	513

IGK458F	122	76	68	78	76	80	21	378	521

D-3

APPENDIX D - GESTATION FOOD CONSUMPTION (CONT’D)

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  10,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-20	0-21

IGK369F	95	65	61	75	76	69	21	346	462

IGK339F	117	73	66	63	72	67	22	341	480

IGK361F	120	72	77	62	68	102	21	381	522

IGK356F	106	60	61	61	67	74	22	323	451

IGK355F	125	68	67	74	78	84	26	371	522

IGK357F	123	65	71	64	77	81	24	358	505

IGK348F	127	71	72	69	77	80	28	369	524

IGK368F	131	71	79	76	81	84	26	391	548

IGK393F	113	61	61	66	66	70	23	324	460

IGK336F	109	62	61	61	62	77	23	323	455

IGK409F	121	73	73	68	68	77	36	359	516

IGK394F NP

	IGK371F	136	74	69	75	75	85	30	378	544

IGK381F	126	71	77	79	86	93	28	406	560

IGK401F	106	68	64	71	74	72	21	349	476

IGK414F	147	83	73	74	68	69	20	367	534

IGK398F	130	77	63	68	70	72	24	350	504

IGK377F	115	72	73	76	81	80	25	382	522

IGK454F	141	82	82	79	80	85	26	408	575

IGK455F	117	75	77	78	74	80	26	384	527

IGK434F	140	71	75	84	78	91	23	399	562

IGK437F	122	67	72	71	85	90	30	385	537

IGK443F	120	71	71	76	78	85	23	381	524

IGK444F	141	77	75	80	86	84	28	402	571

IGK449F	S	83	84	S	91	95	27

D-4

APPENDIX D - GESTATION FOOD CONSUMPTION (CONT’D)

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  20,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD	GD	GD

NUMBER	0-5	5-8	8-11	11-14	14-17	17-20	20-21	5-20	0-21

IGK366F	113	68	63	67	67	76	26	341	480

IGK365F	113	61	58	70	75	80	25	344	482

IGK344F	116	66	66	76	82	86	26	376	518

IGK349F	143	92	85	88	91	97	30	453	626

IGK352F	110	70	74	75	79	88	23	386	519

IGK375F	126	80	72	76	80	86	30	394	550

IGK333F	83	66	S	S	75	87	27

IGK350F	74	57	78	77	72	79	24	363	461

IGK383F	109	61	67	68	71	75	24	342	475

IGK363F	112	59	64	66	64	73	21	326	459

IGK340F	132	72	67	77	84	84	28	384	544

IGK354F	129	67	65	66	69	75	29	342	500

IGK380F	117	71	67	65	74	73	25	350	492

IGK382F	119	69	63	67	76	80	19	355	493

IGK423F	113	62	69	68	83	86	23	368	504

IGK389F	134	71	68	76	84	83	26	382	542

IGK385F	110	69	56	66	67	71	22	329	461

IGK424F	112	75	65	66	75	82	26	363	501

IGK429F	132	60	54	78	87	95	29	374	535

IGK436F	126	67	66	71	75	93	32	372	530

IGK441F	135	67	69	74	80	88	26	378	539

IGK432F	120	66	61	71	78	69	48	345	513

IGK453F NP

	IGK459F	131	60	59	66	74	80	26	339	496

IGK460F	141	73	73	84	86	97	30	413	584

	NOTE: 	GD - GESTATION DAY

NP - NOT PREGNANT

S    - NOT MEASURED DUE TO EXCESS SPILLAGE

D-5

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INCIDENCE OF GROSS POSTMORTEM OBSERVATIONS)

FEMALES

TARGET DOSE

0 MG/M3	2000 MG/M3	10,000 MG/M3	20,000 MG/M3

TOTAL AT TERMINAL SACRIFICE (A)	25	25	25	25

NO OBSERVABLE ABNORMALITIES	25	24	25	25

ALOPECIA: Trunk

	0	1	0	0

NO EVIDENCE OF UTERINE

	IMPLANTATION SITES

	1	1	1	1

NOTE:  (A) - INCLUDES NON-PREGNANT ANIMALS

E-1

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 0 MG/M3

	IGK329F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK327F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK332F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK337F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK331F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK351F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK360F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK334F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK370F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK343F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK373F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK346F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK379F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK342F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK378F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK402F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK419F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-2

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 0 MG/M3 (CONT'D)

	IGK388F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK417F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

	IGK439F  -	ALL TISSUES AND ORGANS:  No observable abnormalities

	IGK431F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK433F  -	 ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK435F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK446F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK447F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-3

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 2000 MG/M3

	IGK328F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK338F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK330F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK341F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK362F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK364F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK358F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK412F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

	IGK416F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK359F  -	GENERAL CONDITION:  Alopecia trunk.

	IGK347F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK335F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK418F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK413F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK425F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK422F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK384F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-4

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 2000 MG/M3 (Cont'd)

	IGK386F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK442F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK466F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK430F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK445F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK452F  -	ALL TISSUES AND ORGANS:  No observable abnormalities

	IGK471F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK458F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-5

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 10,000 MG/M3

	IGK369F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK339F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK361F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK356F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK355F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK357F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK348F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK368F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK393F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK336F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK409F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK394F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

	IGK371F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK381F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK401F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK414F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK398F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-6

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 10,000 MG/M3 (Cont'd)

	IGK377F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK454F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK455F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK434F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK437F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK443F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK444F  -	ALL TISSUES AND ORGANS:  No observable abnormalities

	IGK449F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-7

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 20,000 MG/M3 (Cont'd)

	IGK366F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK365F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK344F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK349F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK352F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK375F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK333F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK350F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK383F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK363F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK340F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK354F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK380F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK382F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK423F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK389F-	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK385F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-8

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE: 20,000 MG/M3 (Cont'd)

	IGK424F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK429F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK436F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK441F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGK432F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	IGK453F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

	IGK459F  -	ALL TISSUES AND ORGANS:  No observable abnormalities

	IGK460F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-9

APPENDIX F - UTERINE IMPLANTATION DATA

(MEAN UTERINE IMPLANTATION DATA BY TARGET DOSE)

(SEE LIST OF ABBREVIATIONS FOR STATISTICAL SYMBOLS ON PAGES 5-1 AND 5-2)

Total	Male	Female

Implantation	Corpora	Total	Fetuses/	Resorptions/

	Live	Fetuses	Fetuses	Resorptions	Sites	Lutea	Dead	Implantation Implantation

FEMALE	A-L-	A-L-	A-L-	A-L	A-L-	A-L-	NT	A-L	A-L

	0 MG/M3

	MEAN	14.92	7.17	7.75	0.63	15.54	16.04	0	0.96	0.04

STD.DEV.	2.19	2.57	2.27	0.77	1.82	1.94	0	0.05	0.05

(N)	24	24	24	24	24	24	24	24	24

	2000 MG/M3

MEAN	15.08	7.33	7.75	0.75	15.83	16.54	0	0.95	0.05

STD.DEV.	2.04	2.43	2.42	0.94	1.99	2.3	0	0.06	0.06

(N)	24	24	24	24	24	24	24	24	24

	10000 MG/M3

MEAN	15.38	7.79	7.58	0.33	15.71	16.25	0	0.98	0.02

STD.DEV.	2.24	1.53	2.32	0.56	2.24	2.74	0	0.04	0.04

(N)	24	24	24	24	24	24	24	24	24

	20000 MG/M3

MEAN	15.25	6.96	8.29	0.33	15.58	16.67	0	0.98	0.02

STD.DEV.	2.11	2.63	2.56	0.56	2.15	3.28	0	0.04	0.04

(N)	24	24	24	24	24	24	24	24	24

F-1

APPENDIX F - UTERINE IMPLANTATION DATA

(MEAN UTERINE IMPLANTATION DATA BY TARGET DOSE)

(SEE LIST OF ABBREVIATIONS FOR STATISTICAL SYMBOLS ON PAGES 5-1 AND 5-2)

F/I	R/I	D/I	Dead/	% Preimplant	% Postimplant	Total	Total	Total

	Tran	Tran	Tran	Implantation	Loss	Loss	Malformations	Variations	Affected

FEMALE	A-L	A-L	A-L-	NT	K-J-	A-L	K-J-	A-L-	A-L

	0 MG/M3

	MEAN	78.114083	11.886500	7.324

3.0	4.2	0.29	1.1	0.9

STD.DEV.	5.545914	5.545880	0.446

3.9	5.4	0.55	1.4	1.2

(N)	24	24	24	24	24	24	24	24	24

	2000 MG/M3

	MEAN	77.649292	12.351208	7.265

4.0	4.7	0.21	1.4	1.0

STD.DEV.	6.041860	6.041705	0.504

5.7	5.9	0.51	1.4	1.0

(N)	24	24	24	24	24	24	24	24	24

	10000 MG/M3

	MEAN	80.309458	9.691042	7.303

2.8	2.1	0.13	1.3	0.5

STD.DEV.	4.000682	4.000675	0.539

5.3	3.6	0.34	1.3	0.7

(N)	24	24	24	24	24	24	24	24	24

	20000 MG/M3

	MEAN	80.278667	9.721917	7.331

5.1	2.1	0.08	1.5	0.4

STD.DEV.	3.980406	3.980252	0.552

10.5	3.6	0.28	1.6	0.7

(N)	24	24	24	24	24	24	24	24	24

F-2

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  0 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGK329F	15	7	8	1	16	16	0	0	0

IGK327F	15	7	8	1	16	16	0	1	3

IGK332F	11	5	6	3	14	14	0	1	0

IGK337F	13	4	9	2	15	15	0	2	0

IGK331F	17	6	11	0	17	18	0	0	2

IGK351F	15	6	9	1	16	17	0	0	0

IGK360F	16	6	10	0	16	16	0	0	1

IGK334F	17	8	9	0	17	17	0	1	0

IGK370F	13	7	6	1	14	15	0	0	1

IGK343F	12	5	7	1	13	14	0	0	5

IGK373F	14	7	7	0	14	14	0	0	2

IGK346F	20	13	7	0	20	20	0	0	3

IGK379F	17	9	8	1	18	19	0	0	1

IGK342F	16	10	6	0	16	18	0	0	1

IGK378F	15	9	6	1	16	16	0	0	0

IGK402F	13	3	10	1	14	16	0	1	0

IGK419F	17	4	13	0	17	18	0	0	0

IGK388F	16	11	5	0	16	16	0	0	0

IGK417F NP

IGK439F	15	11	4	1	16	16	0	1	2

IGK431F	11	5	6	1	12	12	0	0	0

IGK433F	16	9	7	0	16	16	0	0	2

IGK435F	16	9	7	0	16	17	0	0	1

IGK446F	12	7	5	0	12	12	0	0	3

IGK447F	16	4	12	0	16	17	0	0	0

F-3

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  0 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGK329F	75.523	14.478	7.1808

IGK327F	75.523	14.478	7.1808

IGK332F	62.425	27.575	7.6795

IGK337F	68.584	21.417	7.4176

IGK331F	83.035	6.965	6.9653

IGK351F	75.523	14.478	7.1808

IGK360F	82.820	7.181	7.1808

IGK334F	83.035	6.965	6.9653

IGK370F	74.499	15.501	7.6795

IGK343F	73.898	16.102	7.9712

IGK373F	82.321	7.679	7.6795

IGK346F	83.581	6.419	6.4193

IGK379F	76.367	13.633	6.7681

IGK342F	82.820	7.181	7.1808

IGK378F	75.523	14.478	7.1808

IGK402F	74.499	15.501	7.6795

IGK419F	83.035	6.965	6.9653

IGK388F	82.82	7.181	7.1808

IGK417F NP

IGK439F	75.523	14.478	7.1808

IGK431F	73.222	16.779	8.299

IGK433F	82.820	7.181	7.1808

IGK435F	82.820	7.181	7.1808

IGK446F	81.702	8.299	8.299

IGK447F	82.820	7.181	7.1808

F-4

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  2000 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGK328F	14	7	7	1	15	16	0	0	3

IGK338F	15	7	8	0	15	15	0	0	4

IGK330F	15	6	9	0	15	15	0	0	1

IGK341F	12	6	6	0	12	15	0	0	4

IGK362F	12	6	6	2	14	14	0	0	0

IGK364F	16	7	9	1	17	17	0	0	5

IGK358F	16	6	10	1	17	18	0	0	2

IGK412F NP

IGK416F	11	5	6	0	11	11	0	0	0

IGK359F	17	6	11	0	17	17	0	0	2

IGK347F	13	5	8	3	16	17	0	0	1

IGK335F	16	9	7	3	19	21	0	0	0

IGK418F	15	9	6	0	15	17	0	1	0

IGK413F	18	16	2	0	18	21	0	0	1

IGK425F	16	9	7	0	16	17	0	0	2

IGK422F	15	6	9	0	15	15	0	0	0

IGK384F	16	4	12	1	17	18	0	0	1

IGK386F	16	6	10	0	16	16	0	0	0

IGK442F	11	7	4	2	13	13	0	1	1

IGK466F	18	8	10	0	18	18	0	2	2

IGK430F	16	10	6	1	17	16	0	1	1

IGK445F	16	10	6	1	17	18	0	0	1

IGK452F	18	6	12	1	19	20	0	0	1

IGK471F	14	7	7	1	15	16	0	0	0

IGK458F	16	8	8	0	16	16	0	0	1

F-5

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  2000 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGK328F	75.037	14.963	7.4176

IGK338F	82.583	7.418	7.4176

IGK330F	82.583	7.418	7.4176

IGK341F	81.702	8.299	8.299

IGK362F	67.793	22.208	7.6795

IGK364F	75.964	14.036	6.9653

IGK358F	75.964	14.036	6.9653

IGK412F NP

IGK416F	81.330	8.671	8.6708

IGK359F	83.035	6.965	6.9653

IGK347F	64.341	25.659	7.1808

IGK335F	66.587	23.413	6.5868

IGK418F	82.583	7.418	7.4176

IGK413F	83.232	6.768	6.7681

IGK425F	82.820	7.181	7.1808

IGK422F	82.583	7.418	7.4176

IGK384F	75.964	14.036	6.9653

IGK386F	82.820	7.181	7.1808

IGK442F	66.907	23.094	7.9712

IGK466F	83.232	6.768	6.7681

IGK430F	75.964	14.036	6.9653

IGK445F	75.964	14.036	6.9653

IGK452F	76.738	13.263	6.5868

IGK471F	75.037	14.963	7.4176

IGK458F	82.820	7.181	7.1808

F-6

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  10,000 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGK369F	18	8	10	0	18	18	0	0	0

IGK339F	16	8	8	0	16	16	0	0	0

IGK361F	12	8	4	1	13	12	0	0	1

IGK356F	13	7	6	0	13	13	0	0	0

IGK355F	17	10	7	0	17	17	0	0	2

IGK357F	14	9	5	0	14	15	0	0	5

IGK348F	16	9	7	0	16	16	0	0	0

IGK368F	15	8	7	1	16	18	0	1	2

IGK393F	13	8	5	0	13	13	0	0	0

IGK336F	16	6	10	0	16	16	0	0	2

IGK409F	16	5	11	1	17	18	0	0	3

IGK394F NP

IGK371F	16	10	6	0	16	16	0	1	3

IGK381F	19	6	13	0	19	22	0	0	2

IGK401F	15	7	8	0	15	16	0	0	1

IGK414F	16	7	9	1	17	20	0	0	0

IGK398F	12	8	4	0	12	13	0	0	0

IGK377F	13	6	7	0	13	13	0	0	1

IGK454F	16	8	8	0	16	16	0	0	1

IGK455F	12	6	6	0	12	12	0	0	2

IGK434F	20	8	12	0	20	21	0	0	0

IGK437F	13	6	7	2	15	15	0	0	1

IGK443F	16	8	8	1	17	17	0	1	0

IGK444F	17	10	7	0	17	18	0	0	1

IGK449F	18	11	7	1	19	19	0	0	3

F-7

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  10,000 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGK369F	83.232	6.768	6.7681

IGK339F	82.820	7.181	7.1808

IGK361F	73.898	16.102	7.9712

IGK356F	82.029	7.971	7.9712

IGK355F	83.035	6.965	6.9653

IGK357F	82.321	7.679	7.6795

IGK348F	82.820	7.181	7.1808

IGK368F	75.523	14.478	7.1808

IGK393F	82.029	7.971	7.9712

IGK336F	82.820	7.181	7.1808

IGK409F	75.964	14.036	6.9653

IGK394F NP

IGK371F	82.82	7.181	7.1808

IGK381F	83.414	6.587	6.5868

IGK401F	82.583	7.418	7.4176

IGK414F	75.964	14.036	6.9653

IGK398F	81.702	8.299	8.299

IGK377F	82.029	7.971	7.9712

IGK454F	82.820	7.181	7.1808

IGK455F	81.702	8.299	8.299

IGK434F	83.581	6.419	6.4193

IGK437F	68.584	21.417	7.4176

IGK443F	75.964	14.036	6.9653

IGK444F	83.035	6.965	6.9653

IGK449F	76.738	13.263	6.5868

F-8

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  20,000 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGK366F	10	5	5	0	10	10	0	0	1

IGK365F	15	6	9	0	15	15	0	0	1

IGK344F	16	9	7	0	16	16	0	0	6

IGK349F	18	7	11	1	19	19	0	0	0

IGK352F	14	6	8	1	15	16	0	0	1

IGK375F	15	4	11	0	15	15	0	0	1

IGK333F	14	6	8	2	16	19	0	0	0

IGK350F	15	6	9	0	15	28	0	0	0

IGK383F	15	6	9	0	15	15	0	0	0

IGK363F	12	4	8	1	13	15	0	0	5

IGK340F	19	12	7	1	20	20	0	0	2

IGK354F	17	6	11	1	18	20	0	1	4

IGK380F	15	6	9	0	15	16	0	0	1

IGK382F	16	7	9	0	16	16	0	0	2

IGK423F	16	6	10	0	16	16	0	0	0

IGK389F	17	5	12	0	17	18	0	1	0

IGK385F	13	8	5	0	13	13	0	0	1

IGK424F	18	13	5	0	18	18	0	0	2

IGK429F	16	7	9	0	16	16	0	0	0

IGK436F	15	10	5	0	15	15	0	0	3

IGK441F	15	4	11	0	15	15	0	0	0

IGK432F	12	10	2	1	13	16	0	0	2

IGK453F NP

IGK459F	15	3	12	0	15	15	0	0	1

IGK460F	18	11	7	0	18	18	0	0	2

	F-9

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS ON PAGE 5-2)

TARGET DOSE:  20,000 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGK366F	80.903	9.097	9.0975

IGK365F	82.583	7.418	7.4176

IGK344F	82.820	7.181	7.1808

IGK349F	76.738	13.263	6.5868

IGK352F	75.037	14.963	7.4176

IGK375F	82.583	7.418	7.4176

IGK333F	69.296	20.705	7.1808

IGK350F	82.583	7.418	7.4176

IGK383F	82.583	7.418	7.4176

IGK363F	73.898	16.102	7.9712

IGK340F	77.079	12.921	6.4193

IGK354F	76.367	13.633	6.7681

IGK380F	82.583	7.418	7.4176

IGK382F	82.820	7.181	7.1808

IGK423F	82.820	7.181	7.1808

IGK389F	83.035	6.965	6.9653

IGK385F	82.029	7.971	7.9712

IGK424F	83.232	6.768	6.7681

IGK429F	82.820	7.181	7.1808

IGK436F	82.583	7.418	7.4176

IGK441F	82.583	7.418	7.4176

IGK432F	73.898	16.102	7.9712

IGK453F NP

IGK459F	82.583	7.418	7.4176

IGK460F	83.232	6.768	6.7681

NOTE:	NP - ANIMAL NOT PREGNANT

F-10

APPENDIX G - FETAL BODY WEIGHT

(MEAN FETAL BODY WEIGHTS BY TARGET DOSE)

Mean Fetal Weight, the Least Squares Mean Fetal Weighta

Dose Group

(mg/m3)	n litters	n fetuses	observed fetus mean (gm)	Least squares fetus mean (gm)*

0	24	358	5.38	5.38

2,000	24	362	5.46	5.45

10,000	24	369	5.29	5.30

20,000	24	366	5.40	5.42

		a - The least squares mean accounts for litter size.

Mean Fetal Weight by Sex

MALES

FEMALES

0 MG/M3

MEAN

5.52

5.25

STD. DEV.

0.38

0.45

(N)

24

24

2000 MG/M3

	MEAN

5.58

5.34

STD. DEV.

0.45

0.53

(N)

24

24

10,000 MG/M3

	MEAN

5.44

5.13

STD. DEV.

0.39

0.37

(N)

24

24

20,000 MG/M3

	MEAN

5.56

5.28

STD. DEV.

0.47

0.45

(N)

24

24

G-1

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 0 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

	Males	Females

IGK329F	M	5.4	5.8	6.2	5.6	5.6	6.1	5.8

	Mean	5.79	5.49

IGK329F	F	5.6	5.4	5.7	5.1	5.0	5.7	5.7	5.7

S.D.	0.29	0.29

IGK327F	M	6.0	5.5	5.4	5.8	5.6	5.6	5.7

	Mean	5.66	5.50

IGK327F	F	5.5	5.5	6.0	5.4	5.0	5.7	5.5	5.4

S.D.	0.20	0.28

IGK332F	M	6.2	6.2	6.2	6.0	5.7

	Mean	6.06	5.78

IGK332F	F	5.7	5.6	5.9	6.0	6.1	5.4

S.D.	0.22	0.26

IGK337F	M	5.74	6.20	5.88	5.89

Mean	5.93	5.48

IGK337F	F	5.56	5.34	5.42	5.10	5.48	5.00	5.55	5.78	6.09

	S.D.	0.19	0.33

IGK331F	M	5.4	5.3	5.4	5.2	5.3	5.3

Mean	5.32	5.11

IGK331F	F	5.3	5.1	5.3	4.9	5.3	5.2	5.3	4.5	5.5	4.9	4.9

	S.D.	0.08	0.28

IGK351F	M	5.45	5.49	5.86	5.55	6.26	5.69

Mean	5.72	5.48

IGK351F	F	5.12	5.31	5.59	5.53	5.55	5.49	5.61	5.52	5.61

	S.D.	0.31	0.16

IGK360F	M	5.5	5.7	5.0	5.1	5.4	5.6

Mean	5.38	5.14

IGK360F	F	5.3	5.4	5.3	5.1	5.0	5.1	5.1	5.1	5.3	4.7

S.D.	0.28	0.20

IGK334F	M	5.1	4.8	5.4	5.0	4.7	4.8	5.5	5.0

Mean	5.04	4.72

IGK334F	F	4.6	5.0	4.9	4.7	4.5	4.8	4.5	4.9	4.6

	S.D.	0.29	0.19

IGK370F	M	4.8	5.5	5.3	5.1	5.5	5.5	5.6

	Mean	5.33	5.23

IGK370F	F	5.1	5.3	5.6	5.2	5.1	5.1

S.D.	0.29	0.20

IGK343F	M	5.2	5.5	5.8	5.8	5.8

	Mean	5.62	5.34

IGK343F	F	5.3	5.2	5.3	5.0	5.5	5.6	5.5

	S.D.	0.27	0.21

IGK373F	M	5.70	5.98	5.82	5.91	6.06	6.27	6.01

	Mean	5.96	5.67

IGK373F	F	5.64	5.80	5.79	5.58	5.71	5.38	5.79

	S.D.	0.18	0.15

IGK346F	M	5.11	5.38	5.78	4.94	5.10	4.84	6.11	5.60	5.51	5.14	5.15	5.23 4.93

	Mean	5.29	4.98

IGK346F	F	5.31	5.10	5.04	4.76	4.58	5.07	5.02

	S.D.	0.37	0.24

IGK379F	M	5.07	4.95	5.03	5.68	5.95	5.79	5.5	5.12	5.76

	Mean	5.43	5.13

IGK379F	F	4.69	5.10	5.20	5.30	5.27	4.47	5.55	5.48

S.D.	0.39	0.37

IGK342F	M	5.57	5.64	6.10	5.74	5.31	5.21	5.09	5.39	5.48	5.08

Mean	5.46	4.90

IGK342F	F	5.17	5.30	4.34	5.00	4.71	4.88

S.D.	0.32	0.34

G-1

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 0 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

	Males	Females

IGK378F	M	5.21	5.47	5.24	5.64	5.21	5.23	5.78	5.33	5.68

	Mean	5.42	5.28

IGK378F	F	5.28	5.31	5.27	5.20	5.19	5.40

S.D.	0.2	0.08

IGK402F	M	5.60	5.07	5.53

	Mean	5.40	5.06

IGK402F	F	5.08	5.48	5.00	5.23	5.06	4.96	5.06	5.07	4.65	4.98

S.D.	0.29	0.21

IGK419F	M	5.63	5.62	5.82	5.44

Mean	5.63	5.28

IGK419F	F	5.41	5.74	5.61	5.37	5.36	5.09	5.40	5.24	5.09	5.53	5.09	4.76 4.97

	S.D.	0.16	0.27

IGK388F	M	5.23	5.20	4.32	5.24	5.40	5.20	5.85	4.92	4.82	5.32	5.10

	Mean	5.15	4.21

IGK388F	F	2.60	5.36	4.80	4.93	3.36

	S.D.	0.38	1.17

IGK417F NP

IGK439F	M	5.75	5.78	5.55	5.06	5.33	4.51	5.93	5.74	5.62	5.36	5.47

	Mean	5.46	4.49

IGK439F	F	3.71	4.51	5.51	4.23

S.D.	0.40	0.76

IGK431F	M	5.90	6.01	5.88	5.95	5.27

	Mean	5.80	5.72

IGK431F	F	5.35	5.88	5.8	6.05	5.76	5.47

S.D.	0.30	0.26

IGK433F	M	5.98	5.67	5.78	5.73	6.00	5.91	5.78	6.12	5.89

	Mean	5.87	5.34

IGK433F	F	4.12	5.00	5.73	5.45	5.64	5.83	5.59

	S.D.	0.15	0.60

IGK435F	M	5.52	5.32	5.22	5.56	5.65	5.74	5.47	5.28	4.67

	Mean	5.38	5.20

IGK435F	F	5.31	5.38	5.22	5.12	5.20	5.07	5.10

	S.D.	0.32	0.11

IGK446F	M	5.63	5.67	5.91	5.76	5.78	6.08	5.88

	Mean	5.82	5.63

IGK446F	F	5.81	5.58	5.42	5.70	5.62

	S.D.	0.15	0.14

IGK447F	M	5.26	5.57	5.54	5.24

Mean	5.40	5.38

IGK447F	F	5.32	5.42	5.61	5.38	5.56	5.28	5.61	5.49	5.45	5.32	5.37	4.69

S.D.	0.18	5.38

G-2

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 2000 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

Males	Females

IGK328F	M	5.5	5.4	5.7	5.8	5.8	5.7	5.8

Mean	5.67	5.31

IGK328F	F	4.5	5.3	5.2	5.5	5.6	5.6	5.5

S.D.	0.16	5.31

IGK338F	M	7.0	5.7	5.9	7.0	7.3	5.4	7.1

Mean	6.49	5.89

IGK338F	F	7.4	5.2	5.2	5.5	6.7	6.7	5.1	5.3

	S.D.	0.79	5.89

IGK330F	M	5.9	6.6	5.9	6.3	6.0	6.0

	Mean	6.12	5.89

IGK330F	F	5.6	5.7	5.8	6.1	6.2	6.1	5.9	5.8	5.8

S.D.	0.28	5.89

IGK341F	M	5.3	5.2	4.9	5.1	5.5	5.6

	Mean	5.27	5.00

IGK341F	F	4.8	5.1	4.5	5.0	5.5	5.1

	S.D.	0.26	5.00

IGK362F	M	5.6	5.4	5.8	6.3	5.7	5.6

	Mean	5.73	5.32

IGK362F	F	5.1	5.7	5.2	5.2	5.3	5.4

	S.D.	0.31	5.32

IGK364F	M	6.0	5.8	5.4	6.0	5.2	5.5	5.9

Mean	5.69	5.47

IGK364F	F	5.5	5.7	5.9	5.3	5.4	4.9	5.5	5.2	5.8

S.D.	0.32	5.47

IGK358F	M	5.2	5.2	5.6	5.4	5.4	5.5

	Mean	5.38	5.23

IGK358F	F	5.3	5.5	4.7	5.4	5.1	5.1	5.1	5.7	5.0	5.4

	S.D.	0.16	5.23

IGK412F NP

	IGK416F	M	5.84	5.66	6.11	5.91	5.77

Mean	5.86	5.68

IGK416F	F	5.65	5.79	5.51	5.85	5.64	5.62

	S.D.	0.17	5.68

IGK359F	M	5.21	5.28	5.74	5.01	5.46	5.34

	Mean	5.34	5.17

IGK359F	F	4.88	5.29	5.29	5.24	4.84	5.28	5.00	5.35	5.36	5.27	5.11

S.D.	0.25	5.17

IGK347F	M	6.31	6.10	5.82	6.03	5.69

Mean	5.99	5.40

IGK347F	F	5.60	5.97	3.86	5.15	5.40	5.60	5.70	5.89

	S.D.	0.24	5.40

IGK335F	M	5.71	4.80	5.33	5.58	5.05	5.05	5.10	5.30	4.97

Mean	5.21	5.04

IGK335F	F	4.61	5.15	5.37	4.93	5.03	5.23	4.93

S.D.	0.30	5.04

IGK418F	M	4.87	5.19	4.99	5.16	4.62	5.19	5.19	4.94	4.96

Mean	5.01	4.39

IGK418F	F	2.27	5.22	4.78	4.68	4.55	4.82

	S.D.	0.19	4.39

IGK413F	M	5.39	5.43	5.59	5.35	5.91	5.62	5.65	5.71	5.74	5.64	5.68	5.60 5.66	5.14	5.50	5.74	Mean	5.58	5.38

IGK413F	F	5.16	5.60

	S.D.	0.19	5.38

IGK425F	M	6.08	6.17	5.82	5.90	5.72	6.38	6.27	5.70	5.83

Mean	5.99	5.69

IGK425F	F	5.65	5.35	5.76	5.91	5.52	6.13	5.53

S.D.	0.25	5.69

G-3

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 2000 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

Males	Females

IGK422F	M	6.06	5.07	5.40	5.62	5.50	5.60

	Mean	5.54	5.37

IGK422F	F	5.26	5.52	5.29	5.56	5.59	5.49	5.38	5.12	5.10

S.D.	0.32	5.37

IGK384F	M	5.29	5.25	4.89	5.26

	Mean	5.17	5.29

IGK384F	F	4.91	5.18	5.35	5.30	5.43	4.84	5.22	5.25	5.48	5.60	5.54	5.34

	S.D.	0.19	5.29

IGK386F	M	5.77	4.21	6.91	5.76	5.53	5.84

	Mean	5.67	5.90

IGK386F	F	7.25	5.62	6.78	5.43	6.52	5.64	5.54	5.37	5.33	5.48

	S.D.	0.86	5.90

IGK442F	M	5.90	5.74	5.45	5.66	5.67	5.40	5.59

Mean	5.63	4.81

IGK442F	F	5.39	5.59	2.89	5.36

	S.D.	0.17	4.81

IGK466F	M	5.14	5.47	5.57	5.39	5.43	5.96	5.41	5.62

	Mean	5.50	5.27

IGK466F	F	5.33	5.03	5.38	5.42	5.04	5.44	4.87	5.72	5.21	5.30

	S.D.	0.23	5.27

IGK430F	M	4.83	5.29	5.44	5.11	5.62	5.22	5.70	5.48	5.14	5.05

	Mean	5.29	4.99

IGK430F	F	5.20	4.92	5.18	4.86	5.00	4.80

	S.D.	0.27	4.99

IGK445F	M	5.55	5.49	5.98	6.13	5.46	5.43	5.35	5.75	5.24	5.41

	Mean	5.58	5.26

IGK445F	F	5.43	5.62	5.02	5.06	5.17	5.28

	S.D.	0.29	5.26

IGK452F	M	5.11	4.93	5.66	6.16	5.25	5.80

	Mean	5.49	5.40

IGK452F	F	5.41	5.30	5.43	5.34	5.56	5.66	5.58	5.28	5.40	5.59	5.09	5.16

	S.D.	0.47	5.40

IGK471F	M	5.33	5.50	5.61	5.95	5.45	5.77	5.42

Mean	5.58	5.16

IGK471F	F	4.18	5.70	5.33	5.20	5.41	5.25	5.08

S.D.	0.22	5.16

IGK458F	M	5.37	5.52	5.00	5.67	5.08	5.59	6.27	5.42

	Mean	5.49	5.10

IGK458F	F	5.01	5.05	4.87	5.16	4.90	5.03	5.30	5.45

	S.D.	0.39	5.10

G-4

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 10,000 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

Males	Females

IGK369F	M	4.5	4.9	5.3	5.4	4.8	5.1	5.6	5.5

	Mean	5.14	4.94

IGK369F	F	4.8	4.9	5.0	5.1	4.7	4.8	5.0	4.9	5.1	5.1

	S.D.	0.38	4.94

IGK339F	M	5.1	5.2	5.2	5.9	5.9	5.6	5.8	5.8

	Mean	5.56	5.25

IGK339F	F	4.9	5.4	5.1	5.2	5.1	5.6	5.3	5.4

	S.D.	0.34	5.25

IGK361F	M	5.8	5.8	6.2	5.6	5.5	5.9	5.9	6.0

	Mean	5.84	5.43

IGK361F	F	5.4	5.6	5.3	5.4

	S.D.	0.22	5.43

IGK356F	M	5.8	5.8	5.6	5.2	5.4	5.5	5.7

Mean	5.57	5.30

IGK356F	F	5.4	5.2	5.1	5.1	5.6	5.4

	S.D.	0.22	5.30

IGK355F	M	5.4	5.7	3.8	5.2	6.1	6.0	5.5	5.7	5.4	5.7

	Mean	5.45	5.13

IGK355F	F	5.2	5.2	4.6	5.2	5.0	5.6	5.1

S.D.	0.64	5.13

IGK357F	M	4.8	5.5	5.2	5.6	5.3	5.3	5.4	5.2	5.3

Mean	5.29	4.86

IGK357F	F	5.3	5.2	4.7	4.8	4.3

S.D.	0.23	4.86

IGK348F	M	5.7	5.4	5.9	5.7	5.8	5.4	5.7	5.5	6.0

Mean	5.68	5.54

IGK348F	F	5.5	5.7	5.2	5.8	5.9	5.4	5.3

S.D.	0.21	5.54

IGK368F	M	5.2	5.8	5.3	5.9	5.4	5.3	5.4	5.5

	Mean	5.48	5.10

IGK368F	F	4.7	5.3	5.4	5.3	5.0	5.0	5.0

S.D.	0.25	5.10

IGK393F	M	5.13	5.58	5.87	5.56	5.60	5.66	5.51	5.42

	Mean	5.54	5.33

IGK393F	F	5.23	5.35	5.31	5.36	5.38

S.D.	0.21	5.33

IGK336F	M	4.73	5.21	4.41	4.90	4.82	4.81

	Mean	4.81	4.60

IGK336F	F	4.61	4.84	4.53	4.70	4.60	4.84	4.34	4.64	4.60	4.30

	S.D.	0.26	4.60

IGK409F	M	5.67	5.58	5.68	5.47	5.24

Mean	5.53	5.28

IGK409F	F	4.79	5.37	5.17	5.11	5.21	5.12	5.20	5.40	5.68	5.61	5.45

S.D.	0.18	5.28

IGK394F NP

	IGK371F	M	5.39	5.44	5.65	5.77	5.42	5.51	5.56	6.12	6.21	5.98

	Mean	5.71	5.30

IGK371F	F	5.20	5.78	5.31	4.70	5.42	5.41

	S.D.	0.30	5.30

IGK381F	M	4.84	5.46	5.99	5.47	5.49	5.70

	Mean	5.49	5.26

IGK381F	F	4.42	5.25	4.99	5.28	5.00	5.19	5.49	5.67	5.46	5.29	5.96	4.74 5.61

S.D.	0.38	5.26

IGK401F	M	4.79	4.75	5.14	5.02	5.08	5.20	5.19

Mean	5.02	4.74

IGK401F	F	4.34	4.42	4.95	5.18	4.93	5.03	4.58	4.45

	S.D.	0.18	4.74

G-5

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 10,000 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

Males	Females

IGK414F	M	5.06	4.89	5.12	4.93	5.39	5.41	5.26

Mean	5.15	4.97

IGK414F	F	4.81	4.77	5.11	5.05	4.75	4.78	5.08	5.12	5.23

S.D.	0.21	4.97

IGK398F	M	5.06	5.57	5.27	5.23	5.38	5.19	5.31	5.34

	Mean	5.29	5.02

IGK398F	F	5.05	5.01	5.04	4.99

	S.D.	0.15	5.02

IGK377F	M	4.96	6.10	5.99	5.92	5.99	6.35

	Mean	5.89	5.69

IGK377F	F	5.35	5.79	5.91	5.59	5.8	5.66	5.72

S.D.	0.48	5.69

IGK454F	M	5.43	5.57	5.60	5.67	5.01	5.35	5.14	5.42

	Mean	5.40	5.07

IGK454F	F	5.62	4.82	4.98	4.89	5.14	5.23	5.23	4.61

	S.D.	0.23	5.07

IGK455F	M	5.31	5.69	5.55	5.85	6.17	5.43

	Mean	5.67	5.28

IGK455F	F	4.89	4.96	5.45	5.44	5.35	5.59

	S.D.	0.31	5.28

IGK434F	M	5.12	5.07	4.78	4.73	4.90	5.45	4.90	4.77

	Mean	4.97	4.70

IGK434F	F	4.52	4.75	4.76	4.56	4.80	4.85	5.04	4.85	4.65	4.63	4.08	4.90

	S.D.	0.24	4.70

IGK437F	M	5.87	6.36	6.00	6.02	6.48	5.42

	Mean	6.03	5.64

IGK437F	F	5.53	5.08	5.66	5.70	5.86	5.81	5.86

S.D.	0.38	5.64

IGK443F	M	5.35	5.52	5.71	5.41	5.52	5.67	5.25	5.42

	Mean	5.48	5.10

IGK443F	F	4.76	4.79	5.24	5.26	5.44	5.17	5.07	5.09

	S.D.	0.16	5.10

IGK444F	M	5.24	5.47	5.51	5.4	5.34	5.23	5.42	4.94	5.07	5.11

	Mean	5.27	5.19

IGK444F	F	4.97	5.24	5.41	5.54	5.24	5.02	4.92

S.D.	0.19	5.19

IGK449F	M	5.54	5.73	5.20	5.70	5.57	5.65	5.26	5.32	5.28	5.68	5.49

Mean	5.49	5.18

IGK449F	F	5.18	4.91	5.20	5.09	4.97	5.43	5.48

S.D.	0.20	5.18

G-6

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 20,000 MG/M3

ANIMAL

Fetus Weights

NUMBER 	SEX

Males	Females

IGK366F	M	5.8	5.7	5.8	5.7	5.8

Mean	5.76	5.36

IGK366F	F	5.3	5.8	5.2	5.1	5.4

S.D.	0.05	5.36

IGK365F	M	6.0	6.0	5.5	5.3	5.4	5.6

	Mean	5.63	5.53

IGK365F	F	5.3	5.5	5.4	6.2	5.9	5.5	5.4	5.3	5.3

S.D.	0.30	5.53

IGK344F	M	5.2	7.0	5.6	7.1	6.8	7.2	6.7	5.7	7.4

Mean	6.52	5.87

IGK344F	F	5.3	6.7	5.9	5.1	5.5	6.1	6.5

S.D.	0.80	5.87

IGK349F	M	5.4	5.8	5.7	5.8	5.6	5.1	5.5

Mean	5.56	5.28

IGK349F	F	5.6	5.3	5.4	5.5	5.9	5.0	5.4	4.8	4.8	5.2	5.2

S.D.	0.25	5.28

IGK352F	M	5.0	6.1	5.9	5.5	5.8	5.7

	Mean	5.67	5.41

IGK352F	F	5.0	5.5	5.3	5.9	5.7	5.1	5.4	5.4

	S.D.	0.38	5.41

IGK375F	M	5.6	5.8	5.6	5.7

	Mean	5.68	5.50

IGK375F	F	5.1	5.5	6.2	5.8	5.4	5.2	5.3	5.5	5.3	5.8	5.4

S.D.	0.10	5.50

IGK333F	M	5.74	6.04	5.62	5.61	5.98	5.40

	Mean	5.73	5.19

IGK333F	F	5.20	5.23	5.13	5.03	5.19	4.82	5.29	5.63

	S.D.	0.24	5.19

IGK350F	M	4.24	4.73	4.36	5.32	5.30	5.18

	Mean	4.86	4.77

IGK350F	F	4.93	4.78	4.96	4.90	4.84	3.44	5.12	4.97	4.99

S.D.	0.48	4.77

IGK383F	M	4.67	4.93	4.80	4.59	4.81	5.12

	Mean	4.82	4.49

IGK383F	F	4.49	4.21	4.70	4.33	4.15	4.93	4.73	4.29	4.61

S.D.	0.19	4.49

IGK363F	M	5.83	5.94	6.01	5.76

	Mean	5.89	5.60

IGK363F	F	5.86	6.37	5.35	5.75	5.61	5.39	5.53	4.93

	S.D.	0.11	5.60

IGK340F	M	4.60	4.77	5.29	5.40	5.29	5.09	5.25	5.37	5.30	5.81	5.62	4.75

	Mean	5.21	5.12

IGK340F	F	4.82	5.15	5.38	4.88	5.40	5.35	4.88

S.D.	0.36	5.12

IGK354F	M	5.05	5.14	5.42	5.52	5.22	5.45

	Mean	5.30	5.12

IGK354F	F	4.68	5.19	5.12	5.25	5.24	5.23	4.78	5.02	5.21	5.35	5.20

S.D.	0.19	5.12

IGK380F	M	5.48	5.91	5.72	5.45	5.82	5.83

	Mean	5.70	5.38

IGK380F	F	5.30	5.49	5.51	5.21	5.30	5.52	5.40	5.21	5.47

S.D.	0.19	5.38

IGK382F	M	5.07	5.60	5.45	4.93	5.38	5.36	5.39

Mean	5.31	4.85

IGK382F	F	4.70	4.73	5.24	4.83	4.47	5.11	5.13	4.97	4.49

S.D.	0.23	4.85

IGK423F	M	5.35	5.68	5.70	5.56	5.51	5.43

	Mean	5.54	5.46

IGK423F	F	5.54	5.51	5.36	5.42	5.58	5.12	5.17	5.69	5.58	5.63

	S.D.	0.14	5.46

G-7

APPENDIX G -  FETAL BODY WEIGHT

(INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS)

(GRAMS)

TARGET DOSE: 20,000 MG/M3

ANIMAL

               Fetus Weights

NUMBER 	SEX

Males	Females

IGK389F	M	5.43	5.46	5.67	5.26	5.36

Mean	5.44	5.31

IGK389F	F	5.59	5.19	5.05	5.22	5.46	5.15	5.02	5.56	5.26	5.18	5.34	5.64

	S.D.	0.15	5.31

IGK385F	M	5.67	5.51	5.65	5.50	5.50	5.98	5.87	6.11

	Mean	5.72	5.44

IGK385F	F	5.29	5.53	5.43	5.10	5.83

S.D.	0.24	5.44

IGK424F	M	5.17	5.70	5.80	5.54	4.98	5.22	5.73	5.48	5.50	5.77	5.42	5.24 4.89

Mean	5.42	4.77

IGK424F	F	4.99	5.30	5.45	2.77	5.35

S.D.	0.30	4.77

IGK429F	M	5.59	5.62	5.66	5.87	5.49	5.76	5.59

Mean	5.65	5.26

IGK429F	F	5.03	5.54	5.24	5.31	4.81	4.89	5.32	5.68	5.51

S.D.	0.13	5.26

IGK436F	M	4.76	6.07	5.84	5.73	5.73	5.73	5.72	5.86	5.58	3.93

	Mean	5.50	5.48

IGK436F	F	5.51	5.45	5.41	5.63	5.39

S.D.	0.65	5.48

IGK441F	M	5.38	5.44	5.47	5.53

	Mean	5.46	5.16

IGK441F	F	5.37	5.06	5.04	4.97	4.98	4.92	4.85	5.26	5.22	5.45	5.59

S.D.	0.06	5.16

IGK432F	M	5.46	5.92	5.94	5.73	5.95	5.50	6.12	6.14	5.88	5.55

	Mean	5.82	5.33

IGK432F	F	5.38	5.28

	S.D.	0.25	5.33

IGK453F NP

	IGK459F	M	5.85	5.93	5.78

Mean	5.85	5.75

IGK459F	F	5.23	5.68	5.43	5.89	6.16	5.53	5.81	6.08	5.78	5.99	5.88	5.52

	S.D.	0.08	5.75

IGK460F	M	5.66	5.65	5.36	5.22	5.70	5.13	5.63	5.94	5.45	5.69	5.19

Mean	5.51	5.18

IGK460F	F	5.22	5.13	5.30	4.71	5.37	5.53	5.00

S.D.	0.26	5.18

	NOTE: NP - NOT PREGNANT

G-8

APPENDIX H  -  FETAL OBSERVATIONS

(INCIDENCE OF FETAL OBSERVATIONS)

	TARGET DOSE:	0 MG/M3

2000 MG/M3

10,000 MG/M3

20,000 MG/M3

TOTAL FETUSES WITH EXTERNAL VARIATIONS	0/358

0/362

0/369

0/366