ABSTRACT

The developmental toxicity of gasoline with TBA (tert butyl alcohol) vapor condensate (GTVC) 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 maternal toxicity during the first half (GD 5-14) of the exposure period as indicated by statistically significant decreases in food consumption at the GD 5-8, GD 8-11, and GD 11-14 intervals for the 10,000 and 20,000 mg/m3 target concentration groups. The extent of these early decreases in food consumption also produced statistically significant decreases in food consumption for the GD 5-20 interval in the 10,000 and 20,000 mg/m3 target concentration groups and for the GD 0-21 interval in the 20,000 mg/m3 target concentration group.   Statistically significant dose-responsive decreases in body weight change also were evident in the 10,000 mg/m3  and 20,000 mg/m3 target concentration groups for the GD 5–8 interval and in the 20,000 mg/m3 target concentration group at the GD 8-11 interval.  Decreased body weight changes also occurred for the GD 5-21 and GD 0-21 intervals and the GD 0-21C interval when corrected for uterine weight in the 10,000 mg/m3 and 20,000 mg/m3 target concentration groups .  Reduced body weight gain corresponded with statistically significant reduced body weights at GDs 8, 11, 14, 17, 20, and 21 for the 20,000 mg/m3 target concentration group.  However, the impact on late gestation body weight by the statistically significantly reduced gravid uterus weight in 20,000 mg/m3 target concentration group is difficult to determine.  There were no treatment-related statistically significant differences for uterine implantation data.  There were statistically significant, non-dose responsive decreases in the number of corpora lutea in the 2000 and 20,000 mg/m3 target concentration groups.  Since ovulation occurred prior to exposure to the test substance, these decreases were not due to the test substance.   There were also corresponding, non-dose responsive reductions in implantations per litter; these differences were not statistically significant when covaried by corpora lutea counts.  Fetal body weight did not differ between groups when analyzed with litter size as a covariate or with both litter size and fetal sex as covariates; but, when mean corpora lutea count was an additional covariant along with litter size and fetal sex, mean fetal body weight was statistically reduced at 20,000 mg/m3.  Because of the complexity of this analysis and the confounding of the CL count and because no other statistically significant differences were noted in the fetal body weights with the other statistical tests, it is not clear whether exposure to GTVC at 20,000 mg/m3 is directly linked with decreased fetal body weight.  .There were no treatment-related statistically significant differences for external and visceral observations.  There were statistically significant increases in fetuses with skeletal variations and the incidence of rudimentary lumbar ribs in the 20,000 mg/m3 target concentration group.  The increase in fetuses with skeletal variations was due to the incidence of rudimentary lumbar ribs.  As rudimentary supernumerary ribs are often associated with maternal stress, this increase may be  related to the reduced food consumption and reduced body weight changes observed in the dams.  The No Adverse Effect Level for this study was 2000 mg/m3 for maternal toxicity and 10,000 mg/m3 for developmental toxicity (conservatively assuming that the minor developmental effects are adverse).

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		2-2

	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		4-2

		GROSS POSTMORTEM OBSERVATIONS		4-2

		UTERINE IMPLANTATION DATA		4-3

		FETAL BODY WEIGHT		4-3

		FETAL OBSERVATIONS		4-4

			External Observations		4-4

			Visceral Observations		4-5

			Skeletal Observations		4-5

		EXPOSURE AND CHAMBER CONDITIONS		4-6

		DISCUSSION		4-8

		PROTOCOL EXCEPTIONS		4-10

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 Implantation Sites and Corpora Lutea		4-3

4-2.   Mean Fetal Weight and the Least Squares Mean Fetal Weight

	 not Considering CL Count		4-4

4-3.   Mean Fetal Weight and the Least Squares Mean Fetal Weight

	 Considering CL Count		4-4

4-4.   Percent Incidence of Total Skeletal Variations and Rudimentary Lumbar Ribs		4-5

4-5.   Mean Exposure Concentrations (Analytical and Nominal)		4-6

4-6.   Summary of Chamber Uniformity		4-6

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

INHALATION EXPOSURE DATA		I-1

APPENDIX J

ANALYTICAL CHEMISTRY REPORT		J-1

iv

	TABLE OF CONTENTS (CONT’D)

APPENDIX K

STATISTICIAN’S REPORT		K-1

APPENDIX L

HISTORICAL CONTROL DATA		L-1

APPENDIX M

FEED AND WATER ANALYSES		M-1

v

FINAL REPORT

STUDY NUMBER:  171834

Test Substance: Gasoline WITH TBA Vapor Condensate

(MRD-00-718)

Whole-Body Inhalation Developmental Toxicity Study in Rats

with Gasoline WITH TBA Vapor Condensate (MRD-00-718)

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, 40CFR, Part 79.60, 1994 with the following exceptions.

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

DRAFT

QUALITY ASSURANCE STATEMENT  PRIVATE

STUDY NUMBER:	171834

TEST SUBSTANCE:	MRD-00-718

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			05 Nov 01		05 Nov 01			06 Nov 01,

 										06,10 Sep 02

A.M. Viability Check 		10 Sep 02		10 Sep 02			13,16 Sep 02

Animal Transfer			17 Sep 02		17 Sep 02			17,19 Sep 02											01 Jul 01

Animal Health/Sanitation/		24 Sep 02		25 Sep 02			27 Sep 02,

Chamber Cleaning											20 Oct 02

Sample Preparation/Sequence	27 Sep 02,		21 Nov 02			22 Nov 01,

Setup (Analytical)		21 Nov 02								04 Dec 02

Processing Fetal Skeletons		14-16 Oct 02	16 Oct 02			01,08 Mar 07

First Review of Draft Report		04 Mar – 04 Apr 03	04 Apr 03			01,08 Mar 07

Second and Third Review		16,18,19 Jan 07	15 Feb 07			02,04 Apr 07

of Draft Report; First and 		12,13,15 Feb 07

Second Review of Appendix K;

Review Sponsor Comments

Fourth Review of Draft Report;	01 May 08		01 May 08			02 May 08

Review Sponsor Comments

Fifth Review of Draft Report	       17 Sep 08		      19 Sep 08		   23-Sep-08

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 TBA Vapor Condensate (GTVC).  GTVC was administered via whole-body inhalation exposure to pregnant rats during the period of major organogenesis and fetal growth.  GTVC was administered by whole-body inhalation exposure to 25 confirmed-mated Crl:CD®(SD)IGSBR female rats at target concentrations 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 during the first half (GD 5-14) of the exposure period as indicated by statistically significant decreases in food consumption at the GD 5-8, GD 8-11, and GD 11-14 intervals for the 10,000 and 20,000 mg/m3 target concentration groups. The extent of these early decreases in food consumption also produced statistically significant decreases in food consumption for the GD 5-20 interval in the 10,000 and 20,000 mg/m3 target concentration groups and for the GD 0-21 interval in the 20,000 mg/m3 target concentration group.

Statistically significant dose-responsive decreases in body weight change also were evident in the 10,000 mg/m3  and 20,000 mg/m3 target concentration groups for the GD 5–8 interval and in the 20,000 mg/m3 target concentration group at the GD 8-11 interval.  Decreased body weight changes also occurred for the GD 5-21 and GD 0-21 intervals and the GD 0-21C interval when corrected for uterine weight in the 10,000 mg/m3 and 20,000 mg/m3 target concentration groups .  Reduced body weight gain corresponded with statistically significant reduced body weights at GDs 8, 11, 14, 17, 20, and 21 for the 20,000 mg/m3 target concentration group.  However, the impact on late gestation body weight by the statistically significantly reduced gravid uterus weight in 20,000 mg/m3 target concentration group is difficult to determine.

1-1

SUMMARY (CONT'D)

All dams survived to scheduled terminal sacrifice on GD 21.  At the GD 21 cesarean section two 2000 mg/m3 target concentration animals, two 10,000 mg/m3 target concentration animals, and one 20,000 mg/m3 target concentration animal were found to be not pregnant (i.e. no evidence of implantation sites).

All animals were free of clinical or postmortem observations attributable to treatment with GTVC.

There were no treatment-related statistically significant differences between the control and the GTVC treated groups for uterine implantation data or for external observations, and visceral observations on either a fetus or litter basis.  There were statistically significant, non-dose responsive decreases in the number of corpora lutea in the 2000 and 20,000 mg/m3 target concentration groups.  Since ovulation occurred prior to exposure to the test substance, these decreases were not due to the test substance.   There were also corresponding, non-dose responsive reductions in implantations per litter; these differences were not statistically significant when covaried by corpora lutea counts.

Fetal body weight did not differ between groups when analyzed with litter size as a covariate or with both litter size and fetal sex as covariates; but, when mean corpora lutea count was an additional covariant along with litter size and fetal sex, mean fetal body weight was statistically reduced at 20,000 mg/m3.  Because of the complexity of this analysis and the confounding of the CL count and because no other statistically significant differences were noted in the fetal body weights with the other statistical tests, it is not clear whether exposure to GTVC at 20,000 mg/m3 is directly linked with decreased fetal body weight.  .

There were no treatment-related statistically significant differences for external and visceral observations.  The only two fetal observations that were considered related to treatment were statistically significant increases in total fetuses with skeletal variations on a fetus basis and statistically significant increases in rudimentary lumbar ribs on a fetus basis in the 20,000 mg/m3 target concentration group.  As rudimentary supernumerary ribs may be associated with maternal stress, this increase may be related to the reductions in food consumption and body weight changes observed in the dams.

In conclusion, administration of gasoline with TBA condensate to rats by whole-body inhalation exposure during the period of organogenesis and fetal growth produced maternal toxicity during the period of dosing at the target concentrations of 10,000 and 20,000 mg/m3 as indicated by decreased food consumption, decreased body weight change, and reduced body weight, and developmental effects at 20,000 mg/m3.

Therefore, the No Observable Adverse Effect Level for maternal toxicity was the target concentration of 2000 mg/m3 and the No Observable Adverse Effect Level for developmental toxicity in this study was established at the target concentration of 10,000 mg/m3.

1-2

INTRODUCTION

This study was conducted to evaluate the developmental toxicity of Gasoline with TBA Vapor Condensate (MRD-00-718) administered 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 23, 2002

Experimental start date

August 31, 2002

Experimental termination date

November 22, 2002

Inlife Test Period

August 26, 2002 to September 27, 2002

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).

2-1

INTRODUCTION (CONT'D)

Justification of Dosing Route

Exposure by inhalation is a likely route of human exposure.

Justification of Dose Selection

The target high dose of 20,000 mg/m3 was selected based on safety concerns as one-half of the Lower Explosive Limit.  It was selected to provide a margin of safety for the laboratory staff yet achieve a high exposure concentration.  The low dose target (2000 mg/m3) was expected to produce a No Observable Adverse Effect Level (NOAEL) 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. 79.60 CFR Vol. 59, No. 122, 27 June 1994.

EPA, United States Environmental Protection Agency, Vehicle Emissions Inhalation Exposure Guideline. 79.61.

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, Jan 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-00-718

Sponsor Identification:	Gasoline with TBA Vapor Condensate

Supplier:			Chevron Research and Technology Company

Lot #:				API 01-07

Description:			Colorless liquid

Storage Condition:		Ambient outdoor conditions under nitrogen

Date Received:		Container numbersa: 	Expiration Date:

March 18, 2002		1A (1 b), 2A (1 b), 3A (1 b),

				4A (1 b)			March 18, 2007

a - Numbers in () are the Supplier's tank identification numbers

b - Large cylinder number

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 was the responsibility of the Sponsor.  This was not completed when the study initiated, but is currently with 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 four of the 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 until after the end of the exposure phase of the study and then transferred to the analytical chemistry laboratory.  The samples were desorbed 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 from the 20,000 mg/m3 target concentration.  The sample was taken using a multistage cascade impactor.  Preweighed glass fiber filters were used to collect aerosol on each stage, which are associated with specific cutoff diameters for aerodynamic particle size in microns.  Since minimal aerosol was present, no further calculations were performed for the aerodynamic diameter, geometric standard deviation, or the estimated percents of the aerosol less than or equal to 1, 10, and 15 microns in size.

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 13, 2002

Shipping Reference Number:		70258477

Quarantine and Acclimation Period

13 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 (12 - 13 weeks old at the initiation of mating) received for mating purposes from a different colony than the females to assure they were not siblings.  The males were received on August 13, 2002.

Age at Initiation of Gestation (Designated GD 0)

Females:	Approximately 13 weeks

Weight at Initiation of Gestation (Designated GD 0)

Females:	231 to 295 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 Nutrition International, LLC (formerly PMI Feeds, Inc.)

			Richmond, Indiana

Analysis:		Performed by PMI Nutrition International, LLC.  Copies of the feed analyses are maintained in the EMBSI Toxicology Laboratory.  The feed analyses were not conducted by 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 De-ionized Water System.

Analysis:		Periodic analysis is the responsibility of the testing laboratory.  A copy of the results is maintained at the testing laboratory.  The 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:		67.1 to 73.7 degrees Fahrenheit

Humidity:		34.7 to 66.7 percent relative humidity

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

Humidity:		45 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:	7.31 to 11.8 foot-candles

Chamber Room Light Intensity:	31.2 to 43.7 foot-candles

Light intensity was measured three times during the study (the first day of exposures, during the second 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:		70.8 to 82.9 db

Oxygen Level:	20.5 to 20.7%

The oxygen level and the noise level were measured in each exposure chamber on the first day of exposures, during the second week of exposures and on the last day of exposures.

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

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 equilibration 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 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 and variations.  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 liver 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 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 were maintained in the EMBSI Toxicology Laboratory Archives until they were returned to the Sponsor’s 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 was 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.

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.  Two alternative models were used: one model considered exposure group, litter size and fetal sex as explanatory variables while the other model used these variables and included the corpora lutea (CL) as an additional 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).

3-10

EXPERIMENTAL DESIGN (CONT'D)

Statistical Analysis (Cont'd)

The number of implants per dam, the litter size per dam, and the dam uterine weight were analyzed by a standard analysis of variance with CL as a covariate.  When the overall effect of exposure, or the interactions of exposure with CL, was statistically significant the exposure groups’ means were tested pairwise vs. the control group using least squares means (Snedecor and Cochran, 1989).

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

Combined Malformations and Variations for Dead Fetuses

Malformations for All Fetuses

Malformations for Alive Fetuses

Malformations for Dead Fetuses

Variations for All Fetuses

Variations for Alive Fetuses

	Variations for Dead Fetuses

	Combined – Delayed Ossification of the Sternabrae (hypoplastic/unossified)

	Combined – Hypoplastic Vertebral Centra (bifid/dumbbell-shaped)

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 dams survived to scheduled terminal sacrifice on GD 21.  At the GD 21 cesarean section two 2000 mg/m3 target concentration animals, two 10,000 mg/m3 target concentration animals, and one 20,000 mg/m3 target concentration animal were found to be not pregnant (i.e. no evidence of implantation sites).

There were no clinical signs indicative of maternal toxicity.  All dams in all dose groups were free of observable abnormalities during the entire gestation period.

GESTATION BODY WEIGHT

Mean Gestation Body Weight and Body Weight Change:  Appendix C

Individual Gestation Body Weight and Body Weight Change:  Appendix C

Statistician’s Report:  Appendix K

Maternal toxicity was evident as statistically significant differences in mean gestation body weight and mean gestation body weight change in the 20,000 mg/m3 target concentration group and the mean gestation body weight change in the 10,000 mg/m3 target concentration group.  Statistically significant decreases in body weight change were evident in the 10,000 mg/m3 and 20,000 mg/m3 target concentration groups for the GD 5–8 interval and in the 20,000 mg/m3 target concentration group for the GD 8-11 interval.  The extent of these decreases also produced statistically significant decreased body weight change for the GD 5-21 and GD 0-21 intervals for the 10,000 and 20,000 mg/m3 target concentration groups.  The reduced body weight gain also produced statistically significant reduced body weights at GDs 8, 11, 14, 17, 20, and 21 for the 20,000 mg/m3 target concentration group.  These changes appear related to reduced food consumption during the same intervals.  However, the effect on late gestation body weight by the statistically significantly reduced gravid uterus weight in 20,000 mg/m3 target concentration group is difficult to determine.  Additionally, linear trends of decreasing mean body weight were detected in the treatment groups for GD 8, GD 11, GD 14, GD 17, GD 20, and GD 21 as well as the GD 21 weights corrected for the uterine weights (GD 21C).  Linear trends or ordered responses to dose of decreasing mean body weight change also were detected in the treatment groups for the GD 5-8, GD8-11, GD 17-20, GD 5-21, GD 0-21, and GD 0 -21C intervals.  Additional analyses were conducted on the uterine weight data that included CL (corpora lutea) count and a CL count by exposure interaction and indicated a statistically significant decrease in the mean uterine weight in the 20,000 mg/m3 target exposure group when analyzed with a CL count by exposure interaction.

4-1

 GESTATION FOOD CONSUMPTION

Mean Gestation Food Consumption:  Appendix D

Individual Gestation Food Consumption:  Appendix D

There was evidence of maternal toxicity during the first half (GD 5-14) of the exposure period as indicated by statistically significant decreases in food consumption at the GD 5-8, GD 8-11, and GD 11-14 intervals for the 10,000 and 20,000 mg/m3 target concentration groups.  The extent of these decreases also produced statistically significant decreases in food consumption at the GD 5-20 interval for the 10,000 and 20,000 mg/m3 target concentration groups and at the GD 0-21 interval for the 20,000 mg/m3 target concentration group.  These decreases generally coincided with the previously noted decreases in body weight and body weight change.  Additionally, linear trends or ordered responses to dose of decreasing mean food consumption were detected in the treatment groups for the GD 5-8, GD 8-11, GD 11-14, GD 5-20, and GD 0-21 intervals.  There were no effects on gestation food consumption for the 2000 mg/m3 target concentration group.

GROSS POSTMORTEM OBSERVATIONS

Incidence of Gross Postmortem Observations:  Appendix E

Individual Gross Postmortem Observations:  Appendix E

The gross postmortem examination of the dams revealed a uterus that exuded thin brown liquid for one 2000 mg/m3 target concentration dam and dilated renal pelves and a calculus in the bladder for one 10,000 mg/m3 target concentration dam.  All other dams were free of grossly observable abnormalities.

4-2

UTERINE IMPLANTATION DATA

Mean Uterine Implantation Data:  Appendix F

Individual Uterine Implantation Data:  Appendix F

Statistician’s Report:  Appendix K

The uterine implantation data revealed a statistically significant decrease in the number of live male fetuses, implantation sites, and corpora lutea in the 2000 mg/m3 target concentration group.  There also was a statistically significant decrease in the number of corpora lutea in the 20,000 mg/m3 group.  The values and level of statistical significance are presented in Table 4-1. The mean number of corpora lutea was one – two less per litter than observed in the control group.  These decreases were not considered related to treatment as ovulation and fertilization occurred prior to exposure to the test substance.  The difference in mean number of corpora lutea per litter alone is sufficient to explain the difference in the mean number of implantations which occurred at the 2000 mg/m3 target concentration group.  There were no statistically significant decreases in the number of live fetuses or increases in the number of resorptions or dead fetuses.  The statistical analyses indicated an ordered response to dose in the treatment groups for the number of implantation sites and the number of corpora lutea (increasing trend for both).

Table 4-1 - Mean Implantation Sites and Corpora Lutea

Target	Implantation sites	Corpora lutea

0 mg/m3	15.68	16.32

2000 mg/m3	13.30*	14.04*

10,000 mg/m3	14.61	14.91

20,000 mg/m3	14.71	15.13*

			* - p( 0.05

FETAL BODY WEIGHT

Mean Fetal Body Weight:  Appendix G

Individual Fetal Body Weight:  Appendix G

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 in any group when analyzed with litter size as a covariate and without allowing for CL count interaction.  When the fetal weight data were analyzed using an exposure by CL count interaction, the mean fetal weights for the 20,000 mg/m3 target exposure group were statistically significantly lower than the control group.  However, because of the complexities of the analyses, it is not clear that the difference is directly linked with exposure.  The mean fetal weights are presented in Table 4-1 and Table 4-2.  Table 4-1 shows the mean fetal weight analysis without CL count interaction.

4-3

FETAL BODY WEIGHT (CONT’D)

Table 4-2

Mean Fetal Weight, the Least Squares Mean Fetal Weight not Considering CL Count

Exposure Group

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

0	25	385	5.29	5.32

2,000	23	302	5.33	5.29

10,000	23	327	5.29	5.29

20,000	24	345	5.13	 5.16

The bodyweight analysis that included CL count and a CL by exposure interaction indicated a statistically significant difference in the mean fetal litter weights among the exposure groups and an exposure by CL count interaction (p<0.0025 and p<0.0005 respectively); the 20,000 mg/m3 exposure group was different from the 0 exposure group (p<0.02).  When the model as fit without the exposure by CL count interaction there was not a significant difference in fetal weights among the exposure groups (p<0.14).  Table 4-2 shows the mean fetal weight and the least squares mean fetal weight with CL count interaction.

Table 4-3

Mean Fetal Weight, the Least Squares Mean Fetal Weight Considering CL Count

Exposure Group

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

with CL*exposure	Least squares fetus mean (gm)

without CL*exposure

0	25	385	16.3	5.29	5.31	5.31

2,000	23	302	14.0	5.33	5.36	5.30

10,000	23	327	14.9	5.29	5.26 	5.29

20,000	24	345	15.1	5.13	 5.15 *	5.16

               * statistically significantly different from control, p<0.02

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 and visceral variations and malformations.

External Observations

The external observations were limited to single or low incidences of stunted fetuses, edema of the head, malrotated hindpaw and protruding tongue.  Single incidences of adactyly, cleft palate, ectrodactyly, hooked tail, microcephaly, and short tail were evident for Fetus 3 of Dam IGL911.

4-4

FETAL OBSERVATIONS (CONT'D)

Visceral Observations

Visceral observations were minimal and were limited to low incidences of umbilical artery arises from left side of the bladder and single incidences of malpositioned kidney and retinal fold.

Skeletal Observations

There were two statistically significant differences between the control and treated groups for the incidence of skeletal observations:

A statistically significant increase in the incidence of rudimentary lumbar ribs in the 20,000 mg/m3 target concentration group that produced a statistically significant increase in total fetuses with skeletal variations in the 20,000 mg/m3 target concentration group.

The incidence of these findings and the historical control range for this parameter are presented in Table 4-3.  While the incidence of total skeletal variations is statistically significantly increased when compared to the concurrent study control, it is only slightly greater than the upper end of the historical control range.  As rudimentary supernumerary ribs may be associated with maternal stress, this increase may be related to the reduced food consumption and reduced body weight changes.  The biological and developmental toxicological significance of the rudimentary supernumerary ribs are discussed further in the Discussion.

Table 4-4 - Percent Incidence of Total Skeletal Variations and Rudimentary Lumbar Ribs*

Observation	Target   0 mg/m3	Target   2000 mg/m3	Target   10,000 mg/m3 Target   20,000 mg/m3

Fetuses with skeletal variations	12.4	13.6	9.1	22.4

Litters with skeletal variations	60	56.5	56.5	83.3

Historical control range of fetuses with skeletal variations 	5.1 - 21.6

Historical control range of litters with skeletal variations	28.0 - 76

Fetuses with rudimentary lumbar ribs 	8.3	7.1	4.8	17.1

Litters with rudimentary lumbar ribs	48.0	34.8	30.4	66.7

Historical control range – Fetuses with rudimentary lumbar ribs	1.7 - 9.7

Historical control range – Litters with rudimentary lumbar ribs 	12.5 - 40.0

* - (number of fetuses with observation/total number of fetuses observed) x 100

4-5

FETAL OBSERVATIONS (CONT'D)

Skeletal Observations (cont'd)

The other skeletal findings included dumbbell shaped thoracic vertebral anlage, and low incidences of unossified sternebrae, asymmetric sternebrae, hypoplastic sternebrae, short last thoracic rib, bifid thoracic vertebral centra, and malformed lumbar vertebral arch.  Single incidences of bifid sternebrae, extra presacral vertebrae, malformed sacral vertebral arch, multiple malformed skull bones, fused sternebrae, multiple absent forepaw bones, multiple absent hindpaw bones, multiple malformed ribs, multiple malformed vertebrae, and fused ribs also were observed.

EXPOSURE DATA AND CHAMBER CONDITIONS

Summary of Exposure Data:  Appendix I

Analytical Chemistry Report:  Appendix J

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 4-5:

Table 4-5 - Mean Exposure Concentrations (Analytical and Nominal)

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

	Analytical	Nominal	Analytical	Nominal	Analytical	Nominal

Mean	2020	1874	10395	9883	20777	18549

S.D.	105.6	118.6	228.5	233.5	394.0	454.3

Minimum	1717	1683	9985	8976	19881	17335

Maximum	2144	2094	10882	10169	21534	19475

	S.D. - Standard deviation

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 4-6.

Table 4-6 - Summary of Chamber Uniformity

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

Mean	1968	10362	20828

S.D.	47.3	370.4	433

CV (%)	2.4	3.6	2.1

Minimum	1910	9845	20415

Maximum	2038	10972	21990

	S.D. - Standard deviation

	CV - Coefficient of variation

The particle size determination for the control chamber and 20,000 mg/m3 target concentration chamber detected particles at a level of 0.5 mg/m3 for each chamber.  These particles were judged to be ambient background particles (e.g. animal dander) and not from the generation of the test substance.

4-6

EXPOSURE DATA AND CHAMBER CONDITIONS

The relative distribution of hydrocarbons and oxygenate measured on the chamber characterization charcoal tubes that were collected each week of the exposures was in good agreement with that measured in the characterization of neat MRD-00-718 test substance.

The oxygen levels in the chambers ranged from 20.5 to 20.7% at the intervals when they were monitored.  The noise level in the chambers ranged from 70.8 to 82.9 db.  The light intensity in the chamber room ranged from 31.2 foot-candles to 43.7 foot candles.

4-7

DISCUSSION

There were slight signs of maternal toxicity, based on the body weight change and the food consumption data.  The food consumption data indicated a statistically significant decrease from GD 5 through GD 14 in the 10,000 and 20,000 mg/m3 target concentration groups.  The body weight change data for these groups reflected the reduced food consumption for the GD 5-8 interval with statistically significant reductions.  However, the body weight change data only shows a statistically significant decrease for the 20,000 mg/m3 target concentration group at the GD 8-11 interval and no statistical significance in any group at the GD 11-14 interval.  After GD 14 the food consumption and body weight change data were essentially the same as the control values, thus indicating that the animals had adapted to exposure to the test substance.  However, the mean body weights of the 10,000 and 20,000 mg/m3 target concentration groups continued to be depressed after GD 14 when compared to the control group due to the toxicity during GD 5 - 14.

There also were decreases in body weight, body weight change, and food consumption in the 2000 mg/m3 target concentration group that were not statistically significant.  The decreases in body weight, body weight change, and food consumption were considered due to the reduced number of fetuses in the 2000 mg/m3group.  The mean uterine weight, the mean GD21 body weight corrected for the uterine weight, and the mean fetal body weight of the 2000 mg/m3 target concentration group support this conclusion.  Additionally, the number of fetuses were not reduced due to maternal or fetal toxicity, but rather due to the number oocytes produced, fertilized, and implanted prior to exposure to the test substance.  The implantation data for the 2000 mg/m3 target concentration group are discussed below.

There were no treatment-related statistically significant differences for uterine implantation data.  There was a statistically significant decrease in the number of male fetuses in the 2000 mg/m3 target concentration group.  However, this decrease was considered spurious as decreases in male fetuses were not evident in the 10,000 and 20,000 mg/m3 target concentration groups and there was no increase in the number of dead or resorbed fetuses in the 2000 mg/m3 target concentration group that could account for this decrease.  There also were decreases in the number of corpora lutea and implantation sites in the 2000 mg/m3 target concentration group and corpora lutea in the 20,000 mg/m3 target concentration group.  However, these decreases were not considered treatment related as the number of corpora lutea was set at ovulation and the subsequent fertilization of the oocytes.  Both ovulation and fertilization occurred prior to exposure of the animals to the test substance.  The number of implantation sites is determined by the number of corpora lutea minus any pre-implantation loss of fertilized oocytes.  As the exposure to the test substance began after implantation, the number of implantation sites would not be affected by exposure to the test substance.  Additionally, the pre-implantation loss for the 2000 mg/m3 target concentration group was not statistically significantly different from the control group and was well within the historical control range of the laboratory.  As the exposures to the test substance began after the number of corporal lutea and implantation sites were set, the decreases in these parameters were not related to treatment.

4-8

DISCUSSION (CONT’D)

The fetal body weight data were subjected to three different statistical analyses.  First the data were analyzed by a mixed model analysis of variance that provides 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.  Two alternative models were used: one model considered exposure group, litter size, and fetal sex as explanatory variables while the other model used these variables and included the corpora lutea (CL) as an additional covariate.  The analyses with the CL by exposure interaction revealed that the fetal body weights were statistically significantly different from the control group in the 20,000 mg/m3 exposure group.  However, because of the complexity of this analysis and the confounding of the CL count it is not clear that exposure is directly linked with the decreased weights.  No other statistically significant differences were noted in the fetal body weights with this test or the other statistical tests.

There were two related fetal observations that were statistically significantly different from the control.  The first observation was an increased incidence of fetuses with skeletal variations in the 20,000 mg/m3 target concentration group.  While the incidence of total skeletal variations is statistically significantly increased when compared to the concurrent study control, it is only slightly greater than the upper end of the historical control range.  The increase in fetuses with skeletal variations in the 20,000 mg/m3 target concentration group was caused by the increased incidence of rudimentary lumbar ribs which is discussed next.

The second observation was an increased incidence of rudimentary lumbar ribs in the 20,000 mg/m3 target concentration group.  These increased incidences were not within the historical control range for this laboratory.  Increases in skeletal variations such as rudimentary ribs are common and often reversible, and it is not clear they represent an adverse effect (Harris and DeSesso, 1994; Kimmel and Wilson, 1973; Khera, 1981).  Furthermore, rudimentary ribs are frequently  considered to be of low concern in the absence of other conventional signs of embryo toxicity, i.e. malformations, embryo lethality, or fetal weight reduction (Aliverti et al., 1979; Khera, 1981; Holson et al., 1976).  Rudimentary ribs have been associated with maternal toxicity or stress (Harris and DeSesso, 1994; Kimmel and Wilson, 1973).  Therefore, the developmental significance of rudimentary ribs in the high dose fetuses may relate to the maternal toxicity observed in the 20,000 mg/m3 target concentration group during the early portion of the exposure phase of this study.

There were no treatment-related statistically significant differences for external observations, and visceral observations in the fetuses on either a fetus or litter basis. Additionally, there were no statistically significant differences in the fetal body weights of either sex.

In conclusion, administration of gasoline with TBA condensate to rats by whole-body inhalation exposure during the period of organogenesis and fetal growth at target concentrations of 10,000 and 20,000 mg/m3 caused maternal toxicity as indicated by decreased food consumption, decreased body weight, and decreased body weight change.

Therefore, the No Observable Adverse Effect Level for maternal toxicity was 2000 mg/m3 target concentration and the No Observable Adverse Effect Level for developmental toxicity in this study was established at the target concentration of 10,000 mg/m3 (conservatively assuming that the minor developmental effects are adverse).

4-9

PROTOCOL EXCEPTIONS

MEAN CHAMBER CONCENTRATION:  The mean chamber concentration for the 2000 mg/m3 target treatment group chamber was 1717 mg/m3 on September 1, 2002.  The mean chamber concentration for the 2000 mg/m3 target treatment group chamber was 1738 mg/m3 on September 17, 2002.  These deviations were due to problems with the rotometer.  Additionally, on September 16, 2002 the 3-hour concentration was 673 mg/m3.  However, this low concentration did not reduce the mean chamber concentration below the acceptable range.  This low concentration probably was due to the same problem with the rotometer that occurred again on September 17, 2002.

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 outside the protocol-defined range.  The decreased temperature also caused the temperature and humidity in the chambers to be outside the protocol-defined range on numerous occasions.    The individual temperature and humidity deviations are noted in Appendix I as bold italicized values.

VIABILITY CHECK:   One viability check was performed on September 2nd, 7th, and 8th 2002. The protocol requires that two viability checks be performed. All animals that were exposed on those days were observed after the exposure. The only animals that were not observed were those not being exposed.

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.

4-10

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

			       *		      **		Mean significantly different from control

								mean

(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

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

F/I Tran		Fetuses/implantation sites transformed

R/I Tran		Resorptions/implantation sites transformed

D/I Tran		Dead/implantation sites transformed

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

Visceral:	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 anomalies that will not allow the fetus to survive beyond parturition.  Malformations are indicated by a capitalized footnote (e.g. "A").

Developmental variations are anomalies that will not affect the postnatal survival of the fetus.  Developmental variations are indicated by a lower case footnote (e.g. "a").

Observations are anomalies that generally are non-specific anomalies such as stunted, pale coloration or discoloration of tissues, etc.  They are indicated by an asterisk (e.g. "*").

Clarification of location of supernumerary ribs (L1 vs T14)

Supernumerary ribs were classified as occurring at L1 if the number of presacral vertebrae was 26.  If an extra presacral vertebra was present and a supernumerary rib was present, the location was recorded as T14.

5-2

REFERENCES

Aliverti, V., Bonanomi, L., Giavini, E., Leone, V.G., and Mariani, L., 1979.  The Extent of Fetal Ossification as an Index of Delayed Development in Teratogenic Studies in the Rat.  Teratology, 20:  237-242.

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.

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.

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.

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.

Harris, S.B. and DeSesso, J.M., 1994.  Practical Guidance for Evaluating and Interpreting Developmental Toxicity Tests, Journal of Hazardous Materials 39: 245-266.

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

6-1

REFERENCES (CONT'D)

Holson, J.F., Jr., Gaylor, D.W., Schumacher, H.F., Collins, T.F.X., Ruggles, D.I., Keplinger, M.L., and Kennedy, G.L., Jr., 1976.  Teratological Evaluation of FD&C Red No. 2 - A Collaborative Government-Industry Study.  V. Combined Findings and Discussion.  J. Toxicol. Environ. Hlth. 1: 875-885.

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

Kimmel, C.A. and Wilson, J.G., 1973.  Skeletal Deviations in Rats:  Malformations or Variations?, Teratology, 8:  309-316.

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, Proposal for Updating Guideline 414, January 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

GD:

	NUMBER

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

IGL897	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL899	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL874	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL857	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL865	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL876	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL880	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL894	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL902	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL891	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL901	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL904	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL910	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL933	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL956	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL920	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL931	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL953	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL869	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL921	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL928	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL952	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL957	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL988	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL969	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

A-1

APPENDIX A - SURVIVAL BAR GRAPH

TARGET DOSE:  2000 MG/M3

ANIMAL

GD:

	NUMBER

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

IGL889	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL893	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL885	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL890	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL863	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL878	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL882	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL911	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL868	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL912	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL913	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL925	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL944	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGL871	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL922	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL951	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL859	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL943	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL948	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL974	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL888	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL976	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL923	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL924	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL905	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

A-2

APPENDIX A - SURVIVAL BAR GRAPH

TARGET DOSE:  10,000 MG/M3

ANIMAL

GD:

	NUMBER

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

IGL870	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL875	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL862	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL858	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL883	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL896	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL906	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL861	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL903	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL914	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL918	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL907	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL909	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL946	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL954	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL955	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL934	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL973	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGL881	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL917	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL940	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL963	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL983	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGL972	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL895	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

A-3

APPENDIX A - SURVIVAL BAR GRAPH

TARGET DOSE: 20,000 MG/M3

ANIMAL

GD:

	NUMBER

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

IGL866	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL892	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL864	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL872	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL873	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL879	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL884	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL886	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL915	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=N

IGL867	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL898	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL929	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL877	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL937	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL950	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL958	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL945	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL967	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL959	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL962	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL949	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL916	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL938	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL961	(21)	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=	=P

IGL970	(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	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25 25

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

10,000 MG/M3	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23 23	23

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	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25	25 25

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

10,000 MG/M3	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23	23 23	23

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

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

B-1

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

DOSE: 0 MG/M3

ANIMAL

NUMBER	 OBSERVATION

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

IGL897

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

IGL899

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

IGL874

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

IGL857

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

IGL865

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

IGL876

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

IGL880

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

IGL894

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

IGL902

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

IGL891

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

IGL901

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

IGL904

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

IGL910

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

B-2

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

DOSE: 0 MG/M3 (CONT'D)

ANIMAL

NUMBER	 OBSERVATION

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

IGL933

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

IGL956

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

IGL920

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

IGL931

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

IGL953

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

IGL869

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

IGL921

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

IGL928

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

IGL952

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

IGL957

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

IGL988

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

IGL969

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

B-3

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

DOSE: 2000 MG/M3

ANIMAL

NUMBER	 OBSERVATION

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

IGL889

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

IGL893

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

IGL885

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

IGL890

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

IGL863

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

IGL878

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

IGL882

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

IGL911

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

IGL868

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

IGL912

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

IGL913

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

IGL925

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

IGL944NP

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

B-4

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

DOSE: 2000 MG/M3 (CONT'D)

ANIMAL

NUMBER	 OBSERVATION

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

IGL871

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

IGL922

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

IGL951

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

IGL859

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

IGL943

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

IGL948

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

IGL974

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

IGL888

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

IGL976

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

IGL923

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

IGL924

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

IGL905NP

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

B-5

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

DOSE: 10,000 MG/M3

ANIMAL

NUMBER	 OBSERVATION

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

IGL870

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

IGL875

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

IGL862

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

IGL858

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

IGL883

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

IGL896

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

IGL906

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

IGL861

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

IGL903

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

IGL914

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

IGL918

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

IGL907

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

IGL909

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

B-6

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

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

ANIMAL

NUMBER	 OBSERVATION

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

IGL946

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

IGL954

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

IGL955

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

IGL934

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

IGL973NP

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

IGL881

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

IGL917

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

IGL940

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

IGL963

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

IGL983NP

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

IGL972

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

IGL895

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

B-7

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

DOSE: 20,000 MG/M3

ANIMAL

NUMBER	 OBSERVATION

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

IGL866

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

IGL892

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

IGL864

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

IGL872

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

IGL873

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

IGL879

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

IGL884

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

IGL886

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

IGL915NP

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

IGL867

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

IGL898

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

IGL929

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

IGL877

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

B-8

APPENDIX B - GESTATION OBSERVATIONS

(INDIVIDUAL GESTATION OBSERVATIONS BY TARGET DOSE)

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

ANIMAL

NUMBER	 OBSERVATION

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

IGL937

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

IGL950

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

IGL958

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

IGL945

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

IGL967

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

IGL959

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

IGL962

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

IGL949

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

IGL916

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

IGL938

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

IGL961

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

IGL970

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

B-9

APPENDIX C - GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE

(MEAN GESTATION BODY WEIGHT AND BODY WEIGHT CHANGE BY TARGET DOSE)

(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-	AL+	A+L+	A+L+	AL+	AL+	AL+	K+J+	AL+

0 MG/M3

MEAN	260.6	293.2	302.9	316.7	330.0	360.1	409.4	428.4	114.3	314.2

STD.DEV.	16.7	18.8	20.3	21.5	23.7	25.8	30.9	33.2	13.0	23.0

(N)	25	25	25	25	25	25	25	25	25	25

2000 MG/M3

	MEAN	261.0	291.3	299.5	311.3	324.1	351.7	394.6	413.5	100.6	312.9

STD.DEV.	14.0	16.7	16.6	19.9	20.6	21.8	29.3	31.5	25.1	17.7

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

10,000 MG/M3

	MEAN	260.3	290.4	294.5	305.6	316.9	346.0	390.9	410.4	105.5	304.9

STD.DEV.	15.8	14.3	15.5	16.6	18.6	19.3	23.0	24.8	10.7	17.8

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

20,000 MG/M3

    *	   **	   **	    *	    *	    *	   **

	MEAN	260.4	288.9	288.9	298.2	309.9	340.0	385.5	404.3	104.1	300.2

STD.DEV.	14.3	13.0	14.7	15.2	15.9	18.0	20.7	22.4	10.7	19.1

(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 AND BODY WEIGHT CHANGE BY TARGET DOSE)

(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	A-L-	K+J+	A+L+	A-L-	A-L-	K-J	A-L-	A+L+	K+J+	A+L+

0 MG/M3

MEAN	32.5	9.8	13.8	13.2	30.2	49.3	19.0	135.3	167.8	53.5

STD.DEV.	8.5	6.1	4.4	4.1	5.3	6.9	4.4	20.3	23.2	15.6

(N)	25	25	25	25	25	25	25	25	25	25

2000 MG/M3

	MEAN	30.2	8.3	11.8	12.8	27.6	42.9	18.9	122.3	152.5	51.9

STD.DEV.	8.5	5.2	5.1	3.5	9.4	12.0	5.9	25.4	29.1	13.3

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

10,000 MG/M3	    *

  *	   *

	MEAN	30.0	4.1	11.1	11.3	29.1	45.0	19.5	120.0	150.0	44.6

STD.DEV.	6.1	3.0	3.1	5.0	5.8	6.3	5.8	13.0	14.8	12.2

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

20,000 MG/M3	  **	  **

	  **	  **	  **

MEAN	28.5	0	9.3	11.8	30.1	45.5	18.8	115.4	143.8	39.8

STD.DEV.	6.1	5.9	3.6	5.4	5.7	6.4	4.6	15.7	15.4	13.9

(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 BY TARGET DOSE)

(GRAMS)

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

IGL897	267	299	301	327	339	375	431	451	318	133

IGL899	237	279	283	292	303	324	370	386	286	100

IGL874	261	297	315	335	354	380	442	467	342	125

IGL857	250	284	288	298	313	344	398	419	298	121

IGL865	238	267	287	303	313	345	400	419	308	111

IGL876	247	274	278	294	308	336	378	394	296	98

IGL880	261	304	318	330	342	373	422	441	320	121

IGL894	249	278	287	303	318	353	410	435	318	117

IGL902	270	313	322	339	357	387	438	454	342	112

IGL891	275	320	326	335	346	381	432	450	330	120

IGL901	263	295	308	323	337	374	424	445	325	120

IGL904	295	346	359	377	400	435	500	522	376	146

IGL910	252	288	300	312	324	353	401	415	297	118

IGL933	250	281	294	302	308	341	383	405	313	92

IGL956	260	287	301	313	326	362	400	415	310	105

IGL920	238	282	293	312	325	347	394	413	300	113

IGL931	234	258	254	267	278	303	336	345	256	89

IGL953	293	317	323	336	349	378	429	457	323	134

IGL869	257	282	287	293	309	332	379	395	293	102

IGL921	269	299	303	312	325	352	395	414	303	111

IGL928	281	307	322	334	354	382	429	443	334	109

IGL952	267	302	313	326	332	357	405	423	316	107

IGL957	284	303	307	324	339	367	418	434	314	120

IGL988	252	284	301	314	320	349	400	420	302	118

IGL969	266	283	303	317	330	373	421	449	334	115

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

IGL889	276	309	324	345	360	380	442	457	345	112

IGL893	281	323	327	347	356	385	443	457	328	129

IGL885	254	273	283	288	295	312	366	387	279	108

IGL890	275	307	313	321	339	370	415	439	326	113

IGL863	274	305	308	319	334	361	410	437	323	114

IGL878	269	313	313	334	349	385	431	456	338	118

IGL882	248	280	286	296	311	344	387	411	297	114

IGL911	235	282	284	295	311	352	392	406	292	114

IGL868	259	290	302	309	323	364	413	436	326	110

IGL912	246	274	285	297	310	340	390	403	295	108

IGL913	265	285	295	305	321	343	379	405	318	87

IGL925	244	278	285	297	309	339	380	403	308	95

IGL944 NP	241	269	271	272	271	284	292	293	NP	2

IGL871	237	265	266	267	279	324	361	384	295	89

IGL922	269	300	315	327	340	375	418	440	328	112

IGL951	264	288	298	306	320	352	397	411	299	112

IGL859	270	289	294	301	315	336	374	394	300	94

IGL943	250	265	287	306	319	350	403	422	320	102

IGL948	257	301	313	329	345	376	425	445	327	118

IGL974	273	296	307	317	324	328	333	337	320	17

IGL888	268	294	301	312	319	340	389	413	299	114

IGL976	261	288	291	307	312	328	349	359	317	42

IGL923	245	273	282	292	306	326	361	377	287	90

IGL924	284	321	330	343	357	379	418	432	330	102

IGL905 NP	286	304	309	306	299	310	312	310	NP	2

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

IGL870	256	288	295	304	315	330	376	402	312	90

IGL875	241	282	288	299	318	344	394	419	304	115

IGL862	237	272	276	283	292	319	366	374	286	88

IGL858	255	288	295	306	324	359	402	424	316	108

IGL883	259	293	296	312	322	353	394	421	312	109

IGL896	267	300	306	319	333	367	411	428	321	107

IGL906	244	277	276	283	286	323	360	385	278	107

IGL861	263	296	304	311	326	356	399	417	310	107

IGL903	269	296	301	311	325	357	412	426	311	115

IGL914	255	285	286	296	298	333	380	401	293	108

IGL918	254	282	281	285	296	328	366	387	286	101

IGL907	279	303	305	315	331	356	413	435	319	116

IGL909	284	311	313	323	334	370	419	437	322	115

IGL946	256	284	285	295	310	342	392	399	293	106

IGL954	286	307	314	324	342	368	418	444	329	115

IGL955	233	265	264	277	289	315	353	372	279	93

IGL934	251	272	276	287	299	331	374	382	276	106

IGL973 NP	263	301	309	316	298	302	299	301	NP	2

IGL881	267	294	300	316	322	359	408	426	316	110

IGL917	270	299	306	320	335	362	413	434	319	115

IGL940	239	263	269	283	284	303	335	351	274	77

IGL963	274	303	311	327	336	363	401	422	321	101

IGL983 NP	271	295	294	296	292	282	274	276	NP	2

IGL972	259	306	312	325	336	363	400	425	329	96

IGL895	290	313	315	328	335	356	405	428	307	121

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

IGL866	258	284	280	292	301	323	372	393	295	98

IGL892	254	292	290	307	318	344	393	409	298	111

IGL864	234	276	268	273	275	296	336	348	262	86

IGL872	231	265	261	267	285	315	359	373	265	108

IGL873	256	286	286	298	308	330	371	398	300	98

IGL879	269	302	291	301	315	350	393	399	267	132

IGL884	258	278	276	286	297	326	364	383	294	89

IGL886	272	302	302	313	333	359	396	416	318	98

IGL915 NP	266	303	303	305	288	291	294	294	NP	2

IGL867	262	295	293	298	311	351	406	431	306	125

IGL898	270	296	311	318	329	365	412	437	329	108

IGL929	265	289	297	298	312	340	386	403	296	107

IGL877	266	287	284	293	310	348	389	411	298	113

IGL937	238	265	261	269	283	316	369	385	281	104

IGL950	262	287	282	291	308	334	367	387	288	99

IGL958	272	288	294	302	312	346	394	416	311	105

IGL945	289	314	318	329	330	364	406	430	324	106

IGL967	266	300	303	317	332	370	426	446	332	114

IGL959	290	318	312	316	333	359	415	429	325	104

IGL962	252	284	283	291	300	321	370	388	292	96

IGL949	253	287	293	302	309	342	389	410	306	104

IGL916	246	273	275	290	303	338	376	396	309	87

IGL938	265	290	289	299	298	331	372	389	295	94

IGL961	263	295	296	308	326	351	405	423	316	107

IGL970	259	280	289	298	310	341	385	402	297	105

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

IGL897	32	2	26	12	36	56	20	152	184	51

IGL899	42	4	9	11	21	46	16	107	149	49

IGL874	36	18	20	19	26	62	25	170	206	81

IGL857	34	4	10	15	31	54	21	135	169	48

IGL865	29	20	16	10	32	55	19	152	181	70

IGL876	27	4	16	14	28	42	16	120	147	49

IGL880	43	14	12	12	31	49	19	137	180	59

IGL894	29	9	16	15	35	57	25	157	186	69

IGL902	43	9	17	18	30	51	16	141	184	72

IGL891	45	6	9	11	35	51	18	130	175	55

IGL901	32	13	15	14	37	50	21	150	182	62

IGL904	51	13	18	23	35	65	22	176	227	81

IGL910	36	12	12	12	29	48	14	127	163	45

IGL933	31	13	8	6	33	42	22	124	155	63

IGL956	27	14	12	13	36	38	15	128	155	50

IGL920	44	11	19	13	22	47	19	131	175	62

IGL931	24	-4	13	11	25	33	9	87	111	22

IGL953	24	6	13	13	29	51	28	140	164	30

IGL869	25	5	6	16	23	47	16	113	138	36

IGL921	30	4	9	13	27	43	19	115	145	34

IGL928	26	15	12	20	28	47	14	136	162	53

IGL952	35	11	13	6	25	48	18	121	156	49

IGL957	19	4	17	15	28	51	16	131	150	30

IGL988	32	17	13	6	29	51	20	136	168	50

IGL969	17	20	14	13	43	48	28	166	183	68

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	5-21	0-21	0-21C

IGL889	33	15	21	15	20	62	15	148	181	69

IGL893	42	4	20	9	29	58	14	134	176	47

IGL885	19	10	5	7	17	54	21	114	133	25

IGL890	32	6	8	18	31	45	24	132	164	51

IGL863	31	3	11	15	27	49	27	132	163	49

IGL878	44	0	21	15	36	46	25	143	187	69

IGL882	32	6	10	15	33	43	24	131	163	49

IGL911	47	2	11	16	41	40	14	124	171	57

IGL868	31	12	7	14	41	49	23	146	177	67

IGL912	28	11	12	13	30	50	13	129	157	49

IGL913	20	10	10	16	22	36	26	120	140	53

IGL925	34	7	12	12	30	41	23	125	159	64

IGL944 NP	28	2	1	-1	13	8	1	24	52	NP

IGL871	28	1	1	12	45	37	23	119	147	58

IGL922	31	15	12	13	35	43	22	140	171	59

IGL951	24	10	8	14	32	45	14	123	147	35

IGL859	19	5	7	14	21	38	20	105	124	30

IGL943	15	22	19	13	31	53	19	157	172	70

IGL948	44	12	16	16	31	49	20	144	188	70

IGL974	23	11	10	7	4	5	4	41	64	47

IGL888	26	7	11	7	21	49	24	119	145	31

IGL976	27	3	16	5	16	21	10	71	98	56

IGL923	28	9	10	14	20	35	16	104	132	42

IGL924	37	9	13	14	22	39	14	111	148	46

IGL905 NP	18	5	-3	-7	11	2	-2	6	24	NP

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

IGL870	32	7	9	11	15	46	26	114	146	56

IGL875	41	6	11	19	26	50	25	137	178	63

IGL862	35	4	7	9	27	47	8	102	137	49

IGL858	33	7	11	18	35	43	22	136	169	61

IGL883	34	3	16	10	31	41	27	128	162	53

IGL896	33	6	13	14	34	44	17	128	161	54

IGL906	33	-1	7	3	37	37	25	108	141	34

IGL861	33	8	7	15	30	43	18	121	154	47

IGL903	27	5	10	14	32	55	14	130	157	42

IGL914	30	1	10	2	35	47	21	116	146	38

IGL918	28	-1	4	11	32	38	21	105	133	32

IGL907	24	2	10	16	25	57	22	132	156	40

IGL909	27	2	10	11	36	49	18	126	153	38

IGL946	28	1	10	15	32	50	7	115	143	37

IGL954	21	7	10	18	26	50	26	137	158	43

IGL955	32	-1	13	12	26	38	19	107	139	46

IGL934	21	4	11	12	32	43	8	110	131	25

IGL973 NP	38	8	7	-18	4	-3	2	0	38	NP

IGL881	27	6	16	6	37	49	18	132	159	49

IGL917	29	7	14	15	27	51	21	135	164	49

IGL940	24	6	14	1	19	32	16	88	112	35

IGL963	29	8	16	9	27	38	21	119	148	47

IGL983 NP	24	-1	2	-4	-10	-8	2	-19	5	NP

IGL972	47	6	13	11	27	37	25	119	166	70

IGL895	23	2	13	7	21	49	23	115	138	17

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

IGL866	26	-4	12	9	22	49	21	109	135	37

IGL892	38	-2	17	11	26	49	16	117	155	44

IGL864	42	-8	5	2	21	40	12	72	114	28

IGL872	34	-4	6	18	30	44	14	108	142	34

IGL873	30	0	12	10	22	41	27	112	142	44

IGL879	33	-11	10	14	35	43	6	97	130	-2

IGL884	20	-2	10	11	29	38	19	105	125	36

IGL886	30	0	11	20	26	37	20	114	144	46

IGL915 NP	37	0	2	-17	3	3	0	-9	28	NP

IGL867	33	-2	5	13	40	55	25	136	169	44

IGL898	26	15	7	11	36	47	25	141	167	59

IGL929	24	8	1	14	28	46	17	114	138	31

IGL877	21	-3	9	17	38	41	22	124	145	32

IGL937	27	-4	8	14	33	53	16	120	147	43

IGL950	25	-5	9	17	26	33	20	100	125	26

IGL958	16	6	8	10	34	48	22	128	144	39

IGL945	25	4	11	1	34	42	24	116	141	35

IGL967	34	3	14	15	38	56	20	146	180	66

IGL959	28	-6	4	17	26	56	14	111	139	35

IGL962	32	-1	8	9	21	49	18	104	136	40

IGL949	34	6	9	7	33	47	21	123	157	53

IGL916	27	2	15	13	35	38	20	123	150	63

IGL938	25	-1	10	-1	33	41	17	99	124	30

IGL961	32	1	12	18	25	54	18	128	160	53

IGL970	21	9	9	12	31	44	17	122	143	38

NOTE: 	NP - ANIMAL NOT PREGNANT	GD  - GESTATION DAY

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)

(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-	A+L+	K+J+	A+L+	A-L-	A-L-	A-L-	A+L+	K+J+

0 MG/M3

	MEAN	117.3	71.6	71.3	71.1	72.9	77.8	23.9	364.8	505.9

STD.DEV.	13.0	8.2	9.3	8.5	7.8	7.5	3.3	37.7	50.5

(N)	25	25	25	25	25	25	25	25	25

	2000 MG/M3

MEAN	116.1	70.6	68.9	70.5	74.3	76.0	23.8	360.3	500.5

STD.DEV.	11.2	6.6	6.7	6.0	11.3	5.9	3.0	28.6	40.2

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

	10,000 MG/M3	   *	   *	   *

   *

	MEAN	116.0	65.6	64.1	65.1	68.8	73.7	23.6	337	476.5

STD.DEV.	10.6	6.1	5.8	6.4	6.2	6.4	3.0	28.3	39.6

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

	20,000 MG/M3	   **	   **	   **

   **	   **

MEAN	114.7	60.3	60.0	63.5	70.3	76.5	23.2	330.6	468.5

STD.DEV.	9.4	4.6	4.6	4.6	6.5	6.7	3.8	20.8	23.5

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

	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

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

IGL897	115	66	72	67	76	84	26

IGL899	114	70	63	60	65	67	21

IGL874	116	78	77	75	75	81	27

IGL857	109	65	69	69	73	77	24

IGL865	101	71	80	66	70	75	23

IGL876	118	68	66	74	76	79	23

IGL880	130	87	87	80	81	83	25

IGL894	107	67	62	73	74	80	29

IGL902	133	83	85	81	78	80	26

IGL891	126	72	70	73	69	80	21

IGL901	111	69	69	69	72	84	23

IGL904	154	91	92	98	95	98	29

IGL910	122	75	65	72	68	73	19

IGL933	102	65	61	64	66	75	26

IGL956	114	67	69	72	74	76	23

IGL920	127	77	73	72	69	75	20

IGL931	93	52	52	52	56	56	16

IGL953	126	72	66	72	66	77	24

IGL869	111	62	61	61	62	70	22

IGL921	139	80	84	74	83	80	24

IGL928	112	69	72	76	76	76	22

IGL952	117	73	76	68	72	80	24

IGL957	115	65	67	69	71	76	22

IGL988	115	75	78	66	71	76	27

IGL969	105	71	67	75	84	88	31

D-2

APPENDIX D - GESTATION FOOD CONSUMPTION

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  2000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD

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

IGL889	123	77	78	74	77	83	25

IGL893	133	79	79	74	79	77	24

IGL885	110	63	64	57	53	66	22

IGL890	130	73	70	75	77	79	27

IGL863	123	73	70	78	74	77	26

IGL878	134	73	74	76	83	82	26

IGL882	104	65	63	65	73	71	23

IGL911	127	74	76	75	89	86	25

IGL868	122	76	69	73	73	80	24

IGL912	107	69	66	70	68	78	21

IGL913	109	69	68	71	69	69	26

IGL925	112	69	67	71	75	76	25

IGL944 NP	100	61	61	58	62	62	22

IGL871	107	57	56	65	110	74	S

IGL922	127	78	76	77	79	79	27

IGL951	108	67	63	72	74	75	23

IGL859	105	66	58	65	64	73	21

IGL943	98	71	69	74	72	83	24

IGL948	125	79	75	72	86	85	26

IGL974	111	72	71	74	67	70	22

IGL888	111	64	64	62	64	71	23

IGL976	110	62	66	60	63	66	28

IGL923	101	64	62	64	63	69	14

IGL924	133	84	81	78	76	79	22

IGL905 NP	117	73	68	59	66	71	20

D-3

APPENDIX D - GESTATION FOOD CONSUMPTION

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  10,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD

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

IGL870	110	67	63	62	64	69	28

IGL875	111	71	67	68	71	71	22

IGL862	107	58	59	59	68	72	21

IGL858	116	68	N	N	72	76	24

IGL883	122	68	69	67	71	74	26

IGL896	124	77	76	81	84	85	27

IGL906	113	62	62	58	69	69	22

IGL861	113	63	60	70	68	73	24

IGL903	117	69	65	71	77	84	22

IGL914	113	59	57	58	63	67	22

IGL918	107	56	55	60	60	66	20

IGL907	119	71	69	68	71	76	26

IGL909	116	62	66	64	69	75	23

IGL946	105	60	56	60	66	71	19

IGL954	137	73	70	71	74	81	30

IGL955	91	56	57	56	58	60	21

IGL934	104	58	58	61	65	69	18

IGL973 NP	109	71	68	55	54	47	19

IGL881	128	66	68	66	74	79	24

IGL917	115	65	66	71	72	84	26

IGL940	110	64	61	56	62	66	21

IGL963	125	71	72	72	76	78	27

IGL983 NP	106	59	56	50	39	40	15

IGL972	135	75	71	69	60	76	26

IGL895	129	70	64	65	68	74	24

D-4

APPENDIX D - GESTATION FOOD CONSUMPTION

(INDIVIDUAL GESTATION FOOD CONSUMPTION)

(GRAMS)

TARGET DOSE:  20,000 MG/M3

ANIMAL	GD	GD	GD	GD	GD	GD	GD

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

IGL866	108	62	58	57	67	68	20

IGL892	124	64	66	63	71	72	19

IGL864	94	63	64	57	56	69	21

IGL872	139	50	53	58	66	71	18

IGL873	112	60	59	57	60	68	25

IGL879	130	62	61	65	74	67	11

IGL884	107	58	59	65	68	76	26

IGL886	120	68	64	67	72	75	25

IGL915 NP	127	66	62	48	53	51	19

IGL867	120	56	54	64	72	80	24

IGL898	119	65	63	66	75	85	25

IGL929	114	60	55	66	70	79	20

IGL877	106	54	61	66	78	77	24

IGL937	105	53	53	58	65	74	25

IGL950	115	53	51	62	69	69	20

IGL958	112	60	60	63	73	81	27

IGL945	124	64	59	62	62	70	24

IGL967	114	62	63	68	81	92	29

IGL959	117	59	58	61	65	81	23

IGL962	110	66	60	69	68	76	24

IGL949	112	66	62	62	69	79	25

IGL916	107	59	63	69	75	85	27

IGL938	117	58	58	57	69	73	23

IGL961	121	60	68	73	82	83	27

IGL970	105	65	68	69	81	86	24

			NOTE:  GD – GESTATION DAY     NP – NOT PREGNANT

			S – NOT MEASURED DUE TO EXCESS SPILLAGE    N – NOT MEASURED DUE TO OVERSIGHT

D-5

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INCIDENCE OF GROSS POSTMORTEM OBSERVATIONS)

	FEMALES

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

TOTAL AT TERMINAL SACRIFICE (A)	25	25	25	25

NO OBSERVABLE ABNORMALITIES	25	24	24	25

UTERUS: Exuded thin brown liquid	0	1	0	0

KIDNEY: Dilated renal pelvis	0	0	1	0

URINARY BLADDER:  White, hard object	0	0	1	0

NO EVIDENCE OF UTERINE

IMPLANTATION SITES	0	2	2	1

E-1

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE:  0 MG/M3

IGL897F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL899F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL874F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL857F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL865F   - 	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL876F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL880F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL894F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL902F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL891F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL901F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL904F  - 	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL910F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL933F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL956F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL920F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL931F  -	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)

IGL953F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL869F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL921F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL928F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL952F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL957F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL988F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL969F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-3

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE:  2000 MG/M3

IGL889F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL893F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL885F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL890F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL863F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL878F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL882F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL911F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL868F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL912F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL913F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL925F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL944F  - 	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

IGL871F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL922F  -	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)

IGL951F  - 	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL859F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL943F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL948F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL974F  -	UTERUS: Exuded moderate amount of thin brown liquid.

IGL888F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL976F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL923F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL924F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL905F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

E-5

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE:  10,000 MG/M3

IGL870F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL875F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL862F  -  	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL858F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL883F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL896F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL906F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL861F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL903F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL914F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL918F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL907F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL909F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL946F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL954F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL955F -	ALL TISSUES AND ORGANS:  No observable abnormalities.

E-6

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE:  10000 MG/M3 (CONT'D)

IGL934F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL973F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

IGL881F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL917F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL940F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL963F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL983F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

IGL972F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL895F  -	KIDNEY: Dilated renal pelvis, Both.

	URINARY BLADDER: Object in bladder, 1.0 x 0.9 x 0.7 cm, white, hard.

E-7

APPENDIX E - GROSS POSTMORTEM OBSERVATIONS

(INDIVIDUAL GROSS POSTMORTEM OBSERVATIONS)

TARGET DOSE:  20,000 MG/M3

IGL866F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL892F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL864F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL872F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL873F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL879F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL884F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL886F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL915F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

	NOTE:  No evidence of uterine implantation sites.

IGL867F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL898F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL929F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL877F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL937F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL950F  -	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)

IGL958F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL945F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL967F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL959F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL962F  -	ALL TISSUES AND ORGANS:  No observable abnormalities

IGL949F  - 	ALL TISSUES AND ORGANS:  No observable abnormalities

IGL916F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL938F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL961F  -	ALL TISSUES AND ORGANS:  No observable abnormalities.

IGL970F  -	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 AND ABBREVIATIONS)

Total	Male	Female

Implantation	Corpora	Total	Fetuses/	Resorptions/

	Live	Fetuses	Fetuses	Resorptions	Sites	Lutea	Dead	Implantation Implantation

FEMALE	K-J-	A+L-Q+	A-L-	A-L-	KJ	KJ+	K-J-	A-L-	A-L-

0 MG/M3

	MEAN	15.36	7.84	7.52	0.28	15.68	16.32	0.04	0.98	0.02

STD.DEV.	1.78	2.1	2.18	0.61	1.82	1.99	0.2	0.04	0.04

(N)	25	25	25	25	25	25	25	25	25

	2000 MG/M3	   **

	      *	        *

	MEAN	13.13	5.91	7.22	0.17	13.30	14.04	0	0.99	0.01

STD.DEV.	3.62	2.37	2.68	0.49	3.66	3.54	0	0.03	0.03

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

	10,000 MG/M3

MEAN	14.22	7.13	7.09	0.39	14.61	14.91	0	0.97	0.03

STD.DEV.	1.98	2.14	2.27	0.58	1.8	1.78	0	0.05	0.05

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

	20,000 MG/M3

	        *

	MEAN	14.38	6.42	7.96	0.29	14.71	15.13	0	0.98	0.02

STD.DEV.	2.12	1.53	2.07	0.55	2.07	2.66	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 AND ABBREVIATIONS)

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

	Implantation	Tran	Tran	Tran	Loss	Loss	Malformations	Variations	Affected

FEMALE	K-J-	A-L-	A-L-	K-J-	K-J-	A-L-	K-J-	AL-	A-L-

0 MG/M3

	MEAN	0	80.49092	9.2078	7.594	3.7	1.9	0.12	1.0	0.4

STD.DEV.	0	4.194734	4.05511	1.6	5.3	3.8	0.44	1.2	0.7

(N)	25	25	25	25	25	25	25	25	25

	2000 MG/M3

MEAN	0	79.880609	10.119957	8.843	5.4	1.2	0.17	1.0	0.3

STD.DEV.	0	5.653898	5.653812	4.763	11.2	3.4	0.83	1.0	1.1

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

	10,000 MG/M3

MEAN	0	79.428044	10.572435	7.562	2.0	2.8	0.13	0.7	0.5

STD.DEV.	0	4.716547	4.716461	0.501	3.2	4.6	0.46	0.7	0.8

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

	20,000 MG/M3

MEAN	0	79.9575	9.704375	7.542	2.3	2.3	0.08	1.6	0.4

STD.DEV.	0	4.151503	3.962848	0.503	4.1	3.8	0.28	1.2	0.6

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

F-2

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  0 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGL897	18	11	7	0	18	18	0	0	2

IGL899	14	7	7	1	15	16	0	0	0

IGL874	17	11	6	0	17	17	0	0	1

IGL857	16	6	10	0	16	16	0	0	0

IGL865	15	4	11	0	15	15	0	1	2

IGL876	14	9	5	0	15	15	1	0	0

IGL880	15	9	6	0	15	16	0	0	1

IGL894	15	7	8	0	15	17	0	0	1

IGL902	15	7	8	2	17	17	0	0	1

IGL891	17	10	7	1	18	18	0	0	2

IGL901	17	5	12	1	18	22	0	0	0

IGL904	19	12	7	0	19	19	0	0	0

IGL910	15	8	7	0	15	16	0	0	1

IGL933	11	6	5	0	11	12	0	0	1

IGL956	14	9	5	0	14	14	0	0	1

IGL920	16	6	10	0	16	18	0	0	0

IGL931	13	9	4	0	13	14	0	0	2

IGL953	18	10	8	0	18	18	0	0	5

IGL869	14	8	6	0	14	16	0	0	0

IGL921	15	6	9	0	15	15	0	0	0

IGL928	14	8	6	0	14	14	0	0	2

IGL952	14	8	6	2	16	17	0	0	0

IGL957	16	4	12	0	16	16	0	0	1

IGL988	15	8	7	0	15	15	0	2	2

IGL969	17	8	9	0	17	17	0	0	0

F-3

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  0 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGL897	83.232	6.768	6.7681

IGL899	75.037	14.963	7.4176

IGL874	83.035	6.965	6.9653

IGL857	82.82	7.181	7.1808

IGL865	82.583	7.418	7.4176

IGL876	75.037	7.418	14.9633

IGL880	82.583	7.418	7.4176

IGL894	82.583	7.418	7.4176

IGL902	69.941	20.06	6.9653

IGL891	76.367	13.633	6.7681

IGL901	76.367	13.633	6.7681

IGL904	83.414	6.587	6.5868

IGL910	82.583	7.418	7.4176

IGL933	81.33	8.671	8.6708

IGL956	82.321	7.679	7.6795

IGL920	82.82	7.181	7.1808

IGL931	82.029	7.971	7.9712

IGL953	83.232	6.768	6.7681

IGL869	82.321	7.679	7.6795

IGL921	82.583	7.418	7.4176

IGL928	82.321	7.679	7.6795

IGL952	69.296	20.705	7.1808

IGL957	82.82	7.181	7.1808

IGL988	82.583	7.418	7.4176

IGL969	83.035	6.965	6.9653

F-4

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  2000 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGL889	14	8	6	0	14	14	0	0	1

IGL893	17	9	8	0	17	17	0	0	2

IGL885	14	6	8	0	14	14	0	0	0

IGL890	15	8	7	0	15	16	0	0	0

IGL863	16	3	13	0	16	16	0	0	3

IGL878	16	11	5	0	16	18	0	0	3

IGL882	16	6	10	0	16	16	0	0	0

IGL911	14	5	9	1	15	15	0	4	3

IGL868	14	6	8	0	14	14	0	0	0

IGL912	15	8	7	0	15	15	0	0	1

IGL913	11	5	6	0	11	11	0	0	0

IGL925	13	6	7	0	13	13	0	0	0

IGL944 NP

	IGL871	11	8	3	0	11	12	0	0	1

IGL922	15	7	8	0	15	18	0	0	0

IGL951	15	7	8	0	15	16	0	0	0

IGL859	12	6	6	2	14	14	0	0	1

IGL943	13	5	8	0	13	13	0	0	1

IGL948	15	7	8	1	16	16	0	0	2

IGL974	1	0	1	0	1	1	0	0	1

IGL888	15	5	10	0	15	16	0	0	0

IGL976	5	3	2	0	5	10	0	0	1

IGL923	12	4	8	0	12	12	0	0	1

IGL924	13	3	10	0	13	16	0	0	1

IGL905 NP

F-5

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  2000 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGL889	82.321	7.679	7.6795

IGL893	83.035	6.965	6.9653

IGL885	82.321	7.679	7.6795

IGL890	82.583	7.418	7.4176

IGL863	82.820	7.181	7.1808

IGL878	82.820	7.181	7.1808

IGL882	82.820	7.181	7.1808

IGL911	75.037	14.963	7.4176

IGL868	82.321	7.679	7.6795

IGL912	82.583	7.418	7.4176

IGL913	81.330	8.671	8.6708

IGL925	82.029	7.971	7.9712

IGL944 NP

	IGL871	81.330	8.671	8.6708

IGL922	82.583	7.418	7.4176

IGL951	82.583	7.418	7.4176

IGL859	67.793	22.208	7.6795

IGL943	82.029	7.971	7.9712

IGL948	75.523	14.478	7.1808

IGL974	60.000	30.000	30.0002

IGL888	82.583	7.418	7.4176

IGL976	77.079	12.921	12.921

IGL923	81.702	8.299	8.299

IGL924	82.029	7.971	7.9712

IGL905 NP

F-6

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  10,000 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGL870	12	6	6	1	13	13	0	0	0

IGL875	16	11	5	0	16	16	0	0	0

IGL862	11	4	7	0	11	12	0	0	0

IGL858	15	6	9	1	16	16	0	0	0

IGL883	16	5	11	1	17	17	0	2	1

IGL896	14	10	4	1	15	15	0	1	2

IGL906	14	7	7	1	15	16	0	0	1

IGL861	14	5	9	0	14	15	0	0	1

IGL903	16	7	9	0	16	16	0	0	2

IGL914	14	8	6	1	15	16	0	0	1

IGL918	14	9	5	0	14	14	0	0	1

IGL907	16	6	10	0	16	17	0	0	1

IGL909	16	6	10	0	16	16	0	0	0

IGL946	15	10	5	0	15	15	0	0	0

IGL954	15	6	9	0	15	16	0	0	2

IGL955	13	5	8	0	13	14	0	0	1

IGL934	14	10	4	0	14	14	0	0	0

IGL973 NP

	IGL881	14	4	10	1	15	15	0	0	1

IGL917	16	8	8	0	16	16	0	0	0

IGL940	9	6	3	2	11	11	0	0	1

IGL963	13	7	6	0	13	13	0	0	1

IGL983 NP

	IGL972	12	7	5	0	12	12	0	0	0

IGL895	18	11	7	0	18	18	0	0	0

F-7

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  10,000 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGL870	73.898	16.102	7.9712

IGL875	82.820	7.181	7.1808

IGL862	81.330	8.671	8.6708

IGL858	75.523	14.478	7.1808

IGL883	75.964	14.036	6.9653

IGL896	75.037	14.963	7.4176

IGL906	75.037	14.963	7.4176

IGL861	82.321	7.679	7.6795

IGL903	82.820	7.181	7.1808

IGL914	75.037	14.963	7.4176

IGL918	82.321	7.679	7.6795

IGL907	82.820	7.181	7.1808

IGL909	82.820	7.181	7.1808

IGL946	82.583	7.418	7.4176

IGL954	82.583	7.418	7.4176

IGL955	82.029	7.971	7.9712

IGL934	82.321	7.679	7.6795

IGL973 NP

	IGL881	75.037	14.963	7.4176

IGL917	82.820	7.181	7.1808

IGL940	64.761	25.240	8.6708

IGL963	82.029	7.971	7.9712

IGL983 NP

	IGL972	81.702	8.299	8.299

IGL895	83.232	6.768	6.7681

F-8

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  20,000 MG/M3

ANIMAL

	NUMBER	Live	Male	Female	Resorp	Implants	CL	Dead	Mal	Var

IGL866	12	5	7	0	12	12	0	1	1

IGL892	15	9	6	0	15	15	0	0	1

IGL864	12	8	4	0	12	12	0	0	1

IGL872	16	5	11	0	16	16	0	0	2

IGL873	13	4	9	0	13	14	0	0	1

IGL879	21	9	12	0	21	25	0	0	2

IGL884	12	7	5	0	12	13	0	0	2

IGL886	13	8	5	1	14	15	0	0	3

IGL915 NP

	IGL867	17	7	10	1	18	19	0	0	1

IGL898	16	7	9	0	16	16	0	0	0

IGL929	15	8	7	0	15	15	0	0	1

IGL877	16	8	8	0	16	16	0	0	1

IGL937	15	7	8	0	15	15	0	0	1

IGL950	14	6	8	0	14	14	0	0	3

IGL958	15	5	10	0	15	16	0	0	0

IGL945	15	4	11	0	15	15	0	0	1

IGL967	15	7	8	2	17	17	0	0	0

IGL959	13	6	7	1	14	14	0	0	3

IGL962	13	7	6	1	14	15	0	0	4

IGL949	14	4	10	0	14	14	0	0	4

IGL916	11	5	6	1	12	12	0	0	1

IGL938	12	5	7	0	13	13	0	1	3

IGL961	15	7	8	0	15	15	0	0	0

IGL970	15	6	9	0	15	15	0	0	2

F-9

APPENDIX F  - UTERINE IMPLANTATION DATA

(INDIVIDUAL UTERINE IMPLANTATION DATA)

(SEE LIST OF ABBREVIATIONS FOR ABBREVIATIONS)

TARGET DOSE:  20,000 MG/M3

ANIMAL 	F/I	R/I	D/I

NUMBER	Tran	Tran	Tran

IGL866	81.702	8.299	8.299

IGL892	82.583	7.418	7.4176

IGL864	81.702	8.299	8.299

IGL872	82.820	7.181	7.1808

IGL873	82.029	7.971	7.9712

IGL879	83.737	6.264	6.264

IGL884	81.702	8.299	8.299

IGL886	74.499	15.501	7.6795

IGL915 NP

	IGL867	76.367	13.633	6.7681

IGL898	82.820	7.181	7.1808

IGL929	82.583	7.418	7.4176

IGL877	82.820	7.181	7.1808

IGL937	82.583	7.418	7.4176

IGL950	82.321	7.679	7.6795

IGL958	82.583	7.418	7.4176

IGL945	82.583	7.418	7.4176

IGL967	69.941	20.06	6.9653

IGL959	74.499	15.501	7.6795

IGL962	74.499	15.501	7.6795

IGL949	82.321	7.679	7.6795

IGL916	73.222	16.779	8.299

IGL938	73.898	7.971	7.9712

IGL961	82.583	7.418	7.4176

IGL970	82.583	7.418	7.4176

NOTE:	NP - ANIMAL NOT PREGNANT

F-10

APPENDIX G - FETAL BODY WEIGHTS

MEAN FETAL WEIGHT AND LEAST SQUARES MEAN FETAL WEIGHT

Exposure Group

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

0	25	385	5.29	5.32

2,000	23	302	5.33	5.29

10,000	23	327	5.29	5.29

20,000	24	345	5.13	 5.16

MEAN FETAL BODY WEIGHTS BY SEX

MALES

FEMALES

	0 MG/M3

	MEAN

5.40

5.17

	STD. DEV.

0.43

0.42

	(N)

25

25

2000 MG/M3

MEAN

5.50

5.19

	STD. DEV.

0.35

0.38

	(N)

22

23

10,000 MG/M3

MEAN

5.41

5.17

	STD. DEV.

0.44

0.33

	(N)

23

23

20,000 MG/M3

	MEAN

5.29

5.01

	STD. DEV.

0.46

0.37

	(N)

24

24

G-1

APPENDIX G - INDIVIDUAL AND MEAN FETAL BODY WEIGHT AND LITTER WEIGHTS

(GRAMS)

TARGET DOSE: 0 MG/M3

ANIMAL

	Litter Weights	Fetus Weight

	NUMBER 	SEX

Litter

	Males	Females

	IGL897	M	5.21	5.11	5.33	5.36	5.42	6.31	5.29	5.22	5.34	5.38	5.33

	95.02

Mean	5.39	5.10

	IGL897	F	4.94	4.94	5.20	5.43	4.91	5.20	5.10

	S.D.	0.32	0.19

	IGL899	M	5.11	5.73	5.61	4.77	5.29	5.05	5.11

	70.89

Mean	5.24	4.89

	IGL899	F	5.08	4.59	4.85	4.99	4.82	4.88	5.01

	S.D.	0.33	0.16

	IGL874	M	5.35	5.84	5.46	5.64	5.34	5.69	5.96	5.59	5.22	5.72	5.04

	91.92

Mean	5.53	5.18

	IGL874	F	5.24	5.47	5.24	5.05	4.88	5.19

S.D.	0.28	0.20

	IGL857	M	5.70	5.41	5.94	5.49	5.54	5.93

88.57

Mean	5.67	5.46

	IGL857	F	5.24	5.32	5.21	5.30	5.32	5.38	5.80	5.70	5.81	5.48

S.D.	0.23	0.23

	IGL865	M	5.31	5.61	5.41	4.90

76.16

Mean	5.31	4.99

	IGL865	F	4.84	4.74	4.98	5.16	4.84	5.39	4.98	5.07	4.72	5.22	4.99