## DRAFT REPORT 

## StudyTitle 

# In Vivo-In Vitro Rat PeripheralLymphocyteSisterChromatid ExchangeAssay Test Substance GasolineDEEVapor Condensate Author Rarnadevi Gudi, Ph.D. CarenM. Brown,M.S. Study Completion

(Pending finalreport) Performing Laboratov BioReliance 9630 Medical Center Drive Rockville, Maryland 20850

Laboratory StudyNumber AA4ONZ. 130.BTL Subcontractor's Sponsor ProiectNumber 00-6130 Subcontractor's Sponsor Huntingdon Life Sciences PrincetonResearch Center (PRC) MettlersRoad East Millstone,New Jersey 08875-2360

Page 1of

## STATEMENTOF COMPLIANCE The SisterChromatid Exchange BioReliance StudyNo. AA40NZ. 130.BTLwas conducted in compliance with 79.60, CFR Vol. 59, No. 122,27June 1994. This studywas performed according to protocol and BioReliance7s Standard OperatingProcedure for Sister Chromatid Exchange Assay with no exceptions.

1

# 4&- Rarnadevi Gudi, Ph.D. Date PrincipalInvestigator BioReliance Gary

## M. Hoffinan, B.A.; D.A.B.T. Date Study Director Huntingdon Life Sciences

BioReliance 

## StudyNo. :

## AA40NZ. 130.BTL 2

# QualityAssurance Statement
Study Title: 

# INVIVO-IN VITRO RAT PERIPHERALLYMPHOCYTE SISTER CHROMATID EXCHANGE ASSAY Study Number: 

## AA40NZ. 130.BTL Study Director: 

## Ramadevi Gudi, Ph.D.
This study has been divided into a series ofin-processphases. Using a random samplingapproach, Quality Assurance monitors each ofthesephases over a series of studies.Procedures, documentation, equipment records, etc., are examined in orderto assure that the studyis performed 

# in accordance with the 

## U.S. FDA Good LaboratoryPractice Regulations (21 CFR 58), 

## the US. EPA GLPs (40 CFR 792 and 40 CFR 160),the UK GLP Regulations, the JapaneseGLP Standard,and the OECD Principles of Good Laboratory Practice and to assurethat the studyis conducted according to the protocol and relevant Standard Operating Procedures.

. 

## The following are the inspection dates,phases inspected, and report datesof QA inspectionsofthis study.
Inspect On 12-Apr-02

# - 12-Apr-02To Study Dir 12-Apr-02To Mgmt 12-Apr-02 Phase Preparation ofcultures Inspect On 05-Aug-02 

# - 06-Aug-02To Study Dir 06-Aug-02To Mgmt 15-Aug-02 Phase Draft Report

This report describes the methods and procedures used in the study and the reported results accurately reflect the raw data ofthe study. 

# 8hdb Joan M. ~l~owan, A.A.S. DATE QUALITY ASSURANCE

## SPONSOR'S QUALITY ASSURANCE STATEMENT Listed below are the dates that this study was inspected by the Quality Assurance Unit of Huntingdon Life Sciences, East Millstone, New Jersey, and the dates that findings were reported to the Study Director and Management. This report reflects the raw data 

# as far as canbe reasonablyestablished. 

## Reported to Date(s) of StudyDirector and Type of Inspection Inspection Management

Date Quality Assurance Auditor

BioReliance

## Study

## No. :

### AA40NZ. 130.BTL

## SIGNATURE PAGE SCIENTIST The following Scientistwas responsible forthe overall conduct ofthis study:

Ramadevi Gudi, PbD. PrincipalInvestigator BioReliance Date



## SCIENTIFICREVIEW The following Scientists have reviewed and approved this report:

David Jacobson-Kram, Ph.D., DABT Vice-president,Toxicology BioReliance 

## Gary

# M. Hofkan, B.A., DABT Study Director HuntingdonLife Sciences

BioReliance 

## StudyNo. :

## AA40NZ. 130.BTL 

## Date

Date

## In Vivo-In Vitro Rat PeripheralLymphocyte Sister ChromatidExchange Assay DRAFT REPORT
Subcontractor's Sponsor:
StudyDirector: PerformingLaboratory:

Test SubstanceI.D.: SponsorProject Number: BioReliance StudyNo. : 

## Experimental Start Date for SCE: Experimental CompletionDate for SCE:

BioReliance Study

## No. :

## AA4ONZ. 130.BTL 6 

## HuntingdonLife Sciences PrincetonResearch Center (PRC) MettlersRoad East Millstone, New Jersey 08875-2360 Gary Hoffman, B.A., DABT BioReliance 9630Medical CenterDrive Rockville, Maryland 20850 GasolineDIPE Vapor Condensate 00-6130 M40NZ.130.BTL April 11,2002 June 24,2002

## TABLE OF CONTENTS Page

SUMMARY

# .......................................................................................................................................................... 8 

### PURPOSE 

# ............................................................................................ 

# -........................................................... 9 

### CHARACTERIZATION OF TEST

## AND CONTROL SUBSTANCES

# ........................................................ 9 

### MATERIAIS AND 

### METHODS

# .................................................................................................................... 9 

### RESULTSAND 

### DISCUSSION

# ....................................................................................................................... 11 CONCLUSION

# .................................................................................................................................................. 12 REF'ERENCES 

# ..................................................................................................................................................13 DATA TABLES

# ........................................................................................................................................... 14



# ................... APPENDIX A: CONTRACTING SPONSOR'S EXPOSURE DATA 

## AND ANIMAL DATA 21



## BioRelianceStudy

## No

## . :

## AA4ONZ

## .130.BTL

## SUMMARY The test substance, Gasoline DIPE Vapor Condensate, was tested in the rat peripheral lymphocytesisterchromatidexchange (SCE) assayfollowing inhalation exposureofrats. Information on test system, experimental design and methodology will be provided by Huntingdon Life Sciences. All in vivo portions of the study, including inhalation exposures were performedby Huntingdon Life Sciences. Rats were exposed by inhalation to negative (air) control, 2,000, 10,000 and 20,000 mg/m3of GasolineDIPE Vapor Condensate for 4 

## weeks (5 days exposureper week). One additional group of animals (5 males and 5 females) was dosed with 

# 5 mgkg of cyclophosphamide 

# (CP, positive control) by intraperitoneal injection 24 hours prior to blood collection. BioReliancepersonnel collected rat blood samples at 24 hours after the end of a 

# 4 week 

# (5 days per week) exposureperiod. Rat blood samples were cultured and processed for the SCE assay at a BioReliance facility. A minimum of25 second divisionmetaphases per animal were scored for SCEs. At least 100consecutive metaphases per animal were scored for the number ofcells in first-, second-, or third-division metaphase for each animal as an indictor of toxicity (cell cycle delay). At least 1000 cells were scored for mitotic index per animal. A Dunnett's t test for multiple comparisons was performed to compare the SCE frequency of test exposure levels to the negative control fiequency. No statistically significant increase in SCE frequency was observed in males or females in any of the groups exposed to Gasoline DIPE Vapor Condensate. Based on the findings of this study, the test substance, Gasoline DIPE Vapor Condensate, was concluded to be negative for the induction of sister chromatid exchanges in rat peripheral lymphocytes.

BioReliance 

## StudyNo. :

### AA4ONZ. 

## 130.BTL

## PURPOSE 

# The purpose of this study was to evaluate the potential of Gasoline DIPE Vapor Condensate to induce SCEs in rat peripheral lymphocytes followinginhalation exposures.
CHARACTERIZATION OF TESTAND 

## CONTROL SUBSTANCES 

# Information regarding test substance and negativecontrol and their characterizations will be provided by Huntingdon Life Sciences. Cyclophospharnide(CP, CAS No. 60%- 19-2, lot number 1 OSHO568, expiration date 30 June 2002, white powder, storage 2-S°C, purity 99.2%), was obtained fiom the Sigma Chemical Company St. Louis, MO (responsible for its characterization) CP was shipped fiom BioReliance on 08 April 2002, received at Huntingdon Life Sciences on 09 April 2002 and was dissolved and diluted in sterile distilled water at Huntingdon Life Sciences to a stock concentration of0.5 mg/mL foruse as thepositive controlforthe SCE study. CP has been characterized 

# as per the Certificate of Analysis on file with the testing facility. The stability of CP and of the CP mixtures used in this assay was demonstrated by acceptable results that met the criteriafor a valid test. MATERIALS AND 

## METHODS TestSystem 

# Information on the test systemwill be provided by HuntingdonLife Sciences. Sister Chromatid ExchangeAssay 

# Peripheral blood lymphocytes were obtained from Sprague-Dawley rats that were exposedwith negative (air) control, 2000, 10,000 and 20,000 mg/m3ofGasolineDIPE Vapor Condensate or positive control (5 mgkg of CP injected 

# IP at 10 mL/kg, 24 hours prior to sacrifice). Animals were anesthetized with isofluraneby inhalation exposure. Blood samples were collected into sodiumheparin tubes fiom the abdominal aortaby BioReliancepersonnel on site at Huntingdon Life Sciences. The blood samples were transported to BioReliance on the dayofcollectionon ice packs. Cell Cultureand Collection

# ofMetaphase Cells 

# Within 24 hours after blood collection, the whole blood samples were cultured in duplicates per animal in 

# RPMI 1640 culture medium with 25 mM 

# Hepes buffer supplemented, 10% fetal bovine serum, antibiotics (pencillin G, 100

# u/mL and streptomycin sulfate, 0.1 mg/mL), 20 PglrnL 

# phytohemagglutinin and an additional 2 

# rnM L-glutamine. Cultures were initiatedby inoculating 0.5 mL of whole blood per 5 mL of complete medium BioReliance 

## Study

## No. :

### AA40NZ. 130.BTL 9

## in T-25 sterile disposable tissue culture flasks and incubated at 37°C. Approximately 21 hours after initiation of the cultures, the cells were exposed to 5 Pg/mL 

## of bromodeoxyuridine (BrdU, Sigma Co., St. Louis, MO). At approximately 68 hours, 0.2 PgIrnL of colcemid was added to each flask and incubated for approximately 4 hours. At approximately 72 hours, the cells were collected by centrifugationat approximately 1200rpm for about 5 minutes. The cell pellet was resuspended in 5 mL 

## 0.075 M KC1 and incubated at 37*1°C for 20 minutes. At the end of the KC1 treatment and immediately prior to centrifbging, the cells were gently mixed and approximately 0.5 mL of fixative (methano1:glacial acetic acid, 3:l vlv) was added to each tube. The cells were collected by centrifugation, the supernatant aspirated, and the cells were fixed with two washes with approximately3-5 mL 

## of fixative and stored in fixativeovernight or longer at approximately 2-8°C. 

## SlidePreparation To prepare slides, the fixed cells were centrifbged at approximately 1200 rpm for 5 minutes, the supernatantwas aspirated, and the cells were resuspended in 1 mL

## fresh fixative. The cells were collected by centrifugation and the supernatant aspirated, leaving 0.1 to 0.3 mL 

## fixative above the cell pellet. One to two drops of the cell suspension was dropped onto a glass slide and allowed to air dry 

## overnight. Slides were identified by the study number, animal number, replicate tube designation and dateprepared. The dried slides were then stained. 

## Slide Staining The slides were stained by using a modified flourescence-plus-Giemsa technique. Hoechst 33258 stain, 5 

## &mL, was prepared fieshby diluting 40 mL ofHoechst 33258 stock stain 50 Pg/mL 

## in distilled water, with 360 mL 

## phosphate buffer, pH 6.8. The slides were stained in Hoechst, 5 PgImL, for 10 minutes, rinsed 

# in deionized water and dried between sheets of bibulous paper. Three drops ofphosphate buffer was placed on each slide and the buffer covered with a coverslip. The slides were then placed on a slidewarmer maintained at approximately 6W2'C and covered with a "Black Ray" lamp with 15 watt tubes for 4-6 minutes. The coverslips were removed, the slides rinsed in deionized water and counterstainedwith 5% Giemsa solution (fieshlyprepared by diluting 20 mL 

## Giemsa in 380 mL 

## deionized water) for 6-10 minutes. The slides were rinsed in deionized water and left to air

# dry. Evaluation ofSCEs Slideswere coded using random numbers by an individualnot involved with the scoring process. Metaphase cells were examined under oil immersion without prior knowledge of treatment groups. Whenever possible, a minimum of 25 second division metaphases per animal were scored for SCEs. At least 100 consecutive metaphase cells were scored for the number of cells in first-, second- or third-division metaphase for each animal as an indicator oftoxicity (cell cycle delay) (BioReliance SOP# OPGT0442 and OPGT0336). At least 1000 cellswere scored for mitotic index per animal.
BioReliance StudyNo. : 

### AA40NZ. 

## 130.BTL 

## 10

## Evaluation of TestResults The number of SCEs per second-divisionmetaphase cell were presented for each group along with the range of SCEsImetaphasefor animals within a group. SCE frequencies as the grand mean 

# * standard deviation were presented for each group. The Average Generation Time (AGT) is estimated as: = 

## Number of hours in BrdU X 100/ [(number 

# MI cells x l)+(number

# Mz cells x 2)+(number M3 

## cells x 3)]. 

## A Dunnett's t test for multiple comparisons was performed to compare the SCE fiequency of test exposure levels to the negative control frequency, and if ~50.05, that exposure level was considered significant. The conclusion of the study was based on the Principal Investigator's evaluation of all the data, including the biological as well as statistical significance. The following criteria were used as guidelines in evaluationofthis study: The test substance was considered positive if an exposure-level responsive and statistically significant increase is observed over a minimum of two exposure levels. A statistically significant increase at the high exposure level with an exposure-level responsive although not statistically significant increase at lower exposure levels was assessed as suspect. A statistically significant increase at one or more exposure levels with no evidence of an exposure level response was assessed as equivocal or as 

## negative according to the magnitude ofthe response and the number ofexposure levels affected. Criteriafor Determination ofa Valid Test The mean SCEs/celVanimal for the positive control animals must be statistically increased relative to the negative control. Deviations No known deviations fiom the protocol or assay-method SOPS occurred during the conduct ofthis study. Archives All raw data, the protocol and all reports generated at BioReliancewill be maintained according to Standard Operating Procedure OPQP3040 by the BioReliance RAQA unit headquartered at: BioReliance, 14920 Broschart Road, Rockville, 

# MD 20850. After submission of the final report, all of the above will be shipped to Huntingdon Life Sciences to be archived. All studymaterials returned to Huntingdon Life Sciences will first be copied and the copy will be retained in the BioReliance archives for a minimum of 10 years. All specimens, such as microscope slides, will be held in storage as long as the quality affords evaluation at BioReliance until the final report is issued in accordance with the relevant Good Laboratory Practice Regulations. RESULTS

# AND DISCUSSION Sister chromatid exchanges involve a symmetrical exchange at one locus, between sister chromatids of the chromosomes. Giemsa method for the differential staining of sister chromatids by Peny and Wolff (1974a) Wolff and Perry (1974) hav made it possible to BioReliance StudyNo. : 

### AA4ONZ. 130.BTL 11 

# $ BIORELIANCE.

## distinguish between sister chromatids. These techniques involve exposing cells to 5-bromodeoxyuridine (BrdU) for at least 2 rounds of replication so that M2 chromosomes consist of one chromatid unifilarly substituted with BrdU and the other bifilarly substituted. The chromatids of such chromosomes stain differentially with Giemsa stain. The observed SCE represents a recombination between DNA helices in the replicating chromosomes and used as a sensitive cytological end point which correlates with DNA damage. The test substance, Gasoline DIPE Vapor Condensate, was tested in the rat peripheral lymphocyte sisterchromatid exchange (SCE) assay following inhalation exposureofrats. Information on test system, experimental design and methodology will be provided by Huntingdon Life Sciences. All in vivo portions of the study, including inhalation exposures, were performedby Huntingdon Life Sciences. Rats were exposed by inhalation to negative (air) control, 2,000, 10,000 and 20,000 mg/m3of Gasoline DIPE Vapor Condensate for 4 weeks (5 days exposureper week). One additional group of animals (5 males and 

# 5 females) was dosed with 5 mgkg cyclophosphamide (CP, positive control) by intraperitoneal injection 24 hours prior to blood collection. Animals dosed at 5 mgkg of CP were used as the positive control group for the SCE assay. BioReliancepersonnel collectedrat blood samples at 24hours after the end ofa 4 week (5 days per week) exposure period. Rat blood samples were cultured and processed for the SCE assay in a BioReliancefacility. A minimum of25 second division metaphases per animal were scored for SCEs. At least 100consecutive metaphases per animal were scored for the number of cells in first-, second-, or third-division metaphase for each animal as an indictor of toxicity (cell cycle delay). At least 1000 cells are scored for mitotic index per animal. The number of SCEs per second-division metaphase cell were presented for each animal (both males and females) in Tables 1 to 5. The number of MI, M2 and 

# M3 cells out of 100 metaphases and the mitotic index out of 1000 cells per animal are also presented in Tables 

# 1 to 5. The range and the average SCEs per animal and the SCE fi-equenciesas the grand meamstandard deviationper group for males arepresented in Table 6 and for females in Table 

# 7. The Average Generation Time (AGT) andthe mitotic index per group for males are presented in Table 

# 6 and for females in Table 

# 7. A Dunnett's t test for multiple comparisons was performed to compare the average SCE fi-equency of test exposure levels to the negative control fiequency. No statisticallysignificant increase in average SCE fiequency was observed in males or females in any groups exposed to Gasoline DlPE Vapor Condensate. The positive control group (5 mgkg) induced statistically significant increases in SCE fi-equency in both males and females. No appreciable difference was observed in AGT and in mitotic index in the test substance groupsrelative to the negative control group. 

## CONCLUSION The positive control fulfilled the requirements for a valid test. Under the conditions of the assay described in this report, based on the findings of this study,the test substance, GasolineDlPE Vapor Condensate, was concludedto be negative for the induction of sisterchromatid exchanges in rat peripheral lymphocytes.
BioReliance Study

## No. :

### AA40NZ. 

### 130.BTL 12

## REFERENCES Evans, 

# H.J. (1976) Cytological methods for detecting chemicalmutagens, 

# in: A. Hollaender (Ed.), Chemical Mutagens, Principles and Methods fortheirDetection,vol. 4. Plenum Press, New York, 

# NY. MTNITAB User's guide 

# 2: data Analysis and Quality Tools, Release 12for Windows@95 WndowsNTTMFebruary 1998Chapter 3: Analysis ofVariance, 3- 1to3-7. Perry P. and Wolff 

# S. (1974a)New Giemsa method for the differential stainingof sister chromatid, Nature (London) 25 1, 156-158 Wolff 

# S. and Perry P. (1974) Differential Giemsa staining of sisterchromatid and the studyof sisterchromatid exchanges without autoradiography. Chromosoma48,341-353

BioReliance Study

## No. :

## AA4ONZ. 130.BTL 13

## TABLE 1 

## Number of Sister Chromatid Exchanges per cell in Negative Air Control Group Air only Male and Female Rats

Number of SCE's Counted 

# I AnimalNumber

1

## Animal numbers 1081-1085 are males 

## and 1591-1595 are females. 2 

## Number ofMI, M2 

## and M3 cells are obtainedfrom 100metaphases.

Mitotic index; number mitotic figures x 100/1000cells countedlanimal.

BioReliance StudyNo. :

## AA4ONZ. 130.BTL

## TABLE 2
Number of Sister Chromatid Exchanges per cell at 2000 mg/m3of Gasoline

## DIPE Vapor Condensate Male andFemale Rats 

# I Number of SCE's Counted 

# I I I Animal Number 

# I



# 'Animal numbers 2071-2075 are males and 2581-2585 are females.

Number ofMI,M2 andM3 cells are obtained from 100metaphases. Mitoticindex; number mitotic figuresx 100/1000cells countedanimal.

BioReliance StudyNo. : 

## AA4ONZ. 130.BTL

## TABLE 3 

## Number of Sister ChromatidExchanges per cell at 10,000 

## mglm3of Gasoline

## DIPE Vapor Condensate Male and Female Rats 

# I Number of SCE's Counted 

# I

I 

### Animal 

## numbers 3071-3075 aremales and 3581-3585are females. 2 

## Number ofMI,

## M2 andM3 cells are obtainedErom 100metaphases.

Mitoticindex; number mitotic figures 

## x 100/1000cellscountedlanimal.

BioRelianceStudyNo. : 

## AA40NZ. 130.BTL

### TABLE 

## 4 Number of Sister Chromatid Exchanges per cell at 20,000 

### mg/m3 of Gasoline DIPE Vapor Condensate Male andFemaleRats 

## Number of SCE's Counted 

# I AnimalNumber CellNo. 4081 4082 4083 4084 4085 4591 4592 4593 4594 4595 1 67103669869 2 991212875867 3 78103958678 4 768510678109

#~lCells 32 35 37 38 30 42 37 30 36 30 #M2Cells 35 36 30 32 35 38 33 34 30 36 #M3Cells 33 29 33 30 35 20 30 36 24 34 Mitotichdex 6.0 3.0 6.0 10.0 6.0 3.0 8.0 4.0 9.0 6.0
1

## Animal numbers 4081-4085 are males and4591-4595 are females. 2 

## Number ofMI,M2 andM3 cells are obtainedfrom 100metaphases. Mitotic index; numbermitotic figures x 100/1000cells counted/animal.

BioReliance StudyNo. :

## AA40NZ. 130.BTL

### TABLE 

## 5 Number of Sister Chromatid Exchangesper cell at 

## 5

## mgkg Cyclophosphamide Male and Female Rats 

## Number of SCE's Counted



# 'Animal numbers 505 1-5055 are males and 5561-5565 are females. 2 

## Number ofMI, M2 and M3 cells are obtained from 100 metaphases.

Mitotic index; number mitotic figures x 100/1000cells countedlanimal.

BioReliance StudyNo. :

## AA40NZ. 130.BTL

### TABLE 

## 6 Summary of Sister Chromatid Exchange Data 

## -Gasoline DIPE Vapor Condensate Male Rats
Total Range of # 

### of # 

### of SCEs Mean Group Group Treatment Animal Metaphases SCEsper per Animal SCEs Range Mean # 

### Scored Animal Min Max per cell Min Max 

# + Std. Dev.* Air 

## 1081 25 1082 25 1083 25 1084 25 1085 25 GasolineDIPE Vapor Condensate 

## 2000mg/rn3 

## 2071 25 2072 25 2073 25 2074 25 2075 25 GasolineDIPE Vapor Condensate 

## 10,000mg/m3 

## 3071 25 3072 25 3073 25 3074 25 3075 25 GasolineDIPE Vapor Condensate 

## 20,000rng/m3 

## 4081

. 

## 25 4082 25 4083 25 4084 25 4085 25 Cyclophosphamide 

## 5 mg/kg 

## 505 1 25 5052 25 5053 25 5054 25 per per per 4nimal Group Group



# * The standard deviationwas calculatedusing the data of all 

## 125metaphases scored. 

## $ =

### Dunnett's t test 

## (p 50.05) Mitotic Index: (Numberof cells in mitosis out of 

## 1000cells) AGT=Averagegenerationtime: Number ofhours in BrdU X 

## 1001(numberMIcellsx l)+(numberM2 cells

## x 2)+(numberM3 cellsx 

## 3)

BioReliance StudyNo. :

## AA4ONZ. 130.BTL

### TABLE 

## 7 Summary of Sister Chromatid ExchangeData 

## -GasolineDIPE Vapor CondensateFemaleRats SisterChromatidExchange data Total Range of

Air 1591 25 1592 25 1593 25 1594 25 1595 25 GasolineDIPE Vapor Condensate 2000 mglm3 

## 258 1 25 2582 25 2583 25 2584 25

. 

## 2585 25 GasolineDIPE Vapor Condensate 10,000mg/m3 

## 3581 25 3582 25 3583 25 3584 25 3585 25 Gasoline DIPE Vapor Condensate 20,000mg/m3 

## 4591 25 4592 25 4593 25 4594 25 4595 25 

## &T MI # 

## of # 

## of SCES Mean Group Group Treatment Animal Metaphases SCEsper per Animal SCEs Range Mean # 

## Scored Animal Min Max per cell Min Max 

# +Std. Dev.*

Cyclophosphamide 5 mgk 

## 5561 25 576 18 

## - 31 23.0 5562 25 651 20 

## - 33 26.0 5563 25 522 18 

## - 28 20.9 18 to 40 24.3$ f 

## 4.3 5564 25 609 18 

## - 30 24.4 5565 25 679 19 

# - 40 27.2 per per per Animal Group Group



# * The standard deviationwas calculatedusing the 

## data of

## all 125metaphases scored. $ =

## Dunnett's t test @ 

## 10.05) MitoticIndex: (Numberof cells in mitosis out of 1000cells) AGT=Average generationtime: Number ofhours inBrdU

## X 1001(numberMIcellsx l)+(numberM1 cellsx 2)+(numberM3 cellsx 3)

BioReliance StudyNo. :

## AA4ONZ. 130.BTL 20

## AppendixA: 

## Contracting Sponsor's ExposureData and Animal Data



## BioReliance Study

## No. : 

## AA4ONZ. 130.BTL 2

### 1

## Huntingdon Life Sciences 00-6130 Page 1 - 

## 211-DIPE-S Draft Final Report Animal Exposure and Animal Data Preface 

# I Appendix A 

# I INTRODUCTION: The following is data generated at Huntingdon Life Sciences,East Mdlstone, NJ. The separately issued main studyreport should be referencedfor details of the procedures used for test atmosphere 

## generation/characterization and animal evaluations. 

# STUDY DATES: Date of Animal Receipt: 4 March 2002 Experimental Initiation Date: 15March 2002 (in-life) ExperimentalCompletion Date: 11April 2002 (in-life) Draft ReportDate: 

## 6March 2003 

# EXPOSURES AND IN-LIFE SUMMARY: The actual measured results during the exposures were comparable to the targeted exposure levels. There were no exposurerelated effects seen in the test animals with regards to body weights and feed consumption. 

# TABLE OF CONTENTS TABLES A. Chamber Monitoring Results

# ...........................................................................................



# .................................................................................. B. Summaryof Clinical Observations C. Mean Body Weights (grams) 

# ...........................................................................................

........................................................ D. Mean Body Weight ChangefromBaseline (grams)



# ............................................................ E. Mean Feed ConsumptionValues (gramslkglday) F. Individual Clinical Observations 

# .....................................................................................

.................................................................................... G. IndividualBody Weights (grams)



# ................................................. H. IndividualBody Weight Change from Baseline (grams)



# .................................................... I. Individual Feed Consumption Values (gramskglday). J. Animal TerminationHistory 

# ............................................................................................

### Table A GASOLINE DlPEVAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS 00-61 30 

### PAGE 1



### Date Exposure Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 

### Mean S.D. 

### Chamber Monitoring Results Cumulative Exposure Record Group IA 

## - 0 

### mglm3(Air Control)
Nominal (mglm3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

### Mean (mg/m3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

### Analvtical Chamber Concentration Individual MMAD Cum) 0.9053

2.495

2.357

2.187

1.986 0.731 

### Particle Size Determinations GSD TMC (mglm3) 1.20E-02

4.91E-03

7.60E-03

2.32E-03

6.71E-03 4.13E-03 

### Chamber l\i 

### Tem~eraturs wironment InHumiditvTable A GASOLINE DlPE VAPOR CONDENSATE:A 13-WEEK WHOLE-BODY INHALATIONTOXICITY STUDY IN RATS 00-61 30 PAGE 2

Date Ixposure Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean S.D. Chamber Monitoring Results Cumulative Exposure Record Group 

### I9 

## - 0 mg/m3(Air Control)
Nominal (mg/m3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 Mean (mg/m3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 alytical Chamber Concentration Individual MMAD Olm) 0.9933

3.236

1.240

2.023

1.873 1.OO9 Particle Size ?terminal

GSD 1s TMC (mg1m3) 1.41E-02

3.65E-03

4.86E-03

2.81E-03

6.36E-03 5.23E-03 Chamber 

### I M remperature ("C) 23 26 24 24 24 24 24 24 23 24 24 24 24 24 24 24 24 24 24 24 24.0 0.6 ~vironment inHumidity 

# ("4 55 53 5 1 55 53 53 58 54 55 54 58 56 52 56 53 56 56 52 56 55 54.6 1.9Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS

Date Exposure Number

~ -- - 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean S.D. Chamber Monitoring Results Cumulative Exposure Record

Group IIA 

### - 2,000 mg/m3
Nominal (mg/m3)

2160 2190 2190 2160 2130 2180 2050 2090 2030 2170 21 10 2110 2090 2030 2130 2060 2220 1980 2040 2050 2109

67 1 Mean (mgfm3)

1968 2068 2205 2095 2040 2108 1913 1918 1913 2133 2090 2028 1843 1845 1875 2093 2150 1950 1938 1955 alytical Chamber Concentration Individual MMAD bm) 0.794

3.91 1

0.8422

1.438

1.746 1.473 Particle Size !terminai

GSD 1s TMC (mgfm3) 1.19E-02

4.72E-03

4.56E-03

1.53E-03

5.68E-03 4.40E-03 Chamber 

### M Temperature ("'4 23 26 23 23 23 23 23 23 24 24 24 24 24 23 23 23 23 23 24 24 23.5 0.8 00-61 30 PAGE 3

vironment nHumidity (%) 50 50 48 50 49 50 54 5 1 48 48 52 50 47 52 48 51 51 48 47 49 49.7 1.8Table A GASOLINE DlPEVAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS

Date Exposure Number 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean Chamber Monitoring Results Cumulative Exposure Record

Group IIB 

## - 2,000 mglm3
Nominal (mglm3)

2160 2190 2190 2160 2130 2180 2050 2090 2030 2170 21 10 21 10 2090 2030 2130 2060 2220 1980 2040 2050 2109

67 Analytical Chamber Concentration Mean 

## I Individual MMAD Olm) 0.8998

0.9819

0.8897

1.403

1.044 0.243 Particle Size Determinations GSD TMC (mglm3) 1.47E-02

1.76E-03

5.04E-03

1.74E-03

5.81E-03 6.13E-03 00-6130 PAGE 4

Chamber Environment Mean

### Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 00-61 30 

### PAGE 5 

### WHOLE-BODY INHALATION TOXICITY STUDY IN RATS

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

### Mean Chamber Monitoring Results Cumulative Exposure Record

Group IIIA

## - 10,000 

### mg/m3 

# I Nominal (mg/m3)

9980 9530 10000 10200 10100 10300 9370 9690 9940 9390 9540 9670 9830 10000 10600 10000 9470 10000 9880 101 00 

### 9880 321 

### Analvtical Chamber Concentration GSD Particle Size Determinations Mean 

## I Individual TMC (mg/m3) 2.41 E-02

2.91 E-03

5.54E-03

1.78E-03



### 8.58E-03 1.05E-02 MMAD Chamber Environment Mean Temperature ("C)

24 23.6 

### 0.8 Humidity 

### ("A)

49 

### 48.7 1.1

### Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 00-61 30 PAGE 6 WHOLE-BODY INHALATION TOXICITY STUDY IN RATS Chamber Monitoring Results Cumulative Exposure Record

Group lllB -10,000 mg/m3
Date Number

56 9-Apr-02 57 10-Apr-02 20 10100 10780 Mean 9880 S.D. 321 alytical Chamber Concentration Individual Chamber Environment inHumidity 

# ("w 49 49 46 46 46 46 46 45 46 46 46 47 44 47

' 

### 46

45 45 45 48 46 46.2 1.3 Particle Size 

### ns TMC

(m9/m3) 2.44E-02

5.14E-03

5.49E-03

3.29E-03

9.58E-03 9.93E-03 

## I Temperature ("C)

23 23.8 0.7Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS Chamber Monitoring Results

Exposure Number Day
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean Date

S.D. Cumulative Exposure Record Group IVA 

### - 20,000 mg/m3
Nominal

# 1 Mean , alytical Chamber Concentration Individual Particle Size Determinations TMC (m9/m3) 2.44E-02

4.30E-03

7.67E-03

1.09E-03

9.37E-03 1.04E-02 MMAD Olm) 0.7739

2.346

0.8053

1.220

1.286 0.735 Chamber Environment
GSD

1.949

3.191

2.004

1.549

2.173 0.708 Temperature 

### ("C) 25 28 25 24 24 25 25 25 25 25 25 26 26 25 24 24 24 25 25 26 25.1 0.9 00-61 30 PAGE7

InHumidity 

## ("4 52 52 48 5 1 50 50 5 1 49 49 49 48 49 47 50 52 50 50 49 50 5 1 49.9 1.4

### Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 

### WHOLE-BODY INHALATION TOXICITY STUDY IN RATS Chamber Monitoring Results

Number

16-Mar-02

57 

# 1 10-Apr-02 

# 1 20 

### Mean Cumulative Exposure Record Group IVB

## - 20,000 

### mglm3
Nominal (mglm3) 191 00 19400 19000 19300 19800 19000 19500 19300 19300 19600 18400 18600 18700 18900 18800 18900 19100 18800 17600 19700 19040 504 

### Particle Size I Mean (mg/m3) 20430 20680 20980 20580 20800 20730 20750 21030 19850 20380 19930 19650 18930 18830 19250 19900 19700 19880 18230 20350 

### Chamber Environment Mean alytical Chamber Concentration Individual MMAD Olm) 0.7578

0.9018

0.7779

1.517

0.989 0.358 

### Humidity ("h) 5 1 52 49 50 49 49 50 48 5 1 50 50 50 48 49 50 49 48 48 52 50 49.7 1.2 00-61 30 

### PAGE 8Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE B GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS MALES SUMMARY OF CLINICAL OBSERVATIONS

------------------------------------------------------------------------.---------------------------------------------------------- DAY OF STUDY GROUP# -4 27 TOTAL

NORMAL WITHIN NORMAL LIMITS

DEAD TERMINAL SACRIFICEHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE B GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS FEMALES SUMMARY OF CLINICAL OBSERVATIONS

-------------------------------------------------.--------------------------------------------------------------------------------- DAY OF STUDY GROUP# -4 27 TOTAL

................................................................................................................................... # OF ANIMALS EXAMINED 155 255 355 455 5 5 5

NORMAL WITHIN NORMAL LIMITS

DEAD TERMINAL SACRIFICEHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE C GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS MALES MEAN BODY WEIGHTS (GRAMS)

................................................................................................................................... DOSE GROUP: 1 2 3 4 5 DOSE LEVEL (MG/M3): 0 2000 10000 20000 SCE+CONTROL

---------------------------------------------------------------------------------------------------------.------------------------- WEEK 0 MEAN S.D.

N WEEK 1 MEAN S.D.

N MEAN S.D.

N WEEK 2

WEEK 3 MEAN S.D.

N WEEK 4 MEAN 350 349 346 S.D. 6.3 16.5 16.4

N 5 5 5

.......................................................................................... No statistically significant differencesHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE C GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS FEMALES MEAN BODY WEIGHTS (GRAMS)

................................................................................................................................... DOSE GROUP: 1 2 3 4 5 DOSE LEVEL (MG/M~) : 0 2000 10000 20000 SCEtCONTROL

................................................................................................................................... WEEK

WEEK

WEEK

WEEK

WEEK MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE D GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS MALES MEAN BODY WEIGHT CHANGE FROM BASELINE (GRAMS)

------------------------------------------------------------.---------------------------------------------------------------------- DOSE GROUP: 1 2 3 4 5 DOSE LEVEL (MG/M~) : 0 2000 10000 20000 SCE+CONTROL

................................................................................................................................... WEEK 0 TO 1

WEEK 0 TO 2

WEEK 0 TO 3 MEAN S.D.

N MEAN S.D.

N MEAN S.D.
WEEK 0 TO 4 MEAN 225 225 S.D. 12.4 22.3

N 5 5

............................................................................... No statistically significant differencesHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE D GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

WEEK 0 TO 1 MEAN S.D.

N WEEK 0 TO 2 MEAN S.D.

N WEEK 0 TO 3 MEAN S.D.

N WEEK 0 TO 4

-----------------------------. MEAN S.D.

N No statistically significant differencesHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE E GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

WEEK 1 MEAN S.D.

N WEEK 2 MEAN S.D.

N WEEK 3 MEAN S.D.

N WEEK 4 MEAN S.D.

N No statistically significant differencesHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE E GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

WEEK 1

WEEK 2

WEEK 3 MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N

No statistically significant differencesHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS MALES GROUP 1 0 MG/M3

1081 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1082 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1083 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1084 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1085 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS MALES GROUP 2 2000 MG/M3

ANIMAL# OBSERVATIONS DAY OF - 2 STUDY 4 7
2071 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2072 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2073 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2074 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2075 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 3 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS MALES GROUP 3 10000 MG/M3

3071 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3072 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3073 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3074 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3075 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S

MALES GROUP 4 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS 00 MG/M3 PAGE 4

4081 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4082 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4083 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4084 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4085 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 5 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS MALES GROUP 5 SCE+CONTROL

................................................................................................................................... ANIMAL# OBSERVATIONS DAY OF 

### - 2 STUDY 4 7
5051 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5052 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5053 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5054 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5055 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 6 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS FEMALES GROUP 1 0 MG/M3

ANIMAL# OBSERVATIONS DAY OF - 2 STUDY 4 7
1591 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1592 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1593 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1594 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 1595 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 7 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

2581 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2582 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2583 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2584 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 2585 WITHIN NORMAL LIMITS TERMINAL SACRIFICE CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 8 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS FEMALES GROUP 3 10000 MG/M3

ANIMAL# OBSERVATIONS DAY OF 

### - 2 STUDY 4 7
3581 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3582 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3583 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3584 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 3585 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 9 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

4591 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4592 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4593 WITHIN NORMAL LIMITS ' TERMINAL SACRIFICE 4594 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 4595 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 10 TABLE F GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL CLINICAL OBSERVATIONS FEMALES GROUP 5 SCE+CONTROL

................................................................................................................................... DAY OF - 2 ANIMAL# OBSERVATIONS STUDY 4 7

................................................................................................................................... 5561 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5562 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5563 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5564 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 5565 WITHIN NORMAL LIMITS TERMINAL SACRIFICE CODE: 1-SLIGHT 2-MODERATE 3-MARKED P-PRESENTHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 3 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHTS (GRAMS) MALES GROUP 3 10000 MG/M3

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 4 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

WEEK OF STUDY ANIMAL# 0 1 2 3 4

...................................................................................................................................

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 5 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHTS (GRAMS) MALES GROUP 5 SCE+CONTROL

...................................................................................................................................

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 6 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHTS (GRAMS) FEMALES GROUP 1 0 MG/M3

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 7 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

WEEK OF STUDY ANIMAL# 0 1 2 3 4

...................................................................................................................................

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 8 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHTS (GRAMS) FEMALES GROUP 3 10000 MG/M~

................................................................................................................................... WEEK OF STUDY ANIMAL# 0 1 2 3 4

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 9 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHTS (GRAMS) FEMALES GROUP 4 20000 MG/M3

-------------------------------------------.--------------------------------------------------------------------------------------- WEEK OF STUDY ANIMAL# 0 1 2 3 4

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 10 TABLE G GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

WEEK OF STUDY ANIMAL# 0 1 2 3 4

----------------------..-----------------------------------------------------------------------------------------------------------

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 3 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) MALES GROUP 3 10000 MG/M3 WEEK OF STUDY ANIMAL# 0-1 0-2 0-3 0-4

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 4 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) MALES GROUP 4 20000 MG/M3

-----------------------------------------------------------------------------------------.----------------------------------------- WEEK OF STUDY ANIMAL# 0-1 0-2 0-3 0-4

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 5 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) MALES GROUP 5 SCE+CONTROL

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 6 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) FEMALES GROUP 1 0 MG/M3

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 7 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMLJNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) FEMALES GROUP 2 2000 MG/M3

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 8 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) FEMALES GROUP 3 10000 MG/M3

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 9 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) FEMALES GROUP 4 20000 MG/M3

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 10 TABLE H GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) FEMALES GROUP 5 SCE+CONTROL

................................................................................................................................... WEEK OF STUDY ANIMAL# 0-1 0-2 0-3 0-4

...................................................................................................................................

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S

MEAN S.D.

N TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS PAGE 1

--------------------------------.-------------------------------------------------------------------------------- WEEK OF STUDY

1 2 3 4Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) MALES GROUP 2 2000 MG/M3

................................................................................................................................... WEEK OF STUDY ANIMAL# 1 2 3 4

----------------------------.------------------------------------------------------------------------------------------------------ 2071 131 106 93 83 2072 138 123 105 91 2073 136 120 99 89 2074 131 110 95 81 2075 145 126 111 9 9 MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 3 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 4 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) MALES GROUP 4 20000 MG/M3

................................................................................................................................... WEEK OF STUDY ANIMAL# 1 2 3 4

MEAN 

### s .D'.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 5 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) MALES GROUP 5 SCE+CONTROL WEEK OF STUDY

1 2 3 4

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 6 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 7 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

MEAN S.D.

NSF=Spilled FeederHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 8 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) FEMALES GROUP 3 10000 MG/M3



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MEAN S.D.

NSF=Spilled FeederHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 9 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) FEMALES GROUP 4 20000 MG/M3

................................................................................................................................... WEEK OF STUDY ANIMAL# 1 2 3 4

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 10 TABLE I GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) FEMALES GROUP 5 SCE+CONTROL

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY MALES GROUP 1 0 MG/M3

................................................................................................................................... TYPE OF DATE OF WEEK OF STUDY ANIMAL# DEATH DEATH STUDY DAY

...................................................................................................................................Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 2 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY MALES GROUP 2 2000 MG/M3

-------------------------------------------------------------.--------------------------------------------------------------------- TYPE OF DATE OF WEEK OF STUDY ANIMAL# DEATH DEATH STUDY DAY

................................................................................................................................... 2071 TERMINAL SACRIFICE 11-APR-02 4 27 2072 TERMINAL SACRIFICE 11-APR-02 4 27 2073 TERMINAL SACRIFICE 11-APR-02 4 27 2074 TERMINAL SACRIFICE 11-APR-02 4 27 2075 TERMINAL SACRIFICE 11-APR-02 4 27Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 3 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY MALES GROUP 3 10000 MG/M3 TYPE OF

DEATH DATE OF WEEK OF STUDY DEATH STUDY DAY 3071 TERMINAL SACRIFICE 3072 TERMINAL SACRIFICE 3073 TERMINAL SACRIFICE 3074 TERMINAL SACRIFICE 3075 TERMINAL SACRIFICEHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 4 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY MALES GROUP 4 20000 MG/M3

---------------------------------------------------------------------------------.------------------------------------------------- TYPE OF DATE OF WEEK OF STUDY ANIMAL# DEATH DEATH STUDY DAY

--------------------.---.------------------------------------------------.--------------------------------------------------------- 4081 TERMINAL SACRIFICE 11-APR-02 4 27 4082 TERMINAL SACRIFICE 11-APR-02 4 27 4083 TERMINAL SACRIFICE 11-APR-02 4 27 4084 TERMINAL SACRIFICE 11-APR-02 4 27 4085 TERMINAL SACRIFICE 11-APR-02 4 27

...................................................................................................................................Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 5 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY MALES GROUP 5 SCE+CONTROL TYPE OF

DEATH DATE OF WEEK OF STUDY DEATH STUDY DAY TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE

--------------.--------------------------------Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 6 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS

TYPE OF DATE OF WEEK OF STUDY ANIMAL# DEATH DEATH STUDY DAY

...................................................................................................................................Huntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 7 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY FEMALES GROUP 2 2000 MG/M3

2581 TERMINAL SACRIFICE 2582 TERMINAL SACRIFICE 2583 TERMINAL SACRIFICE 2584 TERMINAL SACRIFICE 2585 TERMINAL SACRIFICEHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 8 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTSHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 9 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY FEMALES GROUP 4 20000 MG/M3

-----------------------------------------------------------------------------------------.----------------------------------------- TYPE OF DATE OF WEEK OF STUDY ANIMAL# DEATH DEATH STUDY DAYHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 10 TABLE J GASOLINE DIPE VAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS WITH NEUROTOXICITY ASSESSMENTS AND 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS ANIMAL TERMINATION HISTORY FEMALES GROUP 5 SCE+CONTROL

-------------------------.-------------------------------------------------------------------------.------------------------------- TYPE OF DATE OF WEEK OF STUDY ANIMAL# DEATH DEATH STUDY DAY

................................................................................................................................... 5561 TERMINAL SACRIFICE 11-APR-02 4 27 5562 TERMINAL SACRIFICE 11-APR-02 4 27 5563 TERMINAL SACRIFICE 11-APR-02 4 27 5564 TERMINAL SACRIFICE 11-APR-02 4 27 5565 TERMINAL SACRIFICE 11-APR-02 4 27