## Huntingdon Life Sciences(ERC) ReportNo: 

## APT 

## 0091023700

Study 

## Tirle SATELLITE

## PROCEDUXE GASOLINE

## DIPEVAPOR CONDENSATE 

## RATMICRONUCLEUSTEST

TEST 

## GUIDELINES:

## US EPA Micronucleus Assay 

## 79.64, CFR Vol. 

## 59, No. 

## 122,27June 

## 1994. US EPA 

## (1998) Health 

## Effects Test Guidelines; 

## OPPTS 870.5395

## MammalianErythrocyte Micronucleus Test.
AUTHOR: 

## Christine

## E.Mason, B.Sc. 

## (Hons.)

SUBCONTRACTOR: 

## Huntingdon Life SciencesLtd., 

## Eye Research Centre (ERC) 

## Eye, Suffolk 

## IP23 

## 7Px ENGLAND.

HUNTINGDON SCIENCES 

### LTD 

## (PRC) NO.: 

## 00-6130 HUNTINGDON 

## LIFE SCIENCES 

## LTD(ERC) 

## STUDYNO.: 

## APT1009 SUBCONTRACTOR'S 

### SPONSOR: 

## HuntingdonLife Sciences Princeton Research Center(PRC) MettlersRoad EastMillstone,

## NJ 

## 08875-2360 USA

Page 1 

## of 

## 90

## Huntingdon Life Sciences(ERC) Report No: APT 0091023700


## CONTENTS Page



# ......................... COMPLIANCEWlTH GOOD LABORATORY PRACTICE STANDARDS 4 ERC

. 

## QUALITY ASSURANCE STATEMENT


# ...................................................................... 5



# ...................................................................... PRC


## . QUALITYASSURANCE STATEMENT 6



# ............................................ RESPONSIBLE PERSONNELAND SCIENTIFIC APPROVAL 7 

## SUMMARY


# ................................................................................................................................ INTRODUCTION


# ...................................................................................................................... EXPERIMENTAL PROCEDURE


# ............................................................................................. ASSESSMENT OF RESULTS


# .................................................................................................. MAINTENANCE OF RECORDS


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



# ................................................................................................................................... RESULTS 15 CONCLUSION

# ........................................................................................................................... 15 REFERENCES 

# ........................................................................................................................... 16

## Huntingdon Life Sciences(ERC) ReportNo: APT 0091023700



## CONTENTS 

# . continued TABLES 1

# . Summary of results and statistical analysis


# ...................................................................... 18 

## 2


## . Results for individualanimals

. 

## 24 hour sampling time


# .................................................. 19
APPENDICES 1

# . Historical negative andpositive control values


# ............................................................... 21 2


## . Animal exposureand observations data


# ........................................................................... 23

## Huntingdon Life Sciences(ERC) ReportNo: APT 0091023700
COMPLIANCE WITH GOOD LABORATORY PRACTICE STANDARDS The slide evaluation phase ofthe study described in this report was conductedin compliance with the following Good Laboratory Practice standards and 

## I consider the data generated to be valid. The

## UK Good Laboratory PracticeRegulations 1999(StatutoryInstrument No. 3106). OECD Principles of Good Laboratory Practice (as revised in 1997), ENVMClCHEM(98) 17. EC CommissionDirective 1999111ECof 8

## March 1999 (Official Journal No. L 7718). US EPA 79.60, CFR Vol. 59, No. 122,27June 1994. No compliance is claimed for work presented in the Experimental Procedure -

## In-life phase or Appendix 2 ofthis report.

ChristineE. Mason, B.Sc. (Hons.), PrincipalInvestigator, Huntingdon Life SciencesLtd., ERC. Date



## I am claimingcompliance for the whole studywith the following exceptions: The identity, strength, purity and composition or other characteristics to define the positive control article has not been determined by the Testing Facility. The positive control article has been characterized as per the Certificate of Analysis on file with the Testing Facility. The stability of the positive control article has not been determined by the Testing Facility. Analyses to determine the uniformity (as applicable) or concentration of the positive control mixture were not performed by the Testing Facility. The stability of the positive control article mixture has not been determinedby the Testing Facility.

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

### -- -- 

## Gary 

## M. Hoffman, B.A., D.A.B.T., StudyDirector, Huntingdon Life Sciences Ltd.,PRC. Date

## Huntingdon Life Sciences(ERC) Report No: 

## APT 0091023700


## ERC

# - QUALITY ASSURANCE STATEMENT
The following inspection and audit have been carried out in relation to the slide evaluation phase of this study:


## Study Phase Date of Inspection Date ofReporting ProcessBased Inspection Slide scoring 3 

## July 2002 5 July 2002 

## 6 September2002 6 

## September2002 

## Report Audit
Process Based Inspection: At or about the time this phase of the study was in progress, inspections of routine and repetitive procedures employed on this type of study were carried out. The slide scoring inspection was conducted and reported to appropriate Company Management as indicated above. 

## Report Audit:This appendix has been audited by the Quality Assurance Department. This auditwas conducted and reported to the Principal Investigator and Company Management as indicated above. Study based inspections were not performed on this phase ofthe study. The methods, procedures and observations were found to be accurately described and the reported results ofthis appendix to reflect theraw data.

. . -. .- -. . 

### - 

## Neal Jolly,B.Sc., M.R.Q.A., Group Manager, Department of QualityAssurance, Huntingdon Life Sciences Ltd. Date

## HuntingdonLife Sciences

## (ERC) ReportNo: 

## APT 0091023700
PRC 

# - QUALITY ASSURANCE STATEMENT 

## Listed below are the dates that ths 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. Thisreport reflects theraw data as far as can be reasonably established. Date(s) of Reported to Study Type of Inspection Inspection Director and Management



## Date QualityAssurance Auditor

## HuntingdonLife Sciences(ERC) Report No: 

## APT 0091023700


## RESPONSIBLE PERSONNEL

## AND SCIENTIFIC APPROVAL



## Gary M. Hoffman, B.A., D. A.B .T., StudyDirector Department of SafetyAssessment, PRC. Date

ChristineE. Mason,B.Sc. (Hons.), PrincipalInvestigator Department of Genetic Toxicology, ERC

Chris Davison, B.Sc., Statistician Department of Statistics,ERC Date

Date

## HuntingdonLife Sciences (ERC) Report No: APT 009/023700

SUMMARY


## This satellite micronucleus study was designed to assess the potential induction of micronuclei by Gasoline DIPE Vapor Condensate in bone marrow cells of the rat. Animals were exposed for four weeks (5 days per week) by inhalationadministration ofthe test substanceat exposure levels of 2000, 10000and 20000 mg/m3. The test substance and negative control were administered by inhalation. The negative control group received clean air. A positive control group was dosed on one occasionby intraperitonealinjection, with cyclophosphamide at 40 mgfkg bodyweight. Bone marrow smears were obtained from five male and five female animals in the negative control and each of the test substance groups 24 hours after the 2othexposure and from the positive control group 24 hours after dosing. One smear from each animal was examined for the presence of micronuclei in 2000 immature erythrocytes. The proportion of immature erythrocytes was assessed by examination of at least 1000 erythrocytes from each animal. A record of the incidence of micronucleated mature erythrocyteswas alsokept. No statistically significant increases in the frequency of micronucleated immature erythrocytesand no substantial decrease in the proportion of immature erythrocytes were observed in rats treated with GasolineDPEVapor Condensatecomparedto negative control values (P>0.01in each case). The positive control compound, Cyclophosphamide, produced large, highly significant increases in the frequency of micronucleated immature erythrocytes and a decrease in the proportion of immature erythrocytes(P<O.OO1). It is concluded that Gasoline DPE Vapor Condensate did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by inhalation exposure in this in vivo 

## testprocedure.

## HuntingdonLife Sciences (ERC)ReportNo: APT 0091023700


## INTRODUCTION
The purpose of this satellite micronucleus study was to assess the potential of Gasoline DlPE Vapor Condensate to induce mutagenic effects in rats following inhalation admmistrationusing an 

## in vivo cytogenetic system (Boller and Schmid 1970, MacGregor 

## et a1 

## 1987, Mavournin 

## et a1 

## 1990). The inhalation route was selected for use in this test asthe most likely route of human exposure. The procedures used were based on therecommendations ofthe followingguidelines: US EPA MicronucleusAssay 79.64, CFR Vol. 59, No. 122,27June 1994. US EPA (1998) Health Effects Test Guidelines; OPPTS 870.5395 Mammalian Erythrocyte Micronucleus Test. The bone marrow micronucleus test, originally developed by Matter and Schmid (1971), is a widely employed and internationally accepted short-term assay for identification of genotoxic effects (chromosome damage and aneuploidy) associated with mutagens and carcinogens (Mavournin et 

### a1 

## 1990). This 

## in vivo system allows consideration of various factors including pharmacokinetics, metabolism and DNA repair which cannot be accuratelymodelled in an 

## in vitro system. Young adult rats are chosen for use because of the high rate of cell division in the bone marrow, because of the wealth of background data on this species, and because of their general suitability for toxicological investigations. 

## In mitotic cells in which chromosomal breakage has been caused by the test substance or its metabolites, acentric fragments of the chromosomes do not separate at the anaphase stage of cell division. After telophasethese fragments may not be included in the nuclei of the daughter cells and hence will form single or multiple micronuclei (Howell-Jolly bodies) in the cytoplasm of these cells. Micronuclei are seen in a wide variety of cells, but erythrocytes are chosen for examination since micronuclei are not obscuredby the main nucleus and are therefore easily detected in this cell type (Boller and Schmid 1970). Micronucleated immature erythrocytes appear in the bone marrow approximately 24 hours after induction of chromosome damage. These immature erythrocytes can be differentiated by a variety of staining techniques which rely on their relatively high content of residual RNA. Using the Feulgen method, they stain blue while mature erythrocytes(whch contain little RNA) are counterstainedorange. An increased incidence of micronucleated immature erythrocytes is indicative of recent exposure to a chromosome-damaging agent. A simultaneous marked increase in the incidence of micronucleated mature erythrocytesisnot expected and maybe indicative ofmicronucleus-like artifacts (Schmid 1976). Substances which interfere with the mitotic spindle apparatus will cause non-disjunction (unequal separation of the chromosomes at anaphase resulting in aneuploidy) or lagging chromosomes at anaphase which may not be incorporated into the daughter nuclei. These lagging chromosomes are not excluded from the erythroblast with the main nucleus and hence also give rise to micronuclei. Any toxic effects of the test substance on the nucleated cells may lead either to a reduction in cell division or to cell death. These effects in 

## turn lead to a reduction in the number of nucleated cells and immature erythrocytes; to compensate for this, peripheral blood is shunted into the bone marrow (von Ledebur and Schmid 1973). If the proportion of immature erythrocytes is found to be

## Huntingdon Life Sciences (ERC) ReportNo: 

## APT 0091023700 significantly less than the control value, this is taken as being indicative of toxicity. A very large decreaseintheproportion would be indicative of a cytostatic or cytotoxic effect. The slide evaluation phase of the satellite micronucleus study was performed at the Department of Genetic Toxicology, HuntingdonLife Sciences (ERC), Eye, Suffolk,IP23 7PX, England. The experimental start and completion dates of the slide evaluation phase of the study were 7 May 2002 and 30 July 2002 respectively.

## HuntingdonLife Sciences(ERC) ReportNo: APT 0091023700


## EXPERTMENTALPROCEDURE In-life

## phase The in-life phase of the study was carried out at the Princeton Research Center starting on 15 March 2002 and was completed on 11April 2002. All animals in the negative control and test substance groups were exposed for four weeks (5 daysper week) by inhalation. The non-exposed positive control group was dosed with Cyclophosphamide administered on one occasion by intraperitoneal injection at a volume dosage of 10 mlkg bodyweight. Cyclophosphamide (CP, CAS # 

## 6055-19-2, lot number 1 O8HO568, received 10 April 2002, expiration 30 June 2002, white powder, storage 2-8"C, purity 99.2%), was obtained from the Sigma Chemical Company (responsible for its characterization), and was dissolved and diluted in sterile distilled water at Huntingdon Life Sciences to stock concentrations of 4.0 mglmL for use as the positive control for the micronucleus study. The experimental design is shown below:

Group Treatment ExposureLevel Animal Numbers (mg/m3) Male Female
1 Air 

### control 1081

## - 1085 1591 - 

### 1595 2 Test Substance 2000 2071 

## - 2075 2581 -

### 2585 3 Test Substance 10000 3071 

## - 3075 3581 -

### 3585 4 Test Substance 20000 408 1 -

### 4085 4591 -

### 4595 6 Cyclophosphamide 40 (mgkg) 

### 6051 - 

### 6055 6561

## - 6565 

## Five males and five females from the negative control and each of the test substance groups were sacrificed 24 hours after the final exposure period by isoflurane inhalatiodexsanguination. Five males and five females from the positive control group were sacrificed 24 hours after CP dosing by C02inhalatiodexsanguination. 

## Both femurs were exposed, cut just above the knee and the bone marrow was aspirated into a syringe containing a small volume (about 0.5 mL) of serum. The cells were then flushed into a centrifuge tube of cold serum. The tubes were identified by labels containing the study, group number, and animal number. The bone marrow cells were pelleted by centrifugation at about 150 x g for about 5 min and the supernatant drawn off, leaving a small amount of serum with the cell pellet. The cells were resuspended by aspiration with a pasteur pipette and a small drop of cells was spread onto a clean glass slide. Four slideswere prepared from each animal. The slideswere allowed to air dry, 

## fixedby dipping for about 3 minutes in methanol, and aged overnightor longer prior to staining. Slideswere labelled with experiment and animal number using a 

## lead pencil.

## Huntingdon Life Sciences(ERC) ReportNo: APT 0091023700
Two slides from each animal were despatched to Huntingdon Life Sciences (ERC), Eye, Suffolk, IP23 7PX, England for slide staining and analysis. The remaining 2 smears and the cell pellet (refrigerated)were held in reserve at PRC in case oftechnicalproblems with the first 2 smears. Slide evaluation 

## Due to the presence of mast cell granules in rat bone smears, which appear identical to micronuclei when stained using the Romanowslq methods, a modified Feulgen staining method is employed for the rat micronucleus test in this laboratory. This method specifically stains DNA-containing bodies deep purple while leaving mast cell granules unstained. The method also allows reasonable differentiationofmature and immature erythrocytes and produces permanent preparations. Two slidesfrom each animal were stained as follows: 1. Hydrolysed in Bouin's fluid at roomtemperature for approximately 30hours. 2. Washed three times inpurifiedwater (5 

## minutes per wash). 3. Stainedin Schiffsreagent for one hour atroomtemperature. 4. 

## Washed three times inpurifiedwater (5 minutes per wash). 5. Counter-stained for ten minutes in very dilute (approximately 0.06 gll) aqueous Eosin yellowish. 6. 

## Washed for fiveminutesin purified water. 7. Stained for 30 minutes in Mayer's Haemalum diluted 9 volumes: 1volume with aqueous acridineorange solutioninpurified water (1 mgtrnl). 8. 

## Rinsed inpurified water. 9. Rinsed in running tap water. 10. Washed for 5minutes inpurified water. 11. Ax-dned. 12. Slideswere mounted with coverslips using DPX mountant. 13. The mountantwas allowedto harden at approximately 37OC. 

## NB All stains and Bouin's fluid were filteredimmediatelyprior to use to remove particulatematerial. The stained smears were examined (under code) by light microscopy to determine the incidence of micronucleated cells per 2000 polychromatic erythrocytesper animal. One smear per animal was examined. Theremaining smearswere held temporarily inreserve in case of technicalproblems with the first smear. Micronuclei are identifiedby the following criteria: Large enough to discernmorphological characteristics Shouldpossess a generally rounded shapewith a clearly defined outline Shouldbe deeply stained and similar in colour to the nuclei of other cells 

# -not black Should lie in the same focal plane as the cell

## Huntingdon Life Sciences (ERC) Report No: APT 0091023700 Lack internal structure,ie 

## they arepyknotic There should be no micronucleus-like debris in the area surrounding the cell The proportion of immature erythrocytes for each animal was assessed by examination of at least 1000 erythrocytes. 

## A record of the number of micronucleated mature erythrocytes observed during assessment ofthis proportionwas alsokept asrecommendedby Schd (1976). 

## Deviations from Protocol This phase of the studywas conducted in compliance with the following additional Good Laboratory Practice Standards: the 

## UK Good Laboratory Practice Regulations 1999 (Statutory Instrument No. 3106), the OECD Principles of Good Laboratory Practice (as revised in 1997), ENV/MC/CHEM(98)17 and the EC Commission Directive 19991111EC of 8 March 1999 (Official Journal No. L 7718). The statistical analysis was performed at Huntingdon Life Sciences Ltd., Eye, Suffolk, P23 7PX, England.

ASSESSMENT OF

# RESULTS
The results for each treatment group were compared with the results for the concurrent negative control group using non-parametric statistics. Non-parametric statistical methods were chosen for analysis ofresultsbecause: They are suitedto analysis of data consistingof discretelintegervalues with ties such as the incidenceof micronucleated immature erythrocytes. The methods make few assumptions about the underlying distribution of data and therefore the values do not require transformation to fit a theoretical distribution (where data can be approximately fitted to a normal distribution, the results of nonparametric analysis and classical analysis of variance are very similar). 'Outliers' are frequently found in the proportion of immature erythrocytes for both control and treated animals; non-parametric analysis based on rank does not give these values an undue weighting. For incidences of micronucleated immature erythrocytes, exact one-sided p-values are calculated by permutation (StatXact, CYTEL SofhvareCorporation, Cambridge, Massachussetts). Comparison of several dose levels is made with the concurrent control using the Linear by Linear Association test for trend, in a step-down fashion if significanceis detected (Agresti et al. 1990); for individual intergroup comparisons (ie 

## the positive control group) this procedure simplifies to a straightforward permutation test (Gibbons 1985). For assessment of effects on the proportion of immature erythrocytes, equivalent permutation tests based on rank scores are used, ie 

## exact versions of Wilcoxon's sum ofranks test andJonckheere's test fortrend.

## Huntingdon Life Sciences (ERC) Report No: 

## APT 009/023700
A positive response is normally indicated by a statistically significant dose-related increase in the incidence of micronucleated immature erythrocytes for thk treatment group compared with the concurrent control group (P<0.01); individual andlor group mean values should exceed the laboratory historical control range (Morrisonand Ashby 1995). A negative result is indicated where individual and group mean incidences of micronucleated immature erythrocytes for the group treated with the test substance are not significantly greater than incidencesfor the concurrent control group (P>0.01) and where these values fall within the historical control range. An equivocal response is obtained when the results do not meet the criteria specified for apositive or negative response. Bone marrow cell toxicity (or depression) is normally indicated by a substantial and statistically significantdose-related decreasein the proportionof immature erythrocytes(P<0.01).

MAINTENANCE OF RECORDS
All raw data, samples and specimens arising from the performance of this phase of the study will remain the property ofthe Sponsor. Types of sample and specimen that are unsuitable, by reason of instability, for long term retention and archiving may be disposed of after the periods stated in Huntingdon Life Sciences, Standard Operating Procedures. All other samples and specimens and all raw data will be retained by Huntingdon Life Sciences 

## PRC in its archive for aperiod of oneyear fromthe date on which the StudyDirector signs the finalreport. After such time, the Sponsor will be contacted and their advice sought on the return, disposal or further retention of the materials. If requested, Huntingdon Life Sciences will continue to retain the materials subject to areasonable feebeing agreed with the Sponsor. Huntingdon Life Scienceswill retain the QualityAssurance records relevant to this study and a copy ofthe final report in its archive indefinitely.

## Huntingdon Life Sciences (ERC)ReportNo: 

## APT 0091023700
RESULTS

MICRONUCLEUS TEST 

## Micronucleated immature erythrocyte counts (mie) The test substance did not cause any statistically significant increases in the number of micronucleatedimmature erythrocytes [P>0.011. Cyclophosphamide caused large, highly significant increases in the frequency of micronucleated immature erythrocytes [P<0.0011. 

## Micronucleated mature erythrocytes(mme) The test substance did not cause any substantial increasesin the incidence of micronucleatedmature erythrocytes. 

## Proportionof immature erythrocytes (% 

## ie/[ie 

# +me]) The test substance failed to cause any significant decreases in the proportion of immature erythrocytes [P>0.011. Cyclophosphamide caused statistically significant decreases in the proportion [P<0.001].

CONCLUSION
No statistically significant increases in the frequency of micronucleated immature erythrocytes and no substantial decrease in the proportion of immature erythrocyteswere observed in rats treated with Gasoline DIPE Vapor Condensate compared to negativecontrol values (P>0.01in each case). It is concluded that Gasoline DIPE Vapor Condensate did not show any evidence of causing chromosome damage orbone marrow cell toxicity when administeredby inhalationin this in vivo test procedure.

## Huntingdon Life Sciences(ERC) ReportNo: APT 0091023700
REFERENCES AGRESTI, A., MEHTA, C.R. and PATEL, N.R. (1990) Exact inference for contingency tables with ordered categories.Journal ofthe American Statistical Association, 85,453. BOLLER, K. and SCHMID, W. (1970) Chemical mutagenesis in mammals. The bone marrow of the Chinese hamster as an in vivo test system. Haematological findings after treatment with Trenimon (translation). Humangenetik, 11,34. CYTEL (1995) StatXact 3 

## for Windows:Statistical Software for Exact Nonparametric Inference. Cytel Software Corporation,NC, USA. GIBBONS, J.D. (1985)Nonparametric StatisticalInference, 2nd edition, Marcel Dekker, New York. JONCKHEERE, A.R. (1954) A distribution-fi-ee k-sample test against ordered alternatives. Biometries, 

## 41, 133-145. KRUSKAL, W.H. and WALLIS, W.A. (1952) Use of Ranks in 

## One-Criterion Variance Analysis. Journal oftheAmerican StatisticalAssociation, 47,583-621. KRUSKAL, W.H. and WALLIS, W.A. (1953) Errata for Kruskal-Wallis (1952). Journal of the American StatisticalAssociation, 47,583-62 1. MacGREGOR, J.T., HEDDLE, J.A., HITE, M., MARGOLIN, B.H., RAMEL, C., SALAMONE, M.F., TICE, R.R. and WILD, D. (1987) Guidelines for the conduct of micronucleus assays in mammalian bone marrow erythrocytes. Mutation Research, 189, 103. MATTER, B. and SCHMID, W. (1971) Trenimon-induced chromosomal damage in bone marrow cells of six mammalian species,evaluatedby the micronucleus test. Mutation Research, 12,417. MAVOURNIN, K.H., BLAKEY, D.H., CIMINO, M.C., SALAMONE, M.F. and HEDDLE, J.A. (1990) The in vivo micronucleus assay in mammalian bone marrow andperipheral blood. A report of the US Environmental ProtectionAgency Gene-Tox Program. Mutation Research, 239,29. MORRISON, V. and ASHBY, J. (1995) High resolution rodent bone marrow micronucleus assays of 1,2-dimethylhydrazine :

## implication of systemic toxicity and individual responders. Mutagenesis, 10, 129. SAS INSTITUTE (1989) SAS/STAT User's Guide, Version 

## 6, Fourth Edition, Vo1.2. SAS Institute Inc., Cary,NC, USA. SAS INSTITUTE (1996) SAS/STATSoftware: Changes andEnhancements through Release 6.11. SAS Institute,Cary, NC, USA. SAS INSTITUTE (1996) SAS/STAT Software: Changes and Enhancements for Release 6.12. SAS Institute,Cary,NC, USA.

## HuntingdonLife Sciences (ERC) Report No: APT 0091023700 SCHMID, W. (1976) The micronucleus test for cytogenetic analysis. In: HOLLANDER, A. (ed.) Chemical Mutagens, Principles and Methods for theirDetection, 

## 4, 31.Published by Plenum Press, New York.
von LEDEBUR, M. and SCHMID, W. 

## (1973) The rnicronucleus test. Methodological aspects. MutationResearch, 

## 19, 109. WILCOXON, 

## F. (1945). Individual comparisonsby ranking methods. BiometriesBulletin, 1, 80-83.

## Huntingdon Life Sciences (ERC) Report No: APT 0091023700



## TABLE 1 Summary

## ofresultsand statistical analysis 

## Sampling Treatment Exposure level %

## iel(ie+me)

# t Incidencemie Incidence rnme

time (mg/m" (group mean) (group mean) (groupmean)" 24 Hours Negative control 5 1 0.8 0.0 TS 2000 52 0.8 1.1 TS 10000 49 0.9 1.1 TS 20000 53 0.7 0.8 Cyclophosphamide 40 mgkg 43*** 15.1""" 0.0 TS Gasoline DIPE Vapor Condensate % 

## ie/(ie+me) Proportionof immature erythrocytes mie Number of micronucleated cells observed per 2000 immature erythrocytesexamined mme Number ofmicronucleated cells calculated per 2000mature erythrocytes Results of statistical analysisusing the appropriate nonparametric method of analysisbased on permutation (one-sidedprobabilities): 

# *** P <0.001 (highly significant) otherwise P 

## >0.01 (not significant) 

# 1- Occasional apparent errors of k 

## 1% may occur due to rounding of values for presentation in the table 

# " Formula for calculationof incidence mme (group mean): Sum of mouv incidence mme 

## scoredx 2000 

## Sum of group me 

## scored

## Huntingdon Life Sciences (ERC)ReportNo: APT 

## 0091023700


## TABLE

## 2 Results for individual animals

# - 24 hour sampling time 

# I Treatment Exposure level Animal ie me %

## ie/(ie+me) Incidence Incidence (mg/m') number mie me Negative control 

# - M 1081 486 594 45 0 0 M 1082 593 527 5 3 1 M 1083 650 612 52 1 M 1084 556 515 5 2 1 M 1085 626 522 5 5 1 

## F 1591 567 53 1 52 2 F 1592 567 503 53 0 F 1593 519 594 47 1 F 1594 542 507 52 1 F 1595 564 555 5 0 0 TS 

## 2000 M 2071 532


## . 520 5 1 0 M 2072 572 490 54 0 M 2073 641 547 54 2 M 2074 582 571 50 1 M 2075 600 505 54 2 

## F 2581 603 564 52 0 F 2582 524 517 50 1 

## F 2583 620 566 52 0 F 2584 509 524 49 1 

## F 2585 560 500 5 3 1 TS 

## 10000 M 3071 531

. 

## 536 5 0 1 M 3072 530 510 5 1 1 M 3073 491 585 46 0 M 3074 582 593 5 0 1 M 3075 516 568 48 1 

## F 3581 485 599 45 1 F3582 498 603 45 2 

## F 3583 574 479 5 5 1 F3584 519 536 49 1 

## F 3585 626 603 5 1 0 TS 

## 20000 M 4081 63 5 65 1 49 1 M4082 580 457 56 1 M 4083 642 489 57 1 M 4084 545 535 5 0 0 M 4085 529 50 1 5 1 0 

## F 4591 616 431 5 9 1 F4592 582 555 5 1 1 

## F 4593 665 427 61 0 F4594 518 595 47 1 F 4595 524 574 48 1 TS GasolineDPEVapor Condensate % 

## iel(ie+me) Proportionof immature erythrocytes mie Number of micronucleated cells observedper 

## 2000 immatureerythrocytes me Total number of mature erythrocytesexamined for micronuclei me Number of micronucleated mature erythrocytes observed

## Huntingdon Life Sciences(ERC) Report No: APT 0091023700

TABLE 2

# - continued Results for individual animals

# - 24 hour samplingtime Treatment Dosage Animal ie me % 

## iel(ie+me) Incidence Incidence number mie mme C~clophosphamide 40 mgkg 

## M 605 1 422 604 4 1 13 0 

## M 6052 525 593 47 11 0 

## M 6053 506 63 1 45 7 0 

## M 6054 503 694 42 12 0 

## M 6055 487 551 47 6 0 F6561 419 609 4 1 19 0 F 6562 483 623 44 25 0 F 6563 462 599 44 25 0 F 6564 422 683 3 8 9 0 

## F 6565 473 721 40 24 0 %

## ie/(ie+me) Proportion of immature mie Number of micronucleated cells observedper 2000 immatureerythrocytes me Totalnumber ofmature erythrocytesexamined for micronuclei mme Number of micronucleated mature erythrocytes observed

## Huntingdon Life Sciences (ERC) ReportNo: 

## APT 0091023700



## APPENDIX 

## 1

Historicalnegative controlvalues (1 

### July2000

# - 30June 2002) Frequencyof micronucleated immature erythrocytes(individualanimals)

Number of micronucleatedimmatureerythrocytes (MIEper 2000) Individual man0.79
Historicalnegative controlvalues 

### (1 July2000

# - 30 June 2002) Frequencyof micronucleated immature erythrocytes(Group meanvalues)

Number of 

### micronucleated immature erythrocytes (MIEper 2000) Group man 0.73

## Huntingdon Life Sciences (ERC) ReportNo: 

## APT 0091023700


## APPENDLX 1

# -continued

Historicalpositive controlvalues (1

### July 2000

# - 30 June 2002) Frequencyof micronucleated immature erythrocytes (Individual animals) Cyclophosphamide

Number of micronucleated immature erythrocytes (M

### lEper 2000 

### cells) Individualmean 38.7



### Historicalpositive controlvalues 

### (1July2000

# - 30 June 2002) Frequency of micronucleated immatureerythrocytes (Group meanvalues) Cyclophosphamide

Number of micronucleated immature erythrocytes (MIEper 2000) 

### Group 

### mean 39.9

## Huntingdon Life Sciences(ERC) Report No: 

## APT 0091023700


## APPENDIX2

. 

## ANIMAL 

## EXPOSURE

# AND OBSERVATIONSDATA

## Huntingdon Life Sciences 00-6130 Page 1 2 1 1 -DIPE-S Draft Final Report Animal Exposure and Animal Data Preface 

# I Appendix 2 

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

## and animal evaluations.


# STUDY DATES: Date of Animal Receipt: 

## 4 March 2002 Experimental Initiation Date: 15 March 2002 (in-life) ExperimentalCompletion Date: 11April 2002 (in-life) Draft Report Date: 6 March 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. ChamberMonitoring Results


# ........................................................................................... B. Summaryof Clinical Observations


# .................................................................................. C. Mean Body Weights (grams)


# ........................................................................................... D. Mean Body Weight Change (grams)


# ................................................................................ E. Mean Feed ConsumptionValues (gramslkglday)


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

..................................................................................... F. Individual Clinical Observations



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

# H. IndividualBody Weight Change (grams)


# ........................................................................ I. Individual Feed Consumption Values (grams/kg/day)


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



# ............................................................................................ J. Animal TerminationHistoryTable A GASOLINE DlPEVAPOR CONDENSATE:A 13-WEEK 00-61 30 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 IA

## - 0 mg/m3 (Air Control)

Nominal (w/m3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Mean (mglm3) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 

### 0 0 alytical Chamber Concentration Individual 

### (ms 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 MMAD (crm) 0.9053

2.495

2.357

2.187

1.986 0.731 Particle Size :terminat

GSD 1s TMC (mg/m3) 1.20E-02

4.91 E-03

7.60E-03

2.32E-03

6.71 E-03 4.13E-03 Chamber Environment h, Temperature ("C) 25 27 25 24 24 24 24 24 25 25 25 25 25 24 23 24 23 24 25 25 24.5 0.9 In Humidity 

## (%I 53 54 53 54 52 53 58 53 5 1 52 55 54 50 56 52 55 55 51 51 53 

### 53.3 1.9Table A GASOLINE DlPEVAPOR CONDENSATE: A 13-WEEK WHOLE-BODY INHALATION TOXICITY STUDY IN RATS Chamber Monitoring Results Cumulative Exposure RecordTable A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 00-61 30 WHOLE-BODY INHALATIONTOXICITY STUDY IN RATS Chamber Monitoring Results Cumulative Exposure Record

Group IIA 

### - 2,000 mglrn3 Chamber Environment Particle Size Mean Analytical Chamber Concentration



# --


# - Humidity 

## ("/.I 50 50 48 50 49 50 54 51 48 48 52 50 47 52 48 5 1 51 48 47 49 49.7 1.8 1s TMC

(rnglm3)
1 .I 9E-02

4.72E-03

4.56E-03

1.53E-03

5.68E-03 4.40E-03 remperature ("'3 23 26 23 23 23 23 23 23 24 24 24 24 24 23 23 23 23 23 24 24 23.5 0.8 Date Exposure Number Nominal (mg/m3)

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

67 MMAD (clrn) 0.794

3.911

0.8422

1.438

1.746 1.473 Mean (mglm3)

I968 2068 2205 2095 2040 2108 1913 1918 1913 2133 2090 2028 I843 I845 I875 2093 2150 1950 I938 1955 Individual 

### (ms

1920 2050 2190 2060 2030 2040 1940 1900 1760 2130 2030 2040 1630 1790 1890 2130 2030 1810 2030 1950 2006 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean S.D.Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 00-61 30 WHOLE-BODY INHALATION TOXICITY STUDY IN RATS

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. Nominal (mg/m3)

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

67 Chamber MonitoringResults Cumulative Exposure Record

Grow IIB 

## - 2.000 mdm3

Mean (mg/m3)

2020 2098 2020 2028 2040 2073 1960 I968 1960 I978 1915 1998 2130 1960 1970 2098 2055 I858 1868 1943 alytical Chamber Concentration Individual 

### (ms

2020 2200 201 0 1930 2060 2020 1990 2050 2000 1980 1920 1980 2400 1840 2020 2220 1890 1790 1780 1980 1997 MMAD (vm) 0.8998

0.9819

0.8897

1.403

1.044 0.243 ParticleSize Determinations GSD TMC (mg/m3) 1.47E-02

1.76E-03

5.04E-03

1.74E-03

5.81E-03 6.1 3E-03 n Humidity (%) 52 52 50 52 51 51 55 52 52 50 54 53 48 54 49 54 54 49 52 52 51.8 1.9Table A GASOLINE DlPEVAPOR CONDENSATE: A 13-WEEK 00-61 30 WHOLE-BODY INHALATIONTOXICITY 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 lllA 

### - 10,000 mg/m3

Nominal (mg/m3)

9980 9530 10000 10200 10100 10300 9370 9690 9940 9390 9540 9670 9830 10000 10600 10000 9470 10000 9880 10100 9880 321 1 Mean (mglm3)

9973 lo260 10000 10320 1001 0 9970 9475 9450 9773 9670 9930 1001 0 9790 9970 9730 9745 9098 10450 9828 9945 ~alytical Chamber Concentration Individual Particle Size MMAD (IJm) 0.7927

1.316

0.7720

1.490

1.O93 0.365 sterminat GSD 1s TMC (mglm3)
2.41E-02

2.91 E-03

5.54E-03

1.78E-03

8.58E-03 1.05E-02 Chamber M remperature ("'7 23 26 24 23 23 23 23 23 24 24 24 24 24 23 23 23 23 23 24 24 23.6 0.8 vironment n Humidity (%) 50 50 47 50 50 49 50 48 48 48 48 49 47 50 48 48 49 47 49 49 48.7 1.ITable A GASOLINE DlPEVAPOR CONDENSATE: A 13-WEEK 00-61 30 WHOLE-BODY INHALATIONTOXICITY STUDY IN RATS Chamber Monitoring Results

Date xposure Number
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean S.D. Nominal (m!3/m3)

9980 9530 10000 10200 101 00 10300 9370 9690 9940 9390 9540 9670 9830 10000 10600 10000 9470 10000 9880 10100 9880 321 Cumulative Exposure Record Group lllB -10.000 mg/rn3 Chamber Environment

Mean (mg1rn3)

9983 9325 9980 9548 9510 10110 9188 9573 10430 9818 9493 10070 lo260 9033 lo630 10680 10250 9763 10130 lo780 alytical Chamber Concentration Individual MMAD (IJrn) 0.7866

4.191

0.7259

1.767

1.868 1.621 ParticleSize Determinations GSD TMC (mg1m3) 2.44E-02

5.14E-03

5.49E-03

3.29E-03

9.58E-03 9.93E-03 Temperature ("C) 23 26 23 24 24 24 24 24 23 23 23 24 24 24 24 24 24 24 24 23 23.8 0.7 InHumidity 

## ("/.I 49 49 46 46 46 46 46 45 46 46 46 47 44 47 46 45 45 45 48 46 46.2 1.3Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 00-61 30 WHOLE-BODY INHALATION TOXICITY STUDY IN RATS Chamber Monitoring Results Cumulative Exposure Record

Group IVA 

### - 20,000 mglm3

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. ~alytical Chamber Concentration Nominal (mglm3) 191 00 19400 I9000 I9300 19800 I9000 I9500 I9300 19300 19600 18400 18600 18700 18900 18800 18900 191 00 18800 I7600 19700 19040 504 Individual 1 Mean (mglm3) 19100 19980 19880 19250 19650 19350 20280 19550 20330 20250 19780 19480 20080 20450 20300 19480 20100 19830 I9050 20780 

### (mo I8500 20500 20300 19000 20400 19500 20300 1 9700 20100 1 9700 19800 18900 19700 20200 19800 19000 19500 19500 18800 20800 19850 MMAD (~.rm) 0.7739

2.346

0.8053

1.220

1.286 0.735 Particle Size Determinations GSD TMC (m91m3) 2.44E-02

4.30E-03

7.67E-03

1.09E-03

9.37E-03 1.04E-02 Chamber Environment rn Humidity 

### ("A) 52 52 48 51 50 50 51 49 49 49 48 49 47 50 52 50 50 49 50 51 49.9 1.4Table A GASOLINE DlPE VAPOR CONDENSATE: A 13-WEEK 00-61 30 WHOLE-BODY INHALATION TOXICITY STUDY IN RATS Chamber Monitoring Results Cumulative Exposure Record

Group IVB

## - 20,000 mglm3 Chamber Environment Particle Size Determinations M Temperature ("C) 24 26 24 25 25 25 25 25 24 24 24 24 24 25 25 25 25 25 25 24 24.7 0.6 InHumidity 

## (%I 51 52 49 50 49 49 50 48 5 1 50 50 50 48 49 50 49 48 48 52 50 49.7 1.2 Nominal (mglm3) 19100 19400 19000 19300 19800 19000 19500 19300 19300 19600 I8400 18600 18700 I8900 18800 18900 191 00 18800 I7600 19700 19040

504 Date Exposure Number &tical Chamber Concentration Individual TMC (mglm3) 2.31 E-02

3.14E-03

9.04E-03

2.38E-03

9.42E-03 9.60E-03 MMAD

(~m) 0.7578

0.9018

0.7779

1.517

0.989 0.358 GSD Mean (mglm3) 20430 20680 20980 20580 20800 20730 20750 21030 19850 20380 19930 19650 18930 18830 19250 19900 19700 19880 18230 20350 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 MeanHuntingdon 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

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

# OF ANIMALS EXAMINED 155 255 355 4 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

WEEK

WEEK

WEEK

WEEK

WEEK MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N

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

WEEK 0

WEEK 1 MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N WEEK 2

WEEK 3 MEAN S.D.

N WEEK 4 MEAN S.D.

N -------------- differencesHuntingdon 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

WEEK 0 TO 1 MEAN S.D.

N WEEK 0 TO 2 MEAN S.D.

N WEEK 0 TO 3 MEAN S.D.

N

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

WEEK 0 TO 2

WEEK 0 TO 3

WEEK 0 TO 4 MEAN S.D.

N MEAN S.D.

N MEAN S.D.

N MEANHuntingdon 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 MALES MEAN FEED CONSUMPTION VALUES (GRAMS/KG/DAY)

................................................................................................................................... DOSE GROUP: 1 2 3 4 6 DOSE LEVEL (MG/M3) : 0 2000 10000 20000 MICRO+CONTROL

................................................................................................................................... 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 FEMALES MEAN FEED CONSUMPTION VALUES (GRAMS/KG/DAY)

................................................................................................................................... DOSE GROUP: 1 2 3 4 6 DOSE LEVEL (MG/M3): 0 2000 10000 20000 MICRO+CONTROL

................................................................................................................................... WEEK 1 MEAN S.D.

N MEAN S.D.

N WEEK 2

WEEK 3 MEAN S.D.

N WEEK 4 MEAN S.D.

N ---------------- Statistical key:Huntingdon 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

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

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 PAGE 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

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

6051 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6052 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6053 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6054 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6055 WITHIN NORMAL LIMITS TERMINAL SACRIFICE

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

ANIMAL# OBSERVATIONS DAY OF 

### - 2 STUDY 4 7

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

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 INDIVIDUAL CLINICAL OBSERVATIONS FEMALES GROUP 4 20000 MG/M3

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 6 MICRO+CONTROL

6561 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6562 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6563 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6564 WITHIN NORMAL LIMITS TERMINAL SACRIFICE 6565 WITHIN NORMAL LIMITS P TERMINAL SACRIFICE P

................................................................................................................................... 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 INDIVIDUAL BODY WEIGHTS (GRAMS) MALES GROUP 2 2000 MG/M3

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 INDIVIDUAL BODY WEIGHTS (GRAMS) MALES 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 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 6 MICRO+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

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

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/M3

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

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

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 INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) MALES GROUP 1 0 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 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 INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) MALES GROUP 2 2000 MG/M3

MEAN 62 116 175 225 S.D. 1.8 5.6 13.9 22.3

N 5 5 5 5Huntingdon 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

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/M~

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

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 5
TABLE H GASOLINE DIPE VAPOR C0M)ENSATE: 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 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

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 IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL BODY WEIGHT CHANGE FROM BASELINE (GRAMS) FEMALES GROUP 2 2000 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 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

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

MEAN S.D.

NHuntingdon Life Sciences 00-6130G 211-DIPE-S PAGE 1
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 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

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 INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) MALES GROUP 3 10000 MG/M3

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

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 AM) 4-WEEK IN VIVO GENOTOXICITY AND IMMUNOTOXICITY ASSESSMENTS INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) MALES GROUP 6 MICRO+CONTROL

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 INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) FEMALES GROUP 1 0 MG/M3 WEEK OF STUDY ANIMAL# 1 2 3 4

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 INDIVIDUAL FEED CONSUMPTION VALUES (GRAMS/KG/DAY) FEMALES GROUP 2 2000 MG/M3 WEEK OF STUDY ANIMAL# 1 2 3 4

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

MEAN S.D.

NHuntingdon 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

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 6 MICRO+CONTROL

MEAN S.D.

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

DEATH DATE OF WEEK OF STUDY DEATH STUDY DAY TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICE TERMINAL SACRIFICEHuntingdon 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 3 27 2072 TERMINAL SACRIFICE 11-APR-02 3 27 2073 TERMINAL SACRIFICE 11-APR-02 3 2 7 2074 TERMINAL SACRIFICE 11-APR-02 3 27 2075 TERMINAL SACRIFICE 11-APR-02 3 27

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

................................................................................................................................... 3071 TERMINAL SACRIFICE 11-APR-02 3 27 3072 TERMINAL SACRIFICE 11-APR-02 3 27 3073 TERMINAL SACRIFICE 11-APR-02 3 27 3074 TERMINAL SACRIFICE 11-APR-02 3 27 3075 TERMINAL SACRIFICE 11-APR-02 3 27

...................................................................................................................................Huntingdon 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 DAYHuntingdon 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 GROUP6 MICRO+CONTROL

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

................................................................................................................................... 6051 TERMINAL SACRIFICE 11-APR-02 3 27 6052 TERMINAL SACRIFICE 11-APR-02 3 27 6053 TERMINAL SACRIFICE 11-APR-02 3 27 6054 TERMINAL SACRIFICE 11-APR-02 3 27 6055 TERMINAL SACRIFICE 11-APR-02 3 27

------------------------------------.----------------------------------------------------------------------------------------------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 ANIMAL TERMINATION HISTORY FEMALES GROUP 1 0 MG/M3

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

................................................................................................................................... 1591 TERMINAL SACRIFICE 11-APR-02 3 27 1592 TERMINAL SACRIFICE 11-APR-02 3 27 1593 TERMINAL SACRIFICE 11-APR-02 3 27 1594 TERMINAL SACRIFICE 11-APR-02 3 27 1595 TERMINAL SACRIFICE 11-APR-02 3 27Huntingdon 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

----------------------------.------------------------------------------------------------------------------------------------------ TYPE OF DATE OF WEEK OF STUDY AN I MAL# DEATH DEATH STUDY DAY

-----------------------------------------------------------------------------------.----------------------------------------------- 2581 TERMINAL SACRIFICE 11-APR-02 3 27 2582 TERMINAL SACRIFICE 11-APR-02 3 27 2583 TERMINAL SACRIFICE 11-APR-02 3 2 7 2584 TERMINAL SACRIFICE 11-APR-02 3 2 7 2585 TERMINAL SACRIFICE 11-APR-02 3 27Huntingdon 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 ASSESSMENTS ANIMAL TERMINATION HISTORY FEMALES GROUP 3 10000 MG/M~ TYPE OF

DEATH DATE OF WEEK OF STUDY DEATH STUDY DAY 3581 TERMINAL SACRIFICE 3582 TERMINAL SACRIFICE 3583 TERMINAL SACRIFICE 3584 TERMINAL SACRIFICE 3585 TERMINAL SACRIFICEHuntingdon 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 ASSESSMENTSHuntingdon 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 6 MICRO+CONTROL

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