FINAL REPORT 

Study Title

COMBINED 28-DAY REPEATED DOSE TOXICITY STUDY WITH THE 

REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST 

OF CASTOR OIL, SULFATED, SODIUM SALT, 75% IN RATS BY 

ORAL GAVAGE

Author

M.E.W. de Raaf - Beekhuijzen, MSc.

Test Facility

WIL Research Europe B.V.

Hambakenwetering 7

5231 DD 's-Hertogenbosch

The Netherlands

Laboratory Project Identification

Project 503342

Substance 205003/A

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1. CONTENTS

1. CONTENTS ...................................................................................................................................... 2

2. STATEMENT OF GLP COMPLIANCE............................................................................................. 4

3. QUALITY ASSURANCE STATEMENT ............................................................................................ 5

4. SUMMARY........................................................................................................................................ 6

5. INTRODUCTION .............................................................................................................................. 8

5.1. Preface..................................................................................................................................... 8

5.2. Study plan ................................................................................................................................ 9

5.3. Aims of study............................................................................................................................ 9

5.4. Guidelines ................................................................................................................................ 9

5.5. Storage and retention of records and materials.....................................................................10

6. MATERIALS AND METHODS ........................................................................................................11

6.1. Test substance.......................................................................................................................11

6.1.1. Test substance information ........................................................................................11

6.1.2. Study specific test substance information..................................................................11

6.1.3. Test substance formulation ........................................................................................11

6.1.4. Chemical analysis of dose preparations ....................................................................11

6.2. Test system............................................................................................................................12

6.3. Allocation................................................................................................................................12

6.4. Animal husbandry ..................................................................................................................13

6.5. Treatment...............................................................................................................................14

6.5.1. Parental animals.........................................................................................................14

6.5.2. Pups ...........................................................................................................................14

6.6. Observations ..........................................................................................................................14

6.6.1. Parental animals.........................................................................................................14

6.6.2. Pups ...........................................................................................................................15

6.7. Clinical laboratory investigations............................................................................................16

6.7.1. Haematology ..............................................................................................................16

6.7.2. Clinical biochemistry...................................................................................................17

6.8. Pathology ...............................................................................................................................17

6.8.1. Necropsy parental animals.........................................................................................17

6.8.2. Necropsy pups ...........................................................................................................19

6.8.3. Organ weights ............................................................................................................19

6.8.4. Histotechnology..........................................................................................................19

6.8.5. Histopathology............................................................................................................19

6.9. Electronic data capture ..........................................................................................................20

6.10. Interpretation ..........................................................................................................................20

6.10.1. Calculations................................................................................................................20

6.10.2. Statistical analyses.....................................................................................................21

6.11. List of deviations ....................................................................................................................21

6.11.1. List of protocol deviations...........................................................................................21

6.11.2. List of standard operating procedure deviations ........................................................21

7. RESULTS .......................................................................................................................................22

7.1. Analysis of dose preparations................................................................................................22

7.2. Observations parental animals ..............................................................................................22

7.2.1. Mortality......................................................................................................................22

7.2.2. Clinical signs ..............................................................................................................22

7.2.3. Functional observations .............................................................................................22

7.2.4. Body weights ..............................................................................................................22

7.2.5. Food consumption......................................................................................................22

7.2.6. Haematology ..............................................................................................................23

7.2.7. Clinical biochemistry...................................................................................................23

7.2.8. Macroscopic examination...........................................................................................23

7.2.9. Organ weights ............................................................................................................23

7.2.10. Microscopic examination............................................................................................23

7.3. Reproduction/developmental data .........................................................................................24

7.3.1. Reproduction data......................................................................................................24

7.3.2. Developmental data ...................................................................................................24

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8. DISCUSSION AND CONCLUSION................................................................................................25

9. REFERENCES ...............................................................................................................................26

APPENDICES

APPENDIX 1 SUMMARY TABLES

APPENDIX 2 INDIVIDUAL TABLES

APPENDIX 3 PHASE REPORT FORMULATION ANALYSIS

APPENDIX 4 PHASE REPORT HISTOPATHOLOGY

APPENDIX 5 CERTIFICATE OF ANALYSIS

APPENDIX 6 SUMMARY OF DOSE RANGE FINDING STUDY

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4. SUMMARY

Title

Combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening 

test of Castor Oil, Sulfated, Sodium Salt, 75% in rats by oral gavage.

Guidelines 

The study was based on the following guidelines:

1) OECD 422, Combined Repeated Dose Toxicity Study with the Reproduction/Developmental 

Toxicity Screening Test, March 1996.

2) OPPTS 870.3650, Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test, July 2000.

3) OECD 421, Reproduction/Developmental Toxicity Screening Test, July 1995.

4) OPPTS 870.3550, Reproduction/Developmental Toxicity Screening Test, July 2000.

5) EC No 440/2008 B.7: "Repeated Dose (28 days) Toxicity (oral)", May 2008.

6) OECD 407, Repeated Dose 28-day Oral Toxicity Study in Rodents, October 2008.

7) OPPTS 870.3050, Repeated dose 28-day oral toxicity study in rodents, July 2000.

Rationale for dose levels

Based on the results of a 10-day dose range finding study (Project 503343; see APPENDIX 6), the 

dose levels for this combined 28-day oral gavage study with reproduction/developmental toxicity 

screening test were selected to be 100, 300 and 1000 mg/kg.

Study outline

After acclimatization, four groups of ten male and ten female Wistar Han rats were exposed by oral 

gavage to the test substance at 0, 100, 300 and 1000 mg/kg. Males were exposed for 29 days, i.e. 2 

weeks prior to mating, during mating, and up to termination. Females were exposed for 41-47 days, 

i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of 

lactation.

Evaluated parameters

The following observations and examinations were evaluated: mortality / viability, clinical signs (daily), 

functional observations and locomotor activity (end of treatment), body weight and food consumption 

(at least at weekly intervals), clinical pathology (end of treatment), macroscopy at termination, organ 

weights and histopathology on a selection of tissues, and reproduction/developmental parameters, 

consisting of mating, fertility and conception indices, precoital time, number of corpora lutea and 

implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early 

postnatal pup development (mortality, clinical signs, body weights and macroscopy). Formulations 

were analyzed once after in-life to assess accuracy and homogeneity.

Results

Accuracy and homogeneity of formulations were demonstrated by analyses.

Parental results:

Parental toxicity was observed for males at 1000 mg/kg. This consisted of a subtle increase in severity 

of mononuclear inflammation and in incidence and/or severity of myofiber degeneration in the heart. 

Both findings were slightly above the range of background findings of Wistar (Han) rats of this age. 

Therefore a possible test item-related effect cannot be excluded.

Reproductive results:

No reproduction toxicity was observed up to the highest dose level tested (1000 mg/kg). 

Developmental results:

No developmental toxicity was observed up to the highest dose level tested (1000 mg/kg). 

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Conclusion

In conclusion, treatment with Castor Oil, Sulfated, Sodium Salt, 75% by oral gavage in male and 

female Wistar Han rats at dose levels of 100, 300 and 1000 mg/kg revealed parental toxicity for males 

at 1000 mg/kg. No reproduction and developmental toxicity was observed for treatment up to 1000

mg/kg.

Based on these results, the following No Observed Adverse Effect Levels (NOAEL) were derived: 

Parental NOAEL: 300 mg/kg for males, and

at least 1000 mg/kg for females

Reproduction NOAEL: at least 1000 mg/kg

Developmental NOAEL: at least 1000 mg/kg

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5. INTRODUCTION

5.1. Preface

Information concerning the dose range finding study (Project 503343) is given in APPENDIX 6.

Two project numbers were used to collect online data (project 503342 and 503344). All data was 

reported under Project 503342. 

Sponsor Sulfated Castor Oil Consortium, Society of Chemical

Manufacturers & Affiliates

1850 M Street NW, Suite 700

Washington, DC 20036

USA

Study Monitor

(on behalf of the Sponsor)

Rodney Boatman, Ph.D.

PCA Services

2704 Trail Wood Drive

Durham, NC 27705

USA

Study Director M.E.W. de Raaf - Beekhuijzen, M.Sc.

WIL Research Europe B.V.

Hambakenwetering 7

5231 DD 's-Hertogenbosch

The Netherlands

Tel: +31 73 640 6700

Fax: +31 73 640 6799

Email: manon.beekhuijzen@wilresearch.com

Coordinating Biotechnician J. Schouten (WIL Research Europe B.V.)

Clinical Pathology Dr. M. Stitzinger (WIL Research Europe B.V.)

Analytical Chemistry Until 25 March 2014: M.J.C. Brekelmans, MSc. (Principal 

Scientist, WIL Research Europe B.V.)

From 25 March 2014 onwards: Dr. Ir. E. Baltussen (Principal 

Scientist, WIL Research Europe B.V.)

Histotechnology W. Verhoef (WIL Research Europe B.V.)

Necropsy T.A. Mijnders, Bachelor (WIL Research Europe B.V.)

Histopathology E.J.M. Lambregts, DVM (Principal Scientist, WIL Research 

Europe B.V.)

Quality Assurance C.J. Mitchell, BSc. (WIL Research Europe B.V.)

Email: christine.mitchell@wilresearch.com

Test Facility Management H.H. Emmen, MSc. (WIL Research Europe B.V.)

Email: harry.emmen@wilresearch.com

Test Facility WIL Research Europe B.V.

Hambakenwetering 7

5231 DD ‘s-Hertogenbosch

The Netherlands

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5.2. Study plan

Experimental starting date 02 September 2013 (allocation dose range finding study)

Dose range finding 

study

Treatment 02 to 11 September 2013

Necropsy 11 September 2013

Main study Start treatment 18 September 2013

Start mating 02 October 2013

Blood sampling 17 October 2013 (selected males)

29, 31 October and 01 November 2013 (selected females)

Delivery of litters 24 - 28 October 2013

Necropsy 17 October 2013 (males)

29 October - 04 November 2013 (females and pups)

Experimental completion date 04 November 2013 (end of in-life phase)

5.3. Aims of study

The purpose of this study was to evaluate the potential toxic effects of the test substance when 

administered to rats for a minimum of 28 days and to evaluate the potential of the test substance to 

affect male and female reproductive performance such as gonadal function, mating behaviour, 

conception, parturition and early postnatal development.

Parental, reproduction (up to and including implantation) and developmental (from implantation 

onwards) No Observed Adverse Effect Levels (NOAELs) were evaluated.

This study should provide part of a rational basis for toxicological risk assessment in man.

5.4. Guidelines

The protocol was reviewed and agreed by the Laboratory Animal Welfare Officer and the Ethical 

Committee (DEC 10-81) as required by the Dutch Act on Animal Experimentation (February 1997).

The study procedures described in this report were in compliance with the following guidelines: 

1) Organisation of Economic Co-operation and Development (OECD) Guidelines for Testing of 

Chemicals, Guideline 422, Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test, March 1996.

2) The United States Environmental Protection Agency (EPA) Health Effects Test Guidelines, 

OPPTS 870.3650, Combined Repeated Dose Toxicity Study with the 

Reproduction/Developmental Toxicity Screening Test, July 2000.

In addition, the procedures described in this report essentially conform to the following guidelines: 

3) OECD Guidelines for Testing of Chemicals, Guideline 421, Reproduction/Developmental Toxicity 

Screening Test, July 1995.

4) The United States EPA Health Effects Test Guidelines, OPPTS 870.3550, 

Reproduction/Developmental Toxicity Screening Test, July 2000.

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5) Commission regulation (EC) No 440/2008 Part B: Methods for the Determination of Toxicity and 

other Health Effects; B.7: "Repeated Dose (28 days) Toxicity (oral)". Official Journal of the 

European Union No. L142, May 2008.

6) OECD Guidelines for Testing of Chemicals, Guideline 407, Repeated Dose 28-day Oral Toxicity 

Study in Rodents, October 2008.

7) The United States EPA Health Effects Test Guidelines, OPPTS 870.3050, Repeated dose 28-day 

oral toxicity study in rodents, July 2000.

5.5. Storage and retention of records and materials

Records and materials pertaining to the study, including protocol, raw data, specimens (except 

specimens requiring refrigeration or freezing) and the final report, will be retained in the WIL Research 

Europe archives for a period of at least 2 years after finalization of the report. After this period, the 

sponsor will be contacted to determine how the records and materials should be handled. WIL 

Research Europe will retain information concerning decisions made.

Those specimens requiring refrigeration or freezing will be retained by WIL Research Europe for as 

long as the quality of the specimens permits evaluation but no longer than three months after 

finalization of the report.

WIL Research Europe will retain a test substance sample until the expiry date, but no longer than 10 

years after finalization of the report. After this period the sample will be destroyed.

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6. MATERIALS AND METHODS 

6.1. Test substance

6.1.1. Test substance information

Identification Castor Oil, Sulfated, Sodium Salt, 75%

CAS Number 68187-76-8

Description Clear amber liquid

Batch R-10135-064

Purity/Composition 74.4%

Test substance storage At room temperature in the dark

Stable under storage conditions until 18 July 2014 (expiry date) 

Note:

The concentration test substance was calculated based on the purity determined in project 503335 

[i.e. 74.4%]. This information was not available when the target concentrations were calculated during 

Project 503342, based on the purity supplied by the sponsor [i.e. 70.7%]. See 6.3.

6.1.2. Study specific test substance information

Internal EH&S Risk Assessment No

Purity/composition correction factor 

required

Yes, correction factor is 1.41 (70.7% purity)

Hygroscopic No

Volatile No

Specific Gravity / Density 1.049

pH 7.2 at concentration of 5%

Stability at higher temperatures Yes, maximum temperature 100°C, maximum duration: until dry

Stability in water Yes, >24 hrs., 5%

Solubility in water Complete

6.1.3. Test substance formulation 

Vehicle Water (Elix, Millipore S.A.S., Molsheim, France).

Rationale for vehicle Based on trial formulations performed at WIL Research Europe and 

information provided by the Sponsor. 

Method of formulation Formulations (w/w) were prepared daily within 4 hours prior to dosing and 

were homogenized to a visually acceptable level. Adjustment was made 

for specific gravity/density of the test substance (1.049). A correction was

made for the purity/composition of the test substance. A correction factor 

of 1.41 was used.

Storage conditions At ambient temperature.

6.1.4. Chemical analysis of dose preparations

As the validated method was not finalized yet, formulation samples were collected during in-life (31 

October 2013) and stored in the freezer at ≤-15°C until analyses. However, as the NPOC method was 

not suited to measure the test substance in these frozen samples, additional samples were collected 

after the in-life phase (19 December 2013). These formulations were prepared in the same manner as 

used during the study. 

For quantitative analysis of the test substance in formulation, Total Organic Carbon (TOC) analysis 

was used (see project 503334). Samples of formulations were analyzed for homogeneity (highest and 

lowest concentration) and accuracy of preparation (all concentrations). Stability could not be 

determined since TOC analysis is a general method that does not distinguish original substance from 

hydrolysis product(s); therefore results on stability assessment were not reported.

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Accuracy of preparation was considered acceptable if mean measured concentrations were 90-110% 

of target concentration. Homogeneity was demonstrated if the coefficient of variation was ≤ 10%.

6.2. Test system

Test system Rat: Crl:WI(Han) (outbred, SPF-Quality). Nulliparous and non-pregnant 

females and untreated animals were used at initiation of the study.

Rationale This species and strain of rat has been recognized as appropriate for 

general and reproduction toxicity studies. WIL Research Europe B.V. has 

general and reproduction/developmental historical data in this species 

from the same strain and source. This animal model has been proven to 

be susceptible to the effects of reproductive toxicants.

Source F0 Charles River Deutschland, Sulzfeld, Germany.

Age at start F0-treatment Approximately 11 weeks.

Number of F0-animals 40 females and 40 males.

Acclimatization F0 At least 5 days prior to start of treatment.

Health inspection F0 Upon receipt of the animals. 

Randomization F0 Prior to commencement of treatment, by computer-generated random

algorithm according to body weight, with all animals within ± 20% of the 

sex mean.

Identification F0 Earmark and tattoo.

Mating procedures Following a minimum of 14 days of exposure for the males and females, 

one female was cohabitated with one male of the same treatment group, 

avoiding sibling mating. Detection of mating was confirmed by evidence 

of sperm in the vaginal lavage or by the appearance of an intravaginal 

copulatory plug. This day was designated Day 0 post-coitum. Once 

mating occurred, the males and females were separated. 

Parturition The females were allowed to litter normally. Day 1 of lactation was 

defined as the day when a litter was found completed (i.e. membranes 

and placentas cleaned up, nest build up and/or feeding of pups started). 

Females that were littering were left undisturbed.

Number of pups 430 pups.

Identification of pups On Day 1 of lactation, all pups were individually identified by means of 

subcutaneous injection of Indian ink.

6.3. Allocation

Group Dose level1

mg/kg

Number of animals Animal numbers 

Males Females Males Females

1 0 10 10 01-10 41-50

2 100 10 10 11-20 51-60

3 300 10 10 21-30 61-70

4 1000 10 10 31-40 71-80

1

 Dose levels were based on results of a 10-day dose range finding study (Project 503343; see 

APPENDIX 6) and using a correction factor of 1.41 (based on 70.7% purity). 

Calculating the dose levels using the updated purity (i.e. 74.4%), it would result in dose levels of 105, 

316 and 1052 mg/kg.

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The following 5 animals/sex/group were selected for functional observations, locomotor activity, clinical 

pathology, macroscopic examination (full list), organ weights (full list) and histopathology (see also 

respective paragraphs):

Group Animal numbers 

Males Females 1

1 01-05 42, 43, 44, 45, 47

2 11-15 51, 52, 54, 57, 60

3 21-25 64, 65, 67, 68, 69

4 31-35 73, 75, 76, 78, 80

1 With live pups only.

6.4. Animal husbandry

Room number A0.12 (A0.23 for motor activity measurements).

Conditions Environmental controls for the animal room were set to maintain 18 to 

24°C, a relative humidity of 40 to 70%, approximately 15 room air 

changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to 

these conditions were maintained in the raw data and had no effect on 

the outcome of the study. 

Accommodation

Pre-mating Animals were housed in groups of 5 animals/sex/cage in Macrolon plastic

cages (MIV type, height 18 cm). 

Mating Females were caged together with males on a one-to-one-basis in 

Macrolon plastic cages (MIII type, height 18 cm).

Post-mating Males were housed in their home cage (Macrolon plastic cages, MIV type, 

height 18 cm) with a maximum of 5 animals/cage. Females were

individually housed in Macrolon plastic cages (MIII type, height 18 cm).

Lactation Pups were kept with the dam until termination in Macrolon plastic cages 

(MIII type, height 18 cm). During locomotor activity monitoring of the dams 

the pups were kept warm in their home cage using bottles filled with warm 

water. In order to avoid hypothermia of pups, pups were not left without 

their dam or a bottle filled with warm water for longer than 30-40 minutes.

General Sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, 

France) and paper as cage-enrichment/nesting material (Enviro-dri, Wm. 

Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom) were supplied. 

During locomotor activity monitoring, animals were housed individually in a 

Hi-temp polycarbonate cage (Ancare corp., USA; dimensions: 48.3 x 26.7 x 

20.3 cm) without cage-enrichment, bedding material, food and water.

Diet Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® 

Spezialdiäten GmbH, Soest, Germany). 

Water Free access to tap-water. 

Diet, water, bedding and cage-enrichment/nesting material evaluation for contaminants and/or 

nutrients was performed according to facility standard procedures. There were no findings that could 

interfere with the study.

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6.5. Treatment

6.5.1. Parental animals

Method Oral gavage, using a plastic feeding tube. Formulations were placed on a 

magnetic stirrer during dosing.

Dose volume 5 mL/kg body weight. Actual dose volumes were calculated according to 

the latest body weight.

Frequency Once daily for 7 days per week, approximately the same time each day 

with a maximum of 6 hours difference between the earliest and latest 

dose. 

Exposure period Males were exposed for 29 days, i.e. 2 weeks prior to mating, during 

mating, and up to the day prior to scheduled necropsy. Females were 

exposed for 41-47 days, i.e. during 2 weeks prior to mating, during 

mating, during post-coitum, and during at least 4 days of lactation (up to 

the day prior to scheduled necropsy). Female no. 47 (Group 1) was not 

dosed during littering.

6.5.2. Pups

Pups were not dosed directly but could have potentially be exposed to the test substance in utero, via 

maternal milk or from exposure to maternal urine/faeces.

6.6. Observations

6.6.1. Parental animals

Mortality / Viability At least twice daily. 

Clinical signs Daily from treatment onwards up to the day prior to necropsy, detailed 

clinical observations were made in all animals, at least 1 hour (± 30 min) 

after dosing. Once prior to start of treatment and at weekly intervals 

during the treatment period this was also performed outside the home 

cage in a standard arena. The time of onset, grade and duration of any 

observed sign was recorded. Signs were graded for severity and the 

maximum grade was predefined at 3 or 4. Grades were coded as slight 

(grade 1), moderate (grade 2), severe (grade 3) and very severe 

(grade 4). For certain signs, only its presence (grade 1) or absence 

(grade 0) was scored. In the data tables, the scored grades were

reported, as well as the percentage of animals affected in summary 

tables.

Functional Observations The following tests were performed on the selected 5 animals/sex/group:

- hearing ability *

- pupillary reflex *

- static righting reflex *

- grip strength *

* score 0 = normal/present, score 1 = abnormal/absent

- locomotor activity (recording period: 1-hour under normal laboratory 

light conditions, using a computerized monitoring system, Kinder 

Scientific LLC, Poway, USA). Total movements and ambulations 

were reported. Ambulations represent movements characterized by 

a relocation of the entire body position like walking, whereas total 

movements represent all movements made by the animals, including 

ambulations but also smaller or more fine movements like grooming, 

weaving or movements of the head.

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The selected males were tested during Week 4 of treatment and the 

selected females were tested towards the end of the scheduled lactation 

period (all before blood sampling). These tests were started after 

observation for clinical signs (incl. arena observation, if applicable) at 

least 1 hour (± 30 min) after dosing. 

Body weights Males and females were weighed on the first day of exposure and weekly 

thereafter. Mated females were weighed on Days 0, 4, 7, 11, 14, 17 and 

20 post-coitum and during lactation on Days 1 and 4. 

Food consumption Weekly, except for males and females which were housed together for 

mating and for females without evidence of mating. Food consumption of 

mated females was measured on Days 0, 4, 7, 11, 14, 17 and 20 postcoitum and on Days 1 and 4 of lactation.

Water consumption Subjective appraisal was maintained during the study, but no quantitative 

investigation was introduced as no treatment related effect was 

suspected.

General reproduction data Male number paired with, mating date, confirmation of pregnancy, and 

delivery day were recorded. Pregnant females were examined to detect 

signs of difficult or prolonged parturition, and cage debris of pregnant 

females was examined to detect signs of abortion or premature birth. Any 

deficiencies in maternal care (such as inadequate construction or 

cleaning of the nest, pups left scattered and cold, physical abuse of pups 

or apparently inadequate lactation or feeding) were examined.

6.6.2. Pups

Each litter was examined to determine the following, if practically possible:

Mortality / Viability The numbers of live and dead pups on Day 1 of lactation and daily 

thereafter were determined. If possible, defects or cause of death were

evaluated. 

Clinical signs At least once daily, detailed clinical observations were made for all 

animals.

Body weights Live pups were weighed on Days 1 and 4 of lactation.

Sex Sex was determined for all pups on Days 1 and 4 of lactation.

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6.7. Clinical laboratory investigations

Blood samples were collected at the end of the treatment period on the day of scheduled necropsy 

from the selected 5 animals/sex/group under anaesthesia using isoflurane (Abbott B.V., Hoofddorp, 

The Netherlands) between 7.00 and 10.30 a.m.

The animals were deprived of food overnight (with a maximum of 24 hours) before blood sampling, but 

water was available. Blood samples were drawn from the retro-orbital sinus and collected into tubes 

(Greiner Bio-One GmbH, Kremsmünster, Austria) prepared with K3-EDTA for haematological 

parameters (0.5 mL), with citrate for clotting tests (0.45 mL) and tubes treated with Li-heparin for 

clinical biochemistry parameters (0.5 mL). An additional blood sample (0.25 mL) was collected into 

serum tubes for determination of bile acids. The following parameters were determined:

6.7.1. Haematology

The following haematology parameters were determined in blood prepared with K3-EDTA as an anticoagulant, using the ADVIA® 120 Hematology System (Siemens Healthcare Diagnostics B.V., Breda, 

The Netherlands): 

Parameter (Abbreviation) Unit

White blood cells (WBC) 109/L

Differential leucocyte count:

Neutrophils %WBC

Lymphocytes %WBC

Monocytes %WBC

Eosinophils %WBC

Basophils %WBC

Red blood cells 1012/L

Reticulocytes %RBC

Red blood cell distribution width (RDW) %

Haemoglobin mmol/L

Haematocrit L/L

Mean corpuscular volume (MCV) fL

Mean corpuscular haemoglobin (MCH) fmol

Mean corpuscular haemoglobin concentration (MCHC) mmol/L

Platelets 109/L

The following clotting parameters were determined in plasma prepared with citrate as anti-coagulant, 

using the STA Compact® (Diagnostica Stago S.A.S., Asnières, France): 

Parameter (Abbreviation) Unit 

Prothrombin Time (PT) s

Activated Partial Thromboplastin Time (APTT) s

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6.7.2. Clinical biochemistry

The following clinical biochemistry parameters were determined using the AU400® Chemistry System 

(Beckman Coulter Nederland B.V., Woerden, The Netherlands). All parameters were determined in 

plasma, except for bile acids which were determined in serum:

Parameter (Abbreviation) Unit

Alanine aminotransferase (ALAT) U/L

Aspartate aminotransferase (ASAT) U/L

Alkaline Phosphatase (ALP) U/L

Total protein g/L

Albumin g/L

Total Bilirubin μmol/L

Bile acids μmol/L

Urea mmol/L

Creatinine μmol/L

Glucose mmol/L

Cholesterol mmol/L

Sodium mmol/L

Potassium mmol/L

Chloride mmol/L

Calcium mmol/L

Inorganic Phosphate (Inorg. Phos) mmol/L

6.8. Pathology

6.8.1. Necropsy parental animals

All males and the selected 5 females/group were deprived of food overnight (with a maximum of 24 

hours) prior to planned necropsy, but water was provided. Non-selected females were not deprived of 

food. 

All animals were deeply anaesthetized using isoflurane (Abbott B.V., Hoofddorp, The Netherlands) 

and subsequently exsanguinated and subjected to a full post mortem examination, with special 

attention being paid to the reproductive organs. Descriptions of all macroscopic abnormalities were 

recorded.

Necropsy was conducted on the following days:

Condition Day of necropsy

Females which delivered Lactation Days 5-7.

Females which failed to deliver

(nos. 46, 59, 61, 62, 79)

Post-coitum Days 25-27 (females with evidence of mating) 

Males Following completion of the mating period (a minimum of 28 days of 

dose administration).

The numbers of former implantation sites and corpora lutea were recorded for all paired females. 

Final Report - Page 17 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 18 - 

Samples of the following tissues and organs were collected and fixed in 10% buffered formalin (neutral 

phosphate buffered 4% formaldehyde solution, Klinipath, Duiven, The Netherlands). 

Selected 5 animals/sex/group: 

Identification marks: not processed Ovaries

Adrenal glands (Pancreas)

(Aorta) Peyer's patches [jejunum, ileum] if detectable

Brain - cerebellum, mid-brain, cortex Pituitary gland

Caecum Preputial gland

Cervix Prostate gland

Clitoral gland Rectum

Colon (Salivary glands - mandibular, sublingual)

Coagulation gland Sciatic nerve

Duodenum Seminal vesicles

Epididymides 1 Skeletal muscle

Eyes (with optic nerve (if detectable) and Harderian 

gland) 1

(Skin)

Spinal cord -cervical, midthoracic, lumbar

Female mammary gland area Spleen

Femur including joint Sternum with bone marrow

Heart Stomach

Ileum Testes 1

Jejunum Thymus

Kidneys Thyroid including parathyroid if detectable

(Lacrimal gland, exorbital) (Tongue)

(Larynx) Trachea

Liver Urinary bladder

Lung, infused with formalin Uterus

Lymph nodes - mandibular, mesenteric Vagina

(Nasopharynx) All gross lesions

(Esophagus)

All remaining animals and females which failed to deliver2: 

Cervix Preputial gland

Clitoral gland Prostate gland

Coagulation gland Seminal vesicles

Epididymides 1 Testes 1

Female mammary gland area Uterus

Ovaries Vagina

Identification marks: not processed All gross lesions

1 Fixed in modified Davidson's solution (prepared at WIL Research Europe using Formaldehyde 37-

40%, Ethanol, Acetic acid (glacial) (all Merck, Darmstadt, Germany) and Milli-Ro water (Millipore 

Corporation, Bedford, USA)) and transferred to formalin after fixation for at least 24 hours.

2 In case no macroscopically visible implantation sites were present, nongravid uteri were stained 

using the Salewski technique (Ref. 1) in order to detect any former implantation sites (Salewski 

staining prepared at WIL Research Europe using Ammoniumsulfide-solution 20% (Merck,

Darmstadt, Germany) and Milli-Ro water (Millipore Corporation, Bedford, USA)). 

Tissues/organs mentioned in parentheses were not examined by the pathologist, since no signs of 

toxicity were noted at macroscopic examination.

Final Report - Page 18 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

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6.8.2. Necropsy pups

Pups surviving to planned termination were killed by decapitation on Days 5-7 of lactation. All pups 

were sexed and descriptions of all external abnormalities were recorded. 

6.8.3. Organ weights

Terminal body weight were recorded from all males and the selected 5 females/sex/group. The 

following organ weights were recorded from the following animals on the scheduled day of necropsy:

Selected 5 animals/sex/group: 

Adrenal glands Spleen

Brain Testes

Epididymides Thymus

Heart Uterus (including cervix) 

Kidneys Prostate1

Liver Seminal vesicles including coagulating glands1

Ovaries Thyroid including parathyroid 1 weighed when fixed for at least 24 hours.

All remaining males:

Epididymides

Testes

6.8.4. Histotechnology

All organ and tissue samples, as defined under Histopathology (following section), were processed, 

embedded and cut at a thickness of 2-4 micrometers and stained with haematoxylin and eosin 

(Klinipath, Duiven, The Netherlands).

From the selected 5 males of the control and high dose group, and all males suspected to be infertile,

additional slides of the testes were prepared to examine staging of spermatogenesis. The testes were

processed, sectioned at 3-4 micrometers, and stained with PAS/haematoxylin (Klinipath, Duiven, The 

Netherlands).

6.8.5. Histopathology

The following slides were examined by a pathologist:

- The preserved organs and tissues of the selected 5 animals/sex of Groups 1 and 4. 

- The additional slides of the testes of the selected 5 males of Groups 1 and 4 and all males 

suspected to be infertile or which died before mating to examine staging of spermatogenesis.

- All gross lesions of all animals (all dose groups).

- The heart of all selected 5 males of Groups 2 and 3 and the adrenal glands of all selected 5 

females of Groups 2 and 3, based on (possible) treatment-related changes in these organs in 

Group 4.

- The reproductive organs* of all males that failed to sire and all females that failed to deliver 

healthy pups:

Group Female/Male nos. Reason

1 46 / 06 Not pregnant

2 59 / 19 Not pregnant

3 61 / 21

62 / 22

Not pregnant

Not pregnant

4 79 / 39 Not pregnant

* Reproductive organs included the cervix, clitoral gland, coagulation gland, epididymides, 

ovaries, preputial gland, prostate gland, seminal vesicles, testes, uterus, and vagina.

Final Report - Page 19 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

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All abnormalities were described and included in the report. An attempt was made to correlate gross 

observations with microscopic findings.

A peer review on the histopathology data was performed by a second pathologist.

6.9. Electronic data capture

Observations/measurements in the study were recorded electronically using the following program(s):

- REES Centron Environmental Monitoring system version SQL 2.0 (REES Scientific, Trenton, NJ, 

USA).

- TOXDATA version 8.0 (WIL Research Europe B.V., ‘s-Hertogenbosch, The Netherlands): Mortality / 

Clinical signs / Body weights / Food consumption / Reproduction parameters / Observations pups / 

Organ weights.

- ADVIA® 120 Hematology SystemVersion V.3.1.8.0.MS (Siemens Healthcare Diagnostics B.V., 

Breda, The Netherlands): Haematology.

- STA Compact® version 107.07 (Diagnostica Stago S.A.S., Asnières, France): Clotting parameters.

- AU400® Chemistry System version 8.2A (Beckman Coulter Nederland B.V., Woerden, The 

Netherlands): Clinical biochemistry.

- Motor Monitor version 08356-14 (Kinder Scientific LLC, Poway, USA): Motor activity measurement.

- Pathdata version 6.2D (Pathology Data Systems, Basel, Switzerland): Histopathology.

- Shimadzu TOC-Control V version 2.10 (Shimadzu, Kyoto, Japan): Carbon analysis of formulations. 

Two project numbers were used to collect online data (all data was reported under Project 503342).

Project number Online data

503344 Parental animals: mortality, clinical signs, functional observations (except motor 

activity), body weights and food consumption pre-mating period, body weights 

mating period, food consumption mating period (males only), clinical laboratory 

investigations, macroscopic findings and organ weights

503342 All other data

6.10. Interpretation

6.10.1. Calculations

For each group, the following calculations were performed:

Mating index (%) Number of females mated x 100 Number of females paired

Fertility index (%) Number of pregnant females x 100 Number of females paired

Conception index (%) Number of pregnant females x 100 Number of females mated

Gestation index (%) Number of females bearing live pups x 100 Number of pregnant females

Duration of gestation Number of days between confirmation of mating and the beginning 

of parturition

Percentage live males at 

First Litter Check

Number of live male pups at First Litter Check x 100 Number of live pups at First Litter Check

Percentage live females at 

First Litter Check

Number of live female pups at First Litter Check x 100 Number of live pups at First Litter Check

Final Report - Page 20 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 21 - 

Percentage of postnatal loss Number of dead pups before planned necropsy x 100 Number of live pups at First Litter Check

Viability index Number of live pups before planned necropsy x 100 Number of pups born alive

6.10.2. Statistical analyses

The following statistical methods were used to analyze the data:

- If the variables could be assumed to follow a normal distribution, the Dunnett-test (Ref. 2; many-toone t-test) based on a pooled variance estimate was applied for the comparison of the treated 

groups and the control groups for each sex. 

- The Steel-test (Ref. 3; many-to-one rank test) was applied if the data could not be assumed to 

follow a normal distribution. 

- The Fisher Exact-test (Ref. 4) was applied to frequency data. 

- The Kruskal-Wallis nonparametric ANOVA test (Ref. 5) was applied to motor activity data to 

determine intergroup differences. In case intergroup differences were seen, the Wilcoxon test (Ref. 

6) was applied to compare the treated groups to the control group.

All tests were two-sided and in all cases p < 0.05 was accepted as the lowest level of significance.

Group means were calculated for continuous data and medians were calculated for discrete data 

(scores) in the summary tables. Test statistics were calculated on the basis of exact values for means 

and pooled variances. Individual values, means and standard deviations may have been rounded off 

before printing. Therefore, two groups may display the same printed means for a given parameter, yet 

display different test statistics values.

6.11. List of deviations

6.11.1. List of protocol deviations

1. On Day 4 of lactation, no clinical observations were registered in the computer for pup 5 of litter 

56 (Group 2).

Evaluation: Sufficient information available. Moreover, no findings were noted on Day 3 and 5, 

and its body weight was determined on Day 4.

2. Analysis of stability of the test substance under test conditions was not performed as part of 

this study, since Total Organic Carbon (TOC) analysis is a general method that does not 

distinguish original substance from hydrolysis product(s).

Evaluation: Data from the sponsor indicated stability in water for >24 hours at a concentration 

of 5%. As all formulations (2, 6 and 20%) were prepared daily within 4 hours prior to dosing, it 

can be assumed that the formulations under the current study conditions were also sufficiently 

stable.

3. Carbon analysis of formulations were recorded electronically using Shimadzu TOC-Control V 

version 2.10 (Shimadzu, Kyoto, Japan).

Evaluation: omission from the protocol. Appropriate method was used.

The study integrity was not adversely affected by the deviations.

6.11.2. List of standard operating procedure deviations

Any deviations from standard operating procedures were evaluated and filed in the study file. There 

were no deviations from standard operating procedures that affected the integrity of the study. 

Final Report - Page 21 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 22 - 

7. RESULTS

7.1. Analysis of dose preparations

The concentrations analysed in the formulations of Group 2, Group 3 and Group 4 were in agreement 

with target concentrations (i.e. mean accuracies between 90% and 110%). No test substance was 

detected in the Group 1 formulation. 

The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%). 

For further details, see APPENDIX 3.

7.2. Observations parental animals

For further detail on summary data, see APPENDIX 1 and on individual data, see APPENDIX 2.

7.2.1. Mortality

No mortality occurred during the study period.

7.2.2. Clinical signs

No toxicologically significant clinical signs were noted during the observation period.

Incidental findings that were noted included piloerection and rales. These findings occurred within the 

range of background findings to be expected for rats of this age and strain which are housed and 

treated under the conditions in this study. At the incidence observed, these were considered signs of 

no toxicological relevance.

7.2.3. Functional observations

Hearing ability, pupillary reflex, static righting reflex and grip strength were normal in all selected 

animals. 

The variation in motor activity did not indicate a relation with treatment.

All groups showed a similar habituation profile with very high activity in the first interval that decreased 

over the duration of the test period.

The statistically significant increase noted for number of ambulations for males at 100 mg/kg was not 

considered toxicologically relevant as the individual values were within normal limits and no dose 

response relationship was seen.

7.2.4. Body weights

No toxicologically relevant changes in body weights and body weight gain were noted. 

The statistically significant changes in body weight gain noted for males at 100 mg/kg were not 

considered toxicologically relevant as no dose response relationship was observed and the individual 

values were within normal limits.

7.2.5. Food consumption

Food consumption before or after allowance for body weight was similar between treated and control 

animals.

Final Report - Page 22 of 272 -
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7.2.6. Haematology

Haematological parameters of treated rats were considered not to have been affected by treatment.

The statistically significantly decreased prothrombin time for males treated at 300 mg/kg was

considered to be of no toxicological relevance as this occurred in the absence of a treatment-related 

distribution and remained within the range considered normal for rats of this age and strain.

7.2.7. Clinical biochemistry

Clinical biochemistry parameters of treated rats were considered not to have been affected by 

treatment up to 1000 mg/kg.

7.2.8. Macroscopic examination

Macroscopic observations at necropsy did not reveal any alterations that were considered to have 

arisen as a result of treatment.

The incidence of incidental findings among control and treated animals was within the background 

range of findings that are encountered among rats of this age and strain, and did not show a doserelated incidence trend. 

In addition, one female (no. 64) treated at 300 mg/kg had cannibalised one of her pups during transfer 

from the animal room to the necropsy room. At this single occurrence, it was not considered 

toxicologically significant.

7.2.9. Organ weights

At 1000 mg/kg, increased weights (absolute and relative) of seminal vesicles and uterus were noted. 

In addition, relative kidneys weights were higher for males treated at 300 and 1000 mg/kg.

The statistically significantly decreased absolute liver weights for males treated at 100 mg/kg was 

considered to be of no toxicological relevance as this occurred in the absence of a treatment-related 

distribution and remained within the range considered normal for rats of this age and strain.

Female number 69 (treated at 300 mg/kg) showed an enlarged liver macroscopically which was 

confirmed by a high liver weight. At this single occurrence and without a dose response, it was not 

considered toxicologically relevant.

7.2.10. Microscopic examination

Possible treatment-related findings were recorded in the heart of males and adrenal glands of 

females.

Heart, males:

- an increase in severity (slight degree) of mononuclear inflammation in 1/5 males treated at 1000 

mg/kg, compared to minimal degrees in 1/5 males treated at 0 mg/kg, in 1/5 males at 100 mg/kg and 

in 1/5 males at 300 mg/kg.

- an increase in incidence and/or severity of myofiber degeneration (2/5, up to slight) in males treated 

at 1000 mg/kg, compared to minimal degree in 1/5 males treated at 300 mg/kg and absence of this 

finding in control males and males treated at 100 mg/kg.

Adrenal glands, females:

an increase in incidence of vacuolation of the zona glomerulosa in 4/5 females treated at 1000 mg/kg, 

compared to 1/5 females treated at 0 mg/kg, 1/5 females at 100 mg/kg and 1/5 females at 300 mg/kg.

The remainder of microscopic findings recorded, were within the normal range of background 

pathology encountered in Wistar (Han) rats of this age.

In each group one or two females were not pregnant. No treatment-related findings were recorded in 

the reproductive organs of those females and their matching males. 

Final Report - Page 23 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 24 - 

The spermatogenic staging profiles were normal for all males examined. 

For further details, see APPENDIX 4.

7.3. Reproduction/developmental data

For further detail on summary data, see APPENDIX 1 and on individual data, see APPENDIX 2.

7.3.1. Reproduction data

No toxicologically relevant effects on reproductive parameters were noted.

Mating, fertility and conception indices, precoital time, and number of corpora lutea and implantation 

sites were unaffected by treatment.

At 300 mg/kg, two females (nos. 63 and 70) had a relatively low number of corpora lutea, implantation 

sites and/or living pups at first litter check. As this was not noted at 1000 mg/kg and these low 

numbers are occasionally seen historically in control data, it was not considered toxicologically 

relevant.

7.3.2. Developmental data

No toxicologically relevant effects on gestation index and duration, parturition, maternal care and early 

postnatal pup development (mortality, clinical signs, body weight and macroscopy) were observed.

Parturition/maternal care

No signs of difficult or prolonged parturition were noted among the pregnant females. 

Examination of cage debris of pregnant females revealed no signs of abortion or premature birth. No 

deficiencies in maternal care were observed.

Early postnatal pup development 

Number of dead and living pups at first litter check, postnatal loss, viability index and sex ratio were 

unaffected by treatment, and clinical signs, body weight and external macroscopy did not reveal 

treatment-related findings.

The statistically significantly change noted for sex ratio for pups at 300 mg/kg (71% female pups at 

300 mg/kg compared to 52% female pups at the control group) was not considered toxicologically 

significant as this change was not noted at the higher dose of 1000 mg/kg.

Mortality

Two pups at 100 mg/kg and one pup at 300 mg/kg were found dead or missing during lactation. Pups 

missing were most likely cannibalised. No toxicological relevance was attributed to these dead/missing 

pups since the mortality incidence did not show a dose-related trend and remained within the range 

considered normal for pups of this age.

Observations

Incidental findings of pups consisted of blue spot on several body parts and scabbing of the snout. 

The nature and incidence of these findings remained within the range considered normal for pups of 

this age, and were therefore considered to be of no toxicological relevance.

Body weights

Body weights of pups were considered to have been unaffected by treatment.

Final Report - Page 24 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 25 - 

8. DISCUSSION AND CONCLUSION

Castor Oil, Sulfated, Sodium Salt, 75% was administered by daily oral gavage to male and female 

Wistar Han rats at dose levels of 100, 300 and 1000 mg/kg. Males were exposed for 2 weeks prior to 

mating, during mating, and up to termination (for 29 days). The females were exposed for 2 weeks 

prior to mating, during mating, during post-coitum, and at least 4 days of lactation (for 41-47 days).

Formulation analysis showed that the formulations were prepared accurately and homogenously. 

Parental results:

Parental toxicity was observed for males at 1000 mg/kg. This consisted of a subtle increase in severity 

of mononuclear inflammation and in incidence and/or severity of myofiber degeneration in the heart. 

Both findings were slightly above the range of background findings of Wistar (Han) rats of this age. 

Therefore a possible test item-related effect cannot be excluded.

For females at 1000 mg/kg, an increase in incidence of vacuolation of the zona glomerulosa of the 

adrenal glands was noted. However, based on the minimal degree and absence of other test itemrelated findings in the females, this finding was considered not to be adverse.

At 1000 mg/kg, increased weights (absolute and relative) of seminal vesicles and uterus were noted. 

In addition, relative kidneys weights were higher for males treated at 300 and 1000 mg/kg. In the 

absence of corroborative findings in blood parameters and histopathological examination, these 

changes were not considered toxicologically significant.

No treatment-related changes were noted in any of the remaining parental parameters investigated in 

this study (i.e. clinical appearance, functional observations, body weight, food consumption, clinical 

laboratory investigations, and macroscopic examination).

Reproductive results:

No reproduction toxicity was observed up to the highest dose level tested (1000 mg/kg). 

No toxicologically relevant changes were noted in any of the reproductive parameters investigated in 

this study (i.e. mating, fertility and conception indices, precoital time, and numbers of corpora lutea 

and implantation sites).

Developmental results:

No developmental toxicity was observed up to the highest dose level tested (1000 mg/kg). 

No toxicologically relevant changes were noted in any of the developmental parameters investigated 

in this study (i.e. gestation index and duration, parturition, maternal care and early postnatal pup 

development consisting of mortality, clinical signs, body weight and macroscopy).

In conclusion, treatment with Castor Oil, Sulfated, Sodium Salt, 75% by oral gavage in male and 

female Wistar Han rats at dose levels of 100, 300 and 1000 mg/kg revealed parental toxicity for males 

at 1000 mg/kg. No reproduction and developmental toxicity was observed for treatment up to 1000

mg/kg.

Based on these results, the following No Observed Adverse Effect Levels (NOAEL) were derived: 

Parental NOAEL: 300 mg/kg for males, and

at least 1000 mg/kg for females

Reproduction NOAEL: at least 1000 mg/kg

Developmental NOAEL: at least 1000 mg/kg

Final Report - Page 25 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 26 - 

9. REFERENCES

Ref. 1 Salewski, E. Färbemethode zum makroskopischen Nachweis von Implantationsstellen 

am Uterus der Ratte. [Staining method for a macroscopic test for implantation sites in 

the uterus of the rat]. Naunyn - Schmiedebergs Archiv für Experimentelle Pathologie 

und Pharmakologie, 247, 367 (1964).

Ref. 2 Dunnett C.W., A Multiple Comparison Procedure for Comparing Several Treatments 

with a Control, J. Amer. Stat. Assoc. 50, 1096-1121 (1955).

Ref. 3 Miller R.G., Simultaneous Statistical Inference, Springer Verlag, New York (1981).

Ref. 4 Fisher R.A., Statistical Methods for Research Workers, Oliver and Boyd, Edinburgh 

(1950).

Ref. 5 Kruskal W.H. and Wallis W.A.. Use of ranks in one-criterion variance analysis. Journal 

of the American Statistical Association 47 (260): 583-621, December (1952).

Ref. 6 Wilcoxon, F. Individual comparisons by ranking methods. Biometrics, 1, 80-83 (1945).

Final Report - Page 26 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

APPENDIX 1 SUMMARY TABLES

Final Report - Page 27 of 272 -
 05Nov13 14h12

.: Observation performed, sign not present

%: Percent of affected animals (0=less than 5%, 1=between 5% and 15%,..., A=more than 95%)

G: Median value of the highest individual daily grades

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.1 CLINICAL SIGNS SUMMARY

MALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 1 (CONTROL)

No clinical signs noted .

GROUP 2 (100 MG/KG)

No clinical signs noted .

GROUP 3 (300 MG/KG)

No clinical signs noted .

GROUP 4 (1000 MG/KG)

Breathing .

 Rales (3) G: . . . . . . . . . . . . . . . . . . . . . . . 111. . . .

%: . . . . . . . . . . . . . . . . . . . . . . . 111. . . .

FEMALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 1 (CONTROL)

No clinical signs noted .

GROUP 2 (100 MG/KG)

Skin / fur .

 Piloerection (1) G: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. . . . . . . . . . . .

%: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. . . . . . . . . . . .

GROUP 3 (300 MG/KG)

No clinical signs noted .

GROUP 4 (1000 MG/KG)

Breathing .

 Rales (3) G: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. . . . . .

%: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. . . . . .

- Page 2 - Final Report - Page 28 of 272 -
 05Nov13 14h12

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.2 FUNCTIONAL OBSERVATIONS SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

AT WEEK 4

HEARING MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

PUPIL L MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

PUPIL R MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

STATIC R MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

GRIP MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

AT LACTATION

HEARING MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

PUPIL L MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

PUPIL R MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

STATIC R MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

GRIP MEDIAN 0 0 0 0 .

SCORE 0/1 N 5 5 5 5 .

.

- Page 3 - Final Report - Page 29 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.3 MOTOR ACTIVITY TEST SUMMARY

MALES

AT WEEK 4

GROUP 1

CONTROL

Total Movements MEAN1 3030 4072 3711 2788

ST.DEV 1041 893 1003 507

N 5 5 5 5

Ambulations MEAN1 595 951 * 745 549

ST.DEV 161 194 409 106

N 5 5 5 5

*/** Wilcoxon test significant at 5% (*) or 1% (**) level 

1

 Group mean of all intervals combined

2

 Mean counts per interval.

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

0

200

400

600

800

1000

1200

1400

1 2 3 4 5 6 7 8 9 10 11 12

Counts

Interval (5 min.)

Total Movements Males2

Group 1

Group 2

Group 3

Group 4

0

50

100

150

200

250

300

350

400

1 2 3 4 5 6 7 8 9 10 11 12

Counts

Interval (5 min.)

Ambulations Males2

Group 1

Group 2

Group 3

Group 4

- Page 4 - Final Report - Page 30 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.3 MOTOR ACTIVITY TEST SUMMARY

FEMALES

AT LACTATION

GROUP 1

CONTROL

MEAN1 3608 3515 3992 3789

ST.DEV 1042 711 776 820

N 5 5 5 5

Ambulations MEAN1 789 743 752 835

ST.DEV 484 132 121 243

N 5 5 5 5

*/** Wilcoxon test significant at 5% (*) or 1% (**) level 

1

 Group mean of all intervals combined

2

 Mean counts per interval.

Total Movements

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

0

200

400

600

800

1000

1200

1400

1600

1800

1 2 3 4 5 6 7 8 9 10 11 12

Counts

Interval (5 min.)

Total Movements Females2

Group 1

Group 2

Group 3

Group 4

0

50

100

150

200

250

300

350

1 2 3 4 5 6 7 8 9 10 11 12

Counts

Interval (5 min.)

Ambulations Females2

Group 1

Group 2

Group 3

Group 4

- Page 5 - Final Report - Page 31 of 272 -
 05Nov13 14h12

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.4 BODY WEIGHTS (GRAM) SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAY 1 MEAN 321 318 320 320 .

WEEK 1 ST.DEV 9.1 9.9 7.9 9.3 .

N 10 10 10 10 .

.

DAY 8 MEAN 341 334 337 338 .

WEEK 2 ST.DEV 11.9 12.8 9.8 11.4 .

N 10 10 10 10 .

.

MATING PERIOD

DAY 1 MEAN 364 353 362 357 .

WEEK 1 ST.DEV 13.5 14.5 14.1 11.6 .

N 10 10 10 10 .

.

DAY 8 MEAN 376 361 371 365 .

WEEK 2 ST.DEV 13.4 16.8 15.3 15.5 .

N 10 10 10 10 .

.

DAY 15 MEAN 390 375 385 378 .

WEEK 3 ST.DEV 12.3 18.1 16.5 17.2 .

N 10 10 10 10 .

.

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAY 1 MEAN 197 201 201 202 .

WEEK 1 ST.DEV 4.7 5.1 6.6 8.0 .

N 10 10 10 10 .

.

DAY 8 MEAN 212 213 212 213 .

WEEK 2 ST.DEV 5.1 5.4 8.1 8.9 .

N 10 10 10 10 .

.

MATING PERIOD

DAY 1 MEAN 226 223 229 222 .

WEEK 1 ST.DEV 8.4 7.5 11.1 9.9 .

N 10 10 10 10 .

.

- Page 6 - Final Report - Page 32 of 272 -
 05Nov13 14h29

Explanations for excluded data are listed in the tables of the individual values

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.4 BODY WEIGHTS (GRAM) SUMMARY

FEMALES

F0-GENERATION

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

POST COITUM

DAY 0 MEAN 224 226 226 222 .

ST.DEV. 6.4 5.3 9.4 9.1 .

N 9 9 8 9 .

.

DAY 4 MEAN 240 239 243 237 .

ST.DEV. 9.9 6.7 10.8 8.5 .

N 9 9 8 9 .

.

DAY 7 MEAN 248 248 251 247 .

ST.DEV. 12.3 8.9 11.7 10.1 .

N 9 9 8 9 .

.

DAY 11 MEAN 266 265 269 261 .

ST.DEV. 14.7 11.0 16.3 10.6 .

N 9 9 8 9 .

.

DAY 14 MEAN 279 278 281 276 .

ST.DEV. 16.8 9.9 16.7 9.3 .

N 9 9 8 9 .

.

DAY 17 MEAN 303 300 300 303 .

ST.DEV. 19.9 9.4 21.2 10.8 .

N 9 9 8 9 .

.

DAY 20 MEAN 345 341 336 345 .

ST.DEV. 27.0 15.3 32.3 13.2 .

N 9 9 8 9 .

.

LACTATION

DAY 1 MEAN 266 262 264 263 .

ST.DEV. 15.7 9.8 18.2 13.2 .

N 9 9 8 9 .

.

DAY 4 MEAN 281 277 279 276 .

ST.DEV. 17.5 6.1 18.8 12.8 .

N 9 9 8 9 .

.

- Page 7 - Final Report - Page 33 of 272 -
 05Nov13 14h12

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.5 BODY WEIGHT GAIN (%) SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAY 1 MEAN 0 0 0 0 .

WEEK 1 ST.DEV 0.0 0.0 0.0 0.0 .

N 10 10 10 10 .

.

DAY 8 MEAN 6 5 5 6 .

WEEK 2 ST.DEV 1.8 1.6 0.9 2.5 .

N 10 10 10 10 .

.

MATING PERIOD

DAY 1 MEAN 13 11 13 12 .

WEEK 1 ST.DEV 2.0 2.1 2.5 2.7 .

N 10 10 10 10 .

.

DAY 8 MEAN 17 13 * 16 14 .

WEEK 2 ST.DEV 2.0 2.8 2.8 3.2 .

N 10 10 10 10 .

.

DAY 15 MEAN 21 18 * 20 18 .

WEEK 3 ST.DEV 2.4 3.2 3.0 3.9 .

N 10 10 10 10 .

.

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAY 1 MEAN 0 0 0 0 .

WEEK 1 ST.DEV 0.0 0.0 0.0 0.0 .

N 10 10 10 10 .

.

DAY 8 MEAN 7 6 5 6 .

WEEK 2 ST.DEV 3.5 2.1 2.7 1.6 .

N 10 10 10 10 .

.

MATING PERIOD

DAY 1 MEAN 14 11 14 10 .

WEEK 1 ST.DEV 5.4 3.4 4.8 2.9 .

N 10 10 10 10 .

.

- Page 8 - Final Report - Page 34 of 272 -
 05Nov13 14h29

Explanations for excluded data are listed in the tables of the individual values

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.5 BODY WEIGHT GAIN (%) SUMMARY

FEMALES

F0-GENERATION

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

POST COITUM

DAY 0 MEAN 0 0 0 0 .

ST.DEV. 0.0 0.0 0.0 0.0 .

N 9 9 8 9 .

.

DAY 4 MEAN 7 6 8 7 .

ST.DEV. 2.5 1.9 2.7 1.7 .

N 9 9 8 9 .

.

DAY 7 MEAN 11 10 11 12 .

ST.DEV. 3.6 2.7 3.1 2.6 .

N 9 9 8 9 .

.

DAY 11 MEAN 19 17 19 18 .

ST.DEV. 4.6 3.6 4.1 2.6 .

N 9 9 8 9 .

.

DAY 14 MEAN 25 23 25 25 .

ST.DEV. 5.0 3.6 5.3 3.5 .

N 9 9 8 9 .

.

DAY 17 MEAN 35 32 33 37 .

ST.DEV. 6.1 4.1 7.5 3.7 .

N 9 9 8 9 .

.

DAY 20 MEAN 54 51 49 56 .

ST.DEV. 8.8 6.8 12.8 5.4 .

N 9 9 8 9 .

.

LACTATION

DAY 1 MEAN 0 0 0 0 .

ST.DEV. 0.0 0.0 0.0 0.0 .

N 9 9 8 9 .

.

DAY 4 MEAN 6 6 6 5 .

ST.DEV. 2.0 3.4 2.8 3.7 .

N 9 9 8 9 .

.

- Page 9 - Final Report - Page 35 of 272 -
 05Nov13 14h12

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.6 FOOD CONSUMPTION (G/ANIMAL/DAY) SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAYS 1-8 MEAN 23 23 24 23 .

WEEKS 1-2 ST.DEV 0.9 0.1 0.2 1.7 .

N (CAGE) 2 2 2 2 .

.

DAYS 8-15 MEAN 24 23 23 23 .

WEEKS 2-3 ST.DEV 0.1 0.7 0.4 1.6 .

N (CAGE) 2 2 2 2 .

.

MEAN OF MEANS .

OVER PRE MATI... MEAN 23 23 23 23 .

MATING PERIOD

DAYS 1-8 MEAN 24 23 24 24 .

WEEKS 1-2 ST.DEV 0.4 0.3 0.2 3.8 .

N (CAGE) 2 2 2 2 .

.

DAYS 8-15 MEAN 24 23 24 24 .

WEEKS 2-3 ST.DEV 0.8 0.9 0.2 1.6 .

N (CAGE) 2 2 2 2 .

.

MEAN OF MEANS .

OVER MATING P... MEAN 24 23 24 24 .

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAYS 1-8 MEAN 17 17 17 17 .

WEEKS 1-2 ST.DEV 0.5 0.1 0.7 0.8 .

N (CAGE) 2 2 2 2 .

.

DAYS 8-15 MEAN 17 17 17 17 .

WEEKS 2-3 ST.DEV 0.3 0.2 0.9 0.6 .

N (CAGE) 2 2 2 2 .

.

MEAN OF MEANS .

OVER PRE MATI... MEAN 17 17 17 17 .

- Page 10 - Final Report - Page 36 of 272 -
 05Nov13 14h29

Explanations for excluded data are listed in the tables of the individual values

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.6 FOOD CONSUMPTION (G/ANIMAL/DAY) SUMMARY

FEMALES

F0-GENERATION

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

POST COITUM

DAYS 0-4 MEAN 18 18 19 18 .

ST.DEV. 2.2 2.1 1.8 1.1 .

N 9 9 8 9 .

.

DAYS 4-7 MEAN 22 22 22 22 .

ST.DEV. 2.7 2.0 1.9 0.8 .

N 9 9 8 9 .

.

DAYS 7-11 MEAN 22 21 23 20 .

ST.DEV. 2.9 1.9 3.1 2.5 .

N 9 9 8 9 .

.

DAYS 11-14 MEAN 23 21 23 22 .

ST.DEV. 2.9 1.9 2.7 1.4 .

N 9 9 8 9 .

.

DAYS 14-17 MEAN 22 21 23 22 .

ST.DEV. 2.7 2.1 2.9 1.2 .

N 9 9 8 9 .

.

DAYS 17-20 MEAN 25 24 25 25 .

ST.DEV. 3.2 2.4 4.1 2.1 .

N 9 9 8 9 .

.

.

MEAN OF MEANS 22 21 22 22 .

LACTATION

DAYS 1-4 MEAN 35 33 32 34 .

ST.DEV. 5.5 4.2 6.9 6.0 .

N 9 9 8 9 .

.

- Page 11 - Final Report - Page 37 of 272 -
 05Nov13 14h12

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.7 RELATIVE FOOD CONSUMPTION (G/KG BODY WEIGHT/DAY) SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAYS 1-8 MEAN 68 68 70 68 .

WEEKS 1-2 ST.DEV 1.8 0.9 0.3 4.2 .

N (CAGE) 2 2 2 2 .

.

DAYS 8-15 MEAN 69 68 69 68 .

WEEKS 2-3 ST.DEV 0.4 1.8 1.6 4.1 .

N (CAGE) 2 2 2 2 .

.

MEAN OF MEANS .

OVER PRE MATI... MEAN 69 68 69 68 .

MATING PERIOD

DAYS 1-8 MEAN 64 65 66 65 .

WEEKS 1-2 ST.DEV 0.5 1.6 0.7 10.1 .

N (CAGE) 2 2 2 2 .

.

DAYS 8-15 MEAN 62 61 62 63 .

WEEKS 2-3 ST.DEV 1.4 1.5 0.3 4.5 .

N (CAGE) 2 2 2 2 .

.

MEAN OF MEANS .

OVER MATING P... MEAN 63 63 64 64 .

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

PRE MATING

DAYS 1-8 MEAN 80 80 80 78 .

WEEKS 1-2 ST.DEV 2.0 0.5 2.0 2.9 .

N (CAGE) 2 2 2 2 .

.

DAYS 8-15 MEAN 79 80 82 79 .

WEEKS 2-3 ST.DEV 1.0 1.0 2.9 2.2 .

N (CAGE) 2 2 2 2 .

.

MEAN OF MEANS .

OVER PRE MATI... MEAN 80 80 81 79 .

- Page 12 - Final Report - Page 38 of 272 -
 05Nov13 14h29

Explanations for excluded data are listed in the tables of the individual values

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.7 RELATIVE FOOD CONSUMPTION (G/KG BODY WEIGHT/DAY) SUMMARY

FEMALES

F0-GENERATION

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

POST COITUM

DAYS 0-4 MEAN 75 76 77 76 .

ST.DEV. 6.9 7.5 5.2 3.5 .

N 9 9 8 9 .

.

DAYS 4-7 MEAN 86 89 87 91 .

ST.DEV. 7.0 5.7 5.5 4.5 .

N 9 9 8 9 .

.

DAYS 7-11 MEAN 83 80 84 77 .

ST.DEV. 7.0 4.6 7.0 7.9 .

N 9 9 8 9 .

.

DAYS 11-14 MEAN 81 77 82 80 .

ST.DEV. 5.9 4.8 5.4 3.9 .

N 9 9 8 9 .

.

DAYS 14-17 MEAN 74 69 76 74 .

ST.DEV. 4.4 6.4 5.6 3.0 .

N 9 9 8 9 .

.

DAYS 17-20 MEAN 71 71 74 72 .

ST.DEV. 5.2 5.8 9.1 6.6 .

N 9 9 8 9 .

.

.

MEAN OF MEANS 78 77 80 78 .

LACTATION

DAYS 1-4 MEAN 125 120 115 123 .

ST.DEV. 16.0 14.8 22.6 16.9 .

N 9 9 8 9 .

.

- Page 13 - Final Report - Page 39 of 272 -
 13Mar14 11h25

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503344

APPENDIX 1

1.8 HAEMATOLOGY SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

WBC MEAN 8.8 8.1 9.3 8.4 .

10E9/L ST.DEV 1.9 1.9 3.0 1.1 .

N 5 4 5 5 .

.

Neutrophils MEAN 14.7 16.9 22.5 16.5 .

%WBC ST.DEV 6.8 5.4 4.4 4.7 .

N 5 5 5 5 .

.

Lymphocytes MEAN 82.2 78.9 73.8 80.3 .

%WBC ST.DEV 7.2 5.6 4.6 4.5 .

N 5 5 5 5 .

.

Monocytes MEAN 2.0 2.5 2.3 1.7 .

%WBC ST.DEV 0.5 0.8 0.4 0.1 .

N 5 5 5 5 .

.

Eosinophils MEAN 0.8 1.5 1.2 1.3 .

%WBC ST.DEV 0.3 0.4 0.5 0.4 .

N 5 5 5 5 .

.

Basophils MEAN 0.2 0.2 0.2 0.2 .

%WBC ST.DEV 0.1 0.1 0.1 0.1 .

N 5 5 5 5 .

.

Red blood cells MEAN 9.29 9.14 8.95 9.23 .

10E12/L ST.DEV 0.32 0.46 0.12 0.36 .

N 5 5 5 4 .

.

Reticulocytes MEAN 2.6 2.5 2.5 2.5 .

%RBC ST.DEV 0.5 0.4 0.3 0.2 .

N 5 5 5 4 .

.

RDW MEAN 13.2 12.4 13.1 14.6 .

% ST.DEV 1.1 0.4 0.8 2.2 .

N 5 5 5 4 .

.

Haemoglobin MEAN 11.0 11.0 10.8 10.9 .

mmol/L ST.DEV 0.5 0.3 0.4 0.4 .

N 5 5 5 5 .

.

Haematocrit MEAN 0.480 0.479 0.475 0.481 .

L/L ST.DEV 0.020 0.019 0.012 0.026 .

N 5 5 5 4 .

.

MCV MEAN 51.7 52.4 53.1 52.1 .

fL ST.DEV 0.5 1.3 1.5 1.2 .

N 5 5 5 4 .

.

MCH MEAN 1.19 1.21 1.21 1.18 .

fmol ST.DEV 0.02 0.04 0.04 0.05 .

N 5 5 5 4 .

.

MCHC MEAN 22.96 23.10 22.84 22.70 .

mmol/L ST.DEV 0.31 0.66 0.29 0.67 .

N 5 5 5 4 .

.

Platelets MEAN 879 890 901 872 .

10E9/L ST.DEV 62 55 66 79 .

N 5 5 5 4 .

.

- Page 14 - Final Report - Page 40 of 272 -
 13Mar14 11h25

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503344

APPENDIX 1

1.8 HAEMATOLOGY SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

PT MEAN 18.0 17.4 16.8 * 17.4 .

s ST.DEV 0.8 0.7 0.3 0.7 .

N 5 5 5 5 .

.

APTT MEAN 17.3 19.2 16.9 17.4 .

s ST.DEV 3.5 2.3 2.7 3.1 .

N 5 5 5 5 .

.

- Page 15 - Final Report - Page 41 of 272 -
 13Mar14 11h25

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503344

APPENDIX 1

1.8 HAEMATOLOGY SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

WBC MEAN 4.5 5.3 5.3 5.6 .

10E9/L ST.DEV 0.9 0.8 1.3 0.8 .

N 5 5 4 5 .

.

Neutrophils MEAN 26.6 25.9 26.2 27.7 .

%WBC ST.DEV 4.9 3.1 9.6 5.4 .

N 5 5 5 5 .

.

Lymphocytes MEAN 70.1 71.1 69.2 69.9 .

%WBC ST.DEV 4.9 3.7 9.9 5.3 .

N 5 5 5 5 .

.

Monocytes MEAN 2.3 2.0 3.4 1.6 .

%WBC ST.DEV 0.5 0.9 1.1 0.4 .

N 5 5 5 5 .

.

Eosinophils MEAN 0.8 0.9 1.0 0.6 .

%WBC ST.DEV 0.3 0.7 0.6 0.2 .

N 5 5 5 5 .

.

Basophils MEAN 0.2 0.1 0.1 0.2 .

%WBC ST.DEV 0.1 0.1 0.1 0.1 .

N 5 5 5 5 .

.

Red blood cells MEAN 7.72 7.74 7.74 7.55 .

10E12/L ST.DEV 0.52 0.36 0.24 0.34 .

N 5 5 5 5 .

.

Reticulocytes MEAN 5.3 5.5 4.9 6.4 .

%RBC ST.DEV 2.1 2.1 0.5 2.2 .

N 5 5 5 5 .

.

RDW MEAN 15.5 16.1 13.9 16.2 .

% ST.DEV 2.5 2.3 1.1 1.6 .

N 5 5 5 5 .

.

Haemoglobin MEAN 9.0 9.3 9.1 8.9 .

mmol/L ST.DEV 0.5 0.4 0.5 0.3 .

N 5 5 5 5 .

.

Haematocrit MEAN 0.432 0.440 0.433 0.428 .

L/L ST.DEV 0.029 0.023 0.025 0.004 .

N 5 5 5 5 .

.

MCV MEAN 56.0 56.8 56.0 56.8 .

fL ST.DEV 1.5 1.6 1.7 2.1 .

N 5 5 5 5 .

.

MCH MEAN 1.17 1.20 1.18 1.18 .

fmol ST.DEV 0.02 0.03 0.03 0.04 .

N 5 5 5 5 .

.

MCHC MEAN 20.88 21.23 21.00 20.78 .

mmol/L ST.DEV 0.48 0.63 0.14 0.60 .

N 5 5 5 5 .

.

Platelets MEAN 920 1009 967 1171 .

10E9/L ST.DEV 63 88 282 110 .

N 5 5 5 5 .

.

- Page 16 - Final Report - Page 42 of 272 -
 13Mar14 11h25

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503344

APPENDIX 1

1.8 HAEMATOLOGY SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

PT MEAN 16.5 16.0 16.5 16.2 .

s ST.DEV 0.8 0.4 0.5 0.4 .

N 5 4 5 5 .

.

APTT MEAN 14.8 16.0 15.4 15.0 .

s ST.DEV 1.8 2.2 3.2 2.1 .

N 5 4 5 5 .

.

- Page 17 - Final Report - Page 43 of 272 -
 05Nov13 14h12

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.9 CLINICAL BIOCHEMISTRY SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

ALAT MEAN 45.8 41.0 37.3 45.5 .

U/L ST.DEV 3.9 13.0 5.9 6.5 .

N 5 5 5 5 .

.

ASAT MEAN 75.9 77.9 71.4 81.9 .

U/L ST.DEV 11.7 2.4 7.1 4.4 .

N 5 5 5 5 .

.

ALP MEAN 155 146 109 174 .

U/L ST.DEV 42 57 12 22 .

N 5 5 5 5 .

.

Total protein MEAN 63.9 62.7 63.9 62.0 .

g/L ST.DEV 2.1 2.6 2.1 2.3 .

N 5 5 5 5 .

.

Albumin MEAN 33.1 33.0 32.6 32.3 .

g/L ST.DEV 0.9 1.5 1.2 0.7 .

N 5 5 5 5 .

.

Total bilirubin MEAN 2.1 2.3 1.9 2.6 .

umol/L ST.DEV 0.3 0.4 0.2 0.2 .

N 5 5 5 5 .

.

Urea MEAN 7.6 6.6 6.3 6.9 .

mmol/L ST.DEV 1.2 1.9 0.7 0.8 .

N 5 5 5 5 .

.

Creatinine MEAN 39.0 39.0 40.9 38.2 .

umol/L ST.DEV 1.7 2.1 2.7 2.1 .

N 5 5 5 5 .

.

Glucose MEAN 9.44 8.93 9.57 7.96 .

mmol/L ST.DEV 1.41 1.37 0.64 1.41 .

N 5 5 5 5 .

.

Cholesterol MEAN 1.76 1.66 1.99 1.94 .

mmol/L ST.DEV 0.26 0.32 0.36 0.30 .

N 5 5 5 5 .

.

Bile Acids MEAN 25.6 19.3 16.0 20.1 .

umol/L ST.DEV 31.7 20.9 8.0 4.2 .

N 5 5 5 5 .

.

Sodium MEAN 141.6 142.0 142.5 142.4 .

mmol/L ST.DEV 0.8 0.7 0.7 1.1 .

N 5 5 5 5 .

.

Potassium MEAN 4.08 4.01 4.04 4.06 .

mmol/L ST.DEV 0.22 0.24 0.32 0.25 .

N 5 5 5 5 .

.

Chloride MEAN 104 105 105 105 .

mmol/L ST.DEV 1 1 2 2 .

N 5 5 5 5 .

.

Calcium MEAN 2.66 2.61 2.61 2.61 .

mmol/L ST.DEV 0.06 0.06 0.06 0.05 .

N 5 5 5 5 .

.

- Page 18 - Final Report - Page 44 of 272 -
 05Nov13 14h12

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.9 CLINICAL BIOCHEMISTRY SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

Inorg.Phos MEAN 1.93 1.73 1.84 2.13 .

mmol/L ST.DEV 0.21 0.19 0.14 0.14 .

N 5 5 5 5 .

.

- Page 19 - Final Report - Page 45 of 272 -
 05Nov13 14h12

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.9 CLINICAL BIOCHEMISTRY SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

ALAT MEAN 54.6 51.0 56.1 52.0 .

U/L ST.DEV 12.6 7.3 5.9 10.4 .

N 5 5 5 5 .

.

ASAT MEAN 90.3 79.7 71.1 72.6 .

U/L ST.DEV 24.7 11.6 3.9 3.0 .

N 5 5 5 5 .

.

ALP MEAN 86 96 76 57 .

U/L ST.DEV 31 28 30 17 .

N 5 5 5 5 .

.

Total protein MEAN 65.5 65.6 63.0 63.1 .

g/L ST.DEV 3.4 1.7 2.3 3.0 .

N 5 5 5 5 .

.

Albumin MEAN 33.4 33.5 32.2 32.2 .

g/L ST.DEV 1.5 1.1 1.4 1.8 .

N 5 5 5 5 .

.

Total bilirubin MEAN 2.2 2.1 2.0 2.0 .

umol/L ST.DEV 0.2 0.3 0.3 0.1 .

N 5 5 5 5 .

.

Urea MEAN 8.0 8.0 8.6 7.9 .

mmol/L ST.DEV 1.0 0.5 1.3 1.0 .

N 5 5 5 5 .

.

Creatinine MEAN 44.1 44.2 44.1 42.5 .

umol/L ST.DEV 1.2 1.8 2.1 2.0 .

N 5 5 5 5 .

.

Glucose MEAN 6.60 7.22 6.20 6.70 .

mmol/L ST.DEV 1.19 0.77 0.80 0.94 .

N 5 5 5 5 .

.

Cholesterol MEAN 2.07 1.84 1.72 1.88 .

mmol/L ST.DEV 0.24 0.18 0.42 0.29 .

N 5 5 5 5 .

.

Bile Acids MEAN 32.4 29.9 24.9 31.9 .

umol/L ST.DEV 13.6 14.7 11.3 30.4 .

N 4 5 5 5 .

.

Sodium MEAN 141.1 140.1 140.7 141.4 .

mmol/L ST.DEV 1.1 0.6 0.9 0.8 .

N 5 5 5 5 .

.

Potassium MEAN 3.65 3.69 3.42 3.46 .

mmol/L ST.DEV 0.20 0.31 0.40 0.19 .

N 5 5 5 5 .

.

Chloride MEAN 97 97 96 95 .

mmol/L ST.DEV 3 2 1 2 .

N 5 5 5 5 .

.

Calcium MEAN 2.67 2.66 2.63 2.68 .

mmol/L ST.DEV 0.05 0.04 0.10 0.07 .

N 5 5 5 5 .

.

- Page 20 - Final Report - Page 46 of 272 -
 05Nov13 14h12

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.9 CLINICAL BIOCHEMISTRY SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

Inorg.Phos MEAN 2.11 2.20 2.16 2.15 .

mmol/L ST.DEV 0.23 0.41 0.22 0.26 .

N 5 5 5 5 .

.

- Page 21 - Final Report - Page 47 of 272 -
 13Jan14 08h10

# / ## Fisher's Exact test significant at 5% (#) or 1% (##) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.10 MACROSCOPIC FINDINGS SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

Animals examined 10 10 10 10 .

Animals without findings 8 7 7 6 .

.

Animals affected 2 3 3 4 .

.

Lungs .

 Focus/foci 1 0 0 0 .

Stomach .

 Focus/foci 0 1 0 0 .

 Thickened 0 0 0 1 .

Liver .

 Discolouration 0 0 0 1 .

Kidneys .

 Pelvic dilation 1 0 0 0 .

Testes .

 Agenesis 1 0 0 0 .

Epididymides .

 Nodule(s) 0 0 2 1 .

 Agenesis 1 0 0 0 .

Preputial glands .

 Focus/foci 0 0 0 1 .

Bulbo-urethral gland .

 Enlarged 0 1 2 1 .

Thymus .

 Focus/foci 0 1 0 0 .

 Reduced in size 0 0 0 1 .

Axillary lymph node .

 Enlarged 0 1 0 0 .

Renal lymph node .

 Enlarged 0 1 0 0 .

 Discolouration 0 1 0 0 .

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

Animals examined 10 10 10 10 .

Animals without findings 6 8 8 8 .

.

Animals affected 4 2 2 2 .

.

Stomach .

 Irregular surface 0 0 0 1 .

 Contents: 0 0 1 0 .

Duodenum .

 Thickened 2 0 0 0 .

Jejunum .

 Thickened 2 0 0 0 .

Liver .

 Enlarged 0 0 1 0 .

Kidneys .

 Pelvic dilation 1 0 0 1 .

 Cyst(s) 0 1 0 0 .

Ovaries .

 Cyst(s) 0 1 0 0 .

Clitoral glands .

 Focus/foci 1 0 0 1 .

- Page 22 - Final Report - Page 48 of 272 -
 13Jan14 08h10

# / ## Fisher's Exact test significant at 5% (#) or 1% (##) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.10 MACROSCOPIC FINDINGS SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

 Enlarged 1 0 0 0 .

 Discolouration 1 0 0 0 .

Thymus .

 Focus/foci 1 0 1 0 .

- Page 23 - Final Report - Page 49 of 272 -
 02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.11 ORGAN WEIGHTS (GRAM) SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

BODY W. MEAN 365 350 358 352 .

(GRAM) ST.DEV 12 16 16 14 .

N 10 10 10 10 .

.

BRAIN MEAN 2.08 2.05 2.10 2.10 .

(GRAM) ST.DEV 0.10 0.12 0.10 0.11 .

N 5 5 5 5 .

.

HEART MEAN 1.006 0.913 0.971 0.994 .

(GRAM) ST.DEV 0.019 0.070 0.072 0.090 .

N 5 5 5 5 .

.

LIVER MEAN 8.70 7.80 * 8.84 8.65 .

(GRAM) ST.DEV 0.48 0.37 0.63 0.48 .

N 5 5 5 5 .

.

THYROID MEAN 0.020 0.019 0.016 0.020 .

(GRAM) ST.DEV 0.003 0.002 0.003 0.004 .

N 5 5 4 5 .

.

THYMUS MEAN 0.375 0.327 0.325 0.297 .

(GRAM) ST.DEV 0.062 0.071 0.045 0.092 .

N 5 5 5 5 .

.

KIDNEYS MEAN 2.29 2.22 2.43 2.52 .

(GRAM) ST.DEV 0.12 0.19 0.15 0.09 .

N 5 5 5 5 .

.

ADRENALS MEAN 0.067 0.064 0.063 0.061 .

(GRAM) ST.DEV 0.005 0.013 0.008 0.013 .

N 5 5 5 5 .

.

SPLEEN MEAN 0.605 0.558 0.639 0.570 .

(GRAM) ST.DEV 0.067 0.078 0.073 0.102 .

N 5 5 5 5 .

.

TESTES MEAN 3.57 3.72 3.61 3.61 .

(GRAM) ST.DEV 0.45 0.48 0.20 0.26 .

N 9 10 10 10 .

.

PROSTATE MEAN 0.681 0.781 0.641 0.811 .

(GRAM) ST.DEV 0.123 0.157 0.104 0.145 .

N 5 5 5 5 .

.

EPIDIDYMIDES MEAN 1.212 1.197 1.206 1.162 .

(GRAM) ST.DEV 0.127 0.123 0.175 0.088 .

N 9 10 10 10 .

.

SEMINAL VES MEAN 1.316 1.521 1.187 1.842 ** .

(GRAM) ST.DEV 0.138 0.124 0.171 0.263 .

N 5 5 5 5 .

.

- Page 24 - Final Report - Page 50 of 272 -
 02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.11 ORGAN/BODY WEIGHT RATIOS (%) SUMMARY

MALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

BODY W. MEAN 365 350 358 352 .

(GRAM) ST.DEV 12 16 16 14 .

N 10 10 10 10 .

.

BRAIN MEAN 0.57 0.60 0.59 0.60 .

(%) ST.DEV 0.03 0.03 0.02 0.05 .

N 5 5 5 5 .

.

HEART MEAN 0.275 0.264 0.272 0.283 .

(%) ST.DEV 0.006 0.012 0.013 0.026 .

N 5 5 5 5 .

.

LIVER MEAN 2.38 2.26 2.47 2.46 .

(%) ST.DEV 0.10 0.04 0.11 0.05 .

N 5 5 5 5 .

.

THYROID MEAN 0.005 0.005 0.004 0.006 .

(%) ST.DEV 0.001 0.001 0.001 0.001 .

N 5 5 4 5 .

.

THYMUS MEAN 0.103 0.095 0.091 0.084 .

(%) ST.DEV 0.017 0.020 0.012 0.024 .

N 5 5 5 5 .

.

KIDNEYS MEAN 0.63 0.64 0.68 ** 0.72 ** .

(%) ST.DEV 0.03 0.02 0.02 0.03 .

N 5 5 5 5 .

.

ADRENALS MEAN 0.018 0.019 0.018 0.017 .

(%) ST.DEV 0.001 0.003 0.002 0.003 .

N 5 5 5 5 .

.

SPLEEN MEAN 0.165 0.162 0.179 0.162 .

(%) ST.DEV 0.018 0.023 0.018 0.029 .

N 5 5 5 5 .

.

TESTES MEAN 0.98 1.06 1.01 1.03 .

(%) ST.DEV 0.14 0.14 0.08 0.07 .

N 9 10 10 10 .

.

PROSTATE MEAN 0.186 0.225 0.180 0.231 .

(%) ST.DEV 0.032 0.036 0.030 0.040 .

N 5 5 5 5 .

.

EPIDIDYMIDES MEAN 0.333 0.342 0.337 0.330 .

(%) ST.DEV 0.040 0.033 0.043 0.026 .

N 9 10 10 10 .

.

SEMINAL VES MEAN 0.360 0.441 0.333 0.525 ** .

(%) ST.DEV 0.037 0.040 0.050 0.088 .

N 5 5 5 5 .

.

- Page 25 - Final Report - Page 51 of 272 -
 02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.11 ORGAN WEIGHTS (GRAM) SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

BODY W. MEAN 244 238 252 234 .

(GRAM) ST.DEV 14 8 20 5 .

N 5 5 5 5 .

.

BRAIN MEAN 1.93 1.85 1.90 1.88 .

(GRAM) ST.DEV 0.08 0.06 0.08 0.06 .

N 5 5 5 5 .

.

HEART MEAN 0.789 0.788 0.804 0.733 .

(GRAM) ST.DEV 0.076 0.068 0.045 0.045 .

N 5 5 5 5 .

.

LIVER MEAN 7.87 7.36 9.51 7.27 .

(GRAM) ST.DEV 0.83 0.60 3.02 0.57 .

N 5 5 5 5 .

.

THYROID MEAN 0.013 0.015 0.013 0.015 .

(GRAM) ST.DEV 0.001 0.003 0.002 0.005 .

N 5 5 5 5 .

.

THYMUS MEAN 0.229 0.238 0.249 0.239 .

(GRAM) ST.DEV 0.031 0.040 0.020 0.058 .

N 5 5 5 5 .

.

KIDNEYS MEAN 1.72 1.74 1.76 1.77 .

(GRAM) ST.DEV 0.10 0.12 0.24 0.11 .

N 5 5 5 5 .

.

ADRENALS MEAN 0.080 0.074 0.084 0.071 .

(GRAM) ST.DEV 0.007 0.004 0.022 0.004 .

N 5 5 5 5 .

.

SPLEEN MEAN 0.570 0.516 0.535 0.498 .

(GRAM) ST.DEV 0.103 0.099 0.068 0.067 .

N 5 5 5 5 .

.

OVARIES MEAN 0.126 0.130 0.131 0.135 .

(GRAM) ST.DEV 0.014 0.007 0.014 0.008 .

N 5 5 5 5 .

.

UTERUS MEAN 0.609 0.642 0.654 0.806 * .

(GRAM) ST.DEV 0.070 0.109 0.111 0.097 .

N 5 5 5 5 .

.

- Page 26 - Final Report - Page 52 of 272 -
 02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.11 ORGAN/BODY WEIGHT RATIOS (%) SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

END OF TREATMENT

BODY W. MEAN 244 238 252 234 .

(GRAM) ST.DEV 14 8 20 5 .

N 5 5 5 5 .

.

BRAIN MEAN 0.79 0.78 0.76 0.81 .

(%) ST.DEV 0.07 0.03 0.04 0.03 .

N 5 5 5 5 .

.

HEART MEAN 0.323 0.331 0.319 0.313 .

(%) ST.DEV 0.016 0.026 0.018 0.018 .

N 5 5 5 5 .

.

LIVER MEAN 3.22 3.08 3.79 3.11 .

(%) ST.DEV 0.23 0.18 1.28 0.21 .

N 5 5 5 5 .

.

THYROID MEAN 0.005 0.006 0.005 0.006 .

(%) ST.DEV 0.001 0.001 0.001 0.002 .

N 5 5 5 5 .

.

THYMUS MEAN 0.094 0.100 0.099 0.102 .

(%) ST.DEV 0.009 0.018 0.012 0.023 .

N 5 5 5 5 .

.

KIDNEYS MEAN 0.71 0.73 0.70 0.76 .

(%) ST.DEV 0.04 0.03 0.05 0.04 .

N 5 5 5 5 .

.

ADRENALS MEAN 0.033 0.031 0.033 0.031 .

(%) ST.DEV 0.003 0.001 0.006 0.002 .

N 5 5 5 5 .

.

SPLEEN MEAN 0.233 0.216 0.212 0.213 .

(%) ST.DEV 0.032 0.037 0.024 0.029 .

N 5 5 5 5 .

.

OVARIES MEAN 0.052 0.054 0.052 0.058 .

(%) ST.DEV 0.006 0.002 0.006 0.004 .

N 5 5 5 5 .

.

UTERUS MEAN 0.250 0.269 0.258 0.345 ** .

(%) ST.DEV 0.029 0.041 0.024 0.044 .

N 5 5 5 5 .

.

- Page 27 - Final Report - Page 53 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.12 REPRODUCTION DATA SUMMARY

GROUP 1 GROUP 2 GROUP 3 GROUP 4

CONTROL 100 MG/KG 300 MG/KG 1000 MG/KG

Females paired 10 10 10 10

Females mated 10 10 10 10

Females pregnant 9 9 8 9

Females with living pups on Day 1 9 9 8 9

Mating index (%) 100.0 100.0 100.0 100.0

(Females mated / Females paired) * 100

Fertility index (%) 90.0 90.0 80.0 90.0

(Pregnant females / Females paired) * 100

Conception index (%) 90.0 90.0 80.0 90.0

(Pregnant females / Females mated) * 100

Gestation index (%) 100.0 100.0 100.0 100.0

(Females with living pups on Day 1 / Pregnant females) * 100

- Page 28 - Final Report - Page 54 of 272 -
 05Nov13 14h29

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.13 PRECOITAL TIME

F0-GENERATION - POST COITUM

DAY OF THE

PAIRING PERIOD

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

NUMBER OF FEMALES MATED

1 2 1 3 1 .

2 7 2 2 - .

3 - 4 4 8 .

4 1 3 - 1 .

5 - - 1 - .

.

MEDIAN PRECOITAL TIME 2 3 3 3 .

MEAN PRECOITAL TIME 2.0 2.9 2.4 2.9 .

N 10 10 10 10 .

- Page 29 - Final Report - Page 55 of 272 -
 07Nov13 07h53

+/++ Steel-test significant at 5% (+) or 1% (++) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.14 CORPORA LUTEA AND IMPLANTATION SITES SUMMARY

FEMALES

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

NECROPSY

Corpora Lutea MEAN 15.8 14.9 12.9 14.1 .

ST.DEV 3.0 2.2 3.4 1.8 .

N 9 9 8 9 .

.

Implantations MEAN 13.7 13.2 11.0 13.7 .

ST.DEV 2.4 1.2 4.7 1.9 .

N 9 9 8 9 .

.

- Page 30 - Final Report - Page 56 of 272 -
 05Nov13 14h29

# / ## Fisher's Exact test significant at 5% (#) or 1% (##) level

+/++ Steel-test significant at 5% (+) or 1% (++) level

Viability index = (Number of alive pups before planned necropsy / Number of pups born alive) *100

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.15 DEVELOPMENTAL DATA

F0-GENERATION - LACTATION

GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

.

LITTERS .

 TOTAL 9 9 8 9 .

.

DURATION OF GESTATION .

 MEAN (+) 21.4 21.2 21.5 21.3 .

 ST.DEV. 0.5 0.4 0.8 0.5 .

 N 9 9 8 9 .

.

DEAD PUPS AT FIRST LITTER CHECK .

 LITTERS AFFECTED (#) 0 0 0 0 .

 TOTAL 0 0 0 0 .

 MEAN (+) 0.0 0.0 0.0 0.0 .

 ST.DEV. 0.0 0.0 0.0 0.0 .

 N 9 9 8 9 .

.

LIVING PUPS AT FIRST LITTER CHECK .

 % OF MALES / FEMALES (#) 48 / 52 59 / 41 29 / 71 ## 54 / 46 .

 TOTAL 114 112 85 119 .

 MEAN (+) 12.7 12.4 10.6 13.2 .

 ST.DEV. 2.5 1.7 4.5 2.3 .

 N 9 9 8 9 .

.

POSTNATAL LOSS .

 % OF LIVING PUPS 0.0 1.8 1.2 0.0 .

 LITTERS AFFECTED (#) 0 2 1 0 .

 TOTAL (#) 0 2 1 0 .

 MEAN (+) 0.0 0.2 0.1 0.0 .

 ST.DEV. 0.0 0.4 0.4 0.0 .

 N 9 9 8 9 .

.

VIABILITY INDEX (#) 100.0 98.2 98.8 100.0 .

- Page 31 - Final Report - Page 57 of 272 -
 05Nov13 14h29

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1

1.16 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

DAY SEX GROUP 1

CONTROL

GROUP 2

100 MG/KG

GROUP 3

300 MG/KG

GROUP 4

1000 MG/KG

'

1 M MEAN 6.4 6.4 6.6 6.4 .

ST.DEV. 0.7 0.6 0.7 0.6 .

N 9 9 7 9 .

.

F MEAN 6.1 6.1 6.7 6.1 .

ST.DEV. 0.6 0.5 1.3 0.6 .

N 9 9 8 9 .

.

M+F MEAN 6.2 6.3 6.8 6.3 .

ST.DEV. 0.6 0.6 1.3 0.5 .

N 9 9 8 9 .

.

4 M MEAN 9.8 10.0 10.4 9.8 .

ST.DEV. 1.2 0.9 1.1 1.2 .

N 9 9 7 9 .

.

F MEAN 9.4 9.7 10.6 9.4 .

ST.DEV. 1.1 0.8 2.0 1.2 .

N 9 9 8 9 .

.

M+F MEAN 9.6 9.9 10.7 9.7 .

ST.DEV. 1.1 0.9 1.9 1.2 .

N 9 9 8 9 .

.

- Page 32 - Final Report - Page 58 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

APPENDIX 2 INDIVIDUAL TABLES

Final Report - Page 59 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.1 MORTALITY DATA

MALES

ANIMAL SCHEDULED

SACRIFICE

TREATMENT

FROM TO

'

GROUP 1 (CONTROL)

1 17OCT13 18SEP13 16OCT13 .

2 17OCT13 18SEP13 16OCT13 .

3 17OCT13 18SEP13 16OCT13 .

4 17OCT13 18SEP13 16OCT13 .

5 17OCT13 18SEP13 16OCT13 .

6 17OCT13 18SEP13 16OCT13 .

7 17OCT13 18SEP13 16OCT13 .

8 17OCT13 18SEP13 16OCT13 .

9 17OCT13 18SEP13 16OCT13 .

10 17OCT13 18SEP13 16OCT13 .

GROUP 2 (100 MG/KG)

11 17OCT13 18SEP13 16OCT13 .

12 17OCT13 18SEP13 16OCT13 .

13 17OCT13 18SEP13 16OCT13 .

14 17OCT13 18SEP13 16OCT13 .

15 17OCT13 18SEP13 16OCT13 .

16 17OCT13 18SEP13 16OCT13 .

17 17OCT13 18SEP13 16OCT13 .

18 17OCT13 18SEP13 16OCT13 .

19 17OCT13 18SEP13 16OCT13 .

20 17OCT13 18SEP13 16OCT13 .

GROUP 3 (300 MG/KG)

21 17OCT13 18SEP13 16OCT13 .

22 17OCT13 18SEP13 16OCT13 .

23 17OCT13 18SEP13 16OCT13 .

24 17OCT13 18SEP13 16OCT13 .

25 17OCT13 18SEP13 16OCT13 .

26 17OCT13 18SEP13 16OCT13 .

27 17OCT13 18SEP13 16OCT13 .

28 17OCT13 18SEP13 16OCT13 .

29 17OCT13 18SEP13 16OCT13 .

30 17OCT13 18SEP13 16OCT13 .

GROUP 4 (1000 MG/KG)

31 17OCT13 18SEP13 16OCT13 .

32 17OCT13 18SEP13 16OCT13 .

33 17OCT13 18SEP13 16OCT13 .

34 17OCT13 18SEP13 16OCT13 .

35 17OCT13 18SEP13 16OCT13 .

36 17OCT13 18SEP13 16OCT13 .

37 17OCT13 18SEP13 16OCT13 .

38 17OCT13 18SEP13 16OCT13 .

39 17OCT13 18SEP13 16OCT13 .

40 17OCT13 18SEP13 16OCT13 .

FEMALES

ANIMAL SCHEDULED

SACRIFICE

TREATMENT

FROM TO

'

GROUP 1 (CONTROL)

41 04NOV13 18SEP13 03NOV13 .

42 31OCT13 18SEP13 30OCT13 .

43 31OCT13 18SEP13 30OCT13 .

44 31OCT13 18SEP13 30OCT13 .

45 31OCT13 18SEP13 30OCT13 .

46 29OCT13 18SEP13 28OCT13 .

47 31OCT13 18SEP13 30OCT13 .

- Page 2 - Final Report - Page 60 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.1 MORTALITY DATA

FEMALES

ANIMAL SCHEDULED

SACRIFICE

TREATMENT

FROM TO

'

GROUP 1 (CONTROL)

48 31OCT13 18SEP13 30OCT13 .

49 31OCT13 18SEP13 30OCT13 .

50 31OCT13 18SEP13 30OCT13 .

GROUP 2 (100 MG/KG)

51 01NOV13 18SEP13 31OCT13 .

52 31OCT13 18SEP13 30OCT13 .

53 01NOV13 18SEP13 31OCT13 .

54 31OCT13 18SEP13 30OCT13 .

55 01NOV13 18SEP13 31OCT13 .

56 01NOV13 18SEP13 31OCT13 .

57 31OCT13 18SEP13 30OCT13 .

58 01NOV13 18SEP13 31OCT13 .

59 29OCT13 18SEP13 28OCT13 .

60 31OCT13 18SEP13 30OCT13 .

GROUP 3 (300 MG/KG)

61 01NOV13 18SEP13 31OCT13 .

62 01NOV13 18SEP13 31OCT13 .

63 04NOV13 18SEP13 03NOV13 .

64 29OCT13 18SEP13 28OCT13 .

65 31OCT13 18SEP13 30OCT13 .

66 01NOV13 18SEP13 31OCT13 .

67 31OCT13 18SEP13 30OCT13 .

68 29OCT13 18SEP13 28OCT13 .

69 29OCT13 18SEP13 28OCT13 .

70 01NOV13 18SEP13 31OCT13 .

GROUP 4 (1000 MG/KG)

71 01NOV13 18SEP13 31OCT13 .

72 01NOV13 18SEP13 31OCT13 .

73 31OCT13 18SEP13 30OCT13 .

74 01NOV13 18SEP13 31OCT13 .

75 31OCT13 18SEP13 30OCT13 .

76 31OCT13 18SEP13 30OCT13 .

77 01NOV13 18SEP13 31OCT13 .

78 31OCT13 18SEP13 30OCT13 .

79 29OCT13 18SEP13 28OCT13 .

80 31OCT13 18SEP13 30OCT13 .

- Page 3 - Final Report - Page 61 of 272 -
 05Nov13 14h41

.: Observation performed, sign not present

G: Highest daily grades

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.2 CLINICAL SIGNS

MALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 1 (CONTROL)

ANIMAL 1 .

No clinical signs noted .

ANIMAL 2 .

No clinical signs noted .

ANIMAL 3 .

No clinical signs noted .

ANIMAL 4 .

No clinical signs noted .

ANIMAL 5 .

No clinical signs noted .

ANIMAL 6 .

No clinical signs noted .

ANIMAL 7 .

No clinical signs noted .

ANIMAL 8 .

No clinical signs noted .

ANIMAL 9 .

No clinical signs noted .

ANIMAL 10 .

No clinical signs noted .

GROUP 2 (100 MG/KG)

ANIMAL 11 .

No clinical signs noted .

ANIMAL 12 .

No clinical signs noted .

ANIMAL 13 .

No clinical signs noted .

ANIMAL 14 .

No clinical signs noted .

ANIMAL 15 .

No clinical signs noted .

ANIMAL 16 .

No clinical signs noted .

ANIMAL 17 .

No clinical signs noted .

ANIMAL 18 .

No clinical signs noted .

ANIMAL 19 .

No clinical signs noted .

ANIMAL 20 .

No clinical signs noted .

GROUP 3 (300 MG/KG)

ANIMAL 21 .

No clinical signs noted .

ANIMAL 22 .

No clinical signs noted .

ANIMAL 23 .

No clinical signs noted .

ANIMAL 24 .

No clinical signs noted .

ANIMAL 25 .

No clinical signs noted .

ANIMAL 26 .

No clinical signs noted .

ANIMAL 27 .

No clinical signs noted .

ANIMAL 28 .

No clinical signs noted .

- Page 4 - Final Report - Page 62 of 272 -
 05Nov13 14h41

.: Observation performed, sign not present

G: Highest daily grades

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.2 CLINICAL SIGNS

MALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 3 (300 MG/KG)

ANIMAL 29 .

No clinical signs noted .

ANIMAL 30 .

No clinical signs noted .

GROUP 4 (1000 MG/KG)

ANIMAL 31 .

No clinical signs noted .

ANIMAL 32 .

No clinical signs noted .

ANIMAL 33 .

No clinical signs noted .

ANIMAL 34 .

No clinical signs noted .

ANIMAL 35 .

No clinical signs noted .

ANIMAL 36 .

Breathing .

 Rales (3) G: . . . . . . . . . . . . . . . . . . . . . . . 111. . . .

ANIMAL 37 .

No clinical signs noted .

ANIMAL 38 .

No clinical signs noted .

ANIMAL 39 .

No clinical signs noted .

ANIMAL 40 .

No clinical signs noted .

FEMALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 1 (CONTROL)

ANIMAL 41 .

No clinical signs noted .

ANIMAL 42 .

No clinical signs noted .

ANIMAL 43 .

No clinical signs noted .

ANIMAL 44 .

No clinical signs noted .

ANIMAL 45 .

No clinical signs noted .

ANIMAL 46 .

No clinical signs noted .

ANIMAL 47 .

No clinical signs noted .

ANIMAL 48 .

No clinical signs noted .

ANIMAL 49 .

No clinical signs noted .

ANIMAL 50 .

No clinical signs noted .

GROUP 2 (100 MG/KG)

ANIMAL 51 .

No clinical signs noted .

- Page 5 - Final Report - Page 63 of 272 -
 05Nov13 14h41

.: Observation performed, sign not present

G: Highest daily grades

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.2 CLINICAL SIGNS

FEMALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 2 (100 MG/KG)

ANIMAL 52 .

No clinical signs noted .

ANIMAL 53 .

No clinical signs noted .

ANIMAL 54 .

No clinical signs noted .

ANIMAL 55 .

No clinical signs noted .

ANIMAL 56 .

Skin / fur .

 Piloerection (1) G: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. . . . . . . . . . . .

ANIMAL 57 .

No clinical signs noted .

ANIMAL 58 .

No clinical signs noted .

ANIMAL 59 .

No clinical signs noted .

ANIMAL 60 .

No clinical signs noted .

GROUP 3 (300 MG/KG)

ANIMAL 61 .

No clinical signs noted .

ANIMAL 62 .

No clinical signs noted .

ANIMAL 63 .

No clinical signs noted .

ANIMAL 64 .

No clinical signs noted .

ANIMAL 65 .

No clinical signs noted .

ANIMAL 66 .

No clinical signs noted .

ANIMAL 67 .

No clinical signs noted .

ANIMAL 68 .

No clinical signs noted .

ANIMAL 69 .

No clinical signs noted .

ANIMAL 70 .

No clinical signs noted .

GROUP 4 (1000 MG/KG)

ANIMAL 71 .

No clinical signs noted .

ANIMAL 72 .

No clinical signs noted .

ANIMAL 73 .

No clinical signs noted .

ANIMAL 74 .

No clinical signs noted .

ANIMAL 75 .

Breathing .

 Rales (3) G: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. . . . .

ANIMAL 76 .

No clinical signs noted .

ANIMAL 77 .

No clinical signs noted .

ANIMAL 78 .

No clinical signs noted .

- Page 6 - Final Report - Page 64 of 272 -
 05Nov13 14h41

.: Observation performed, sign not present

G: Highest daily grades

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.2 CLINICAL SIGNS

FEMALES

PRE MATING REPRO PERIOD

SIGN (MAX. GRADE)

(LOCATION)

WEEK:

DAY:

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

1

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

.

6

.

7

4

1

.

2

.

3

.

4

.

5

.

6

.

7

.

1

.

2

.

3

.

4

.

5

'

GROUP 4 (1000 MG/KG)

ANIMAL 79 .

No clinical signs noted .

ANIMAL 80 .

No clinical signs noted .

- Page 7 - Final Report - Page 65 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.3 FUNCTIONAL OBSERVATIONS

MALES

AT WEEK 4

ANIMAL HEARING

SCORE 0/1

PUPIL L

SCORE 0/1

PUPIL R

SCORE 0/1

STATIC R

SCORE 0/1

GRIP

SCORE 0/1

'

GROUP 1 (CONTROL)

1 0 0 0 0 0 .

2 0 0 0 0 0 .

3 0 0 0 0 0 .

4 0 0 0 0 0 .

5 0 0 0 0 0 .

GROUP 2 (100 MG/KG)

11 0 0 0 0 0 .

12 0 0 0 0 0 .

13 0 0 0 0 0 .

14 0 0 0 0 0 .

15 0 0 0 0 0 .

GROUP 3 (300 MG/KG)

21 0 0 0 0 0 .

22 0 0 0 0 0 .

23 0 0 0 0 0 .

24 0 0 0 0 0 .

25 0 0 0 0 0 .

GROUP 4 (1000 MG/KG)

31 0 0 0 0 0 .

32 0 0 0 0 0 .

33 0 0 0 0 0 .

34 0 0 0 0 0 .

35 0 0 0 0 0 .

FEMALES

AT LACTATION

ANIMAL HEARING

SCORE 0/1

PUPIL L

SCORE 0/1

PUPIL R

SCORE 0/1

STATIC R

SCORE 0/1

GRIP

SCORE 0/1

'

GROUP 1 (CONTROL)

42 0 0 0 0 0 .

43 0 0 0 0 0 .

44 0 0 0 0 0 .

45 0 0 0 0 0 .

47 0 0 0 0 0 .

GROUP 2 (100 MG/KG)

51 0 0 0 0 0 .

52 0 0 0 0 0 .

54 0 0 0 0 0 .

57 0 0 0 0 0 .

60 0 0 0 0 0 .

GROUP 3 (300 MG/KG)

64 0 0 0 0 0 .

65 0 0 0 0 0 .

67 0 0 0 0 0 .

68 0 0 0 0 0 .

69 0 0 0 0 0 .

GROUP 4 (1000 MG/KG)

73 0 0 0 0 0 .

75 0 0 0 0 0 .

76 0 0 0 0 0 .

78 0 0 0 0 0 .

- Page 8 - Final Report - Page 66 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.3 FUNCTIONAL OBSERVATIONS

FEMALES

AT LACTATION

ANIMAL HEARING

SCORE 0/1

PUPIL L

SCORE 0/1

PUPIL R

SCORE 0/1

STATIC R

SCORE 0/1

GRIP

SCORE 0/1

'

GROUP 4 (1000 MG/KG)

80 0 0 0 0 0 .

- Page 9 - Final Report - Page 67 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.4 MOTOR ACTIVITY TEST - TOTAL MOVEMENTS

MALES 

AT WEEK 4

1 2 3 4 5 6 7 8 9 10 11 12 Total

1 618 338 300 224 209 287 83 24 36 11 211 29 2370

2 407 170 252 370 253 261 278 59 40 101 24 6 2221

3 1161 1088 1177 524 491 154 14 24 116 21 19 25 4814

4 756 707 310 232 588 260 36 5 27 4 36 2 2963

5 914 483 268 47 2 424 518 105 0 21 0 0 2782

11 1018 694 577 258 39 534 79 10 4 5 10 2 3230

12 785 521 296 406 306 802 158 2 4 48 0 120 3448

13 987 1107 344 368 391 320 149 32 23 60 0 5 3786

14 1488 1083 820 1104 451 313 34 0 2 138 2 0 5435

15 941 761 239 821 265 426 345 196 14 21 261 172 4462

21 278 287 185 195 117 140 135 142 175 169 296 100 2219

22 999 510 553 432 279 248 271 270 111 7 290 190 4160

23 813 1021 694 501 473 327 207 513 131 9 0 0 4689

24 616 601 736 565 348 366 232 343 173 3 17 309 4309

25 611 485 304 465 352 59 315 413 105 0 1 70 3180

31 858 453 362 273 48 18 125 302 23 6 4 4 2476

32 868 607 446 297 441 267 54 0 0 14 13 24 3031

33 1136 780 503 330 564 144 7 1 20 40 23 11 3559

34 354 579 459 395 159 96 29 67 419 1 0 3 2561

35 714 469 429 134 319 46 6 36 72 6 73 7 2311

GROUP 3 (300 MG/KG)

ANIMAL Interval (5 min.)

GROUP 1 (CONTROL)

GROUP 2 (100 MG/KG)

GROUP 4 (1000 MG/KG)

- Page 10 - Final Report - Page 68 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.4 MOTOR ACTIVITY TEST - AMBULATIONS

MALES 

AT WEEK 4

1 2 3 4 5 6 7 8 9 10 11 12 Total

1 206 107 87 52 51 64 18 0 4 0 53 0 642

2 61 36 44 67 49 37 48 1 0 25 1 0 369

3 213 195 216 49 91 3 0 8 14 0 2 1 792

4 107 161 66 40 101 30 4 0 0 0 0 0 509

5 198 141 53 0 0 113 138 15 0 4 0 0 662

11 220 175 151 29 0 141 17 0 0 0 0 0 733

12 237 118 71 113 72 200 3 0 0 4 0 1 819

13 250 379 92 122 130 97 5 0 0 25 0 0 1100

14 404 277 213 181 91 16 0 0 0 16 0 0 1198

15 183 182 37 163 74 79 67 25 0 0 56 38 904

21 3 8 3 1 1 2 2 0 1 5 6 0 32

22 230 160 150 127 79 43 82 77 2 0 80 52 1082

23 97 242 168 68 99 82 7 101 28 0 0 0 892

24 108 117 139 118 79 70 42 76 41 0 2 67 859

25 186 146 62 128 86 3 73 129 17 0 1 31 862

31 218 85 97 79 1 0 39 63 0 0 0 0 582

32 155 115 92 52 87 50 1 0 0 0 0 2 554

33 213 116 56 64 82 2 1 0 0 19 0 0 553

34 58 198 164 85 3 0 0 14 153 0 0 0 675

35 142 56 101 16 64 1 0 1 2 0 0 0 383

GROUP 3 (300 MG/KG)

GROUP 4 (1000 MG/KG)

ANIMAL Interval (5 min.)

GROUP 1 (CONTROL)

GROUP 2 (100 MG/KG)

- Page 11 - Final Report - Page 69 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.4 MOTOR ACTIVITY TEST - TOTAL MOVEMENTS

FEMALES

AT LACTATION

1 2 3 4 5 6 7 8 9 10 11 12 Total

42 583 371 408 249 279 355 67 209 12 99 26 8 2666

43 650 420 296 252 61 383 109 31 24 371 125 6 2728

44 797 573 392 251 279 304 0 35 216 631 419 83 3980

45 1097 362 520 355 180 2 114 504 311 1 0 23 3469

47 1076 494 354 362 528 292 356 400 311 377 379 267 5196

51 968 525 145 250 29 120 314 12 9 8 541 134 3055

52 886 409 214 53 145 2 108 46 30 36 775 264 2968

54 1197 512 162 199 238 37 121 11 12 35 53 408 2985

57 582 338 241 344 251 364 263 380 246 601 217 295 4122

60 1098 691 176 536 259 333 252 258 267 89 228 257 4444

64 821 537 500 244 469 28 431 478 93 1 28 435 4065

65 1051 506 416 639 242 69 394 457 133 325 235 6 4473

67 1174 680 691 478 258 397 116 334 40 380 78 272 4898

68 341 455 302 204 265 397 427 53 178 379 300 334 3635

69 622 560 275 49 96 83 4 202 19 78 612 287 2887

73 456 261 365 307 408 328 233 98 42 7 24 5 2534

75 904 507 395 268 389 278 309 545 171 309 213 414 4702

76 789 572 544 213 109 162 76 33 8 388 276 391 3561

78 874 665 626 55 184 890 277 245 20 0 10 43 3889

80 851 418 353 288 357 284 98 113 465 53 347 633 4260

GROUP 3 (300 MG/KG)

GROUP 4 (1000 MG/KG)

ANIMAL Interval (5 min.)

GROUP 1 (CONTROL)

GROUP 2 (100 MG/KG)

- Page 12 - Final Report - Page 70 of 272 -
CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.4 MOTOR ACTIVITY TEST - AMBULATIONS

FEMALES

AT LACTATION

1 2 3 4 5 6 7 8 9 10 11 12 Total

42 81 55 73 37 40 66 1 0 0 20 0 0 373

43 178 42 26 42 0 82 0 0 0 66 6 0 442

44 229 127 70 36 97 76 0 1 53 135 77 1 902

45 242 52 93 81 22 0 18 103 44 0 0 1 656

47 360 146 86 101 176 76 101 124 60 101 138 103 1572

51 256 141 19 63 0 21 99 0 0 1 179 22 801

52 241 73 19 15 33 0 0 0 0 1 186 39 607

54 329 80 11 57 7 0 31 2 2 0 10 67 596

57 193 54 5 59 41 78 55 101 7 162 38 53 846

60 268 135 22 86 41 45 52 41 58 24 39 55 866

64 184 94 127 1 109 5 81 85 13 0 0 99 798

65 257 68 67 97 31 1 101 107 13 66 43 1 852

67 186 93 133 58 57 87 9 69 0 77 0 62 831

68 69 121 48 36 41 89 74 1 46 79 73 49 726

69 134 111 75 2 1 2 1 32 0 1 142 52 553

73 125 3 95 17 96 90 36 23 0 1 1 0 487

75 241 106 85 73 55 32 20 162 25 72 35 121 1027

76 189 98 120 59 0 39 1 1 0 91 97 81 776

78 198 109 119 1 51 178 53 74 0 0 0 0 783

80 278 79 49 63 124 58 1 27 115 0 111 198 1103

GROUP 4 (1000 MG/KG)

ANIMAL Interval (5 min.)

GROUP 2 (100 MG/KG)

GROUP 3 (300 MG/KG)

GROUP 1 (CONTROL)

- Page 13 - Final Report - Page 71 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.5 BODY WEIGHTS (GRAM)

MALES

PRE MATING MATING PERIOD

DAYS

WEEKS

ANIMAL

1

1

8

2

1

1

8

2

15

3

22

4

29

5

36

6

'

GROUP 1 (CONTROL)

1 328 352 382 391 402 .

2 321 342 367 378 391 .

3 327 344 366 373 389 .

4 333 347 372 385 395 .

5 312 333 353 364 388 .

6 304 314 335 346 361 .

7 328 350 372 386 404 .

8 328 354 375 387 398 .

9 314 342 364 376 393 .

10 319 333 355 370 381 .

GROUP 2 (100 MG/KG)

11 323 337 353 354 365 .

12 323 341 360 377 391 .

13 314 334 350 358 369 .

14 332 350 366 381 397 .

15 294 301 314 320 333 .

16 316 337 352 356 368 .

17 319 329 358 367 388 .

18 315 339 362 370 383 .

19 322 336 356 364 381 .

20 322 338 357 360 374 .

GROUP 3 (300 MG/KG)

21 326 344 373 376 391 .

22 324 344 375 381 399 .

23 323 336 364 377 393 .

24 305 321 336 348 359 .

25 317 336 363 370 388 .

26 331 353 380 398 410 .

27 320 334 345 351 365 .

28 323 343 372 382 397 .

29 320 339 360 368 381 .

30 308 323 352 359 368 .

GROUP 4 (1000 MG/KG)

31 334 347 357 367 374 .

32 321 340 359 373 384 .

33 321 347 366 383 395 .

34 322 343 362 368 384 .

35 303 326 334 342 348 .

36 318 334 352 362 379 .

37 312 313 342 344 350 .

38 322 348 369 383 392 .

39 311 336 362 351 375 .

40 332 348 369 381 398 .

- Page 14 - Final Report - Page 72 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.5 BODY WEIGHTS (GRAM)

FEMALES

PRE MATING MATING PERIOD

DAYS

WEEKS

ANIMAL

1

1

8

2

1

1

8

2

15

3

22

4

29

5

36

6

'

GROUP 1 (CONTROL)

41 197 207 213 .

42 193 208 229 .

43 202 214 225 .

44 199 219 240 .

45 195 217 237 .

46 206 214 218 .

47 202 204 222 .

48 191 210 219 .

49 194 209 225 .

50 195 218 230 .

GROUP 2 (100 MG/KG)

51 208 216 227 .

52 198 215 224 .

53 208 221 234 .

54 193 208 224 .

55 200 205 213 .

56 201 213 215 .

57 200 219 233 .

58 194 206 213 .

59 200 210 224 .

60 205 215 226 .

GROUP 3 (300 MG/KG)

61 210 222 232 .

62 191 202 210 .

63 202 211 228 .

64 210 216 245 .

65 198 217 234 .

66 198 203 213 .

67 198 217 242 .

68 195 201 227 .

69 201 205 234 .

70 209 221 227 .

GROUP 4 (1000 MG/KG)

71 201 216 229 .

72 205 221 231 .

73 202 214 229 .

74 210 225 233 .

75 186 199 206 .

76 191 201 210 .

77 200 207 214 .

78 204 211 215 .

79 213 223 229 .

80 203 217 227 .

- Page 15 - Final Report - Page 73 of 272 -
 05Nov13 14h47

<NP> Non-pregnant

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.5 BODY WEIGHTS (GRAM)

FEMALES

F0-GENERATION

POST COITUM LACTATION

DAYS

ANIMAL

0 4 7 11 14 17 20 1 4

'

GROUP 1 (CONTROL)

41 219 229 233 250 260 288 329 249 261 .

42 227 242 249 270 291 309 353 265 289 .

43 222 233 239 252 264 282 317 247 259 .

44 233 250 258 277 292 319 364 284 301 .

45 230 250 259 282 297 325 379 282 301 .

46 <NP> 219 243 247 260 245 234 248 --- --- .

47 216 231 236 251 261 285 321 258 265 .

48 214 230 239 257 266 279 313 256 272 .

49 227 240 251 266 282 304 347 263 283 .

50 226 255 269 290 302 332 385 290 300 .

GROUP 2 (100 MG/KG)

51 233 244 249 263 274 289 319 256 278 .

52 221 233 240 260 274 298 342 258 277 .

53 230 247 252 267 278 300 344 268 278 .

54 218 231 237 250 266 288 331 248 270 .

55 221 238 242 261 274 303 343 254 276 .

56 228 244 261 275 294 303 334 271 278 .

57 232 249 262 289 296 320 375 270 292 .

58 226 236 247 261 274 296 334 258 272 .

59 <NP> 216 238 247 259 250 242 249 --- --- .

60 229 233 243 263 276 300 346 278 276 .

GROUP 3 (300 MG/KG)

61 <NP> 251 262 269 271 266 262 258 --- --- .

62 <NP> 232 241 242 243 251 257 240 --- --- .

63 228 249 253 265 270 279 293 255 273 .

64 237 258 267 297 313 340 391 298 318 .

65 226 246 250 269 284 299 343 249 270 .

66 210 222 228 242 256 276 315 236 255 .

67 237 246 253 272 281 305 350 269 290 .

68 215 239 247 259 280 303 346 265 281 .

69 227 250 262 282 292 313 350 271 279 .

70 226 237 245 262 274 282 298 266 267 .

GROUP 4 (1000 MG/KG)

71 229 244 251 267 282 303 339 281 285 .

72 231 244 251 271 283 311 357 272 293 .

73 227 237 249 265 282 315 358 264 276 .

74 226 247 256 275 289 318 363 283 290 .

75 203 222 232 248 269 292 337 255 272 .

76 213 228 237 243 259 289 332 257 257 .

77 222 233 247 261 271 297 334 256 267 .

78 217 232 238 254 271 293 331 246 260 .

79 <NP> 229 256 256 261 258 248 257 --- --- .

80 227 243 264 264 279 310 358 251 282 .

- Page 16 - Final Report - Page 74 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.6 BODY WEIGHT GAIN (%)

MALES

PRE MATING MATING PERIOD

DAYS

WEEKS

ANIMAL

1

1

8

2

1

1

8

2

15

3

22

4

29

5

36

6

'

GROUP 1 (CONTROL)

1 0 7 16 19 23 .

2 0 7 14 18 22 .

3 0 5 12 14 19 .

4 0 4 12 16 19 .

5 0 7 13 17 24 .

6 0 3 10 14 19 .

7 0 7 13 18 23 .

8 0 8 14 18 21 .

9 0 9 16 20 25 .

10 0 4 11 16 19 .

GROUP 2 (100 MG/KG)

11 0 4 9 10 13 .

12 0 6 11 17 21 .

13 0 6 11 14 18 .

14 0 5 10 15 20 .

15 0 2 7 9 13 .

16 0 7 11 13 16 .

17 0 3 12 15 22 .

18 0 8 15 17 22 .

19 0 4 11 13 18 .

20 0 5 11 12 16 .

GROUP 3 (300 MG/KG)

21 0 6 14 15 20 .

22 0 6 16 18 23 .

23 0 4 13 17 22 .

24 0 5 10 14 18 .

25 0 6 15 17 22 .

26 0 7 15 20 24 .

27 0 4 8 10 14 .

28 0 6 15 18 23 .

29 0 6 13 15 19 .

30 0 5 14 17 19 .

GROUP 4 (1000 MG/KG)

31 0 4 7 10 12 .

32 0 6 12 16 20 .

33 0 8 14 19 23 .

34 0 7 12 14 19 .

35 0 8 10 13 15 .

36 0 5 11 14 19 .

37 0 0 10 10 12 .

38 0 8 15 19 22 .

39 0 8 16 13 21 .

40 0 5 11 15 20 .

- Page 17 - Final Report - Page 75 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.6 BODY WEIGHT GAIN (%)

FEMALES

PRE MATING MATING PERIOD

DAYS

WEEKS

ANIMAL

1

1

8

2

1

1

8

2

15

3

22

4

29

5

36

6

'

GROUP 1 (CONTROL)

41 0 5 8 .

42 0 8 19 .

43 0 6 11 .

44 0 10 21 .

45 0 11 22 .

46 0 4 6 .

47 0 1 10 .

48 0 10 15 .

49 0 8 16 .

50 0 12 18 .

GROUP 2 (100 MG/KG)

51 0 4 9 .

52 0 9 13 .

53 0 6 13 .

54 0 8 16 .

55 0 3 7 .

56 0 6 7 .

57 0 10 17 .

58 0 6 10 .

59 0 5 12 .

60 0 5 10 .

GROUP 3 (300 MG/KG)

61 0 6 10 .

62 0 6 10 .

63 0 4 13 .

64 0 3 17 .

65 0 10 18 .

66 0 3 8 .

67 0 10 22 .

68 0 3 16 .

69 0 2 16 .

70 0 6 9 .

GROUP 4 (1000 MG/KG)

71 0 7 14 .

72 0 8 13 .

73 0 6 13 .

74 0 7 11 .

75 0 7 11 .

76 0 5 10 .

77 0 4 7 .

78 0 3 5 .

79 0 5 8 .

80 0 7 12 .

- Page 18 - Final Report - Page 76 of 272 -
 05Nov13 14h47

<NP> Non-pregnant

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.6 BODY WEIGHT GAIN (%)

FEMALES

F0-GENERATION

POST COITUM LACTATION

DAYS

ANIMAL

0 4 7 11 14 17 20 1 4

'

GROUP 1 (CONTROL)

41 0 5 6 14 19 32 50 0 5 .

42 0 7 10 19 28 36 56 0 9 .

43 0 5 8 14 19 27 43 0 5 .

44 0 7 11 19 25 37 56 0 6 .

45 0 9 13 23 29 41 65 0 7 .

46 <NP> 0 11 13 19 12 7 13 --- --- .

47 0 7 9 16 21 32 49 0 3 .

48 0 7 12 20 24 30 46 0 6 .

49 0 6 11 17 24 34 53 0 8 .

50 0 13 19 28 34 47 70 0 3 .

GROUP 2 (100 MG/KG)

51 0 5 7 13 18 24 37 0 9 .

52 0 5 9 18 24 35 55 0 7 .

53 0 7 10 16 21 30 50 0 4 .

54 0 6 9 15 22 32 52 0 9 .

55 0 8 10 18 24 37 55 0 9 .

56 0 7 14 21 29 33 46 0 3 .

57 0 7 13 25 28 38 62 0 8 .

58 0 4 9 15 21 31 48 0 5 .

59 <NP> 0 10 14 20 16 12 15 --- --- .

60 0 2 6 15 21 31 51 0 -1 .

GROUP 3 (300 MG/KG)

61 <NP> 0 4 7 8 6 4 3 --- --- .

62 <NP> 0 4 4 5 8 11 3 --- --- .

63 0 9 11 16 18 22 29 0 7 .

64 0 9 13 25 32 43 65 0 7 .

65 0 9 11 19 26 32 52 0 8 .

66 0 6 9 15 22 31 50 0 8 .

67 0 4 7 15 19 29 48 0 8 .

68 0 11 15 20 30 41 61 0 6 .

69 0 10 15 24 29 38 54 0 3 .

70 0 5 8 16 21 25 32 0 0 .

GROUP 4 (1000 MG/KG)

71 0 7 10 17 23 32 48 0 1 .

72 0 6 9 17 23 35 55 0 8 .

73 0 4 10 17 24 39 58 0 5 .

74 0 9 13 22 28 41 61 0 2 .

75 0 9 14 22 33 44 66 0 7 .

76 0 7 11 14 22 36 56 0 0 .

77 0 5 11 18 22 34 50 0 4 .

78 0 7 10 17 25 35 53 0 6 .

79 <NP> 0 12 12 14 13 8 12 --- --- .

80 0 7 16 16 23 37 58 0 12 .

- Page 19 - Final Report - Page 77 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.7 FOOD CONSUMPTION (G/ANIMAL/DAY)

MALES

PRE MATING MATING PERIOD

DAYS

WEEKS

CAGE

1-8

1-2

8-15

2-3

1-8

1-2

8-15

2-3

'

GROUP 1 (CONTROL)

1 24 24 24 25 .

2 23 24 24 23 .

GROUP 2 (100 MG/KG)

3 23 22 24 22 .

4 23 23 23 24 .

GROUP 3 (300 MG/KG)

5 23 24 25 24 .

6 24 23 24 24 .

GROUP 4 (1000 MG/KG)

7 24 24 26 25 .

8 22 22 21 23 .

FEMALES

PRE MATING MATING PERIOD

DAYS

WEEKS

CAGE

1-8

1-2

8-15

2-3

1-8

1-2

8-15

2-3

'

GROUP 1 (CONTROL)

9 17 17 .

10 17 17 .

GROUP 2 (100 MG/KG)

11 17 17 .

12 17 17 .

GROUP 3 (300 MG/KG)

13 17 18 .

14 17 17 .

GROUP 4 (1000 MG/KG)

15 17 17 .

16 16 16 .

- Page 20 - Final Report - Page 78 of 272 -
 05Nov13 14h47

<NP> Non-pregnant

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.7 FOOD CONSUMPTION (G/ANIMAL/DAY)

FEMALES

F0-GENERATION

POST COITUM LACTATION

DAYS

ANIMAL

0-4 4-7 7-11 11-14 14-17 17-20 1-4

'

GROUP 1 (CONTROL)

41 16 19 18 18 20 22 35 .

42 20 24 25 26 24 27 41 .

43 16 20 20 21 20 23 23 .

44 19 22 23 24 23 24 38 .

45 17 23 25 25 25 28 38 .

46 <NP> 19 20 21 16 13 15 --- .

47 17 18 20 19 19 21 34 .

48 17 20 21 22 20 23 34 .

49 18 21 22 23 22 23 32 .

50 23 26 27 27 27 31 41 .

GROUP 2 (100 MG/KG)

51 17 20 20 20 16 19 37 .

52 17 21 21 20 21 24 33 .

53 20 23 22 23 23 27 37 .

54 16 19 19 20 20 22 36 .

55 20 20 22 20 22 26 33 .

56 21 25 24 25 19 24 24 .

57 20 24 25 23 22 25 37 .

58 20 23 21 21 22 26 32 .

59 <NP> 16 21 22 16 17 15 --- .

60 15 22 19 22 22 25 32 .

GROUP 3 (300 MG/KG)

61 <NP> 22 24 23 16 15 17 --- .

62 <NP> 20 20 17 19 20 14 --- .

63 20 23 21 22 20 24 28 .

64 21 25 29 28 29 34 40 .

65 21 21 24 24 23 26 34 .

66 17 20 20 19 19 22 36 .

67 17 21 21 21 23 26 41 .

68 17 19 21 23 22 23 33 .

69 20 23 26 24 23 20 24 .

70 17 22 22 24 23 24 23 .

GROUP 4 (1000 MG/KG)

71 18 23 20 22 22 26 33 .

72 18 22 21 22 22 23 41 .

73 18 23 21 22 23 21 36 .

74 19 24 24 25 25 28 45 .

75 17 23 21 23 23 26 32 .

76 17 22 15 20 22 26 26 .

77 19 22 21 20 21 23 33 .

78 16 22 18 22 21 24 27 .

79 <NP> 18 20 20 16 13 14 --- .

80 20 22 22 23 23 25 34 .

- Page 21 - Final Report - Page 79 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.8 RELATIVE FOOD CONSUMPTION (G/KG BODY WEIGHT/DAY)

MALES

PRE MATING MATING PERIOD

DAYS

WEEKS

CAGE

1-8

1-2

8-15

2-3

1-8

1-2

8-15

2-3

'

GROUP 1 (CONTROL)

1 69 69 65 63 .

2 67 70 64 61 .

GROUP 2 (100 MG/KG)

3 69 66 66 60 .

4 68 69 64 62 .

GROUP 3 (300 MG/KG)

5 69 70 66 62 .

6 70 68 65 62 .

GROUP 4 (1000 MG/KG)

7 71 71 72 66 .

8 65 66 57 60 .

FEMALES

PRE MATING MATING PERIOD

DAYS

WEEKS

CAGE

1-8

1-2

8-15

2-3

1-8

1-2

8-15

2-3

'

GROUP 1 (CONTROL)

9 81 80 .

10 79 79 .

GROUP 2 (100 MG/KG)

11 80 79 .

12 80 80 .

GROUP 3 (300 MG/KG)

13 82 85 .

14 79 80 .

GROUP 4 (1000 MG/KG)

15 80 81 .

16 76 78 .

- Page 22 - Final Report - Page 80 of 272 -
 05Nov13 14h47

<NP> Non-pregnant

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.8 RELATIVE FOOD CONSUMPTION (G/KG BODY WEIGHT/DAY)

FEMALES

F0-GENERATION

POST COITUM LACTATION

DAYS

ANIMAL

0-4 4-7 7-11 11-14 14-17 17-20 1-4

'

GROUP 1 (CONTROL)

41 71 80 72 71 69 68 135 .

42 84 96 94 88 78 76 143 .

43 69 82 77 78 71 74 89 .

44 75 85 81 81 72 65 125 .

45 69 90 89 84 78 73 126 .

46 <NP> 76 81 81 64 57 62 --- .

47 74 78 80 74 68 65 128 .

48 73 84 83 81 73 72 126 .

49 76 85 82 82 72 67 112 .

50 89 98 92 88 81 81 136 .

GROUP 2 (100 MG/KG)

51 70 80 75 72 57 61 132 .

52 71 88 81 72 70 71 120 .

53 79 93 82 82 77 78 134 .

54 70 82 77 75 69 66 135 .

55 82 84 82 73 73 77 118 .

56 85 96 87 86 62 71 86 .

57 78 93 85 77 68 68 126 .

58 84 93 81 78 73 77 118 .

59 <NP> 68 85 85 64 69 60 --- .

60 63 92 73 80 73 73 115 .

GROUP 3 (300 MG/KG)

61 <NP> 84 89 84 61 57 65 --- .

62 <NP> 84 81 68 76 78 58 --- .

63 78 90 78 80 72 81 103 .

64 81 95 96 91 85 87 126 .

65 83 85 87 86 76 75 125 .

66 78 89 81 76 70 71 142 .

67 70 83 78 76 75 75 140 .

68 72 77 79 81 72 67 116 .

69 81 88 93 81 72 58 85 .

70 71 91 83 88 83 82 85 .

GROUP 4 (1000 MG/KG)

71 75 92 76 79 73 78 117 .

72 75 89 77 78 72 65 139 .

73 75 91 77 78 73 59 130 .

74 76 94 85 85 78 76 156 .

75 78 99 85 87 80 78 116 .

76 73 91 60 77 75 77 101 .

77 82 90 79 75 72 70 124 .

78 70 91 72 80 71 72 105 .

79 <NP> 71 78 77 62 54 53 --- .

80 80 82 83 82 74 70 122 .

- Page 23 - Final Report - Page 81 of 272 -
 13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.9 HAEMATOLOGY

MALES

END OF TREATMENT

ANIMAL WBC

10E9/L

Neutrophils

%WBC

Lymphocytes

%WBC

Monocytes

%WBC

Eosinophils

%WBC

GROUP 1 (CONTROL)

1 9.0 17.3 79.6 1.9 0.8

2 8.1 10.4 87.4 1.2 0.8

3 9.0 11.7 84.8 2.5 0.6

4 11.6 8.8 88.5 1.8 0.7

5 6.3 25.4 70.8 2.4 1.3

GROUP 2 (100 MG/KG)

11 9.4 16.5 80.3 1.5 1.3

12 9.8 16.0 78.8 3.1 1.9

13 7.1 25.8 69.5 3.2 1.4

14 --- 11.0 84.0 3.0 2.0

15 5.9 15.1 81.9 1.8 1.0

GROUP 3 (300 MG/KG)

21 6.9 24.3 72.0 2.3 1.3

22 8.6 19.6 76.0 2.3 2.0

23 14.5 18.5 78.7 1.8 0.7

24 8.3 20.9 75.6 2.0 1.4

25 8.2 29.3 66.8 2.9 0.8

GROUP 4 (1000 MG/KG)

31 9.9 17.3 79.1 1.9 1.4

32 9.3 17.5 79.2 1.8 1.4

33 8.0 14.9 82.7 1.5 0.7

34 7.1 22.8 74.3 1.7 1.0

35 7.8 9.9 86.4 1.7 1.8

MALES

END OF TREATMENT

ANIMAL Basophils

%WBC

Red blood cells

10E12/L

Reticulocytes

%RBC

RDW

%

Haemoglobin

mmol/L

GROUP 1 (CONTROL)

1 0.4 9.48 2.4 14.0 11.5

2 0.2 9.39 2.1 12.4 11.2

3 0.3 9.42 2.3 12.2 11.2

4 0.2 9.45 2.7 12.6 11.0

5 0.1 8.73 3.5 14.6 10.3

GROUP 2 (100 MG/KG)

11 0.3 9.87 2.0 11.9 11.3

12 0.3 9.16 2.5 12.7 11.3

13 0.1 9.15 2.8 12.0 11.0

14 0.0 8.84 2.3 12.8 10.7

15 0.2 8.67 2.9 12.7 10.9

GROUP 3 (300 MG/KG)

21 0.1 9.04 2.2 12.2 11.2

22 0.2 8.96 2.7 13.6 10.8

23 0.3 9.07 2.5 12.9 10.4

24 0.2 8.79 2.4 12.7 10.6

25 0.2 8.88 2.9 14.2 11.2

GROUP 4 (1000 MG/KG)

31 0.2 8.79 2.4 17.9 10.9

32 0.2 --- --- --- 10.8

33 0.1 9.39 2.7 13.7 10.9

34 0.3 9.63 2.3 12.9 11.5

- Page 24 - Final Report - Page 82 of 272 -
 13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.9 HAEMATOLOGY

MALES

END OF TREATMENT

ANIMAL Basophils

%WBC

Red blood cells

10E12/L

Reticulocytes

%RBC

RDW

%

Haemoglobin

mmol/L

GROUP 4 (1000 MG/KG)

35 0.1 9.10 2.4 13.9 10.3

MALES

END OF TREATMENT

ANIMAL Haematocrit

L/L

MCV

fL

MCH

fmol

MCHC

mmol/L

Platelets

10E9/L

GROUP 1 (CONTROL)

1 0.489 51.6 1.21 23.42 936

2 0.492 52.3 1.19 22.75 846

3 0.490 52.0 1.19 22.89 813

4 0.486 51.5 1.16 22.63 953

5 0.445 50.9 1.18 23.10 845

GROUP 2 (100 MG/KG)

11 0.499 50.5 1.15 22.68 844

12 0.483 52.8 1.24 23.47 847

13 0.494 54.0 1.20 22.17 879

14 0.460 52.0 1.22 23.35 902

15 0.458 52.8 1.26 23.81 978

GROUP 3 (300 MG/KG)

21 0.489 54.1 1.24 22.98 873

22 0.477 53.2 1.20 22.63 811

23 0.459 50.6 1.15 22.73 993

24 0.468 53.2 1.20 22.58 908

25 0.482 54.2 1.26 23.29 918

GROUP 4 (1000 MG/KG)

31 0.459 52.2 1.24 23.70 902

32 --- --- --- --- ---

33 0.491 52.3 1.16 22.27 847

34 0.513 53.3 1.20 22.51 777

35 0.459 50.5 1.13 22.33 962

MALES

END OF TREATMENT

ANIMAL PT

s

APTT

s

'

GROUP 1 (CONTROL)

1 16.6 12.2 .

2 18.0 18.0 .

3 18.3 15.5 .

4 18.8 21.0 .

5 18.1 19.9 .

GROUP 2 (100 MG/KG)

11 16.8 20.7 .

12 18.5 15.3 .

13 17.9 19.7 .

14 17.1 21.1 .

15 16.9 19.4 .

- Page 25 - Final Report - Page 83 of 272 -
 13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.9 HAEMATOLOGY

MALES

END OF TREATMENT

ANIMAL PT

s

APTT

s

'

GROUP 3 (300 MG/KG)

21 16.5 14.8 .

22 16.8 19.9 .

23 17.3 19.9 .

24 16.9 15.3 .

25 16.5 14.8 .

GROUP 4 (1000 MG/KG)

31 17.5 19.8 .

32 17.4 17.2 .

33 17.0 19.8 .

34 16.8 12.2 .

35 18.5 18.2 .

FEMALES

END OF TREATMENT

ANIMAL WBC

10E9/L

Neutrophils

%WBC

Lymphocytes

%WBC

Monocytes

%WBC

Eosinophils

%WBC

GROUP 1 (CONTROL)

42 4.9 27.5 69.5 1.5 1.3

43 4.8 28.2 68.3 2.6 0.7

44 5.2 25.6 70.9 2.6 0.8

45 3.0 32.5 64.2 2.3 0.8

47 4.4 19.0 77.7 2.6 0.6

GROUP 2 (100 MG/KG)

51 4.7 30.7 66.1 2.2 1.0

52 6.3 24.0 73.0 1.0 2.0

54 6.2 27.2 68.4 3.5 0.6

57 4.8 24.5 73.3 1.6 0.4

60 4.7 23.0 74.8 1.8 0.4

GROUP 3 (300 MG/KG)

64 5.7 25.0 72.2 2.3 0.3

65 3.5 20.5 75.8 2.9 0.7

67 --- 16.0 79.0 4.0 1.0

68 6.7 28.0 65.0 5.0 2.0

69 5.4 41.4 54.1 3.0 1.2

GROUP 4 (1000 MG/KG)

73 5.8 35.2 62.5 1.5 0.6

75 5.3 22.9 74.9 1.1 0.8

76 6.3 28.8 69.3 1.6 0.3

78 6.2 22.1 75.2 2.0 0.6

80 4.4 29.6 67.7 1.9 0.6

FEMALES

END OF TREATMENT

ANIMAL Basophils

%WBC

Red blood cells

10E12/L

Reticulocytes

%RBC

RDW

%

Haemoglobin

mmol/L

GROUP 1 (CONTROL)

42 0.1 7.78 4.0 14.9 9.1

43 0.2 7.71 9.0 19.6 9.1

- Page 26 - Final Report - Page 84 of 272 -
 13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.9 HAEMATOLOGY

FEMALES

END OF TREATMENT

ANIMAL Basophils

%WBC

Red blood cells

10E12/L

Reticulocytes

%RBC

RDW

%

Haemoglobin

mmol/L

GROUP 1 (CONTROL)

44 0.2 7.98 4.5 13.5 9.2

45 0.1 6.86 4.9 15.9 8.2

47 0.2 8.26 4.2 13.4 9.4

GROUP 2 (100 MG/KG)

51 0.1 7.85 3.2 13.9 9.3

52 0.0 8.27 6.1 14.0 9.8

54 0.3 7.71 5.0 18.2 9.6

57 0.2 7.32 8.7 18.7 8.8

60 0.1 7.53 4.5 15.7 9.2

GROUP 3 (300 MG/KG)

64 0.1 7.67 4.5 14.2 8.8

65 0.2 7.85 4.8 12.6 9.3

67 0.0 8.08 4.5 13.1 9.8

68 0.0 7.63 5.5 14.5 8.9

69 0.2 7.45 5.3 15.2 8.6

GROUP 4 (1000 MG/KG)

73 0.2 7.43 7.3 16.3 8.7

75 0.3 7.69 6.3 15.5 8.9

76 0.2 7.11 5.2 15.4 8.9

78 0.2 8.02 3.7 14.9 9.4

80 0.1 7.48 9.4 19.0 8.6

FEMALES

END OF TREATMENT

ANIMAL Haematocrit

L/L

MCV

fL

MCH

fmol

MCHC

mmol/L

Platelets

10E9/L

GROUP 1 (CONTROL)

42 0.448 57.6 1.17 20.40 983

43 0.443 57.4 1.18 20.55 974

44 0.440 55.2 1.15 20.87 832

45 0.380 55.4 1.20 21.64 886

47 0.448 54.2 1.14 20.95 923

GROUP 2 (100 MG/KG)

51 0.427 54.4 1.18 21.72 1102

52 0.479 57.9 1.18 20.41 888

54 0.444 57.6 1.24 21.59 985

57 0.426 58.1 1.20 20.70 980

60 0.423 56.2 1.22 21.73 1090

GROUP 3 (300 MG/KG)

64 0.414 53.9 1.14 21.16 842

65 0.446 56.9 1.19 20.88 778

67 0.470 58.3 1.22 20.92 678

68 0.428 56.0 1.17 20.89 1274

69 0.407 54.7 1.16 21.14 1265

GROUP 4 (1000 MG/KG)

73 0.423 57.0 1.16 20.44 1170

75 0.430 56.0 1.16 20.73 1078

76 0.425 59.8 1.25 20.84 1046

78 0.432 53.9 1.17 21.75 1261

80 0.428 57.1 1.15 20.16 1299

- Page 27 - Final Report - Page 85 of 272 -
 13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.9 HAEMATOLOGY

FEMALES

END OF TREATMENT

ANIMAL PT

s

APTT

s

'

GROUP 1 (CONTROL)

42 15.6 13.6 .

43 16.4 14.7 .

44 15.8 12.5 .

45 17.2 16.7 .

47 17.5 16.5 .

GROUP 2 (100 MG/KG)

51 16.2 18.9 .

52 15.4 14.9 .

54 --- --- .

57 16.1 16.4 .

60 16.3 13.9 .

GROUP 3 (300 MG/KG)

64 17.0 16.3 .

65 16.0 20.4 .

67 16.0 14.5 .

68 16.8 12.1 .

69 16.8 13.8 .

GROUP 4 (1000 MG/KG)

73 16.4 16.3 .

75 16.7 17.2 .

76 15.5 13.6 .

78 16.2 15.8 .

80 16.1 12.1 .

- Page 28 - Final Report - Page 86 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.10 CLINICAL BIOCHEMISTRY

MALES

END OF TREATMENT

ANIMAL ALAT

U/L

ASAT

U/L

ALP

U/L

Total protein

g/L

Albumin

g/L

GROUP 1 (CONTROL)

1 47.4 74.9 145 67.2 33.9

2 42.7 74.0 95 62.3 31.9

3 51.8 95.4 194 64.9 34.2

4 42.3 64.4 197 62.9 32.8

5 44.9 70.7 144 62.2 32.8

GROUP 2 (100 MG/KG)

11 34.5 75.9 159 63.3 33.0

12 63.9 80.0 234 63.9 34.2

13 37.0 75.0 81 64.4 34.0

14 31.8 80.4 142 58.1 30.5

15 37.9 78.2 116 64.0 33.1

GROUP 3 (300 MG/KG)

21 27.5 68.3 123 66.6 34.0

22 40.7 80.9 109 61.8 31.1

23 42.6 66.5 103 65.4 33.7

24 37.1 76.9 118 61.8 31.9

25 38.4 64.6 93 63.7 32.5

GROUP 4 (1000 MG/KG)

31 44.4 88.6 161 61.8 32.3

32 43.3 83.5 201 63.0 32.6

33 36.9 78.2 184 64.7 33.0

34 48.6 78.2 180 62.0 32.4

35 54.4 80.8 144 58.4 31.1

MALES

END OF TREATMENT

ANIMAL Total bilirubin

umol/L

Urea

mmol/L

Creatinine

umol/L

Glucose

mmol/L

Cholesterol

mmol/L

GROUP 1 (CONTROL)

1 2.1 6.5 41.0 7.81 2.09

2 1.9 7.2 36.8 10.38 1.72

3 2.6 7.5 38.6 8.06 1.68

4 2.1 9.6 40.4 10.93 1.91

5 1.9 7.3 38.0 10.00 1.39

GROUP 2 (100 MG/KG)

11 2.6 6.8 41.0 9.49 1.46

12 2.8 9.6 38.0 10.50 1.79

13 1.9 4.5 36.2 7.60 1.59

14 2.4 5.7 38.6 7.39 1.30

15 1.9 6.4 41.0 9.67 2.14

GROUP 3 (300 MG/KG)

21 1.8 5.9 39.2 9.30 2.51

22 2.1 5.6 38.6 9.14 1.68

23 1.9 7.2 39.8 10.66 1.72

24 2.1 5.9 41.6 9.63 2.22

25 1.8 6.8 45.3 9.11 1.82

GROUP 4 (1000 MG/KG)

31 2.9 6.8 35.6 7.15 1.84

32 2.7 5.8 38.0 8.34 2.46

33 2.4 8.0 40.4 8.63 1.70

34 2.6 7.2 36.8 9.66 1.77

- Page 29 - Final Report - Page 87 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.10 CLINICAL BIOCHEMISTRY

MALES

END OF TREATMENT

ANIMAL Total bilirubin

umol/L

Urea

mmol/L

Creatinine

umol/L

Glucose

mmol/L

Cholesterol

mmol/L

GROUP 4 (1000 MG/KG)

35 2.3 6.8 40.4 6.01 1.92

MALES

END OF TREATMENT

ANIMAL Bile Acids

umol/L

Sodium

mmol/L

Potassium

mmol/L

Chloride

mmol/L

Calcium

mmol/L

GROUP 1 (CONTROL)

1 10.0 142.7 4.08 104 2.73

2 5.4 141.7 4.09 106 2.56

3 81.0 140.8 4.11 104 2.70

4 23.0 140.8 4.38 103 2.66

5 8.5 142.2 3.75 102 2.64

GROUP 2 (100 MG/KG)

11 7.8 141.7 4.06 104 2.70

12 55.7 141.2 4.23 105 2.56

13 6.9 143.1 3.90 105 2.63

14 18.4 141.8 4.21 106 2.57

15 7.6 142.4 3.66 104 2.61

GROUP 3 (300 MG/KG)

21 12.8 142.5 3.83 104 2.65

22 16.5 142.7 4.25 106 2.57

23 18.2 142.3 3.71 102 2.68

24 27.1 141.7 4.48 106 2.54

25 5.3 143.5 3.91 105 2.62

GROUP 4 (1000 MG/KG)

31 25.8 142.2 4.17 104 2.56

32 19.5 141.6 4.44 104 2.67

33 21.9 144.2 3.90 105 2.65

34 19.1 141.7 3.92 103 2.63

35 14.4 142.1 3.85 107 2.55

MALES

END OF TREATMENT

ANIMAL Inorg.Phos

mmol/L

'

GROUP 1 (CONTROL)

1 1.88 .

2 1.66 .

3 2.00 .

4 1.89 .

5 2.24 .

GROUP 2 (100 MG/KG)

11 1.71 .

12 1.71 .

13 1.76 .

14 2.00 .

15 1.46 .

- Page 30 - Final Report - Page 88 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.10 CLINICAL BIOCHEMISTRY

MALES

END OF TREATMENT

ANIMAL Inorg.Phos

mmol/L

'

GROUP 3 (300 MG/KG)

21 1.85 .

22 1.99 .

23 1.75 .

24 1.96 .

25 1.65 .

GROUP 4 (1000 MG/KG)

31 2.14 .

32 2.21 .

33 2.22 .

34 2.18 .

35 1.88 .

FEMALES

END OF TREATMENT

ANIMAL ALAT

U/L

ASAT

U/L

ALP

U/L

Total protein

g/L

Albumin

g/L

GROUP 1 (CONTROL)

42 57.5 72.2 47 70.2 35.3

43 45.7 84.3 108 67.0 34.4

44 42.0 88.4 86 61.3 31.4

45 74.3 132.8 123 63.4 32.9

47 53.6 73.8 64 65.7 33.2

GROUP 2 (100 MG/KG)

51 56.8 96.0 120 68.5 35.1

52 53.5 83.9 125 64.9 32.5

54 57.7 81.2 68 65.2 32.6

57 40.8 67.0 101 64.3 33.4

60 46.2 70.2 67 65.2 34.0

GROUP 3 (300 MG/KG)

64 53.6 66.5 57 59.8 30.0

65 51.2 72.9 52 64.0 32.5

67 66.3 75.7 117 62.0 31.8

68 54.8 73.0 101 66.0 33.7

69 54.7 67.6 55 63.0 32.8

GROUP 4 (1000 MG/KG)

73 50.7 74.4 39 66.2 33.6

75 48.2 69.8 75 63.7 32.1

76 44.1 71.2 68 58.5 29.2

78 46.8 76.9 65 62.0 32.7

80 70.1 70.7 40 64.9 33.4

FEMALES

END OF TREATMENT

ANIMAL Total bilirubin

umol/L

Urea

mmol/L

Creatinine

umol/L

Glucose

mmol/L

Cholesterol

mmol/L

GROUP 1 (CONTROL)

42 2.1 6.3 43.5 5.95 2.19

43 2.5 8.4 43.5 5.50 2.29

- Page 31 - Final Report - Page 89 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.10 CLINICAL BIOCHEMISTRY

FEMALES

END OF TREATMENT

ANIMAL Total bilirubin

umol/L

Urea

mmol/L

Creatinine

umol/L

Glucose

mmol/L

Cholesterol

mmol/L

GROUP 1 (CONTROL)

44 2.1 8.3 45.9 5.84 1.69

45 2.2 7.8 44.7 8.27 2.00

47 1.9 9.1 42.9 7.43 2.19

GROUP 2 (100 MG/KG)

51 1.9 7.9 42.2 7.84 1.66

52 2.5 8.5 47.1 7.06 2.00

54 2.3 8.5 44.1 7.70 1.97

57 1.9 7.2 44.1 7.54 1.63

60 1.8 7.9 43.5 5.94 1.95

GROUP 3 (300 MG/KG)

64 1.7 8.1 40.9 5.74 1.62

65 2.4 9.6 43.5 6.44 1.39

67 2.3 7.4 46.5 6.02 1.56

68 1.7 10.3 44.4 7.45 2.46

69 1.8 7.7 45.1 5.35 1.58

GROUP 4 (1000 MG/KG)

73 1.9 8.5 44.7 7.63 2.25

75 2.1 7.3 40.4 5.40 1.95

76 1.8 7.3 41.7 6.55 2.01

78 2.1 6.9 41.1 6.30 1.55

80 2.1 9.4 44.7 7.60 1.63

FEMALES

END OF TREATMENT

ANIMAL Bile Acids

umol/L

Sodium

mmol/L

Potassium

mmol/L

Chloride

mmol/L

Calcium

mmol/L

GROUP 1 (CONTROL)

42 44.5 139.9 3.82 97 2.67

43 14.1 142.4 3.74 97 2.73

44 30.4 140.3 3.32 93 2.60

45 --- 142.2 3.66 95 2.69

47 40.7 140.9 3.73 101 2.66

GROUP 2 (100 MG/KG)

51 49.8 140.5 3.76 96 2.69

52 36.5 140.6 3.60 97 2.64

54 32.2 139.5 4.19 96 2.68

57 15.1 139.4 3.38 94 2.60

60 15.9 140.4 3.53 100 2.71

GROUP 3 (300 MG/KG)

64 14.1 139.2 3.27 96 2.52

65 16.2 140.9 3.86 95 2.57

67 42.5 140.5 3.71 95 2.70

68 24.2 141.2 2.84 96 2.75

69 27.5 141.7 3.44 96 2.59

GROUP 4 (1000 MG/KG)

73 26.0 141.4 3.46 94 2.74

75 20.4 141.3 3.39 97 2.68

76 11.4 142.1 3.35 96 2.57

78 16.2 142.0 3.31 93 2.67

80 85.3 140.1 3.78 97 2.76

- Page 32 - Final Report - Page 90 of 272 -
 05Nov13 14h41

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.10 CLINICAL BIOCHEMISTRY

FEMALES

END OF TREATMENT

ANIMAL Inorg.Phos

mmol/L

'

GROUP 1 (CONTROL)

42 1.86 .

43 2.46 .

44 2.17 .

45 2.14 .

47 1.94 .

GROUP 2 (100 MG/KG)

51 1.88 .

52 2.09 .

54 2.80 .

57 2.41 .

60 1.80 .

GROUP 3 (300 MG/KG)

64 1.87 .

65 2.36 .

67 2.28 .

68 2.31 .

69 1.99 .

GROUP 4 (1000 MG/KG)

73 2.33 .

75 2.13 .

76 1.76 .

78 2.09 .

80 2.44 .

- Page 33 - Final Report - Page 91 of 272 -
 13Jan14 08h16

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.11 MACROSCOPIC FINDINGS

MALES

ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

'

GROUP 1 (CONTROL)

1 Kidneys Right side: pelvic dilation. Scheduled sacrifice, 17Oct2013 .

Testes Right side: agenesis. .

Epididymides Right side: agenesis. .

2 Lungs Focus/foci, many, reddish. Scheduled sacrifice, 17Oct2013 .

3 No findings noted Scheduled sacrifice, 17Oct2013 .

4 No findings noted Scheduled sacrifice, 17Oct2013 .

5 No findings noted Scheduled sacrifice, 17Oct2013 .

6 No findings noted Scheduled sacrifice, 17Oct2013 .

7 No findings noted Scheduled sacrifice, 17Oct2013 .

8 No findings noted Scheduled sacrifice, 17Oct2013 .

9 No findings noted Scheduled sacrifice, 17Oct2013 .

10 No findings noted Scheduled sacrifice, 17Oct2013 .

GROUP 2 (100 MG/KG)

11 Thymus Right side: focus/foci, many, reddish. Scheduled sacrifice, 17Oct2013 .

12 No findings noted Scheduled sacrifice, 17Oct2013 .

13 Stomach Glandular mucosa: focus/foci, Scheduled sacrifice, 17Oct2013 .

isolated, reddish. .

Renal lymph node Left side: enlarged. .

Left side: discolouration, dark red. .

14 Bulbo-urethral gland Left side: enlarged. Scheduled sacrifice, 17Oct2013 .

Axillary lymph node Right side: enlarged. .

15 No findings noted Scheduled sacrifice, 17Oct2013 .

16 No findings noted Scheduled sacrifice, 17Oct2013 .

17 No findings noted Scheduled sacrifice, 17Oct2013 .

18 No findings noted Scheduled sacrifice, 17Oct2013 .

19 No findings noted Scheduled sacrifice, 17Oct2013 .

20 No findings noted Scheduled sacrifice, 17Oct2013 .

GROUP 3 (300 MG/KG)

21 Bulbo-urethral gland Both sides: enlarged. Scheduled sacrifice, 17Oct2013 .

22 Epididymides Right side, tail: nodule(s), isolated, Scheduled sacrifice, 17Oct2013 .

yellowish, soft. .

Bulbo-urethral gland Left side: enlarged. .

23 No findings noted Scheduled sacrifice, 17Oct2013 .

24 No findings noted Scheduled sacrifice, 17Oct2013 .

25 No findings noted Scheduled sacrifice, 17Oct2013 .

26 Epididymides Right side, tail: nodule(s), d=14x10 mm, Scheduled sacrifice, 17Oct2013 .

yellowish, soft. .

27 No findings noted Scheduled sacrifice, 17Oct2013 .

28 No findings noted Scheduled sacrifice, 17Oct2013 .

29 No findings noted Scheduled sacrifice, 17Oct2013 .

30 No findings noted Scheduled sacrifice, 17Oct2013 .

GROUP 4 (1000 MG/KG)

31 Stomach Limiting ridge: thickened. Scheduled sacrifice, 17Oct2013 .

Thymus Reduced in size. .

32 Epididymides Right side, tail: nodule(s), d=6x6 mm, Scheduled sacrifice, 17Oct2013 .

yellowish, soft. .

Bulbo-urethral gland Right side: enlarged. .

33 No findings noted Scheduled sacrifice, 17Oct2013 .

34 Preputial glands Left side: focus/foci, d=3x2 mm, Scheduled sacrifice, 17Oct2013 .

gray-white. .

35 Liver Discolouration, dark red. Scheduled sacrifice, 17Oct2013 .

36 No findings noted Scheduled sacrifice, 17Oct2013 .

37 No findings noted Scheduled sacrifice, 17Oct2013 .

38 No findings noted Scheduled sacrifice, 17Oct2013 .

39 No findings noted Scheduled sacrifice, 17Oct2013 .

40 No findings noted Scheduled sacrifice, 17Oct2013 .

- Page 34 - Final Report - Page 92 of 272 -
 13Jan14 08h16

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.11 MACROSCOPIC FINDINGS

FEMALES

ALL NECROPSIES

ANIMAL ORGAN FINDING DAY OF DEATH

'

GROUP 1 (CONTROL)

41 No findings noted Scheduled sacrifice, 04Nov2013 .

42 Duodenum Wall: thickened. Scheduled sacrifice, 31Oct2013 .

Jejunum Wall: thickened. .

43 Thymus Focus/foci, many, reddish. Scheduled sacrifice, 31Oct2013 .

44 Kidneys Both sides: pelvic dilation. Scheduled sacrifice, 31Oct2013 .

Clitoral glands Left side: enlarged. .

Left side: discolouration, tan. .

45 No findings noted Scheduled sacrifice, 31Oct2013 .

46 No findings noted Scheduled sacrifice, 29Oct2013 .

47 Duodenum Wall: thickened. Scheduled sacrifice, 31Oct2013 .

Jejunum Wall: thickened. .

Clitoral glands Right side: focus/foci, d=2x2 mm, .

reddish. .

48 No findings noted Scheduled sacrifice, 31Oct2013 .

49 No findings noted Scheduled sacrifice, 31Oct2013 .

50 No findings noted Scheduled sacrifice, 31Oct2013 .

GROUP 2 (100 MG/KG)

51 Ovaries Right side: cyst(s), d=3x3 mm, Scheduled sacrifice, 01Nov2013 .

watery-clear. .

52 No findings noted Scheduled sacrifice, 31Oct2013 .

53 No findings noted Scheduled sacrifice, 01Nov2013 .

54 Kidneys Right side: cyst(s), d=2x2 mm, Scheduled sacrifice, 31Oct2013 .

watery-clear. .

55 No findings noted Scheduled sacrifice, 01Nov2013 .

56 No findings noted Scheduled sacrifice, 01Nov2013 .

57 No findings noted Scheduled sacrifice, 31Oct2013 .

58 No findings noted Scheduled sacrifice, 01Nov2013 .

59 No findings noted Scheduled sacrifice, 29Oct2013 .

60 No findings noted Scheduled sacrifice, 31Oct2013 .

GROUP 3 (300 MG/KG)

61 No findings noted Scheduled sacrifice, 01Nov2013 .

62 No findings noted Scheduled sacrifice, 01Nov2013 .

63 No findings noted Scheduled sacrifice, 04Nov2013 .

64 Stomach Contents: remains of pup. Scheduled sacrifice, 29Oct2013 .

65 No findings noted Scheduled sacrifice, 31Oct2013 .

66 No findings noted Scheduled sacrifice, 01Nov2013 .

67 No findings noted Scheduled sacrifice, 31Oct2013 .

68 No findings noted Scheduled sacrifice, 29Oct2013 .

69 Liver Enlarged. Scheduled sacrifice, 29Oct2013 .

Thymus Focus/foci, many, reddish. .

70 No findings noted Scheduled sacrifice, 01Nov2013 .

GROUP 4 (1000 MG/KG)

71 No findings noted Scheduled sacrifice, 01Nov2013 .

72 No findings noted Scheduled sacrifice, 01Nov2013 .

73 Stomach Glandular mucosa: irregular surface. Scheduled sacrifice, 31Oct2013 .

Clitoral glands Right side: focus/foci, isolated, tan. .

74 No findings noted Scheduled sacrifice, 01Nov2013 .

75 No findings noted Scheduled sacrifice, 31Oct2013 .

76 No findings noted Scheduled sacrifice, 31Oct2013 .

77 Kidneys Right side: pelvic dilation. Scheduled sacrifice, 01Nov2013 .

78 No findings noted Scheduled sacrifice, 31Oct2013 .

79 No findings noted Scheduled sacrifice, 29Oct2013 .

80 No findings noted Scheduled sacrifice, 31Oct2013 .

- Page 35 - Final Report - Page 93 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN WEIGHTS (GRAM)

MALES

END OF TREATMENT

ANIMAL BODY W.

(GRAM)

BRAIN

(GRAM)

HEART

(GRAM)

LIVER

(GRAM)

THYROID

(GRAM)

THYMUS

(GRAM)

GROUP 1 (CONTROL)

1 371 2.13 0.991 9.45 0.020 0.384

2 365 2.02 1.001 8.63 0.021 0.414

3 362 2.21 0.987 8.26 0.020 0.450

4 372 2.11 1.030 8.86 0.015 0.334

5 359 1.95 1.022 8.32 0.022 0.295

6 337 --- --- --- --- ---

7 379 --- --- --- --- ---

8 377 --- --- --- --- ---

9 369 --- --- --- --- ---

10 361 --- --- --- --- ---

GROUP 2 (100 MG/KG)

11 341 1.98 0.924 7.73 0.022 0.307

12 365 2.00 0.916 8.14 0.018 0.362

13 347 2.20 0.884 7.91 0.017 0.431

14 363 2.16 1.017 8.02 0.016 0.248

15 311 1.93 0.826 7.19 0.020 0.287

16 350 --- --- --- --- ---

17 364 --- --- --- --- ---

18 361 --- --- --- --- ---

19 350 --- --- --- --- ---

20 352 --- --- --- --- ---

GROUP 3 (300 MG/KG)

21 363 2.20 0.948 8.75 0.019 0.268

22 365 2.14 1.017 9.42 0.017 0.318

23 361 1.99 0.986 9.38 0.014 0.377

24 334 2.01 0.859 7.88 --- 0.299

25 362 2.19 1.043 8.75 0.013 0.365

26 384 --- --- --- --- ---

27 338 --- --- --- --- ---

28 376 --- --- --- --- ---

29 356 --- --- --- --- ---

30 341 --- --- --- --- ---

GROUP 4 (1000 MG/KG)

31 345 2.17 0.936 8.38 0.016 0.159

32 358 2.23 1.126 8.99 0.021 0.355

33 366 1.96 1.018 9.09 0.019 0.391

34 358 2.01 0.890 8.87 0.026 0.323

35 333 2.15 1.000 7.94 0.016 0.255

36 355 --- --- --- --- ---

37 327 --- --- --- --- ---

38 366 --- --- --- --- ---

39 347 --- --- --- --- ---

40 367 --- --- --- --- ---

MALES

END OF TREATMENT

ANIMAL KIDNEYS

(GRAM)

ADRENALS

(GRAM)

SPLEEN

(GRAM)

TESTES

(GRAM)

PROSTATE

(GRAM)

EPIDIDYMIDES

(GRAM)

GROUP 1 (CONTROL)

1 2.46 0.069 0.631 --- 0.563 ---

2 2.30 0.073 0.545 3.18 0.685 1.206

3 2.27 0.059 0.691 3.86 0.601 1.190

4 2.30 0.069 0.627 3.20 0.881 1.184

5 2.12 0.067 0.529 3.43 0.676 1.093

- Page 36 - Final Report - Page 94 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN WEIGHTS (GRAM)

MALES

END OF TREATMENT

ANIMAL KIDNEYS

(GRAM)

ADRENALS

(GRAM)

SPLEEN

(GRAM)

TESTES

(GRAM)

PROSTATE

(GRAM)

EPIDIDYMIDES

(GRAM)

GROUP 1 (CONTROL)

6 --- --- --- 3.52 --- 1.253

7 --- --- --- 3.04 --- 1.087

8 --- --- --- 3.67 --- 1.097

9 --- --- --- 3.68 --- 1.317

10 --- --- --- 4.53 --- 1.482

GROUP 2 (100 MG/KG)

11 2.22 0.073 0.684 4.60 0.834 1.412

12 2.36 0.082 0.542 3.95 0.972 1.221

13 2.21 0.059 0.571 3.98 0.607 1.196

14 2.38 0.059 0.516 3.34 0.862 1.276

15 1.91 0.049 0.478 3.23 0.630 1.014

16 --- --- --- 3.34 --- 1.094

17 --- --- --- 4.28 --- 1.283

18 --- --- --- 3.37 --- 1.087

19 --- --- --- 3.31 --- 1.094

20 --- --- --- 3.76 --- 1.297

GROUP 3 (300 MG/KG)

21 2.49 0.068 0.578 3.11 0.528 1.022

22 2.49 0.060 0.618 3.71 0.650 1.244

23 2.55 0.074 0.738 3.67 0.807 1.217

24 2.17 0.054 0.570 3.50 0.633 1.138

25 2.43 0.057 0.692 3.69 0.589 1.182

26 --- --- --- 3.59 --- 1.659

27 --- --- --- 3.75 --- 1.215

28 --- --- --- 3.60 --- 1.043

29 --- --- --- 3.84 --- 1.155

30 --- --- --- 3.69 --- 1.185

GROUP 4 (1000 MG/KG)

31 2.60 0.066 0.487 3.50 0.820 1.147

32 2.60 0.052 0.517 4.12 0.643 1.403

33 2.46 0.076 0.711 3.56 0.789 1.120

34 2.56 0.068 0.491 3.34 1.041 1.107

35 2.39 0.045 0.645 3.55 0.764 1.172

36 --- --- --- 3.37 --- 1.119

37 --- --- --- 3.42 --- 1.130

38 --- --- --- 3.48 --- 1.159

39 --- --- --- 3.79 --- 1.102

40 --- --- --- 3.96 --- 1.161

MALES

END OF TREATMENT

ANIMAL SEMINAL VES

(GRAM)

'

GROUP 1 (CONTROL)

1 1.257 .

2 1.474 .

3 1.118 .

4 1.410 .

5 1.323 .

6 --- .

7 --- .

8 --- .

9 --- .

10 --- .

- Page 37 - Final Report - Page 95 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN WEIGHTS (GRAM)

MALES

END OF TREATMENT

ANIMAL SEMINAL VES

(GRAM)

'

GROUP 2 (100 MG/KG)

11 1.551 .

12 1.540 .

13 1.329 .

14 1.675 .

15 1.509 .

16 --- .

17 --- .

18 --- .

19 --- .

20 --- .

GROUP 3 (300 MG/KG)

21 1.340 .

22 1.154 .

23 1.320 .

24 1.207 .

25 0.915 .

26 --- .

27 --- .

28 --- .

29 --- .

30 --- .

GROUP 4 (1000 MG/KG)

31 2.245 .

32 1.708 .

33 1.534 .

34 1.849 .

35 1.872 .

36 --- .

37 --- .

38 --- .

39 --- .

40 --- .

- Page 38 - Final Report - Page 96 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN/BODY WEIGHT RATIOS (%)

MALES

END OF TREATMENT

ANIMAL BODY W.

(GRAM)

BRAIN

(%)

HEART

(%)

LIVER

(%)

THYROID

(%)

THYMUS

(%)

GROUP 1 (CONTROL)

1 371 0.57 0.267 2.55 0.005 0.104

2 365 0.55 0.274 2.36 0.006 0.113

3 362 0.61 0.273 2.28 0.006 0.124

4 372 0.57 0.277 2.38 0.004 0.090

5 359 0.54 0.285 2.32 0.006 0.082

6 337 --- --- --- --- ---

7 379 --- --- --- --- ---

8 377 --- --- --- --- ---

9 369 --- --- --- --- ---

10 361 --- --- --- --- ---

GROUP 2 (100 MG/KG)

11 341 0.58 0.271 2.27 0.006 0.090

12 365 0.55 0.251 2.23 0.005 0.099

13 347 0.63 0.255 2.28 0.005 0.124

14 363 0.59 0.280 2.21 0.004 0.068

15 311 0.62 0.266 2.31 0.006 0.092

16 350 --- --- --- --- ---

17 364 --- --- --- --- ---

18 361 --- --- --- --- ---

19 350 --- --- --- --- ---

20 352 --- --- --- --- ---

GROUP 3 (300 MG/KG)

21 363 0.61 0.261 2.41 0.005 0.074

22 365 0.59 0.279 2.58 0.005 0.087

23 361 0.55 0.273 2.60 0.004 0.104

24 334 0.60 0.257 2.36 --- 0.090

25 362 0.60 0.288 2.42 0.004 0.101

26 384 --- --- --- --- ---

27 338 --- --- --- --- ---

28 376 --- --- --- --- ---

29 356 --- --- --- --- ---

30 341 --- --- --- --- ---

GROUP 4 (1000 MG/KG)

31 345 0.63 0.271 2.43 0.005 0.046

32 358 0.62 0.315 2.51 0.006 0.099

33 366 0.53 0.278 2.48 0.005 0.107

34 358 0.56 0.249 2.48 0.007 0.090

35 333 0.64 0.300 2.38 0.005 0.077

36 355 --- --- --- --- ---

37 327 --- --- --- --- ---

38 366 --- --- --- --- ---

39 347 --- --- --- --- ---

40 367 --- --- --- --- ---

MALES

END OF TREATMENT

ANIMAL KIDNEYS

(%)

ADRENALS

(%)

SPLEEN

(%)

TESTES

(%)

PROSTATE

(%)

EPIDIDYMIDES

(%)

GROUP 1 (CONTROL)

1 0.66 0.019 0.170 --- 0.152 ---

2 0.63 0.020 0.149 0.87 0.188 0.330

3 0.63 0.016 0.191 1.07 0.166 0.329

4 0.62 0.019 0.169 0.86 0.237 0.318

5 0.59 0.019 0.147 0.96 0.188 0.304

- Page 39 - Final Report - Page 97 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN/BODY WEIGHT RATIOS (%)

MALES

END OF TREATMENT

ANIMAL KIDNEYS

(%)

ADRENALS

(%)

SPLEEN

(%)

TESTES

(%)

PROSTATE

(%)

EPIDIDYMIDES

(%)

GROUP 1 (CONTROL)

6 --- --- --- 1.04 --- 0.372

7 --- --- --- 0.80 --- 0.287

8 --- --- --- 0.97 --- 0.291

9 --- --- --- 1.00 --- 0.357

10 --- --- --- 1.26 --- 0.411

GROUP 2 (100 MG/KG)

11 0.65 0.021 0.201 1.35 0.245 0.414

12 0.65 0.022 0.148 1.08 0.266 0.335

13 0.64 0.017 0.165 1.15 0.175 0.345

14 0.66 0.016 0.142 0.92 0.237 0.352

15 0.62 0.016 0.154 1.04 0.203 0.326

16 --- --- --- 0.95 --- 0.313

17 --- --- --- 1.18 --- 0.352

18 --- --- --- 0.93 --- 0.301

19 --- --- --- 0.95 --- 0.313

20 --- --- --- 1.07 --- 0.368

GROUP 3 (300 MG/KG)

21 0.69 0.019 0.159 0.86 0.145 0.282

22 0.68 0.016 0.169 1.02 0.178 0.341

23 0.71 0.020 0.204 1.02 0.224 0.337

24 0.65 0.016 0.171 1.05 0.190 0.341

25 0.67 0.016 0.191 1.02 0.163 0.327

26 --- --- --- 0.93 --- 0.432

27 --- --- --- 1.11 --- 0.359

28 --- --- --- 0.96 --- 0.277

29 --- --- --- 1.08 --- 0.324

30 --- --- --- 1.08 --- 0.348

GROUP 4 (1000 MG/KG)

31 0.75 0.019 0.141 1.02 0.238 0.332

32 0.73 0.015 0.144 1.15 0.180 0.392

33 0.67 0.021 0.194 0.97 0.216 0.306

34 0.71 0.019 0.137 0.93 0.291 0.309

35 0.72 0.014 0.194 1.06 0.229 0.352

36 --- --- --- 0.95 --- 0.315

37 --- --- --- 1.05 --- 0.346

38 --- --- --- 0.95 --- 0.317

39 --- --- --- 1.09 --- 0.318

40 --- --- --- 1.08 --- 0.316

MALES

END OF TREATMENT

ANIMAL SEMINAL VES

(%)

'

GROUP 1 (CONTROL)

1 0.339 .

2 0.404 .

3 0.309 .

4 0.379 .

5 0.369 .

6 --- .

7 --- .

8 --- .

9 --- .

10 --- .

- Page 40 - Final Report - Page 98 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN/BODY WEIGHT RATIOS (%)

MALES

END OF TREATMENT

ANIMAL SEMINAL VES

(%)

'

GROUP 2 (100 MG/KG)

11 0.455 .

12 0.422 .

13 0.383 .

14 0.461 .

15 0.485 .

16 --- .

17 --- .

18 --- .

19 --- .

20 --- .

GROUP 3 (300 MG/KG)

21 0.369 .

22 0.316 .

23 0.366 .

24 0.361 .

25 0.253 .

26 --- .

27 --- .

28 --- .

29 --- .

30 --- .

GROUP 4 (1000 MG/KG)

31 0.651 .

32 0.477 .

33 0.419 .

34 0.516 .

35 0.562 .

36 --- .

37 --- .

38 --- .

39 --- .

40 --- .

- Page 41 - Final Report - Page 99 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN WEIGHTS (GRAM)

FEMALES

END OF TREATMENT

ANIMAL BODY W.

(GRAM)

BRAIN

(GRAM)

HEART

(GRAM)

LIVER

(GRAM)

THYROID

(GRAM)

THYMUS

(GRAM)

GROUP 1 (CONTROL)

41 --- --- --- --- --- ---

42 248 2.01 0.854 8.82 0.012 0.231

43 226 1.90 0.691 6.81 0.015 0.202

44 259 1.84 0.823 7.88 0.013 0.227

45 255 1.86 0.852 8.51 0.012 0.279

46 --- --- --- --- --- ---

47 232 2.02 0.725 7.34 0.013 0.205

48 --- --- --- --- --- ---

49 --- --- --- --- --- ---

50 --- --- --- --- --- ---

GROUP 2 (100 MG/KG)

51 235 1.95 0.680 7.02 0.013 0.227

52 235 1.82 0.776 6.87 0.018 0.308

53 --- --- --- --- --- ---

54 230 1.79 0.805 7.25 0.016 0.227

55 --- --- --- --- --- ---

56 --- --- --- --- --- ---

57 249 1.87 0.815 8.40 0.010 0.217

58 --- --- --- --- --- ---

59 --- --- --- --- --- ---

60 243 1.84 0.865 7.26 0.016 0.209

GROUP 3 (300 MG/KG)

61 --- --- --- --- --- ---

62 --- --- --- --- --- ---

63 --- --- --- --- --- ---

64 288 1.97 0.871 9.48 0.013 0.243

65 237 1.84 0.828 7.79 0.014 0.231

66 --- --- --- --- --- ---

67 249 1.98 0.786 7.81 0.011 0.233

68 245 1.89 0.765 7.72 0.015 0.261

69 243 1.81 0.772 14.75 0.014 0.278

70 --- --- --- --- --- ---

GROUP 4 (1000 MG/KG)

71 --- --- --- --- --- ---

72 --- --- --- --- --- ---

73 235 1.90 0.703 8.02 0.012 0.216

74 --- --- --- --- --- ---

75 240 1.88 0.804 7.49 0.018 0.340

76 229 1.78 0.703 7.09 0.022 0.230

77 --- --- --- --- --- ---

78 228 1.92 0.751 6.46 0.011 0.196

79 --- --- --- --- --- ---

80 237 1.94 0.703 7.28 0.011 0.214

FEMALES

END OF TREATMENT

ANIMAL KIDNEYS

(GRAM)

ADRENALS

(GRAM)

SPLEEN

(GRAM)

OVARIES

(GRAM)

UTERUS

(GRAM)

'

GROUP 1 (CONTROL)

41 --- --- --- --- --- .

42 1.87 0.092 0.516 0.138 0.652 .

43 1.59 0.075 0.522 0.131 0.650 .

44 1.69 0.074 0.731 0.132 0.596 .

45 1.76 0.078 0.609 0.129 0.655 .

- Page 42 - Final Report - Page 100 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN WEIGHTS (GRAM)

FEMALES

END OF TREATMENT

ANIMAL KIDNEYS

(GRAM)

ADRENALS

(GRAM)

SPLEEN

(GRAM)

OVARIES

(GRAM)

UTERUS

(GRAM)

'

GROUP 1 (CONTROL)

46 --- --- --- --- --- .

47 1.68 0.079 0.470 0.101 0.492 .

48 --- --- --- --- --- .

49 --- --- --- --- --- .

50 --- --- --- --- --- .

GROUP 2 (100 MG/KG)

51 1.79 0.074 0.383 0.121 0.523 .

52 1.65 0.070 0.560 0.134 0.704 .

53 --- --- --- --- --- .

54 1.60 0.071 0.479 0.122 0.529 .

55 --- --- --- --- --- .

56 --- --- --- --- --- .

57 1.90 0.079 0.651 0.135 0.689 .

58 --- --- --- --- --- .

59 --- --- --- --- --- .

60 1.77 0.075 0.507 0.136 0.763 .

GROUP 3 (300 MG/KG)

61 --- --- --- --- --- .

62 --- --- --- --- --- .

63 --- --- --- --- --- .

64 2.18 0.120 0.601 0.139 0.834 .

65 1.74 0.085 0.469 0.121 0.531 .

66 --- --- --- --- --- .

67 1.60 0.077 0.460 0.126 0.644 .

68 1.72 0.080 0.552 0.151 0.654 .

69 1.59 0.060 0.595 0.117 0.609 .

70 --- --- --- --- --- .

GROUP 4 (1000 MG/KG)

71 --- --- --- --- --- .

72 --- --- --- --- --- .

73 1.77 0.071 0.580 0.130 0.912 .

74 --- --- --- --- --- .

75 1.94 0.065 0.427 0.136 0.670 .

76 1.66 0.076 0.539 0.141 0.876 .

77 --- --- --- --- --- .

78 1.76 0.072 0.432 0.142 0.750 .

79 --- --- --- --- --- .

80 1.71 0.073 0.510 0.124 0.821 .

- Page 43 - Final Report - Page 101 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN/BODY WEIGHT RATIOS (%)

FEMALES

END OF TREATMENT

ANIMAL BODY W.

(GRAM)

BRAIN

(%)

HEART

(%)

LIVER

(%)

THYROID

(%)

THYMUS

(%)

GROUP 1 (CONTROL)

41 --- --- --- --- --- ---

42 248 0.81 0.344 3.56 0.005 0.093

43 226 0.84 0.306 3.01 0.007 0.089

44 259 0.71 0.318 3.04 0.005 0.088

45 255 0.73 0.334 3.34 0.005 0.109

46 --- --- --- --- --- ---

47 232 0.87 0.313 3.16 0.006 0.088

48 --- --- --- --- --- ---

49 --- --- --- --- --- ---

50 --- --- --- --- --- ---

GROUP 2 (100 MG/KG)

51 235 0.83 0.289 2.99 0.006 0.097

52 235 0.77 0.330 2.92 0.008 0.131

53 --- --- --- --- --- ---

54 230 0.78 0.350 3.15 0.007 0.099

55 --- --- --- --- --- ---

56 --- --- --- --- --- ---

57 249 0.75 0.327 3.37 0.004 0.087

58 --- --- --- --- --- ---

59 --- --- --- --- --- ---

60 243 0.76 0.356 2.99 0.007 0.086

GROUP 3 (300 MG/KG)

61 --- --- --- --- --- ---

62 --- --- --- --- --- ---

63 --- --- --- --- --- ---

64 288 0.69 0.302 3.29 0.005 0.084

65 237 0.78 0.349 3.29 0.006 0.097

66 --- --- --- --- --- ---

67 249 0.79 0.316 3.14 0.004 0.094

68 245 0.77 0.312 3.15 0.006 0.107

69 243 0.75 0.318 6.07 0.006 0.114

70 --- --- --- --- --- ---

GROUP 4 (1000 MG/KG)

71 --- --- --- --- --- ---

72 --- --- --- --- --- ---

73 235 0.81 0.299 3.41 0.005 0.092

74 --- --- --- --- --- ---

75 240 0.79 0.335 3.12 0.008 0.142

76 229 0.78 0.307 3.10 0.010 0.100

77 --- --- --- --- --- ---

78 228 0.84 0.329 2.83 0.005 0.086

79 --- --- --- --- --- ---

80 237 0.82 0.297 3.07 0.005 0.090

FEMALES

END OF TREATMENT

ANIMAL KIDNEYS

(%)

ADRENALS

(%)

SPLEEN

(%)

OVARIES

(%)

UTERUS

(%)

'

GROUP 1 (CONTROL)

41 --- --- --- --- --- .

42 0.75 0.037 0.208 0.056 0.263 .

43 0.70 0.033 0.231 0.058 0.288 .

44 0.65 0.029 0.282 0.051 0.230 .

45 0.69 0.031 0.239 0.051 0.257 .

- Page 44 - Final Report - Page 102 of 272 -
 02Dec13 08h04

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.12 ORGAN/BODY WEIGHT RATIOS (%)

FEMALES

END OF TREATMENT

ANIMAL KIDNEYS

(%)

ADRENALS

(%)

SPLEEN

(%)

OVARIES

(%)

UTERUS

(%)

'

GROUP 1 (CONTROL)

46 --- --- --- --- --- .

47 0.73 0.034 0.203 0.044 0.212 .

48 --- --- --- --- --- .

49 --- --- --- --- --- .

50 --- --- --- --- --- .

GROUP 2 (100 MG/KG)

51 0.76 0.031 0.163 0.051 0.223 .

52 0.70 0.030 0.238 0.057 0.300 .

53 --- --- --- --- --- .

54 0.69 0.031 0.208 0.053 0.230 .

55 --- --- --- --- --- .

56 --- --- --- --- --- .

57 0.76 0.032 0.261 0.054 0.277 .

58 --- --- --- --- --- .

59 --- --- --- --- --- .

60 0.73 0.031 0.209 0.056 0.314 .

GROUP 3 (300 MG/KG)

61 --- --- --- --- --- .

62 --- --- --- --- --- .

63 --- --- --- --- --- .

64 0.76 0.042 0.209 0.048 0.290 .

65 0.73 0.036 0.198 0.051 0.224 .

66 --- --- --- --- --- .

67 0.64 0.031 0.185 0.051 0.259 .

68 0.70 0.033 0.225 0.062 0.267 .

69 0.65 0.025 0.245 0.048 0.251 .

70 --- --- --- --- --- .

GROUP 4 (1000 MG/KG)

71 --- --- --- --- --- .

72 --- --- --- --- --- .

73 0.75 0.030 0.247 0.055 0.388 .

74 --- --- --- --- --- .

75 0.81 0.027 0.178 0.057 0.279 .

76 0.72 0.033 0.235 0.062 0.383 .

77 --- --- --- --- --- .

78 0.77 0.032 0.189 0.062 0.329 .

79 --- --- --- --- --- .

80 0.72 0.031 0.215 0.052 0.346 .

- Page 45 - Final Report - Page 103 of 272 -
 05Nov13 14h47

<NP> Non-pregnant

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.13 GENERAL REPRODUCTION DATA

F0-GENERATION - POST COITUM

FEMALE

NUMBER

MALE

NUMBER

MATING

DATE

PREGNANT SCHEDULE DELIVERY

RECORDED

NECROPSY

DATE

'

GROUP 1 (CONTROL)

41 1 06OCT2013 YES BREEDING 28OCT2013 04NOV2013 .

42 2 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

43 3 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

44 4 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

45 5 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

46 <NP> 6 03OCT2013 NO --- --- 29OCT2013 .

47 7 03OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

48 8 04OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

49 9 04OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

50 10 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

GROUP 2 (100 MG/KG)

51 11 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

52 12 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

53 13 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

54 14 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

55 15 06OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

56 16 06OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

57 17 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

58 18 06OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

59 <NP> 19 03OCT2013 NO --- --- 29OCT2013 .

60 20 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

GROUP 3 (300 MG/KG)

61 <NP> 21 05OCT2013 NO --- --- 01NOV2013 .

62 <NP> 22 07OCT2013 NO --- --- 01NOV2013 .

63 23 05OCT2013 YES BREEDING 28OCT2013 04NOV2013 .

64 24 03OCT2013 YES BREEDING 24OCT2013 29OCT2013 .

65 25 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

66 26 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

67 27 04OCT2013 YES BREEDING 25OCT2013 31OCT2013 .

68 28 03OCT2013 YES BREEDING 24OCT2013 29OCT2013 .

69 29 03OCT2013 YES BREEDING 24OCT2013 29OCT2013 .

70 30 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

GROUP 4 (1000 MG/KG)

71 31 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

72 32 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

73 33 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

74 34 05OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

75 35 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

76 36 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

77 37 06OCT2013 YES BREEDING 27OCT2013 01NOV2013 .

78 38 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

79 <NP> 39 03OCT2013 NO --- --- 29OCT2013 .

80 40 05OCT2013 YES BREEDING 26OCT2013 31OCT2013 .

- Page 46 - Final Report - Page 104 of 272 -
 07Nov13 07h54

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.14 CORPORA LUTEA AND IMPLANTATION SITES

FEMALES

NECROPSY

ANIMAL Corpora Lutea Implantations

'

GROUP 1 (CONTROL)

41 19.0 14.0 .

42 15.0 14.0 .

43 11.0 10.0 .

44 16.0 16.0 .

45 18.0 17.0 .

46 --- --- .

47 18.0 14.0 .

48 11.0 10.0 .

49 16.0 13.0 .

50 18.0 15.0 .

GROUP 2 (100 MG/KG)

51 19.0 12.0 .

52 14.0 14.0 .

53 17.0 12.0 .

54 15.0 14.0 .

55 11.0 11.0 .

56 15.0 14.0 .

57 14.0 14.0 .

58 14.0 14.0 .

59 --- --- .

60 15.0 14.0 .

GROUP 3 (300 MG/KG)

61 --- --- .

62 --- --- .

63 5.0 4.0 .

64 15.0 13.0 .

65 13.0 13.0 .

66 15.0 15.0 .

67 14.0 14.0 .

68 16.0 13.0 .

69 13.0 13.0 .

70 12.0 3.0 .

GROUP 4 (1000 MG/KG)

71 12.0 11.0 .

72 17.0 16.0 .

73 16.0 16.0 .

74 14.0 14.0 .

75 13.0 13.0 .

76 12.0 12.0 .

77 13.0 13.0 .

78 14.0 12.0 .

79 --- --- .

80 16.0 16.0 .

Non pregnant female nos. 46, 59, 61, 62 and 79 all had 0 corpora lutea and 0 implantation sites 

- Page 47 - Final Report - Page 105 of 272 -
 05Nov13 14h50

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.15 DEVELOPMENTAL DATA PER LITTER

FEMALES

F0-GENERATION - LACTATION

- FIRST LITTER CHECK -

LITTER DURATION OF

GESTATION

DEAD PUPS

M F

LIVING PUPS

M F TOT.

P.NATAL

LOSS

M

F

'

GROUP 1 (CONTROL)

41 22 0 0 8 6 14 0 0 .

42 21 0 0 7 7 14 0 0 .

43 21 0 0 6 3 9 0 0 .

44 21 0 0 8 7 15 0 0 .

45 21 0 0 5 11 16 0 0 .

47 22 0 0 5 6 11 0 0 .

48 22 0 0 5 4 9 0 0 .

49 22 0 0 6 6 12 0 0 .

50 21 0 0 5 9 14 0 0 .

.

TOTAL 0 0 55 59 114 0 0 .

N 9 9 9 9 9 9 9 9 .

MEAN 21.4 0.0 0.0 6.1 6.6 12.7 0.0 0.0 .

ST.DEV. 0.5 0.0 0.0 1.3 2.4 2.5 0.0 0.0 .

- Page 48 - Final Report - Page 106 of 272 -
 05Nov13 14h50

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.15 DEVELOPMENTAL DATA PER LITTER

FEMALES

F0-GENERATION - LACTATION

- FIRST LITTER CHECK -

LITTER DURATION OF

GESTATION

DEAD PUPS

M F

LIVING PUPS

M F TOT.

P.NATAL

LOSS

M

F

'

GROUP 2 (100 MG/KG)

51 22 0 0 8 3 11 0 0 .

52 21 0 0 10 3 13 0 0 .

53 22 0 0 5 7 12 0 0 .

54 21 0 0 8 6 14 0 0 .

55 21 0 0 8 4 12 0 0 .

56 21 0 0 4 6 10 0 1 .

57 21 0 0 10 5 15 0 1 .

58 21 0 0 6 5 11 0 0 .

60 21 0 0 7 7 14 0 0 .

.

TOTAL 0 0 66 46 112 0 2 .

N 9 9 9 9 9 9 9 9 .

MEAN 21.2 0.0 0.0 7.3 5.1 12.4 0.0 0.2 .

ST.DEV. 0.4 0.0 0.0 2.1 1.5 1.7 0.0 0.4 .

- Page 49 - Final Report - Page 107 of 272 -
 05Nov13 14h50

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.15 DEVELOPMENTAL DATA PER LITTER

FEMALES

F0-GENERATION - LACTATION

- FIRST LITTER CHECK -

LITTER DURATION OF

GESTATION

DEAD PUPS

M F

LIVING PUPS

M F TOT.

P.NATAL

LOSS

M

F

'

GROUP 3 (300 MG/KG)

63 23 0 0 0 4 4 0 0 .

64 21 0 0 3 10 13 1 0 .

65 21 0 0 8 4 12 0 0 .

66 22 0 0 5 9 14 0 0 .

67 21 0 0 3 11 14 0 0 .

68 21 0 0 2 11 13 0 0 .

69 21 0 0 3 9 12 0 0 .

70 22 0 0 1 2 3 0 0 .

.

TOTAL 0 0 25 60 85 1 0 .

N 8 8 8 8 8 8 8 8 .

MEAN 21.5 0.0 0.0 3.1 7.5 10.6 0.1 0.0 .

ST.DEV. 0.8 0.0 0.0 2.5 3.6 4.5 0.4 0.0 .

- Page 50 - Final Report - Page 108 of 272 -
 05Nov13 14h50

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.15 DEVELOPMENTAL DATA PER LITTER

FEMALES

F0-GENERATION - LACTATION

- FIRST LITTER CHECK -

LITTER DURATION OF

GESTATION

DEAD PUPS

M F

LIVING PUPS

M F TOT.

P.NATAL

LOSS

M

F

'

GROUP 4 (1000 MG/KG)

71 22 0 0 4 6 10 0 0 .

72 22 0 0 8 8 16 0 0 .

73 21 0 0 7 8 15 0 0 .

74 22 0 0 10 5 15 0 0 .

75 21 0 0 6 6 12 0 0 .

76 21 0 0 4 8 12 0 0 .

77 21 0 0 9 3 12 0 0 .

78 21 0 0 9 2 11 0 0 .

80 21 0 0 7 9 16 0 0 .

.

TOTAL 0 0 64 55 119 0 0 .

N 9 9 9 9 9 9 9 9 .

MEAN 21.3 0.0 0.0 7.1 6.1 13.2 0.0 0.0 .

ST.DEV. 0.5 0.0 0.0 2.1 2.4 2.3 0.0 0.0 .

- Page 51 - Final Report - Page 109 of 272 -
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.16 BODY WEIGHTS OF PUPS PER LITTER (GRAM)

F0-GENERATION - LACTATION

LITTER SEX DAY 1 DAY 4

'

GROUP 1 (CONTROL)

41 M 6.8 10.5 .

F 6.3 9.8 .

M+F 6.6 10.2 .

.

42 M 6.0 9.5 .

F 5.8 9.1 .

M+F 5.9 9.3 .

.

43 M 6.0 9.1 .

F 5.4 8.2 .

M+F 5.8 8.8 .

.

44 M 5.2 7.7 .

F 5.2 8.0 .

M+F 5.2 7.9 .

.

45 M 5.8 8.4 .

F 5.5 8.2 .

M+F 5.6 8.3 .

.

47 M 7.1 11.1 .

F 6.6 10.4 .

M+F 6.8 10.7 .

.

48 M 6.7 10.9 .

F 6.8 10.8 .

M+F 6.7 10.8 .

.

49 M 7.4 10.8 .

F 6.7 10.4 .

M+F 7.1 10.6 .

.

50 M 6.7 10.6 .

F 6.2 9.8 .

M+F 6.4 10.1 .

.

GROUP 2 (100 MG/KG)

51 M 7.0 10.9 .

F 6.5 10.3 .

M+F 6.9 10.7 .

.

52 M 5.8 9.2 .

F 6.0 9.3 .

M+F 5.9 9.2 .

.

53 M 7.5 11.8 .

F 7.3 11.4 .

M+F 7.3 11.6 .

.

54 M 5.8 9.7 .

F 5.4 8.8 .

M+F 5.6 9.3 .

.

55 M 6.8 10.1 .

F 6.5 9.7 .

M+F 6.7 10.0 .

.

56 M 6.4 10.2 .

F 6.0 10.0 .

M+F 6.1 10.1 .

.

- Page 52 - Final Report - Page 110 of 272 -
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.16 BODY WEIGHTS OF PUPS PER LITTER (GRAM)

F0-GENERATION - LACTATION

LITTER SEX DAY 1 DAY 4

'

GROUP 2 (100 MG/KG)

57 M 6.4 10.0 .

F 5.9 9.7 .

M+F 6.2 9.9 .

.

58 M 6.0 9.1 .

F 5.7 8.8 .

M+F 5.9 9.0 .

.

60 M 6.0 8.9 .

F 5.9 9.1 .

M+F 5.9 9.0 .

.

GROUP 3 (300 MG/KG)

63 F 9.2 14.4 .

M+F 9.2 14.4 .

.

64 M 6.8 11.7 .

F 6.2 10.6 .

M+F 6.3 10.9 .

.

65 M 6.2 9.4 .

F 5.9 9.1 .

M+F 6.1 9.3 .

.

66 M 6.8 10.0 .

F 6.2 9.2 .

M+F 6.4 9.5 .

.

67 M 6.0 9.4 .

F 5.7 9.2 .

M+F 5.8 9.2 .

.

68 M 6.3 10.3 .

F 6.0 9.8 .

M+F 6.0 9.9 .

.

69 M 6.2 10.0 .

F 5.9 9.6 .

M+F 6.0 9.7 .

.

70 M 8.0 12.2 .

F 8.4 13.0 .

M+F 8.3 12.7 .

.

GROUP 4 (1000 MG/KG)

71 M 7.8 12.4 .

F 7.3 11.7 .

M+F 7.5 12.0 .

.

72 M 6.5 9.9 .

F 6.5 9.6 .

M+F 6.5 9.7 .

.

73 M 6.0 9.1 .

F 5.7 8.8 .

M+F 5.8 8.9 .

.

74 M 6.7 11.3 .

F 6.4 10.5 .

M+F 6.6 11.0 .

.

- Page 53 - Final Report - Page 111 of 272 -
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.16 BODY WEIGHTS OF PUPS PER LITTER (GRAM)

F0-GENERATION - LACTATION

LITTER SEX DAY 1 DAY 4

'

GROUP 4 (1000 MG/KG)

75 M 5.9 8.8 .

F 5.8 9.0 .

M+F 5.8 8.9 .

.

76 M 5.9 9.3 .

F 6.1 9.6 .

M+F 6.0 9.5 .

.

77 M 6.3 9.8 .

F 5.7 8.9 .

M+F 6.2 9.6 .

.

78 M 6.4 9.5 .

F 5.9 8.9 .

M+F 6.3 9.4 .

.

80 M 6.1 8.6 .

F 5.4 7.6 .

M+F 5.7 8.0 .

.

- Page 54 - Final Report - Page 112 of 272 -
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 1 (CONTROL)

41 1 M 6.9 10.7 .

2 M 6.7 10.0 .

3 M 7.4 10.9 .

4 M 6.7 10.0 .

5 M 6.8 10.2 .

6 M 6.6 10.6 .

7 M 6.6 10.4 .

8 M 7.0 11.1 .

9 F 5.9 9.4 .

10 F 6.7 10.7 .

11 F 6.2 9.6 .

12 F 6.3 9.6 .

13 F 6.8 9.8 .

14 F 6.2 9.6 ..

42 1 M 6.3 9.8 .

2 M 6.2 9.2 .

3 M 5.8 9.6 .

4 M 6.1 9.4 .

5 M 6.3 9.8 .

6 M 6.0 9.6 .

7 M 5.8 9.4 .

8 F 5.9 9.4 .

9 F 6.2 9.9 .

10 F 5.6 8.9 .

11 F 5.9 8.8 .

12 F 5.2 7.9 .

13 F 6.0 9.6 .

14 F 5.7 9.1 ..

43 1 M 6.1 9.1 .

2 M 5.6 8.7 .

3 M 5.9 9.4 .

4 M 5.8 8.9 .

5 M 6.4 9.6 .

6 M 6.1 8.9 .

7 F 5.7 8.6 .

8 F 5.5 8.5 .

9 F 4.9 7.6 ..

44 1 M 5.4 8.3 .

2 M 5.7 7.5 .

3 M 5.0 8.0 .

4 M 4.5 6.5 .

5 M 5.6 8.4 .

6 M 5.3 8.0 .

7 M 4.6 6.8 .

8 F 5.6 8.8 .

9 F 5.4 8.4 .

10 F 5.2 8.2 .

11 F 5.0 7.4 .

12 F 5.4 8.4 .

13 M 5.6 8.4 .

14 F 4.8 6.8 .

15 F 5.4 8.1 ..

45 1 M 5.6 8.3 .

2 M 5.9 7.9 .

3 M 5.9 8.9 .

4 M 5.5 8.5 .

5 M 6.1 8.4 .

6 F 5.9 8.8 .

- Page 55 - Final Report - Page 113 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 1 (CONTROL)

7 F 5.2 8.2 .

8 F 5.5 8.5 .

9 F 5.5 8.2 .

10 F 5.7 8.6 .

11 F 5.4 7.4 .

12 F 5.4 7.6 .

13 F 5.6 8.1 .

14 F 5.3 8.0 .

15 F 6.1 9.1 .

16 F 5.1 7.5 ..

47 1 M 6.7 11.0 .

2 M 7.2 10.9 .

3 M 7.8 12.0 .

4 M 6.9 11.1 .

5 M 6.6 10.7 .

6 F 6.4 10.5 .

7 F 6.7 10.5 .

8 F 6.7 10.7 .

9 F 6.4 10.1 .

10 F 7.1 10.9 .

11 F 6.6 9.9 ..

48 1 M 6.5 11.1 .

2 M 7.0 11.3 .

3 M 6.7 10.4 .

4 M 6.9 11.4 .

5 M 6.2 10.3 .

6 F 7.0 10.9 .

7 F 6.5 10.7 .

8 F 7.2 11.3 .

9 F 6.5 10.2 ..

49 1 M 7.4 11.4 .

2 M 7.4 10.8 .

3 M 6.9 10.0 .

4 M 7.7 10.5 .

5 M 7.2 11.1 .

6 M 7.9 10.9 .

7 F 6.4 9.9 .

8 F 6.9 10.5 .

9 F 6.8 10.8 .

10 F 7.0 10.6 .

11 F 6.5 10.2 .

12 F 6.7 10.5 ..

50 1 M 6.6 10.8 .

2 M 6.6 10.5 .

3 M 6.6 10.5 .

4 M 7.1 10.8 .

5 M 6.5 10.6 .

6 F 6.6 10.0 .

7 F 5.6 9.5 .

8 F 5.7 9.4 .

9 F 6.5 10.3 .

10 F 5.8 9.0 .

11 F 6.6 9.9 .

12 F 6.3 10.5 .

13 F 6.2 10.1 .

14 F 6.3 9.4 ..

- Page 56 - Final Report - Page 114 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 2 (100 MG/KG)

51 1 M 7.1 10.8 .

2 M 7.4 11.4 .

3 M 7.5 11.4 .

4 M 7.1 10.8 .

5 M 7.1 11.3 .

6 M 6.5 9.9 .

7 M 7.2 11.0 .

8 F 7.3 11.2 .

9 F 5.6 9.2 .

10 M 6.6 10.2 .

11 F 6.7 10.4 ..

52 1 M 6.6 10.2 .

2 M 5.0 8.0 .

3 M 5.6 8.9 .

4 M 6.2 9.5 .

5 M 5.7 8.8 .

6 M 5.8 9.1 .

7 M 6.4 9.7 .

8 M 5.4 8.6 .

9 M 6.0 9.7 .

10 M 5.8 9.4 .

11 F 6.0 9.5 .

12 F 6.2 9.6 .

13 F 5.7 8.7 ..

53 1 M 7.3 11.4 .

2 M 7.4 11.8 .

3 M 7.4 11.3 .

4 M 7.5 12.3 .

5 M 7.6 12.1 .

6 F 7.5 12.2 .

7 F 7.2 11.4 .

8 F 7.4 11.8 .

9 F 6.4 9.9 .

10 F 7.3 11.0 .

11 F 7.5 12.3 .

12 F 7.6 11.5 ..

54 1 M 5.5 9.6 .

2 M 5.3 8.7 .

3 M 6.2 9.9 .

4 M 6.0 10.1 .

5 M 6.1 10.5 .

6 M 5.8 9.4 .

7 M 6.1 10.1 .

8 M 5.2 9.2 .

9 F 5.4 9.2 .

10 F 5.2 8.6 .

11 F 6.0 10.0 .

12 F 4.9 8.0 .

13 F 5.6 8.5 .

14 F 5.4 8.6 ..

55 1 M 6.8 10.3 .

2 M 6.7 9.8 .

3 M 7.3 10.5 .

4 M 6.2 9.9 .

5 M 7.4 10.7 .

6 M 6.4 9.8 .

7 M 6.4 9.4 .

8 M 7.1 10.8 .

- Page 57 - Final Report - Page 115 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 2 (100 MG/KG)

9 F 6.7 9.7 .

10 F 6.7 10.0 .

11 F 6.4 9.5 .

12 F 6.3 9.4 ..

56 1 M 6.6 10.6 .

2 M 6.1 9.5 .

3 M 6.4 10.4 .

4 M 6.4 10.3 .

5 F 5.8 9.6 .

6 F 5.0 -- .

7 F 6.2 10.4 .

8 F 6.1 9.8 .

9 F 6.2 10.0 .

10 F 6.4 10.5 ..

57 1 M 6.5 10.2 .

2 M 5.0 6.7 .

3 M 6.8 10.4 .

4 M 6.6 10.6 .

5 M 6.7 10.8 .

6 M 6.7 10.4 .

7 M 6.7 11.2 .

8 M 6.5 9.9 .

9 M 6.1 9.7 .

10 M 6.3 10.3 .

11 F 5.2 -- .

12 F 5.9 9.4 .

13 F 6.3 10.2 .

14 F 6.3 9.8 .

15 F 5.8 9.3 ..

58 1 M 6.0 9.1 .

2 M 6.2 9.0 .

3 M 6.0 8.7 .

4 M 6.4 10.1 .

5 M 6.0 9.1 .

6 M 5.5 8.5 .

7 F 5.8 9.2 .

8 F 5.8 8.7 .

9 F 5.5 8.3 .

10 F 5.9 9.4 .

11 F 5.7 8.5 ..

60 1 M 6.2 9.6 .

2 M 5.4 7.7 .

3 M 6.1 9.4 .

4 M 6.4 9.6 .

5 M 6.4 9.6 .

6 M 5.8 8.1 .

7 M 5.5 8.4 .

8 F 5.5 7.8 .

9 F 5.6 8.6 .

10 F 6.1 9.4 .

11 F 5.9 9.1 .

12 F 6.3 9.9 .

13 F 6.0 8.9 .

14 F 5.9 9.7 ..

GROUP 3 (300 MG/KG)

63 1 F 9.6 14.6 .

- Page 58 - Final Report - Page 116 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 3 (300 MG/KG)

2 F 8.8 13.8 .

3 F 9.5 14.8 .

4 F 9.1 14.4 ..

64 1 M 7.0 12.5 .

2 M 6.5 11.0 .

3 M 6.9 11.6 .

4 F 5.9 10.5 .

5 F 6.1 10.4 .

6 F 6.8 11.1 .

7 F 6.3 11.0 .

8 F 6.1 10.4 .

9 F 6.0 10.5 .

10 F 6.0 10.6 .

11 F 5.9 10.0 .

12 F 6.5 11.1 .

13 F 6.0 10.4 ..

65 1 M 6.2 9.3 .

2 M 6.7 10.0 .

3 M 6.4 9.3 .

4 M 6.1 9.3 .

5 M 6.3 9.8 .

6 M 6.1 9.3 .

7 M 6.1 9.4 .

8 M 6.0 9.2 .

9 F 5.4 8.7 .

10 F 6.2 9.6 .

11 F 5.9 9.0 .

12 F 6.0 9.2 ..

66 1 M 7.1 10.7 .

2 M 7.2 10.2 .

3 M 6.6 9.6 .

4 M 6.7 9.4 .

5 M 6.6 10.3 .

6 F 5.9 9.0 .

7 F 6.9 10.3 .

8 F 6.0 9.0 .

9 F 6.1 9.0 .

10 F 6.6 10.0 .

11 F 6.0 8.7 .

12 F 6.3 8.9 .

13 F 5.9 9.0 .

14 F 6.2 8.9 ..

67 1 M 6.3 9.8 .

2 M 5.8 9.2 .

3 M 5.8 9.2 .

4 F 6.0 9.7 .

5 F 5.6 8.8 .

6 F 5.5 8.7 .

7 F 5.2 8.7 .

8 F 5.8 9.2 .

9 F 6.0 9.8 .

10 F 5.4 8.7 .

11 F 5.7 8.9 .

12 F 6.0 9.4 .

13 F 6.2 10.4 .

14 F 5.7 8.7 ..

68 1 M 6.4 10.5 .

- Page 59 - Final Report - Page 117 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 3 (300 MG/KG)

2 M 6.1 10.1 .

3 F 6.4 10.3 .

4 F 6.1 10.1 .

5 F 6.0 9.6 .

6 F 5.9 10.1 .

7 F 5.8 9.4 .

8 F 5.7 9.9 .

9 F 5.8 9.7 .

10 F 6.0 9.5 .

11 F 5.8 9.5 .

12 F 6.0 9.9 .

13 F 6.1 9.8 ..

69 1 M 6.2 10.4 .

2 M 6.0 9.9 .

3 M 6.4 9.8 .

4 F 5.4 9.2 .

5 F 5.9 9.4 .

6 F 5.8 9.8 .

7 F 6.0 9.9 .

8 F 6.1 9.3 .

9 F 6.2 10.1 .

10 F 5.9 9.7 .

11 F 5.8 9.6 .

12 F 5.9 9.7 ..

70 1 M 8.0 12.2 .

2 F 8.4 12.8 .

3 F 8.4 13.1 ..

GROUP 4 (1000 MG/KG)

71 1 M 7.8 12.3 .

2 M 7.7 12.3 .

3 M 7.5 11.9 .

4 M 8.2 13.1 .

5 F 6.7 11.1 .

6 F 7.1 11.6 .

7 F 7.1 11.6 .

8 F 7.7 12.3 .

9 F 7.4 11.7 .

10 F 7.6 12.0 ..

72 1 M 6.6 10.1 .

2 M 6.6 10.1 .

3 M 6.3 9.6 .

4 M 6.6 11.1 .

5 M 6.6 10.2 .

6 M 6.0 9.0 .

7 M 6.7 9.8 .

8 M 6.3 9.4 .

9 F 6.7 9.9 .

10 F 6.8 9.5 .

11 F 6.6 8.8 .

12 F 7.0 9.9 .

13 F 6.2 9.9 .

14 F 5.7 9.3 .

15 F 6.4 9.8 .

16 F 6.2 9.3 ..

73 1 M 6.3 10.1 .

2 M 5.7 8.9 .

- Page 60 - Final Report - Page 118 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 4 (1000 MG/KG)

3 M 6.5 9.5 .

4 M 5.5 8.4 .

5 M 5.9 9.3 .

6 M 6.1 9.4 .

7 M 5.7 8.3 .

8 F 5.9 8.7 .

9 F 5.4 8.4 .

10 F 5.7 8.4 .

11 F 5.4 8.3 .

12 F 5.7 9.0 .

13 F 6.1 9.9 .

14 F 5.9 9.3 .

15 F 5.6 8.1 ..

74 1 M 7.0 11.9 .

2 M 7.4 12.1 .

3 M 6.7 11.0 .

4 M 6.9 11.4 .

5 M 6.9 11.8 .

6 M 6.7 11.8 .

7 M 7.0 12.1 .

8 M 7.0 11.0 .

9 M 7.2 11.6 .

10 M 4.7 7.9 .

11 F 6.9 11.1 .

12 F 6.4 10.4 .

13 F 6.2 10.3 .

14 F 6.2 9.8 .

15 F 6.5 11.0 ..

75 1 M 5.9 8.8 .

2 M 6.4 9.2 .

3 M 5.9 8.7 .

4 F 6.0 9.0 .

5 M 4.6 7.4 .

6 M 6.6 9.7 .

7 M 5.9 8.9 .

8 F 6.2 9.4 .

9 F 6.0 9.5 .

10 F 5.8 9.3 .

11 F 4.9 7.5 .

12 F 6.0 9.2 ..

76 1 M 4.9 8.6 .

2 M 5.8 8.6 .

3 M 6.1 9.6 .

4 M 6.6 10.3 .

5 F 6.5 10.1 .

6 F 5.5 8.6 .

7 F 6.2 9.8 .

8 F 6.5 10.3 .

9 F 6.7 10.5 .

10 F 6.0 9.3 .

11 F 5.2 8.3 .

12 F 6.1 9.9 ..

77 1 M 6.4 10.0 .

2 M 6.9 10.6 .

3 M 6.3 9.9 .

4 M 6.1 9.6 .

5 M 6.3 9.8 .

6 M 5.8 8.8 .

- Page 61 - Final Report - Page 119 of 272 

-
 05Nov13 14h47

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.17 BODY WEIGHTS OF PUPS (GRAM)

F0-GENERATION - LACTATION

LITTER PUP SEX DAY 1 DAY 4

'

GROUP 4 (1000 MG/KG)

7 M 6.8 10.1 .

8 M 6.3 9.4 .

9 M 6.3 9.7 .

10 F 5.6 8.9 .

11 F 5.7 8.9 .

12 F 5.8 9.0 .

.

78 1 M 6.4 9.7 .

2 M 6.7 9.6 .

3 M 6.1 8.7 .

4 M 6.4 9.1 .

5 M 6.7 9.8 .

6 M 6.1 9.3 .

7 M 6.4 9.8 .

8 M 6.6 10.1 .

9 M 6.2 9.3 .

10 F 5.9 8.8 .

11 F 6.0 9.0 .

.

80 1 M 6.3 8.9 .

2 M 6.1 8.4 .

3 M 6.0 8.6 .

4 M 6.0 8.2 .

5 M 6.1 8.6 .

6 M 6.1 8.8 .

7 M 6.2 8.8 .

8 F 5.1 7.3 .

9 F 5.4 7.4 .

10 F 5.6 8.1 .

11 F 5.4 7.4 .

12 F 5.0 7.3 .

13 F 5.6 7.7 .

14 F 5.2 7.2 .

15 F 5.7 7.7 .

16 F 5.6 8.1 .

.

- Page 62 - Final Report - Page 120 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

LITTER 41 1 M DAY 7 Planned Necropsy FLC No findings .

28OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 63 - Final Report - Page 121 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

LITTER 42 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

- Page 64 - Final Report - Page 122 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

- Page 65 - Final Report - Page 123 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 43 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 66 - Final Report - Page 124 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 44 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

- Page 67 - Final Report - Page 125 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 68 - Final Report - Page 126 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 45 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

- Page 69 - Final Report - Page 127 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

7 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 70 - Final Report - Page 128 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 5 No findings .

LLC No findings .

MACRO No findings .

16 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 47 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

- Page 71 - Final Report - Page 129 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 48 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 72 - Final Report - Page 130 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 49 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 73 - Final Report - Page 131 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 50 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

- Page 74 - Final Report - Page 132 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 75 - Final Report - Page 133 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 1 (CONTROL)

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

GROUP 2 (100 MG/KG)

LITTER 51 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

- Page 76 - Final Report - Page 134 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 52 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

- Page 77 - Final Report - Page 135 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

MACRO No findings .

8 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 53 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

- Page 78 - Final Report - Page 136 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 54 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 79 - Final Report - Page 137 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

- Page 80 - Final Report - Page 138 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 55 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 81 - Final Report - Page 139 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 56 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 82 - Final Report - Page 140 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 2 Missing FLC No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 57 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

- Page 83 - Final Report - Page 141 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 4 Missing FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

- Page 84 - Final Report - Page 142 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

LITTER 58 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 85 - Final Report - Page 143 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 60 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC Blue spot head .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC Blue spot head and snout .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 86 - Final Report - Page 144 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 2 (100 MG/KG)

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

GROUP 3 (300 MG/KG)

LITTER 63 1 F DAY 7 Planned Necropsy FLC No findings .

28OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

2 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

- Page 87 - Final Report - Page 145 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

LLC No findings .

MACRO No findings .

3 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

4 F DAY 7 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

DAY 6 No findings .

LLC No findings .

MACRO No findings .

LITTER 64 1 M DAY 5 Other FLC No findings .

24OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC Cannibalism .

MACRO Cannibalism .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

- Page 88 - Final Report - Page 146 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

8 F DAY 5 Planned Necropsy FLC Scabs snout and blue spot left hind leg .

DAY 2 Scabs snout .

DAY 3 Scabs snout .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC Scabs snout .

DAY 2 Scabs snout .

DAY 3 Scabs snout .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 65 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

- Page 89 - Final Report - Page 147 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

- Page 90 - Final Report - Page 148 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

LITTER 66 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

- Page 91 - Final Report - Page 149 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 67 1 M DAY 6 Planned Necropsy FLC No findings .

25OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

4 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 6 Planned Necropsy FLC No findings .

- Page 92 - Final Report - Page 150 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 6 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

DAY 5 No findings .

- Page 93 - Final Report - Page 151 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

LLC No findings .

MACRO No findings .

LITTER 68 1 M DAY 5 Planned Necropsy FLC No findings .

24OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 94 - Final Report - Page 152 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 69 1 M DAY 5 Planned Necropsy FLC No findings .

24OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

- Page 95 - Final Report - Page 153 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 3 (300 MG/KG)

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 70 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

GROUP 4 (1000 MG/KG)

LITTER 71 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 96 - Final Report - Page 154 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 72 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 97 - Final Report - Page 155 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 98 - Final Report - Page 156 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

16 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 73 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 99 - Final Report - Page 157 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 74 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

- Page 100 - Final Report - Page 158 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 101 - Final Report - Page 159 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 75 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 102 - Final Report - Page 160 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 76 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 103 - Final Report - Page 161 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 77 1 M DAY 5 Planned Necropsy FLC No findings .

27OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 104 - Final Report - Page 162 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 105 - Final Report - Page 163 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 78 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 106 - Final Report - Page 164 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

LITTER 80 1 M DAY 5 Planned Necropsy FLC No findings .

26OCT2013 DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

2 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

3 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

4 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

5 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

6 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

7 M DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

8 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

9 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

- Page 107 - Final Report - Page 165 of 272 -
 07Nov13 08h01

LLC - LAST LITTER CHECK, MACRO - MACROSCOPIC FINDINGS

FLC - FIRST LITTER CHECK, DAY P.P. - CLINICAL SIGNS ,

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 2

2.18 MORTALITY, CLINICAL SIGNS AND MACROSCOPY OF PUPS

FEMALES

F0-GENERATION - LACTATION

LITTER

DELIVERY

PUP END OF P.P. PHASE FINDINGS

'

GROUP 4 (1000 MG/KG)

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

10 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

11 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

12 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

13 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

14 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

15 F DAY 5 Planned Necropsy FLC Scabs snout .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

16 F DAY 5 Planned Necropsy FLC No findings .

DAY 2 No findings .

DAY 3 No findings .

DAY 4 No findings .

LLC No findings .

MACRO No findings .

- Page 108 - Final Report - Page 166 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

APPENDIX 2

- Page 109 - 

2.19 KEY TO MISSING VALUES/REMARKS CLINICAL LABORATORY INVESTIGATIONS AND ORGAN WEIGHTS

End of Treatment 

Haematology: 

Animal(s):

14, 67 --- = Technical error for WBC

32 --- = Technical error for Red blood cells, RDW, Haematocrit, MCV, MCH, MCHC and Platelets. 

Because of the technical error in RBC, relative reticulocyte counts (2.4% of RBC) are also not 

reported.

54 --- = Citrate sample clotted 

14, 52, 67, 68 Differential leucocyte count was also performed manually because 

of a technical error / an abnormal plot in the automated count and these results are reported

Clinical Biochemistry: 

Serum sample of the following animal was haemolytic. Therefore the following parameter was not included in the tables: 

Animal:

45 Bile Acids 23.9 μmol/L

Organ weights: 

For this animal, the right epididymis and testis were not present (agenesis). Therefore the following values were not 

included in the tables.

Animal no. 1 Epididymis 0.641 gram (only left weight)

Testis 2.399 gram (only left weight)

The following weight was excluded from the tables as this value was unrealistic and no macroscopic abnormalities for the 

thyroid were noted.

Animal no. 24 Thyroid 0.074 gram

Final Report - Page 167 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

APPENDIX 3 PHASE REPORT FORMULATION ANALYSIS 

Final Report - Page 168 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 2 - 

1. CONTENTS

1. CONTENTS ...................................................................................................................................... 2

2. REPORT APPROVAL ...................................................................................................................... 3

3. SUMMARY........................................................................................................................................ 4

4. INTRODUCTION .............................................................................................................................. 5

4.1. Preface...................................................................................................................................... 5

4.2. Aim of the study ........................................................................................................................ 5

5. MATERIALS AND METHODS .......................................................................................................... 5

5.1. Reagents ................................................................................................................................... 5

5.2. Samples .................................................................................................................................... 5

5.3. Analytical method...................................................................................................................... 6

5.3.1. Analytical conditions ....................................................................................................... 6

5.3.2. Preparation of the calibration solutions........................................................................... 6

5.3.3. Sample measurements................................................................................................... 6

5.3.4. Calibration curves ........................................................................................................... 6

5.4. Electronic data capture ............................................................................................................. 6

5.4.1. Formulas ......................................................................................................................... 7

5.5. Specifications ............................................................................................................................ 7

6. RESULTS ......................................................................................................................................... 8

6.1. Procedural recovery samples.................................................................................................... 8

6.2. Test samples............................................................................................................................. 8

TABLES

Table 1 Procedural recovery samples .............................................................................................. 9

Table 2 Accuracy and homogeneity test........................................................................................... 9

Final Report - Page 169 of 272 -
- Page 170 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 4 - 

3. SUMMARY

The purpose of this part of the study was to determine the accuracy of preparation and homogeneity of 

the test substance in formulations. 

Accuracy of preparation

The concentrations analysed in the formulations of Group 2, Group 3 and Group 4 were in agreement 

with target concentrations (i.e. mean accuracies between 90% and 110%). 

No test substance was detected in the Group 1 formulation. 

Homogeneity

The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%). 

Final Report - Page 171 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 5 - 

4. INTRODUCTION

4.1. Preface

Study plan analytical phase Start : 19 December 2013

Completion : 20 December 2013

4.2. Aim of the study

The purpose of the analytical phase was to determine the accuracy of preparation and homogeneity of 

the test substance in formulations. Stability could not be determined since Total Organic Carbon 

(TOC) analysis is a general method that does not distinguish original substance from hydrolysis 

product(s).

5. MATERIALS AND METHODS 

5.1. Reagents

Water Tap water purified by a Milli-Q water purification system 

(Millipore, Bedford, MA, USA)

Milli-RO water Tap-water purified by reverse osmosis (Millipore)

Potassium hydrogen phthalate Merck, Darmstadt, Germany

Sodium carbonate Merck

Sodium hydrogen carbonate VWR International, Leuven, Belgium

All reagents were of analytical grade, unless specified otherwise. 

5.2. Samples 

Accuracy and homogeneity were determined for formulations prepared after the in-life phase. These 

formulations were prepared similarly as those used during the in-life phase.

Accurately weighed samples of approximately 500 and 1000 mg were taken in duplicate from the 

formulations using a pipette and were transferred into volumetric flasks of 50, 100 or 250 ml. Accuracy 

samples were taken at middle position (50% height) or at top, middle and bottom position (90%, 50% 

and 10% height). The samples taken at 90%, 50% and 10% height were also used for the 

determination of the homogeneity of the formulations. 

Final Report - Page 172 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 6 - 

5.3. Analytical method

For quantitative analysis of the test substance in formulation, Total Organic Carbon (TOC) analysis 

was used (see project 503334). A calibration curve Total Carbon (TC) was obtained with potassium 

hydrogenphthalate standard solutions in the range of 100 – 1000 mg C/l and a calibration curve 

Inorganic Carbon (IC) with sodium hydrogen carbonate/sodium carbonate standard solutions in the 

range of 0.2-10 mg C/l. TOC was calculated by subtraction of the IC results from the TC results. 

This analytical technique does not require validation. To calculate test substance concentration from 

the measured carbon concentration, the carbon content of the test substance was determined in 

project 503334 (i.e. 54.48%) 

5.3.1. Analytical conditions

Instrument TOC-Vcph total organic carbon analyzer with a ASI-V 

autosampler (Shimadzu, Kyoto, Japan)

Instrument mode TOC

Injection volume 50 - 65 μl 

Number of repeats 3 

5.3.2. Preparation of the calibration solutions

Stock solutions 

TC stock solutions of potassium hydrogen phthalate were prepared in Milli-RO water at a

concentration of 1000 mg C/l. 

IC stock solutions of sodium hydrogen carbonate and sodium carbonate were prepared in Milli-RO 

water at a concentration of 1000 mg C/l. The stock solution was diluted with Milli-RO water to obtain a 

concentration of 10 mg C/l. 

Calibration solutions

TC calibration solutions in the concentration range 100 – 1000 mg C/l were prepared from a stock

solution and/or a dilution of the stock solution with water. 

IC calibration solutions in the concentration range 0.2 – 10 mg C/l were prepared from a stock solution

and/or a dilution of the stock solution with water.

5.3.3. Sample measurements

Calibration solutions and test samples were analysed in singlefold (mean of 3 repeats). 

5.3.4. Calibration curves

Calibration curves for TC and IC were constructed using four concentrations. For each concentration, 

the mean response of three injections was used. Linear regression analysis was performed using the 

least squares method. 

5.4. Electronic data capture

System control, data acquisition and data processing were performed using the following programme:

- Shimadzu TOC-Control V version 2.10 (Shimadzu, Kyoto, Japan): Carbon analysis.

Temperature, relative humidity and/or atmospheric pressure during sample storage and/or 

performance of the studies was monitored continuously using the following programme:

- REES Centron Environmental Monitoring system version SQL 2.0 (REES Scientific, Trenton, NJ, 

USA).

Final Report - Page 173 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 7 - 

5.4.1. Formulas

The concentration test substance was calculated based on the purity determined in project 503335 

[i.e. 74.4%]. This information was not available when the target concentrations were calculated. The

target concentrations were based on the purity supplied by the sponsor [i.e. 70.7%]. 

Response (R) mean concentration organic carbon in solution [mg C/l]

Analysed concentration (CA) /g][mg 100

%purity

 w

V

 d 

%C

100

A RC ××××=

where:

%C = organic carbon content of the test substance

 [i.e. 54.48%, determined in Project 503334]

d = dilution factor

w = weight sample [mg]

V = volume volumetric flask [ml]

%purity = purity of the test substance

 [i.e. 74.4%, determined in Project 503335]

Recovery [%] 100 C

C

N

A ×

where:

CN = nominal concentration [mg/g]

Accuracy [%] 100 C

C

T

A ×

where:

CT = target concentration [mg/g]

Relative difference (relative diff.) [%] 100 C

CC

0

0t × −

where:

Ct = mean concentration of stored samples [mg/g]

C0 = mean concentration of non-stored samples [mg/g]

5.5. Specifications

Preparation of formulations was considered acceptable if the mean accuracy was in the range 

90-110% of the target concentration and if the coefficient of variation was ≤ 10%. Formulations were 

considered stable if the relative difference between the stored and freshly taken samples was ≤ 10%.

Final Report - Page 174 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 8 - 

6. RESULTS

6.1. Procedural recovery samples

The results of the procedural recovery samples are given in Table 1.

The mean recoveries of the procedural recovery samples fell within the criterion of 90-110%. It 

demonstrated that the analytical method was adequate for the determination of the test substance in 

the test samples.

6.2. Test samples

The results of the test samples are given in Table 2.

Accuracy of preparation

In the Group 1 formulation, no test substance was detected.

The concentrations analysed in the formulations of Group 2, Group 3 and Group 4 were in agreement 

with target concentrations (i.e. mean accuracies between 90% and 110%).

Homogeneity

The formulations of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%).

Final Report - Page 175 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 9 - 

TABLES

Table 1 Procedural recovery samples

Date of 

preparation

Date of 

analysis

Target 

concentration

[mg/g]

Prepared

concentration

[mg/g]

Analysed 

concentration

[mg/g]

Recovery

[%]

Mean recovery 

(coefficient of 

variation) 

[%]

19-Dec-2013 19-Dec-2013 20 18.4 16.5 89 90

18.9 16.9 89 (0.91)

19.8 17.8 90

19.6 17.9 91

19.7 17.9 91

19-Dec-2013 19-Dec-2013 200 211 190 90 90

214 194 90 (0.44)

210 191 91

211 191 91

212 190 90

Table 2 Accuracy and homogeneity test

Group Date of 

analysis 

Sample 

position

Concentration

[mg/g]

Accuracy

[%]

Homogeneity 

(coefficient of 

variation)

[%]

Target Analysed Individual Mean

1 19-Dec-2013 50% height 0.00 n.d. n.a. n.a. n.a.

0.00 n.d. n.a.

2 19-Dec-2013 90% height 20.0 18.4 92 92 0.29

20.0 18.5 92

50% height 20.0 18.4 92

20.0 18.4 92

10% height 20.0 18.3 92

20.0 18.5 92

3 19-Dec-2013 90% height 60.0 56.0 93 93 n.a.

60.0 56.0 93

4 19-Dec-2013 90% height 200 186 93 93 0.29

200 185 93

50% height 200 186 93

200 186 93

10% height 200 184 92

200 185 93

n.d. Not detected. 

n.a. Not applicable.

Final Report - Page 176 of 272 -
Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

APPENDIX 4 PHASE REPORT HISTOPATHOLOGY

Final Report - Page 177 of 272 -
PATHOLOGY REPORT PAGE : 2/ 91

 TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF CONTENTS 

—————————————————————————————————————————————————————————————————————————

 PAGE : 

 

 AUTHENTICATION 3

 

 

PRINCIPAL SECTION 

 SUMMARY 4

 

 METHODS 5

 

 RESULTS 8

 

 DISCUSSION AND CONCLUSIONS 9

 

 

 EXPLANATION OF CODES AND SYMBOLS 10

 

 

SUMMARY TABLES 

 SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX 

 STATUS AT NECROPSY: K0 

 Incidence table — Selected findings with grades 11

 

 NUMBER OF ANIMALS WITH 

 MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

 STATUS AT NECROPSY: K0 

 Incidence table — All microscopic findings 13

 

 

INDIVIDUAL ANIMAL DATA 

 TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 24

 

 ANIMAL HEADING DATA DOSE GROUP 01 40

 TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 01 41

 

 ANIMAL HEADING DATA DOSE GROUP 02 58

 TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 02 59

 

 ANIMAL HEADING DATA DOSE GROUP 03 66

 TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 03 67

 

 ANIMAL HEADING DATA DOSE GROUP 04 73

 TEXT OF GROSS AND MICROSCOPIC FINDINGS DOSE GROUP 04 74

 

Final Report - Page 178 of 272 -
- Page 179 of 272 -
PATHOLOGY REPORT PAGE : 4/ 91

PRINCIPAL SECTION TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

SUMMARY 

—————————————————————————————————————————————————————————————————————————

Pathomorphologic examination was performed on 80 Wistar(Han) rats (40 

males, 40 females) which had been subjected to a combined 28-day dose 

toxicity study and reproduction/developmental toxicity screening test

with test item Castor Oil, Sulfated, Sodium Salt, 75%. 

The rats were assigned to four dose groups, each containing 10 males and 

10 females. The test item was administered once daily by gavage at doses 

of 100, 300 and 1000 mg/kg (dose Groups 2, 3 and 4 respectively). The 

rats of the control Group 1 received the vehicle, water (Elix), alone. 

The males and females were exposed from 2 weeks prior to mating, during 

mating, and up to the day prior to necropsy for at least 28 days.

All rats were necropsied. Histopathologic examination was performed on an 

extensive list of organs and tissues from 5 selected males and females of 

Group 1 and Group 4, heart of the selected males and adrenal glands of 

the selected females of Groups 2 and 3, as well as all organs with 

macroscopic findings from all rats. 

In addition, the reproductive organs of animals that failed to sire or 

deliver healthy pups were examined. Additional slides of the testes were 

made of the selected males of Groups 1 and 4 and males suspected 

infertile and stained with PAS/haematoxylin to assess spermatogenesis.

All rats survived their scheduled study period.

There were no test item-related macroscopic findings.

Possible test item-related microscopic findings were noted in males and 

females treated at 1000 mg/kg:

- Heart, males: a subtle increase in severity of mononuclear 

inflammation (1/5, slight) and in incidence and/or severity (2/5, 

minimal and slight) of myofiber degeneration. Both findings are

slightly above the range of background findings of Wistar (Han) rats 

of this age. Therefore a possible test item-related effect cannot be 

excluded.

- Adrenal glands, females: an increase in incidence of vacuolation of 

the zona glomerulosa (up to 4/5). However, based on the minimal degree 

and absence of other test item-related findings in the females, this 

finding was considered not to be adverse.

In each Group one or two females were not pregnant. No treatment-related 

findings were recorded in the reproductive organs of those females and 

their matching males.

Spermatogenic staging profiles were normal for all males examined.

In conclusion, the administration of Castor Oil, Sulfated, Sodium Salt, 

75% by once daily gavage to Wistar (Han) rats at doses up to 1000 mg/kg 

for at least a total of 28 days of dosing resulted in possible adverse 

test item-related microscopic findings in the heart of males treated at 

1000 mg/kg.

Final Report - Page 180 of 272 -
PATHOLOGY REPORT PAGE : 5/ 91

PRINCIPAL SECTION TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

METHODS 

—————————————————————————————————————————————————————————————————————————

Study Design

Group Dose level

mg/kg 

b.w./day

Number of 

animals Animal numbers Selected animals

Males Females Males Females Males Females

1 0 10 10 01-10 41-50 01-05 42,43,44,45,47

2 100 10 10 11-20 51-60 11-15 51,52,54,57,60

3 300 10 10 21-30 61-70 21-25 64,65,67,68,69

4 1000 10 10 31-40 71-80 31-35 73,75,76,78,80

Administration of the Test Item

The males and females were exposed from 2 weeks prior to mating, during 

mating, and up to the day prior to necropsy for at least 28 days. The 

test item Castor Oil, Sulfated, Sodium Salt, 75% was administered once 

daily by gavage at doses of 100, 300 or 1000 mg/kg to dose Groups 2, 3 

and 4 respectively. The rats of the control Group 1 received the vehicle, 

water (Elix), alone. 

Necropsy and Histopathology

At the end of the assigned study period all animals were killed by 

exsanguination under isoflurane anaesthesia. Males were killed after the 

mating period, females were killed on Lactation Day 5 or shortly 

thereafter or on post-coitum Days 25-27.

Complete necropsies were performed on all animals/sex/group at necropsy 

and all macroscopic abnormalities were recorded. From each Group, five 

males and five females were selected (see Study Design). 

From the 5 selected animals/sex/group the terminal body weight and the 

weights of the adrenal glands, brain, epididymides, heart, kidneys, 

liver, ovaries, spleen, testes, thymus, thyroid including parathyroid and 

uterus (including cervix) were recorded at necropsy. Weights of prostate, 

seminal vesicles including coagulating glands were recorded after 

fixation for at least 24 hours. 

From all remaining males the terminal body weight and the weight of 

testes and epididymides were recorded. Body and organ weights are 

reported in the main toxicology report.

Representative tissue samples of the following organs from the 5 selected 

males and females of each Group were preserved: 

Adrenal glands(2), [aorta], bone-sternum(1) and femur including joint(1), 

bone marrow-sternum(1), brain (cerebellum, mid-brain, cortex)(3), 

clitoral gland(2), epididymides(2), [esophagus], eyes(2)[with optic nerve 

and Harderian glands], female mammary gland area (1), heart(1), 

kidneys(2), [lacrimal glands-exorbital], large intestine(3): caecum, 

colon and rectum, [larynx], liver(2), lungs(2), lymph nodes-mandibular(2) 

and mesenteric(1), [nasopharynx], ovaries(2), [pancreas], pituitary 

gland(1), preputial glands(2), prostate gland(1), [salivary glandsmandibular and sublingual], sciatic nerve(1), seminal vesicles(2) with 

Final Report - Page 181 of 272 -
PATHOLOGY REPORT PAGE : 6/ 91

PRINCIPAL SECTION TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

METHODS 

—————————————————————————————————————————————————————————————————————————

coagulating gland(2), skeletal muscle(1), [skin], small intestine(3): 

duodenum, jejunum and ileum with Peyer's patches, spinal cord(3)-

cervical, midthoracic and lumbar, spleen(1), stomach(1), testes(2), 

thymus(1), thyroid glands(2) with parathyroid glands(2), [tongue], 

trachea(1), urinary bladder(1), uterus(3), uterine cervix(1), vagina(1) 

and all gross lesions.

From the remaining animals, the reproductive organs (listed in bold), the 

female mammary gland area and all gross lesions were preserved. 

Testes, epididymides and eyes with optic nerves and Harderian glands were 

initially fixed in Modified Davidson's solution. All other organ samples 

were fixed in 10% buffered formalin (neutral phosphate buffered 4% 

formaldehyde solution). 

Following fixation, organs (except those listed in brackets) from 5 

selected males and females of Group 1 (0 mg/kg) and Group 4 (1000 mg/kg), 

and all organs with macroscopic findings from all rats were trimmed, 

processed and embedded in paraffin wax. Sections were cut at a thickness 

of 2-4 micrometers and stained with hematoxylin and eosin. Numbers of 

sections made are given in parentheses. 

Extra sections of testes cut at a thickness of 3-4 micrometers stained by 

the PAS method from the selected males of Groups 1 and 4 were prepared 

for spermatogenesis staging.

Additional sections were prepared from the reproductive organs (listed in 

bold) of rats that failed to sire or deliver healthy pups, including 

extra sections of the testes for spermatogenesis staging. 

Following examination of the above tissues, extra sections of the heart 

of the selected males and adrenal glands of the selected females of 

Groups 2 and 3 were prepared to examine possible treatment-related 

effects.

All sections were examined by light microscopy in the period 06 November 

– 03 December 2013.

Data Compilation

The animal data and macroscopic findings were electronically transferred 

from the necropsy raw data files of Toxdata system® into the computer 

system PathData© where the microscopic findings were recorded by the 

undersigned pathologist using on-line input under pathology number: 

31316LAA.

Final Report - Page 182 of 272 -
PATHOLOGY REPORT PAGE : 7/ 91

PRINCIPAL SECTION TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

METHODS 

—————————————————————————————————————————————————————————————————————————

The incidence of microscopic findings is presented in tabular form: 

“Incidence table – Selected findings” and “Incidence table - All 

microscopic findings*”. The microscopic findings are also presented in 

tabular form under “Table of individual microscopic findings (AOFT = 

Animal Organ Finding Table)”. All macroscopic and microscopic findings 

are given for each animal in text form under "Text of Gross and 

Microscopic Findings". All tables are created by computer.

*N.A.D. = No Abnormalities Detected. 

Histopathological changes were described according to distribution, 

severity and morphological character. Severity scores were assigned as 

follows:

Grade "1": Minimal / very few / very small.

Grade "2": Slight / few / small.

Grade "3": Moderate / moderate number / moderate size.

Grade "4": Marked / many / large.

Grade "5": Massive / extensive number / extensive size.

Grade "p": Finding present, grading not scored.

In the case of findings in bilaterally affected paired organs, the 

severity score of the worst affected organ was recorded and a comment was 

made listing the severity score in the contralateral organ. 

Peer Review

Microscopic findings were subjected to a review by J.F.M. Lensen, PhD 

(Dutch CRP/TP Certified Toxicologic Pathologist, WIL Research Europe 

B.V.) whereby the reviewer and study pathologist reached consensus.

Final Report - Page 183 of 272 -
PATHOLOGY REPORT PAGE : 8/ 91

PRINCIPAL SECTION TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

RESULTS 

—————————————————————————————————————————————————————————————————————————

Mortality 

All rats survived their scheduled study period.

Macroscopic findings

There were no test item-related macroscopic findings.

The recorded macroscopic findings were considered to be spontaneous in 

nature and did not distinguish treated animals from the controls.

Microscopic findings 

Possible treatment-related findings were recorded in the heart of males 

and adrenal glands of females.

Heart, males: 

- an increase in severity (slight degree) of mononuclear inflammation in 

1/5 males treated at 1000 mg/kg, compared to minimal degrees in 1/5 

males treated at 0 mg/kg, in 1/5 males at 100 mg/kg and in 1/5 males at 

300 mg/kg.

- an increase in incidence and/or severity of myofiber degeneration (2/5, 

up to slight) in males treated at 1000 mg/kg, compared to minimal degree 

in 1/5 males treated at 300 mg/kg and absence of this finding in males 

treated at 100 mg/kg and 0 mg/kg.

Adrenal glands, females:

- an increase in incidence of vacuolation of the zona glomerulosa in 4/5 

females treated at 1000 mg/kg, compared to 1/5 females treated at 0 

mg/kg, 1/5 females at 100 mg/kg and 1/5 females at 300 mg/kg.

The remainder of microscopic findings recorded, were within the normal 

range of background pathology encountered in Wistar (Han) rats of this 

age.

Reproductive performance

The following pairs did not have offspring (all: not pregnant):

Group 1 ( 0 mg/kg/day): 6 and 46 

Group 2 ( 100 mg/kg/day): 19 and 59 

Group 3 ( 300 mg/kg/day): 21 and 61, 22 and 62

Group 4 (1000 mg/kg/day): 39 and 79

No cause for the failure to sire or deliver healthy offspring could be 

established from the sections examined.

The spermatogenic staging profiles were normal for all males examined. 

Final Report - Page 184 of 272 -
PATHOLOGY REPORT PAGE : 9/ 91

PRINCIPAL SECTION TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

DISCUSSION AND CONCLUSIONS 

—————————————————————————————————————————————————————————————————————————

Possible test item-related microscopic findings were noted in males and 

females treated at 1000 mg/kg:

- Heart, males: a subtle increase in severity of mononuclear 

inflammation (1/5, slight) and in incidence and/or severity (2/5, 

minimal and slight) of myofiber degeneration. Both findings are

slightly above the range of background findings of Wistar (Han) rats 

of this age. Therefore a possible test item-related effect cannot be 

excluded.

- Adrenal glands, females: an increase in incidence of vacuolation of 

the zona glomerulosa (up to 4/5). However, based on the minimal degree 

and absence of other test item-related findings in the females, this 

finding was considered not to be adverse.

In conclusion, the administration of Castor Oil, Sulfated, Sodium Salt, 

75% by once daily gavage to Wistar (Han) rats at doses up to 1000 mg/kg 

for at least a total of 28 days of dosing resulted in possible adverse 

test item-related microscopic findings in the heart of males treated at 

1000 mg/kg.

Final Report - Page 185 of 272 -
PATHOLOGY REPORT PAGE : 10/ 91

 TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

EXPLANATION OF CODES AND SYMBOLS 

—————————————————————————————————————————————————————————————————————————

CODES AND SYMBOLS USED AT ANIMAL LEVEL:

————————————————————————————————————————

M = Male animal 

F = Female animal 

K0 = Terminal sacrifice group 

CODES AND SYMBOLS USED AT ORGAN LEVEL:

———————————————————————————————————————

G = Gross observation checked off histologically 

' = Histologic examination not required 

+ = Organ examined, findings present 

— = Organ examined, no pathologic findings noted (AOFT only) 

( = Only one of paired organs examined/present 

CODES AND SYMBOLS USED AT FINDING LEVEL:

—————————————————————————————————————————

GRADE 1 = Minimal / very few / very small 

GRADE 2 = Slight / few / small 

GRADE 3 = Moderate / moderate number / moderate size 

GRADE 4 = Marked / many / large 

P = Finding present, severity not scored 

( = Finding unilateral in paired organs 

* = Comment in text of individual animal data 

Final Report - Page 186 of 272 -
PATHOLOGY REPORT PAGE : 11/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14 

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — Selected findings with grades 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

HEART : 5 5 5 5 

— Inflamm.,mononuclear 

 GRADE 1 : 1 1 1 — 

 GRADE 2 : — — — 1 

 

 TOTAL AFFECTED : 1 1 1 1 

 MEAN GRADE/TISS.AFF.: 1.0 1.0 1.0 2.0 

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

— Myofiber degenerat. 

 GRADE 1 : — — 1 1 

 GRADE 2 : — — — 1 

 

 TOTAL AFFECTED : — — 1 2 

 MEAN GRADE/TISS.AFF.: — — 1.0 1.5 

—————————————————————————————————————————————————————————————————————————

ADRENAL GLANDS : 5 — — 5 

— Vacuolation, z. glom 

 GRADE 1 : — — — 1 

 

 TOTAL AFFECTED : — — — 1 

 MEAN GRADE/TISS.AFF.: — — — 1.0 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 187 of 272 -
PATHOLOGY REPORT PAGE : 12/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

SUMMARY INCIDENCE OF GRADINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — Selected findings with grades 

—————————————————————————————————————————————————————————————————————————

 SEX : FEMALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

ADRENAL GLANDS : 5 5 5 5 

— Vacuolation, z. glom 

 GRADE 1 : 1 1 1 4 

 

 TOTAL AFFECTED : 1 1 1 4 

 MEAN GRADE/TISS.AFF.: 1.0 1.0 1.0 1.0 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 188 of 272 -
PATHOLOGY REPORT PAGE : 13/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

BRAIN : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SPINAL CORD — CERV. : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SPINAL CORD — THOR. : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SPINAL CORD — LUMBAR : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SCIATIC NERVE : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

HEART : 5 5 5 5 

 N.A.D. : 4 4 4 3 

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

— Inflamm.,mononuclear: 1 1 1 1 

— Myofiber degenerat. : — — 1 2 

—————————————————————————————————————————————————————————————————————————

TRACHEA : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

LUNG : 5 — — 5 

— Mineraliz., vascular: 1 — — 3 

— Alv. macrophages : 2 — — 3 

— Inflamm. infiltrate : 3 — — 1 

— Alveolar inflamm. : 4 — — 3 

— Osseous metaplasia : 1 — — 1 

— Inflamm., vascular : 1 — — — 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 189 of 272 -
PATHOLOGY REPORT PAGE : 14/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

STOMACH : 5 1 — 5 

 N.A.D. : 4 — — 3 

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

— Infiltrate, glandul.: — — — 1 

— Inflamm. lim. ridge : 1 — — 1 

— Vacuol. lim. ridge : 1 — — 1 

— Congestion : — 1 — — 

— Hyperkerat.lim.ridge: 1 — — 2 

—————————————————————————————————————————————————————————————————————————

DUODENUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

JEJUNUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

ILEUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

PEYER'S PATCHES : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

CECUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

COLON : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

RECTUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

LIVER : 5 — — 5 

 N.A.D. : — — — — 

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

— Congestion : — — — 1 

— Hemopoietic cells : 1 — — — 

— Inflamm. cell foci : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 190 of 272 -
PATHOLOGY REPORT PAGE : 15/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

KIDNEYS : 5 — — 5 

 N.A.D. : 1 — — — 

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

— Glomerulosclerosis : — — — 1 

— Glomerulonephritis : 1 — — — 

— Pelvic dilation : 1 — — — 

— Hyperpl. urothel. : — — — 1 

— Inflamm., interstit.: 3 — — 1 

— Infiltrate, inflamm.: — — — 1 

— Basophilia, tubular : 3 — — 4 

— Hyalin droplets, : — — — 2 

—————————————————————————————————————————————————————————————————————————

URINARY BLADDER : 5 — — 5 

 N.A.D. : 5 — — 4 

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

— Hyperpl. urothelium,: — — — 1 

—————————————————————————————————————————————————————————————————————————

TESTES : 6 1 2 6 

 N.A.D. : 5 1 1 6 

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

— Seminiferous atrophy: — — 1 — 

— Macro "Agenesis", : 1 — — — 

—————————————————————————————————————————————————————————————————————————

TESTES, PAS STAGING : 6 1 2 6 

— All stages present : 6 1 2 6 

—————————————————————————————————————————————————————————————————————————

EPIDIDYMIDES : 6 1 3 6 

 N.A.D. : 5 1 — 5 

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

— Sperm granuloma : — — 2 1 

— Semin. cell debris : — — 1 — 

— Macro "Agenesis", : 1 — — — 

—————————————————————————————————————————————————————————————————————————

PROSTATE GLAND : 6 1 2 6 

 N.A.D. : 4 1 1 5 

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

— Inflamm. lymphocytic: — — 1 — 

— Infiltrate, inflam. : 2 — — 1 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 191 of 272 -
PATHOLOGY REPORT PAGE : 16/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

COAGULATING GLANDS : 6 1 2 6 

 N.A.D. : 6 1 2 6 

—————————————————————————————————————————————————————————————————————————

SEMINAL VESICLES : 6 1 2 6 

 N.A.D. : 5 1 2 6 

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

— Single cell necrosis: 1 — — — 

—————————————————————————————————————————————————————————————————————————

PREPUTIAL GLANDS : 6 1 2 6 

 N.A.D. : 5 1 1 5 

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

— Inflamm. lymphocytic: 1 — 1 — 

— Dilated duct : — — — 1 

—————————————————————————————————————————————————————————————————————————

BULBOURETHRAL GLANDS : — 1 2 1 

— Macro noted, : — 1 2 1 

—————————————————————————————————————————————————————————————————————————

PITUITARY GLAND : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

THYROID GLAND : 5 — — 5 

 N.A.D. : 2 — — 3 

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

— Ectopic thymus : 1 — — — 

— Hypertrophy, : 2 — — 2 

—————————————————————————————————————————————————————————————————————————

PARATHYROID GLANDS : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

ADRENAL GLANDS : 5 — — 5 

 N.A.D. : 5 — — 4 

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

— Vacuolation, z. glom: — — — 1 

—————————————————————————————————————————————————————————————————————————

SPLEEN : 5 — — 5 

 N.A.D. : 1 — — — 

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

— Hemopoietic foci : 4 — — 5 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 192 of 272 -
PATHOLOGY REPORT PAGE : 17/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

BONE MARROW — STERN. : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

THYMUS : 5 1 — 5 

 N.A.D. : 5 — — 5 

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

— Congestion : — 1 — — 

—————————————————————————————————————————————————————————————————————————

AXILLARY LYMPH NODES : — 1 — — 

 N.A.D. : — 1 — — 

—————————————————————————————————————————————————————————————————————————

MESENT. LYMPH NODE : 5 — — 5 

 N.A.D. : 4 — — 5 

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

— Macrophage foci : 1 — — — 

—————————————————————————————————————————————————————————————————————————

MANDIB.LYMPH NODES : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

RENAL LYMPH NODE : — 1 — — 

— Congestion, : — 1 — — 

— Histiocytosis, : — 1 — — 

—————————————————————————————————————————————————————————————————————————

SKELETAL MUSCLE : 5 — — 5 

 N.A.D. : 3 — — 3 

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

— Myofiber degeneratio: 2 — — 2 

— Inflammat., mononucl: 2 — — 1 

—————————————————————————————————————————————————————————————————————————

BONE, STERNUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

FEMOROTIBIAL JOINT : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 193 of 272 -
PATHOLOGY REPORT PAGE : 18/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : MALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

EYES : 5 — — 5 

 N.A.D. : 4 — — 4 

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

— Corneal hyperplasia,: — — — 1 

— Retinal dysplasia : 1 — — — 

—————————————————————————————————————————————————————————————————————————

FEMUR : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 194 of 272 -
PATHOLOGY REPORT PAGE : 19/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : FEMALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

BRAIN : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SPINAL CORD — CERV. : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SPINAL CORD — THOR. : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SPINAL CORD — LUMBAR : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SCIATIC NERVE : 5 — — 5 

 N.A.D. : 5 — — 4 

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

— Myelin fragmentation: — — — 1 

—————————————————————————————————————————————————————————————————————————

HEART : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

TRACHEA : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

LUNG : 5 — — 5 

— Mineraliz., vascular: 1 — — — 

— Alv. macrophages : 1 — — 1 

— Inflamm. infiltrate : 1 — — 1 

— Alveolar inflamm. : 1 — — 3 

— Microgranuloma, : 1 — — — 

— Osseous metaplasia : 1 — — 1 

—————————————————————————————————————————————————————————————————————————

STOMACH : 5 — — 5 

 N.A.D. : 5 — — 3 

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

— Infiltrate, glandul.: — — — 1 

— Hyperpl., forestom. : — — — 1 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 195 of 272 -
PATHOLOGY REPORT PAGE : 20/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : FEMALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

DUODENUM : 5 — — 5 

 N.A.D. : 3 — — 5 

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

— Hypertrophy, villi : 2 — — — 

—————————————————————————————————————————————————————————————————————————

JEJUNUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

ILEUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

PEYER'S PATCHES : 5 — — 5 

 N.A.D. : 4 — — 4 

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

— Mineraliz., focal : — — — 1 

— Vacuolation : 1 — — — 

—————————————————————————————————————————————————————————————————————————

CECUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

COLON : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

RECTUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

LIVER : 5 — 1 5 

 N.A.D. : 1 — — — 

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

— Hemopoietic cells : 1 — 1 4 

— Inflamm. cell foci : 4 — 1 5 

— (Peri)biliary infl. : — — — 1 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 196 of 272 -
PATHOLOGY REPORT PAGE : 21/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : FEMALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

KIDNEYS : 5 1 — 6 

 N.A.D. : 3 — — 4 

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

— Pelvic dilation : — — — 1 

— Cyst(s) : — 1 — — 

— Hyperpl. urothel. : 1 — — — 

— Inflamm., interstit.: 1 1 — 1 

— Basophilia, tubular : — — — 1 

—————————————————————————————————————————————————————————————————————————

URINARY BLADDER : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

OVARIES : 6 1 2 6 

 N.A.D. : 6 1 2 6 

—————————————————————————————————————————————————————————————————————————

OVIDUCTS : — 1 — — 

 N.A.D. : — 1 — — 

—————————————————————————————————————————————————————————————————————————

UTERUS : 6 1 2 6 

 N.A.D. : 1 1 2 1 

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

— Implantation site(s): 5 — — 5 

—————————————————————————————————————————————————————————————————————————

UTERINE CERVIX : 6 1 2 6 

 N.A.D. : 6 1 2 6 

—————————————————————————————————————————————————————————————————————————

VAGINA : 6 1 2 6 

— Parturition debris : 5 — — 5 

— Diestrus phase : 1 — 1 1 

— Estrus phase : — 1 — — 

— Proestrus phase : — — 1 — 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 197 of 272 -
PATHOLOGY REPORT PAGE : 22/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : FEMALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

CLITORAL GLANDS : 6 1 2 6 

 N.A.D. : 3 1 2 3 

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

— Granuloma : — — — 1 

— Inflamm., lymphocyt.: 2 — — 1 

— Inflamm., mixed : — — — 1 

— Dilated duct : 2 — — 1 

—————————————————————————————————————————————————————————————————————————

PITUITARY GLAND : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

THYROID GLAND : 5 — — 5 

 N.A.D. : 5 — — 4 

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

— Ectopic thymus : — — — 1 

—————————————————————————————————————————————————————————————————————————

PARATHYROID GLANDS : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

ADRENAL GLANDS : 5 5 5 5 

 N.A.D. : 4 4 4 1 

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

— Extracapsular nodule: — — — 1 

— Vacuolation, z. glom: 1 1 1 4 

—————————————————————————————————————————————————————————————————————————

SPLEEN : 5 — — 5 

 N.A.D. : — — — — 

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

— Hemopoietic foci : 5 — — 5 

— Hemosiderin pigment : — — — 3 

—————————————————————————————————————————————————————————————————————————

BONE MARROW — STERN. : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 198 of 272 -
PATHOLOGY REPORT PAGE : 23/ 91

SUMMARY TABLES TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

NUMBER OF ANIMALS WITH MICROSCOPIC FINDINGS BY ORGAN/GROUP/SEX 

STATUS AT NECROPSY: K0 

Incidence table — All microscopic findings 

—————————————————————————————————————————————————————————————————————————

 SEX : FEMALE

 DOSE GROUP: 01 02 03 04 

 NO.ANIMALS: 10 10 10 10 

—————————————————————————————————————————————————————————————————————————

THYMUS : 5 — 1 5 

 N.A.D. : 4 — — 4 

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

— Congestion : 1 — 1 — 

— Epithelial hyperpl. : — — — 1 

—————————————————————————————————————————————————————————————————————————

MESENT. LYMPH NODE : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

MANDIB.LYMPH NODES : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

F.MAMMARY GLAND AREA : 5 — — 5 

— Glandul. development: 5 — — 5 

—————————————————————————————————————————————————————————————————————————

SKELETAL MUSCLE : 5 — — 5 

 N.A.D. : 4 — — 3 

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

— Myofiber degeneratio: 1 — — 2 

— Inflammat., mononucl: — — — 1 

—————————————————————————————————————————————————————————————————————————

BONE, STERNUM : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

FEMOROTIBIAL JOINT : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

EYES : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

FEMUR : 5 — — 5 

 N.A.D. : 5 — — 5 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 199 of 272 -
PATHOLOGY REPORT PAGE : 24/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 1 2 3 4 5 6 7 8 9 10 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

BRAIN — — — — — ' ' ' ' ' 

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

SPINAL CORD — CERV. — — — — — ' ' ' ' ' 

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

SPINAL CORD — THOR. — — — — — ' ' ' ' ' 

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

SPINAL CORD — LUMBAR — — — — — ' ' ' ' ' 

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

SCIATIC NERVE — — — — — ' ' ' ' ' 

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

HEART — — — + — ' ' ' ' ' 

— Inflamm.,mononuclear . . . 1. . 

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

TRACHEA — — — — — ' ' ' ' ' 

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

LUNG + +G + + + ' ' ' ' ' 

— Mineraliz., vascular . . . 1. . 

— Alv. macrophages . 1. 1. . . 

— Inflamm. infiltrate . 1. . 1. 1. 

— Alveolar inflamm. 1. 2. 1. 2. . 

— Osseous metaplasia . . . 1. . 

— Inflamm., vascular . . 1. . . 

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

STOMACH — + — — — ' ' ' ' ' 

— Inflamm. lim. ridge . 1. . . . 

— Vacuol. lim. ridge . 1. . . . 

— Hyperkerat.lim.ridge . 1. . . . 

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

DUODENUM — — — — — ' ' ' ' ' 

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

JEJUNUM — — — — — ' ' ' ' ' 

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

ILEUM — — — — — ' ' ' ' ' 

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

PEYER'S PATCHES — — — — — ' ' ' ' ' 

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

CECUM — — — — — ' ' ' ' ' 

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

COLON — — — — — ' ' ' ' ' 

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

Final Report - Page 200 of 272 -
PATHOLOGY REPORT PAGE : 25/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 1 2 3 4 5 6 7 8 9 10 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

RECTUM — — — — — ' ' ' ' ' 

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

LIVER + + + + + ' ' ' ' ' 

— Hemopoietic cells . 1. . . . 

— Inflamm. cell foci 1. 1. 2. 1. 1. 

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

KIDNEYS +G + — + + ' ' ' ' ' 

— Glomerulonephritis ( 1. . . . . 

— Pelvic dilation ( P. . . . . 

— Inflamm., interstit. ( 1. . . ( 1. ( 1. 

— Basophilia, tubular 1. 1. . . 1. 

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

URINARY BLADDER — — — — — ' ' ' ' ' 

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

TESTES ( +G — — — — — ' ' ' ' 

— Macro "Agenesis", ( P. . . . . . 

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

TESTES, PAS STAGING ( + + + + + + ' ' ' ' 

— All stages present ( P. P. P. P. P. P. 

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

EPIDIDYMIDES ( +G — — — — — ' ' ' ' 

— Macro "Agenesis", ( P. . . . . . 

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

PROSTATE GLAND + — + — — — ' ' ' ' 

— Infiltrate, inflam. 1. . 2. . . . 

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

COAGULATING GLANDS — — — — — — ' ' ' ' 

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

SEMINAL VESICLES — — — + — — ' ' ' ' 

— Single cell necrosis . . . 1. . . 

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

PREPUTIAL GLANDS — + — — — — ' ' ' ' 

— Inflamm. lymphocytic . ( 1. . . . . 

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

PITUITARY GLAND — — — — — ' ' ' ' ' 

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

THYROID GLAND + — + — + ' ' ' ' ' 

— Ectopic thymus . . . . ( P. 

— Hypertrophy, 1. . 1. . . 

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

Final Report - Page 201 of 272 -
PATHOLOGY REPORT PAGE : 26/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 1 2 3 4 5 6 7 8 9 10 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

PARATHYROID GLANDS — — — — — ' ' ' ' ' 

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

ADRENAL GLANDS — — — — — ' ' ' ' ' 

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

SPLEEN + — + + + ' ' ' ' ' 

— Hemopoietic foci 1. . 1. 1. 2. 

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

BONE MARROW — STERN. — — — — — ' ' ' ' ' 

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

THYMUS — — — — — ' ' ' ' ' 

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

MESENT. LYMPH NODE + — — — — ' ' ' ' ' 

— Macrophage foci 1. . . . . 

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

MANDIB.LYMPH NODES — — — — — ' ' ' ' ' 

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

SKELETAL MUSCLE + — — + — ' ' ' ' ' 

— Myofiber degeneratio 1. . . 1. . 

— Inflammat., mononucl 1. . . 1. . 

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

BONE, STERNUM — — — — — ' ' ' ' ' 

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

FEMOROTIBIAL JOINT — — — — — ' ' ' ' ' 

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

EYES — — — — + ' ' ' ' ' 

— Retinal dysplasia . . . . ( 1. 

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

FEMUR — — — — — ' ' ' ' ' 

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

Final Report - Page 202 of 272 -
PATHOLOGY REPORT PAGE : 27/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 41 42 43 44 45 46 47 48 49 50 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

BRAIN ' — — — — ' — ' ' ' 

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

SPINAL CORD — CERV. ' — — — — ' — ' ' ' 

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

SPINAL CORD — THOR. ' — — — — ' — ' ' ' 

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

SPINAL CORD — LUMBAR ' — — — — ' — ' ' ' 

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

SCIATIC NERVE ' — — — — ' — ' ' ' 

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

HEART ' — — — — ' — ' ' ' 

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

TRACHEA ' — — — — ' — ' ' ' 

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

LUNG ' + + + + ' + ' ' ' 

— Mineraliz., vascular 1. . . . . 

— Alv. macrophages . . . . 1. 

— Inflamm. infiltrate 1. . . . . 

— Alveolar inflamm. . . 1* . . 

— Microgranuloma, . . . 1. . 

— Osseous metaplasia . 1. . . . 

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

STOMACH ' — — — — ' — ' ' ' 

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

DUODENUM ' +G — — — ' +G ' ' ' 

— Hypertrophy, villi 1. . . . 1. 

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

JEJUNUM ' —G — — — ' —G ' ' ' 

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

ILEUM ' — — — — ' — ' ' ' 

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

PEYER'S PATCHES ' — — + — ' — ' ' ' 

— Vacuolation . . 1. . . 

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

CECUM ' — — — — ' — ' ' ' 

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

COLON ' — — — — ' — ' ' ' 

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

RECTUM ' — — — — ' — ' ' ' 

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

Final Report - Page 203 of 272 -
PATHOLOGY REPORT PAGE : 28/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 41 42 43 44 45 46 47 48 49 50 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

LIVER ' + + + — ' + ' ' ' 

— Hemopoietic cells . 1. . . . 

— Inflamm. cell foci 1. 1. 1. . 1. 

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

KIDNEYS ' — — — + ' + ' ' ' 

— Hyperpl. urothel. . . . 1. . 

— Inflamm., interstit. . . . . ( 1. 

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

URINARY BLADDER ' — — — — ' — ' ' ' 

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

OVARIES ' — — — — — — ' ' ' 

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

UTERUS ' + + + + — + ' ' ' 

— Implantation site(s) P. P. P. P. . P. 

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

UTERINE CERVIX ' — — — — — — ' ' ' 

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

VAGINA ' + + + + + + ' ' ' 

— Parturition debris P. P. P. P. . P. 

— Diestrus phase . . . . P. . 

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

CLITORAL GLANDS ' — — +G + — +G ' ' ' 

— Inflamm., lymphocyt. . . . 1. . ( 1. 

— Dilated duct . . ( 4. . . ( 2. 

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

PITUITARY GLAND ' — — — — ' — ' ' ' 

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

THYROID GLAND ' — — — — ' — ' ' ' 

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

PARATHYROID GLANDS ' — — — — ' — ' ' ' 

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

ADRENAL GLANDS ' — + — — ' — ' ' ' 

— Vacuolation, z. glom . ( 1. . . . 

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

SPLEEN ' + + + + ' + ' ' ' 

— Hemopoietic foci 2. 3. 3. 2. 1. 

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

BONE MARROW — STERN. ' — — — — ' — ' ' ' 

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

Final Report - Page 204 of 272 -
PATHOLOGY REPORT PAGE : 29/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 41 42 43 44 45 46 47 48 49 50 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

THYMUS ' — +G — — ' — ' ' ' 

— Congestion . P. . . . 

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

MESENT. LYMPH NODE ' — — — — ' — ' ' ' 

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

MANDIB.LYMPH NODES ' — — — — ' — ' ' ' 

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

F.MAMMARY GLAND AREA ' + + + + ' + ' ' ' 

— Glandul. development P. P. P. P. P. 

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

SKELETAL MUSCLE ' — + — — ' — ' ' ' 

— Myofiber degeneratio . 1. . . . 

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

BONE, STERNUM ' — — — — ' — ' ' ' 

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

FEMOROTIBIAL JOINT ' — — — — ' — ' ' ' 

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

EYES ' — — — — ' — ' ' ' 

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

FEMUR ' — — — — ' — ' ' ' 

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

Final Report - Page 205 of 272 -
PATHOLOGY REPORT PAGE : 30/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 02, 100 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 11 12 13 14 15 16 17 18 19 20 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

HEART — — + — — ' ' ' ' ' 

— Inflamm.,mononuclear . . 1. . . 

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

STOMACH ' ' +G ' ' ' ' ' ' ' 

— Congestion P. 

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

TESTES ' ' ' ' ' ' ' ' — ' 

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

TESTES, PAS STAGING ' ' ' ' ' ' ' ' + ' 

— All stages present P. 

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

EPIDIDYMIDES ' ' ' ' ' ' ' ' — ' 

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

PROSTATE GLAND ' ' ' ' ' ' ' ' — ' 

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

COAGULATING GLANDS ' ' ' ' ' ' ' ' — ' 

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

SEMINAL VESICLES ' ' ' ' ' ' ' ' — ' 

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

PREPUTIAL GLANDS ' ' ' ' ' ' ' ' — ' 

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

BULBOURETHRAL GLANDS ' ' ' ( +G ' ' ' ' ' ' 

— Macro noted, ( P. 

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

THYMUS +G ' ' ' ' ' ' ' ' ' 

— Congestion P. 

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

AXILLARY LYMPH NODES ' ' ' —G ' ' ' ' ' ' 

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

RENAL LYMPH NODE ' ' +G ' ' ' ' ' ' ' 

— Congestion, P. 

— Histiocytosis, 2. 

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

Final Report - Page 206 of 272 -
PATHOLOGY REPORT PAGE : 31/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 02, 100 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 51 52 53 54 55 56 57 58 59 60 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

KIDNEYS ' ' ' ( +G ' ' ' ' ' ' 

— Cyst(s) ( 2. 

— Inflamm., interstit. ( 1. 

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

OVARIES ' ' ' ' ' ' ' ' — ' 

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

OVIDUCTS —G ' ' ' ' ' ' ' ' ' 

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

UTERUS ' ' ' ' ' ' ' ' — ' 

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

UTERINE CERVIX ' ' ' ' ' ' ' ' — ' 

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

VAGINA ' ' ' ' ' ' ' ' + ' 

— Estrus phase P. 

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

CLITORAL GLANDS ' ' ' ' ' ' ' ' — ' 

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

ADRENAL GLANDS — + ' — ' ' — ' ' — 

— Vacuolation, z. glom . 1. . . . 

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

Final Report - Page 207 of 272 -
PATHOLOGY REPORT PAGE : 32/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 03, 300 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 21 22 23 24 25 26 27 28 29 30 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

HEART + — — — — ' ' ' ' ' 

— Inflamm.,mononuclear 1. . . . . 

— Myofiber degenerat. 1. . . . . 

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

TESTES + — ' ' ' ' ' ' ' ' 

— Seminiferous atrophy 2. . 

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

TESTES, PAS STAGING + + ' ' ' ' ' ' ' ' 

— All stages present P. P. 

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

EPIDIDYMIDES + +G ' ' ' ( +G ' ' ' ' 

— Sperm granuloma . 2. ( 4. 

— Semin. cell debris 1. . . 

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

PROSTATE GLAND + — ' ' ' ' ' ' ' ' 

— Inflamm. lymphocytic 1. . 

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

COAGULATING GLANDS — — ' ' ' ' ' ' ' ' 

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

SEMINAL VESICLES — — ' ' ' ' ' ' ' ' 

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

PREPUTIAL GLANDS + — ' ' ' ' ' ' ' ' 

— Inflamm. lymphocytic ( 1. . 

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

BULBOURETHRAL GLANDS +G ( +G ' ' ' ' ' ' ' ' 

— Macro noted, P. ( P. 

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

Final Report - Page 208 of 272 -
PATHOLOGY REPORT PAGE : 33/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA 

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 03, 300 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 61 62 63 64 65 66 67 68 69 70 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

LIVER ' ' ' ' ' ' ' ' +G ' 

— Hemopoietic cells 1. 

— Inflamm. cell foci 1. 

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

OVARIES — — ' ' ' ' ' ' ' ' 

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

UTERUS — — ' ' ' ' ' ' ' ' 

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

UTERINE CERVIX — — ' ' ' ' ' ' ' ' 

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

VAGINA + + ' ' ' ' ' ' ' ' 

— Diestrus phase . P. 

— Proestrus phase P. . 

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

CLITORAL GLANDS — — ' ' ' ' ' ' ' ' 

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

ADRENAL GLANDS ' ' ' — + ' — — — ' 

— Vacuolation, z. glom . 1. . . . 

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

THYMUS ' ' ' ' ' ' ' ' +G ' 

— Congestion P. 

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

Final Report - Page 209 of 272 -
PATHOLOGY REPORT PAGE : 34/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 31 32 33 34 35 36 37 38 39 40 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

BRAIN — — — — — ' ' ' ' ' 

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

SPINAL CORD — CERV. — — — — — ' ' ' ' ' 

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

SPINAL CORD — THOR. — — — — — ' ' ' ' ' 

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

SPINAL CORD — LUMBAR — — — — — ' ' ' ' ' 

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

SCIATIC NERVE — — — — — ' ' ' ' ' 

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

HEART + — — + — ' ' ' ' ' 

— Inflamm.,mononuclear . . . 2. . 

— Myofiber degenerat. 1. . . 2. . 

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

TRACHEA — — — — — ' ' ' ' ' 

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

LUNG + + + + + ' ' ' ' ' 

— Mineraliz., vascular . 1. 1. . 1. 

— Alv. macrophages 1. 1. . . 2. 

— Inflamm. infiltrate . . . 1. . 

— Alveolar inflamm. 1. 1. 1. . . 

— Osseous metaplasia . . . . 1. 

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

STOMACH +G — — — + ' ' ' ' ' 

— Infiltrate, glandul. . . . . 1. 

— Inflamm. lim. ridge . . . . 1. 

— Vacuol. lim. ridge . . . . 1. 

— Hyperkerat.lim.ridge 1. . . . 2. 

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

DUODENUM — — — — — ' ' ' ' ' 

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

JEJUNUM — — — — — ' ' ' ' ' 

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

ILEUM — — — — — ' ' ' ' ' 

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

PEYER'S PATCHES — — — — — ' ' ' ' ' 

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

CECUM — — — — — ' ' ' ' ' 

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

Final Report - Page 210 of 272 -
PATHOLOGY REPORT PAGE : 35/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 31 32 33 34 35 36 37 38 39 40 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

COLON — — — — — ' ' ' ' ' 

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

RECTUM — — — — — ' ' ' ' ' 

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

LIVER + + + + +G ' ' ' ' ' 

— Congestion . . . . 1. 

— Inflamm. cell foci 1. 1. 1. 1. 1. 

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

KIDNEYS + + + + + ' ' ' ' ' 

— Glomerulosclerosis . . . . ( 1. 

— Hyperpl. urothel. . . . . ( 1. 

— Inflamm., interstit. . ( 1. . . . 

— Infiltrate, inflamm. . . ( 1. . . 

— Basophilia, tubular ( 1. . ( 1. ( 1. ( 1. 

— Hyalin droplets, . . 1. 1. . 

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

URINARY BLADDER — — + — — ' ' ' ' ' 

— Hyperpl. urothelium, . . 1. . . 

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

TESTES — — — — — ' ' ' — ' 

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

TESTES, PAS STAGING + + + + + ' ' ' + ' 

— All stages present P. P. P. P. P. P. 

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

EPIDIDYMIDES — +G — — — ' ' ' — ' 

— Sperm granuloma . ( 3. . . . . 

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

PROSTATE GLAND — — — + — ' ' ' — ' 

— Infiltrate, inflam. . . . 1. . . 

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

COAGULATING GLANDS — — — — — ' ' ' — ' 

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

SEMINAL VESICLES — — — — — ' ' ' — ' 

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

PREPUTIAL GLANDS — — — +G — ' ' ' — ' 

— Dilated duct . . . ( 2. . . 

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

BULBOURETHRAL GLANDS ' ( +G ' ' ' ' ' ' ' ' 

— Macro noted, ( P. 

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

Final Report - Page 211 of 272 -
PATHOLOGY REPORT PAGE : 36/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 31 32 33 34 35 36 37 38 39 40 

 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 MK0 

—————————————————————————————————————————————————————————————————————————

PITUITARY GLAND — — — — — ' ' ' ' ' 

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

THYROID GLAND — + + — — ' ' ' ' ' 

— Hypertrophy, . 1. 1. . . 

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

PARATHYROID GLANDS — — — — ( — ' ' ' ' ' 

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

ADRENAL GLANDS — — — — + ' ' ' ' ' 

— Vacuolation, z. glom . . . . 1. 

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

SPLEEN + + + + + ' ' ' ' ' 

— Hemopoietic foci 1. 1. 1. 1. 1. 

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

BONE MARROW — STERN. — — — — — ' ' ' ' ' 

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

THYMUS —G — — — — ' ' ' ' ' 

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

MESENT. LYMPH NODE — — — — — ' ' ' ' ' 

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

MANDIB.LYMPH NODES — — — — — ' ' ' ' ' 

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

SKELETAL MUSCLE + — + — — ' ' ' ' ' 

— Myofiber degeneratio 1. . 1. . . 

— Inflammat., mononucl . . 1. . . 

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

BONE, STERNUM — — — — — ' ' ' ' ' 

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

FEMOROTIBIAL JOINT — — — — — ' ' ' ' ' 

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

EYES — — — — + ' ' ' ' ' 

— Corneal hyperplasia, . . . . 1. 

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

FEMUR — — — — — ' ' ' ' ' 

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

Final Report - Page 212 of 272 -
PATHOLOGY REPORT PAGE : 37/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 71 72 73 74 75 76 77 78 79 80 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

BRAIN ' ' — ' — — ' — ' — 

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

SPINAL CORD — CERV. ' ' — ' — — ' — ' — 

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

SPINAL CORD — THOR. ' ' — ' — — ' — ' — 

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

SPINAL CORD — LUMBAR ' ' — ' — — ' — ' — 

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

SCIATIC NERVE ' ' — ' — — ' + ' — 

— Myelin fragmentation . . . 1. . 

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

HEART ' ' — ' — — ' — ' — 

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

TRACHEA ' ' — ' — — ' — ' — 

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

LUNG ' ' + ' + + ' + ' + 

— Alv. macrophages . . 1. . . 

— Inflamm. infiltrate . 1. . . . 

— Alveolar inflamm. 1. . . 1. 1* 

— Osseous metaplasia . . 1. . . 

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

STOMACH ' ' +G ' + — ' — ' — 

— Infiltrate, glandul. . 1. . . . 

— Hyperpl., forestom. 1. . . . . 

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

DUODENUM ' ' — ' — — ' — ' — 

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

JEJUNUM ' ' — ' — — ' — ' — 

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

ILEUM ' ' — ' — — ' — ' — 

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

PEYER'S PATCHES ' ' — ' + — ' — ' — 

— Mineraliz., focal . 1. . . . 

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

CECUM ' ' — ' — — ' — ' — 

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

COLON ' ' — ' — — ' — ' — 

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

RECTUM ' ' — ' — — ' — ' — 

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

Final Report - Page 213 of 272 -
PATHOLOGY REPORT PAGE : 38/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 71 72 73 74 75 76 77 78 79 80 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

LIVER ' ' + ' + + ' + ' + 

— Hemopoietic cells 1. 1. 1. . 1. 

— Inflamm. cell foci 1. 1. 1. 1. 1. 

— (Peri)biliary infl. . 1. . . . 

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

KIDNEYS ' ' — ' — — ( +G — ' + 

— Pelvic dilation . . . ( P. . . 

— Inflamm., interstit. . . . . . ( 1. 

— Basophilia, tubular . . . . . ( 1. 

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

URINARY BLADDER ' ' — ' — — ' — ' — 

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

OVARIES ' ' — ' — — ' — — — 

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

UTERUS ' ' + ' + + ' + — + 

— Implantation site(s) P. P. P. P. . P. 

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

UTERINE CERVIX ' ' — ' — — ' — — — 

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

VAGINA ' ' + ' + + ' + + + 

— Parturition debris P. P. P. P. . P. 

— Diestrus phase . . . . P. . 

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

CLITORAL GLANDS ' ' +G ' + + ' — — — 

— Granuloma . ( 3. . . . . 

— Inflamm., lymphocyt. . ( 1. . . . . 

— Inflamm., mixed . . ( 2. . . . 

— Dilated duct ( 2. . . . . . 

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

PITUITARY GLAND ' ' — ' — — ' — ' — 

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

THYROID GLAND ' ' — ' — + ' — ' — 

— Ectopic thymus . . ( P. . . 

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

PARATHYROID GLANDS ' ' — ' — — ' — ' — 

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

ADRENAL GLANDS ' ' + ' + — ' + ' + 

— Extracapsular nodule . . . ( P. . 

— Vacuolation, z. glom 1. 1. . 1. 1. 

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

Final Report - Page 214 of 272 -
PATHOLOGY REPORT PAGE : 39/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TABLE OF INDIVIDUAL MICROSCOPIC FINDINGS (AOFT) 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

ANIMAL NUMBER : 

 71 72 73 74 75 76 77 78 79 80 

 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 FK0 

—————————————————————————————————————————————————————————————————————————

SPLEEN ' ' + ' + + ' + ' + 

— Hemopoietic foci 3. 2. 2. 1. 3. 

— Hemosiderin pigment . 1. 1. 1. . 

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

BONE MARROW — STERN. ' ' — ' — — ' — ' — 

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

THYMUS ' ' + ' — — ' — ' — 

— Epithelial hyperpl. 1. . . . . 

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

MESENT. LYMPH NODE ' ' — ' — — ' — ' — 

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

MANDIB.LYMPH NODES ' ' — ' — — ' — ' — 

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

F.MAMMARY GLAND AREA ' ' + ' + + ' + ' + 

— Glandul. development P. P. P. P. P. 

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

SKELETAL MUSCLE ' ' + ' — — ' — ' + 

— Myofiber degeneratio 1. . . . 1. 

— Inflammat., mononucl . . . . 1. 

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

BONE, STERNUM ' ' — ' — — ' — ' — 

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

FEMOROTIBIAL JOINT ' ' — ' — — ' — ' — 

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

EYES ' ' — ' — — ' — ' — 

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

FEMUR ' ' — ' — — ' — ' — 

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

Final Report - Page 215 of 272 -
PATHOLOGY REPORT PAGE : 40/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

ANIMAL HEADING DATA 

DOSE GROUP : 01, CONTROL 

—————————————————————————————————————————————————————————————————————————

 

 ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF 

 NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

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

 1 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 2 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 3 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 4 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 5 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 6 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 7 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 8 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 9 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 10 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

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

 41 F K0 K0 47 18—SEP—13 03—NOV—13 04—NOV—13

 42 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 43 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 44 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 45 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 46 F K0 K0 41 18—SEP—13 28—OCT—13 29—OCT—13

 47 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 48 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 49 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 50 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

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

Final Report - Page 216 of 272 -
PATHOLOGY REPORT PAGE : 41/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 1

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

* NECROPSY FINDINGS

 KIDNEYS:

 01: RIGHT SIDE: PELVIC DILATION. 

 TESTES:

 01: RIGHT SIDE: AGENESIS. 

 EPIDIDYMIDES:

 01: RIGHT SIDE: AGENESIS. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar inflammation, mononuclear, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Glomerulonephritis, focal, unilateral, grade 1 

 —Pelvic dilation, unilateral 

 This finding corresponds to necropsy observation no: 01.

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

 —Basophilia, tubular, corticomedullary, bilateral, grade 1 

 TESTES:

 Only one of paired organs examined/present 

 —Macro "Agenesis", unilateral 

 This finding corresponds to necropsy observation no: 01.

 TESTES, PAS STAGING:

 Only one of paired organs examined/present 

 —All stages present, unilateral 

 EPIDIDYMIDES:

 Only one of paired organs examined/present 

 —Macro "Agenesis", unilateral 

 This finding corresponds to necropsy observation no: 01.

Final Report - Page 217 of 272 -
PATHOLOGY REPORT PAGE : 42/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 1

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

 PROSTATE GLAND:

 —Infiltrate, inflammatory cells, lymphocytic, grade 1 

 THYROID GLANDS:

 —Hypertrophy, follicular, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 MESENTERIC LYMPH NODE:

 —Macrophage foci, grade 1 

 SKELETAL MUSCLE:

 —Myofiber degeneration, grade 1 

 —Inflammation, mononuclear, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, URINARY BLADDER, COAGULATING GLANDS 

 (ANTERIOR PROSTATE), SEMINAL VESICLES, PREPUTIAL GLANDS (INGUINAL

 GLANDS), PITUITARY GLAND, PARATHYROID GLANDS, ADRENAL GLANDS, 

 BONE MARROW — STERNAL, THYMUS, MANDIBULAR LYMPH NODES, BONE 

 (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 218 of 272 -
PATHOLOGY REPORT PAGE : 43/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 2

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

* NECROPSY FINDINGS

 LUNG:

 01: FOCUS/FOCI, MANY, REDDISH. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar macrophage foci, grade 1 

 —Inflammatory cell infiltrate, peri— vascular/bronchial,

 grade 1 

 —Alveolar inflammation, mixed, grade 2 

 This finding corresponds to necropsy observation no: 01.

 STOMACH:

 —Inflammation, limiting ridge, grade 1 

 —Vacuolation, limiting ridge, grade 1 

 —Hyperkeratose limiting ridge, grade 1 

 LIVER:

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Basophilia, tubular, corticomedullary, bilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 PREPUTIAL GLANDS (INGUINAL GLANDS):

 —Inflammation lymphocytic, unilateral, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 219 of 272 -
PATHOLOGY REPORT PAGE : 44/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 2

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON,

 RECTUM, URINARY BLADDER, TESTES, EPIDIDYMIDES, PROSTATE GLAND, 

 COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL VESICLES, 

 PITUITARY GLAND, THYROID GLANDS, PARATHYROID GLANDS, ADRENAL 

 GLANDS, SPLEEN, BONE MARROW — STERNAL, THYMUS, MESENTERIC LYMPH 

 NODE, MANDIBULAR LYMPH NODES, SKELETAL MUSCLE, BONE (STERNUM), 

 FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 3

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar macrophage foci, grade 1 

 —Alveolar inflammation, mixed, grade 1 

 —Inflammation, vascular, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 2 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 PROSTATE GLAND:

 —Infiltrate, inflammatory cells, lymphocytic, grade 2 

Final Report - Page 220 of 272 -
PATHOLOGY REPORT PAGE : 45/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 3

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

 THYROID GLANDS:

 —Hypertrophy, follicular, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, KIDNEYS, URINARY BLADDER, TESTES, 

 EPIDIDYMIDES, COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL 

 VESICLES, PREPUTIAL GLANDS (INGUINAL GLANDS), PITUITARY GLAND, 

 PARATHYROID GLANDS, ADRENAL GLANDS, BONE MARROW — STERNAL, 

 THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, SKELETAL 

 MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 4

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

Final Report - Page 221 of 272 -
PATHOLOGY REPORT PAGE : 46/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 4

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

* MICROSCOPIC FINDINGS

 HEART:

 —Inflammation mononuclear, focal (right ventricle), grade 1 

 LUNG:

 —Mineralization, vascular, grade 1 

 —Inflammatory cell infiltrate, peri— vascular/bronchial,

 grade 1 

 —Alveolar inflammation, mononuclear, grade 2 

 —Osseous metaplasia, focal, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 SEMINAL VESICLES:

 —Single cell necrosis (apoptosis), increased, bilateral,

 grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 SKELETAL MUSCLE:

 —Myofiber degeneration, grade 1 

 —Inflammation, mononuclear, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 222 of 272 -
PATHOLOGY REPORT PAGE : 47/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 4

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, TRACHEA, 

 STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON,

 RECTUM, URINARY BLADDER, TESTES, EPIDIDYMIDES, PROSTATE GLAND, 

 COAGULATING GLANDS (ANTERIOR PROSTATE), PREPUTIAL GLANDS 

 (INGUINAL GLANDS), PITUITARY GLAND, THYROID GLANDS, PARATHYROID 

 GLANDS, ADRENAL GLANDS, BONE MARROW — STERNAL, THYMUS, MESENTERIC

 LYMPH NODE, MANDIBULAR LYMPH NODES, BONE (STERNUM), FEMOROTIBIAL 

 JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 5

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Inflammatory cell infiltrate, peri— vascular/bronchial,

 grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

 —Basophilia, tubular, corticomedullary, bilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

Final Report - Page 223 of 272 -
PATHOLOGY REPORT PAGE : 48/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 5

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

 THYROID GLANDS:

 —Ectopic thymus, unilateral 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 2 

 EYES:

 —Retinal dysplasia (rosettes), unilateral, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, URINARY BLADDER, TESTES, EPIDIDYMIDES, 

 PROSTATE GLAND, COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL 

 VESICLES, PREPUTIAL GLANDS (INGUINAL GLANDS), PITUITARY GLAND, 

 PARATHYROID GLANDS, ADRENAL GLANDS, BONE MARROW — STERNAL, 

 THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, SKELETAL 

 MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 6

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

Final Report - Page 224 of 272 -
PATHOLOGY REPORT PAGE : 49/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 6

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

* MICROSCOPIC FINDINGS

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— TESTES, EPIDIDYMIDES, PROSTATE GLAND, COAGULATING GLANDS 

 (ANTERIOR PROSTATE), SEMINAL VESICLES, PREPUTIAL GLANDS (INGUINAL

 GLANDS). 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 225 of 272 -
PATHOLOGY REPORT PAGE : 50/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 42

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

* NECROPSY FINDINGS

 DUODENUM:

 01: WALL: THICKENED. 

 JEJUNUM:

 01: WALL: THICKENED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Mineralization, vascular, grade 1 

 —Inflammatory cell infiltrate, peri— vascular/bronchial,

 grade 1 

 DUODENUM:

 —Hypertophy, duodenal villi, grade 1 

 This finding corresponds to necropsy observation no: 01.

 JEJUNUM:

 No microscopic finding corresponding to necropsy observation no. 01.

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 2 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 226 of 272 -
PATHOLOGY REPORT PAGE : 51/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14 

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 42

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON, 

 RECTUM, KIDNEYS, URINARY BLADDER, OVARIES, UTERINE CERVIX, 

 CLITORAL GLANDS, PITUITARY GLAND, THYROID GLANDS, PARATHYROID 

 GLANDS, ADRENAL GLANDS, BONE MARROW — STERNAL, THYMUS, MESENTERIC

 LYMPH NODE, MANDIBULAR LYMPH NODES, SKELETAL MUSCLE, BONE 

 (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 43

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

* NECROPSY FINDINGS

 THYMUS:

 01: FOCUS/FOCI, MANY, REDDISH. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Osseous metaplasia, focal, grade 1 

 LIVER:

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

Final Report - Page 227 of 272 -
PATHOLOGY REPORT PAGE : 52/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 43

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

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, unilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 3 

 THYMUS:

 —Congestion 

 This finding corresponds to necropsy observation no: 01.

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 SKELETAL MUSCLE:

 —Myofiber degeneration, focal, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, KIDNEYS, URINARY BLADDER, OVARIES, UTERINE 

 CERVIX, CLITORAL GLANDS, PITUITARY GLAND, THYROID GLANDS, 

 PARATHYROID GLANDS, BONE MARROW — STERNAL, MESENTERIC LYMPH NODE,

 MANDIBULAR LYMPH NODES, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES, 

 FEMUR. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 228 of 272 -
PATHOLOGY REPORT PAGE : 53/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 44

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

* NECROPSY FINDINGS

 CLITORAL GLANDS:

 01: LEFT SIDE: ENLARGED. 

 02: LEFT SIDE: DISCOLOURATION, TAN. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar inflammation, mixed, grade 1 

 with free and phagocytosed erythrocytes. 

 PEYER'S PATCHES:

 —Vacuolation, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 CLITORAL GLANDS:

 —Dilated duct, with retained content(s), unilateral, grade 4 

 This finding corresponds to necropsy observations nos: 01,02.

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 3 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 229 of 272 -
PATHOLOGY REPORT PAGE : 54/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 44

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM,

 KIDNEYS, URINARY BLADDER, OVARIES, UTERINE CERVIX, PITUITARY 

 GLAND, THYROID GLANDS, PARATHYROID GLANDS, ADRENAL GLANDS, BONE 

 MARROW — STERNAL, THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH

 NODES, SKELETAL MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES,

 FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 45

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Microgranuloma, grade 1 

 KIDNEYS:

 —Hyperplasia, pelvic urothelium, focal, bilateral, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 CLITORAL GLANDS:

 —Inflammation lymphocytic, bilateral, grade 1 

Final Report - Page 230 of 272 -
PATHOLOGY REPORT PAGE : 55/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 45

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

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 2 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, LIVER, URINARY BLADDER, OVARIES, UTERINE 

 CERVIX, PITUITARY GLAND, THYROID GLANDS, PARATHYROID GLANDS, 

 ADRENAL GLANDS, BONE MARROW — STERNAL, THYMUS, MESENTERIC LYMPH 

 NODE, MANDIBULAR LYMPH NODES, SKELETAL MUSCLE, BONE (STERNUM), 

 FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 41 * ANIMAL NO. : 46

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 VAGINA:

 —Diestrus phase 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 231 of 272 -
PATHOLOGY REPORT PAGE : 56/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 46

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

* ORGANS WITHOUT ABNORMALITIES

— OVARIES, UTERUS, UTERINE CERVIX, CLITORAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 47

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

* NECROPSY FINDINGS

 DUODENUM:

 01: WALL: THICKENED. 

 JEJUNUM:

 01: WALL: THICKENED. 

 CLITORAL GLANDS:

 01: RIGHT SIDE: FOCUS/FOCI, D=2X2 MM, REDDISH. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar macrophage foci, grade 1 

 DUODENUM:

 —Hypertophy, duodenal villi, grade 1 

 This finding corresponds to necropsy observation no: 01.

 JEJUNUM:

 No microscopic finding corresponding to necropsy observation no. 01.

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

Final Report - Page 232 of 272 -
PATHOLOGY REPORT PAGE : 57/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 01, CONTROL FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 47

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

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 CLITORAL GLANDS:

 —Inflammation lymphocytic, unilateral, grade 1 

 —Dilated duct, unilateral, grade 2 

 This finding corresponds to necropsy observation no: 01.

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON, 

 RECTUM, URINARY BLADDER, OVARIES, UTERINE CERVIX, PITUITARY 

 GLAND, THYROID GLANDS, PARATHYROID GLANDS, ADRENAL GLANDS, BONE 

 MARROW — STERNAL, THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH

 NODES, SKELETAL MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES,

 FEMUR. 

—————————————————————————————————————————————————————————————————————————

 — ALL OTHER ANIMALS IN DOSE GROUP WITHOUT PATHOLOGICAL FINDINGS —

—————————————————————————————————————————————————————————————————————————

Final Report - Page 233 of 272 -
PATHOLOGY REPORT PAGE : 58/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

ANIMAL HEADING DATA 

DOSE GROUP : 02, 100 MG/KG 

—————————————————————————————————————————————————————————————————————————

 

 ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF 

 NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

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

 11 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 12 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 13 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 14 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 15 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 16 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 17 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 18 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 19 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 20 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

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

 51 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 52 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 53 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 54 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 55 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 56 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 57 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 58 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 59 F K0 K0 41 18—SEP—13 28—OCT—13 29—OCT—13

 60 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

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

Final Report - Page 234 of 272 -
PATHOLOGY REPORT PAGE : 59/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 11

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

* NECROPSY FINDINGS

 THYMUS:

 01: RIGHT SIDE: FOCUS/FOCI, MANY, REDDISH. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 HEART:

 Organ examined, no pathologic findings noted 

 THYMUS:

 —Congestion 

 This finding corresponds to necropsy observation no: 01.

* ORGANS WITHOUT ABNORMALITIES

— HEART. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 13

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

* NECROPSY FINDINGS

 STOMACH:

 01: GLANDULAR MUCOSA: FOCUS/FOCI, ISOLATED, REDDISH. 

 RENAL LYMP NODE:

 01: LEFT SIDE: DISCOLOURATION, DARK RED. 

 02: LEFT SIDE: ENLARGED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

Final Report - Page 235 of 272 -
PATHOLOGY REPORT PAGE : 60/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 13

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

* MICROSCOPIC FINDINGS

 HEART:

 —Inflammation mononuclear, focal (interventricular wall),

 grade 1 

 STOMACH:

 —Congestion 

 This finding corresponds to necropsy observation no: 01.

 RENAL LYMP NODE:

 —Congestion 

 This finding corresponds to necropsy observation no: 01.

 —Histiocytosis, incl. erythrophaogytosis and brown pigment,

 grade 2 

 This finding corresponds to necropsy observation no: 02.

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 14

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

* NECROPSY FINDINGS

 BULBOURETHRAL GLANDS:

 01: LEFT SIDE: ENLARGED. 

 AXILLARY LYMPH NODES:

 01: RIGHT SIDE: ENLARGED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

Final Report - Page 236 of 272 -
PATHOLOGY REPORT PAGE : 61/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 14

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

* MICROSCOPIC FINDINGS

 BULBOURETHRAL GLANDS:

 Only one of paired organs examined/present 

 —Macro noted, normal histology, lots of luminal contents., 

 unilateral 

 This finding corresponds to necropsy observation no: 01.

 AXILLARY LYMPH NODES:

 No microscopic finding corresponding to necropsy observation no. 01.

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— HEART, AXILLARY LYMPH NODES. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 19

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 237 of 272 -
PATHOLOGY REPORT PAGE : 62/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 19

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

* ORGANS WITHOUT ABNORMALITIES

— TESTES, EPIDIDYMIDES, PROSTATE GLAND, COAGULATING GLANDS 

 (ANTERIOR PROSTATE), SEMINAL VESICLES, PREPUTIAL GLANDS (INGUINAL

 GLANDS). 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 238 of 272 -
PATHOLOGY REPORT PAGE : 63/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 44 * ANIMAL NO. : 51

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

* NECROPSY FINDINGS

 OVIDUCTS:

 01: RIGHT SIDE: CYST(S), D=3X3 MM, WATERY—CLEAR. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 OVIDUCTS:

 No microscopic finding corresponding to necropsy observation no. 01.

 NO MICROSCOPIC FINDINGS NOTED.

* ORGANS WITHOUT ABNORMALITIES 

— OVIDUCTS, ADRENAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 52

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

Final Report - Page 239 of 272 -
PATHOLOGY REPORT PAGE : 64/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 52

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

* MICROSCOPIC FINDINGS

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 54

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

* NECROPSY FINDINGS

 KIDNEYS:

 01: RIGHT SIDE: CYST(S), D=2X2 MM, WATERY—CLEAR. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 KIDNEYS:

 Only one of paired organs examined/present 

 —Cyst(s), unilateral, grade 2 

 This finding corresponds to necropsy observation no: 01.

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

 ADRENAL GLANDS:

 Organ examined, no pathologic findings noted 

* ORGANS WITHOUT ABNORMALITIES

— ADRENAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 240 of 272 -
PATHOLOGY REPORT PAGE : 65/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 02, 100 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 41 * ANIMAL NO. : 59

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 VAGINA:

 —Estrus phase 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— OVARIES, UTERUS, UTERINE CERVIX, CLITORAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

 — ALL OTHER ANIMALS IN DOSE GROUP WITHOUT PATHOLOGICAL FINDINGS —

—————————————————————————————————————————————————————————————————————————

Final Report - Page 241 of 272 -
PATHOLOGY REPORT PAGE : 66/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

ANIMAL HEADING DATA 

DOSE GROUP : 03, 300 MG/KG 

—————————————————————————————————————————————————————————————————————————

 

 ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF 

 NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

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

 21 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 22 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 23 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 24 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 25 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 26 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 27 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 28 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 29 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 30 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

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

 61 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 62 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 63 F K0 K0 47 18—SEP—13 03—NOV—13 04—NOV—13

 64 F K0 K0 41 18—SEP—13 28—OCT—13 29—OCT—13

 65 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 66 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 67 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 68 F K0 K0 41 18—SEP—13 28—OCT—13 29—OCT—13

 69 F K0 K0 41 18—SEP—13 28—OCT—13 29—OCT—13

 70 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

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

Final Report - Page 242 of 272 -
PATHOLOGY REPORT PAGE : 67/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 03, 300 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 21

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

* NECROPSY FINDINGS

 BULBOURETHRAL GLANDS:

 01: BOTH SIDES: ENLARGED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 HEART:

 —Inflammation mononuclear, focal (interventricular wall),

 grade 1 

 —Myofiber degeneration, focal (interventricular wall), grade 1 

 TESTES:

 —Seminiferous tubular atrophy, multifocal, bilateral, grade 2 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 EPIDIDYMIDES:

 —Seminiferous cell debris, bilateral, grade 1 

 PROSTATE GLAND:

 —Inflammation lymphocytic, grade 1 

 PREPUTIAL GLANDS (INGUINAL GLANDS):

 —Inflammation lymphocytic, unilateral, grade 1 

 BULBOURETHRAL GLANDS:

 —Macro noted, normal histology, lots of luminal contents., 

 bilateral 

 This finding corresponds to necropsy observation no: 01.

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL VESICLES. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 243 of 272 -
PATHOLOGY REPORT PAGE : 68/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 03, 300 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 22

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

* NECROPSY FINDINGS

 EPIDIDYMIDES:

 01: RIGHT SIDE, TAIL: NODULE(S), ISOLATED, YELLOWISH, SOFT. 

 BULBOURETHRAL GLANDS:

 01: LEFT SIDE: ENLARGED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 EPIDIDYMIDES:

 —Sperm granuloma, multifocal, bilateral, grade 2 

 This finding corresponds to necropsy observation no: 01.

 BULBOURETHRAL GLANDS:

 Only one of paired organs examined/present 

 —Macro noted, normal histology, lots of luminal contents., 

 unilateral 

 This finding corresponds to necropsy observation no: 01.

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— HEART, TESTES, PROSTATE GLAND, COAGULATING GLANDS (ANTERIOR 

 PROSTATE), SEMINAL VESICLES, PREPUTIAL GLANDS (INGUINAL GLANDS). 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 244 of 272 -
PATHOLOGY REPORT PAGE : 69/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 03, 300 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 26

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

* NECROPSY FINDINGS

 EPIDIDYMIDES:

 01: RIGHT SIDE, TAIL: NODULE(S), D=14X10 MM, YELLOWISH, SOFT. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 EPIDIDYMIDES:

 Only one of paired organs examined/present 

 —Sperm granuloma, unilateral, grade 4 

 This finding corresponds to necropsy observation no: 01.

—————————————————————————————————————————————————————————————————————————

Final Report - Page 245 of 272 -
PATHOLOGY REPORT PAGE : 70/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 03, 300 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 44 * ANIMAL NO. : 61

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 VAGINA:

 —Proestrus phase 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— OVARIES, UTERUS, UTERINE CERVIX, CLITORAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 44 * ANIMAL NO. : 62

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 VAGINA:

 —Diestrus phase 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 246 of 272 -
PATHOLOGY REPORT PAGE : 71/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 03, 300 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 62

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

* ORGANS WITHOUT ABNORMALITIES

— OVARIES, UTERUS, UTERINE CERVIX, CLITORAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 65

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 41 * ANIMAL NO. : 69

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

* NECROPSY FINDINGS

 LIVER:

 01: ENLARGED. 

 THYMUS:

 01: FOCUS/FOCI, MANY, REDDISH. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

Final Report - Page 247 of 272 -
PATHOLOGY REPORT PAGE : 72/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 03, 300 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 69

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

* MICROSCOPIC FINDINGS

 LIVER:

 No microscopic finding corresponding to necropsy observation no. 01.

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 ADRENAL GLANDS: 

 Organ examined, no pathologic findings noted 

 THYMUS:

 —Congestion 

 This finding corresponds to necropsy observation no: 01.

* ORGANS WITHOUT ABNORMALITIES

— ADRENAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

 — ALL OTHER ANIMALS IN DOSE GROUP WITHOUT PATHOLOGICAL FINDINGS —

—————————————————————————————————————————————————————————————————————————

Final Report - Page 248 of 272 -
PATHOLOGY REPORT PAGE : 73/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

ANIMAL HEADING DATA 

DOSE GROUP : 04, 1000 MG/KG 

—————————————————————————————————————————————————————————————————————————

 

 ANIMAL SEX DEFINED AND FINAL TEST FIRST AND LAST DATE OF 

 NUMBER M/F STATE OF NECROPSY DAYS DAY UNDER TEST NECROPSY

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

 31 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 32 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 33 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 34 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 35 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 36 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 37 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 38 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 39 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

 40 M K0 K0 29 18—SEP—13 16—OCT—13 17—OCT—13

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

 71 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 72 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 73 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 74 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 75 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 76 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 77 F K0 K0 44 18—SEP—13 31—OCT—13 01—NOV—13

 78 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

 79 F K0 K0 41 18—SEP—13 28—OCT—13 29—OCT—13

 80 F K0 K0 43 18—SEP—13 30—OCT—13 31—OCT—13

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

Final Report - Page 249 of 272 -
PATHOLOGY REPORT PAGE : 74/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 31

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

* NECROPSY FINDINGS

 STOMACH:

 01: LIMITING RIDGE: THICKENED. 

 THYMUS:

 01: REDUCED IN SIZE. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 HEART:

 —Myofiber degeneration, focal (left ventricle), grade 1 

 LUNG:

 —Alveolar macrophage foci, grade 1 

 —Alveolar inflammation, mixed, grade 1 

 STOMACH:

 —Hyperkeratose limiting ridge, grade 1 

 This finding corresponds to necropsy observation no: 01.

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Basophilia, tubular, corticomedullary, unilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 THYMUS:

 No microscopic finding corresponding to necropsy observation no. 01.

 SKELETAL MUSCLE:

 —Myofiber degeneration, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 250 of 272 -
PATHOLOGY REPORT PAGE : 75/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 31

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, TRACHEA, 

 DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON, RECTUM, 

 URINARY BLADDER, TESTES, EPIDIDYMIDES, PROSTATE GLAND, 

 COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL VESICLES, 

 PREPUTIAL GLANDS (INGUINAL GLANDS), PITUITARY GLAND, THYROID 

 GLANDS, PARATHYROID GLANDS, ADRENAL GLANDS, BONE MARROW — 

 STERNAL, THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, 

 BONE (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 32

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

* NECROPSY FINDINGS

 EPIDIDYMIDES:

 01: RIGHT SIDE, TAIL: NODULE(S), D=6X6 MM, YELLOWISH, SOFT. 

 BULBOURETHRAL GLANDS:

 01: RIGHT SIDE: ENLARGED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Mineralization, vascular, grade 1 

 —Alveolar macrophage foci, grade 1 

 —Alveolar inflammation, mononuclear, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

Final Report - Page 251 of 272 -
PATHOLOGY REPORT PAGE : 76/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 32

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

 KIDNEYS:

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 EPIDIDYMIDES:

 —Sperm granuloma, unilateral, grade 3 

 This finding corresponds to necropsy observation no: 01.

 BULBOURETHRAL GLANDS:

 Only one of paired organs examined/present 

 —Macro noted, normal histology, lots of luminal contents., 

 unilateral 

 This finding corresponds to necropsy observation no: 01.

 THYROID GLANDS:

 —Hypertrophy, follicular, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, URINARY BLADDER, TESTES, PROSTATE GLAND, 

 COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL VESICLES, 

 PREPUTIAL GLANDS (INGUINAL GLANDS), PITUITARY GLAND, PARATHYROID 

 GLANDS, ADRENAL GLANDS, BONE MARROW — STERNAL, THYMUS, MESENTERIC

 LYMPH NODE, MANDIBULAR LYMPH NODES, SKELETAL MUSCLE, BONE 

 (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 252 of 272 -
PATHOLOGY REPORT PAGE : 77/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 33

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Mineralization, vascular, grade 1 

 —Alveolar inflammation, mononuclear, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Infiltrate, inflammatory cells, lymphocytic, perivascular, 

 unilateral, grade 1 

 —Basophilia, tubular, corticomedullary, unilateral, grade 1 

 —Hyalin droplets, tubular, bilateral, grade 1 

 URINARY BLADDER:

 —Hyperplasia urothelium, focal, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 THYROID GLANDS:

 —Hypertrophy, follicular, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 SKELETAL MUSCLE:

 —Myofiber degeneration, grade 1 

 —Inflammation, mononuclear, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 253 of 272 -
PATHOLOGY REPORT PAGE : 78/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 33

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, TESTES, EPIDIDYMIDES, PROSTATE GLAND, 

 COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL VESICLES, 

 PREPUTIAL GLANDS (INGUINAL GLANDS), PITUITARY GLAND, PARATHYROID 

 GLANDS, ADRENAL GLANDS, BONE MARROW — STERNAL, THYMUS, MESENTERIC

 LYMPH NODE, MANDIBULAR LYMPH NODES, BONE (STERNUM), FEMOROTIBIAL 

 JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 34

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

* NECROPSY FINDINGS

 PREPUTIAL GLANDS (INGUINAL GLANDS):

 01: LEFT SIDE: FOCUS/FOCI, D=3X2 MM, GRAY—WHITE. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 HEART:

 —Inflammation mononuclear, multifocal (right ventricle),

 grade 2 

 —Myofiber degeneration, multifocal (right ventricle), grade 2 

 LUNG:

 —Inflammatory cell infiltrate, peri— vascular/bronchial,

 grade 1 

Final Report - Page 254 of 272 -
PATHOLOGY REPORT PAGE : 79/ 91 

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 34

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

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Basophilia, tubular, corticomedullary, unilateral, grade 1 

 —Hyalin droplets, tubular, bilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 PROSTATE GLAND:

 —Infiltrate, inflammatory cells, lymphocytic, grade 1 

 PREPUTIAL GLANDS (INGUINAL GLANDS):

 —Dilated duct, unilateral, grade 2 

 This finding corresponds to necropsy observation no: 01.

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, TRACHEA, 

 STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON,

 RECTUM, URINARY BLADDER, TESTES, EPIDIDYMIDES, COAGULATING GLANDS

 (ANTERIOR PROSTATE), SEMINAL VESICLES, PITUITARY GLAND, THYROID 

 GLANDS, PARATHYROID GLANDS, ADRENAL GLANDS, BONE MARROW — 

 STERNAL, THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, 

 SKELETAL MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR.

—————————————————————————————————————————————————————————————————————————

Final Report - Page 255 of 272 -
PATHOLOGY REPORT PAGE : 80/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 35

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

* NECROPSY FINDINGS

 LIVER:

 01: DISCOLOURATION, DARK RED. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Mineralization, vascular, grade 1 

 —Alveolar macrophage foci, grade 2 

 —Osseous metaplasia, focal, grade 1 

 STOMACH:

 —Lymphogranulocytic infiltrate, glandular mucosa, grade 1 

 —Inflammation, limiting ridge, lymphogranulocytic, grade 1 

 —Vacuolation, limiting ridge, grade 1 

 —Hyperkeratose limiting ridge, grade 2 

 LIVER:

 —Congestion, grade 1 

 This finding corresponds to necropsy observation no: 01.

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Glomerulosclerosis, focal, unilateral, grade 1 

 —Hyperplasia, pelvic urothelium, focal (papilla), unilateral,

 grade 1 

 —Basophilia, tubular, corticomedullary, unilateral, grade 1 

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 PARATHYROID GLANDS:

 Only one of paired organs examined/present 

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

Final Report - Page 256 of 272 -
PATHOLOGY REPORT PAGE : 81/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 35

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

 EYES:

 —Corneal hyperplasia, focal, bilateral, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON,

 RECTUM, URINARY BLADDER, TESTES, EPIDIDYMIDES, PROSTATE GLAND, 

 COAGULATING GLANDS (ANTERIOR PROSTATE), SEMINAL VESICLES, 

 PREPUTIAL GLANDS (INGUINAL GLANDS), PITUITARY GLAND, THYROID 

 GLANDS, PARATHYROID GLANDS, BONE MARROW — STERNAL, THYMUS, 

 MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, SKELETAL MUSCLE, 

 BONE (STERNUM), FEMOROTIBIAL JOINT, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 29 * ANIMAL NO. : 39

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 TESTES, PAS STAGING:

 —All stages present, bilateral 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 257 of 272 -
PATHOLOGY REPORT PAGE : 82/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG MALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 39

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

* ORGANS WITHOUT ABNORMALITIES

— TESTES, EPIDIDYMIDES, PROSTATE GLAND, COAGULATING GLANDS 

 (ANTERIOR PROSTATE), SEMINAL VESICLES, PREPUTIAL GLANDS (INGUINAL

 GLANDS). 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 258 of 272 -
PATHOLOGY REPORT PAGE : 83/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 73

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

* NECROPSY FINDINGS

 STOMACH:

 01: GLANDULAR MUCOSA: IRREGULAR SURFACE. 

 CLITORAL GLANDS:

 01: RIGHT SIDE: FOCUS/FOCI, ISOLATED, TAN. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar inflammation, mixed, grade 1 

 STOMACH:

 No microscopic finding corresponding to necropsy observation no. 01.

 —Hyperplasia, squamous epithelium, diffuse, grade 1 

 LIVER:

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 CLITORAL GLANDS:

 —Dilated duct, unilateral, grade 2 

 This finding corresponds to necropsy observation no: 01.

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 3 

 THYMUS:

 —Epithelial hyperplasia, grade 1 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

Final Report - Page 259 of 272 -
PATHOLOGY REPORT PAGE : 84/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 73

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

 SKELETAL MUSCLE:

 —Myofiber degeneration, focal, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON,

 RECTUM, KIDNEYS, URINARY BLADDER, OVARIES, UTERINE CERVIX, 

 PITUITARY GLAND, THYROID GLANDS, PARATHYROID GLANDS, BONE MARROW 

 — STERNAL, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, BONE 

 (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 75

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Inflammatory cell infiltrate, peri— vascular/bronchial,

 grade 1 

 STOMACH:

 —Lymphogranulocytic infiltrate, glandular mucosa, lymphoc.,

 grade 1 

Final Report - Page 260 of 272 -
PATHOLOGY REPORT PAGE : 85/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 75

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

 PEYER'S PATCHES:

 —Mineralization, focal, grade 1 

 LIVER:

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 —(Peri)biliary inflammation, lymphocytic, focal, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 CLITORAL GLANDS:

 —Granuloma, unilateral, grade 3 

 —Inflammation lymphocytic, unilateral, grade 1 

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 2 

 —Hemosiderin pigment, grade 1 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, KIDNEYS,

 URINARY BLADDER, OVARIES, UTERINE CERVIX, PITUITARY GLAND, 

 THYROID GLANDS, PARATHYROID GLANDS, BONE MARROW — STERNAL, 

 THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODES, SKELETAL 

 MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES, FEMUR. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 261 of 272 -
PATHOLOGY REPORT PAGE : 86/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 76

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar macrophage foci, grade 1 

 —Osseous metaplasia, focal, grade 1 

 LIVER:

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 CLITORAL GLANDS:

 —Inflammation, mixed, unilateral, grade 2 

 THYROID GLANDS:

 —Ectopic thymus, unilateral 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 2 

 —Hemosiderin pigment, grade 1 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 262 of 272 -
PATHOLOGY REPORT PAGE : 87/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 76

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, KIDNEYS, URINARY BLADDER, OVARIES, UTERINE 

 CERVIX, PITUITARY GLAND, PARATHYROID GLANDS, ADRENAL GLANDS, BONE

 MARROW — STERNAL, THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH

 NODES, SKELETAL MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES,

 FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 44 * ANIMAL NO. : 77

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

* NECROPSY FINDINGS

 KIDNEYS:

 01: RIGHT SIDE: PELVIC DILATION. 

 NO OTHER NECROPSY OBSERVATIONS NOTED

* MICROSCOPIC FINDINGS

 KIDNEYS:

 Only one of paired organs examined/present 

 —Pelvic dilation, unilateral 

 This finding corresponds to necropsy observation no: 01.

—————————————————————————————————————————————————————————————————————————

Final Report - Page 263 of 272 -
PATHOLOGY REPORT PAGE : 88/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 78

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 SCIATIC NERVE:

 —Myelin fragmentation, focal/multifocal, grade 1 

 LUNG:

 —Alveolar inflammation, mixed, grade 1 

 LIVER:

 —Inflammatory cell foci, lymphocytic, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 ADRENAL GLANDS:

 —Extracapsular nodule, unilateral 

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 1 

 —Hemosiderin pigment, grade 1 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 264 of 272 -
PATHOLOGY REPORT PAGE : 89/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

 CONT./FF. ANIMAL NO. : 78

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, HEART, TRACHEA, STOMACH, 

 DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, CECUM, COLON, RECTUM, 

 KIDNEYS, URINARY BLADDER, OVARIES, UTERINE CERVIX, CLITORAL 

 GLANDS, PITUITARY GLAND, THYROID GLANDS, PARATHYROID GLANDS, BONE

 MARROW — STERNAL, THYMUS, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH

 NODES, SKELETAL MUSCLE, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES,

 FEMUR. 

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 41 * ANIMAL NO. : 79

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 VAGINA:

 —Diestrus phase 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

* ORGANS WITHOUT ABNORMALITIES

— OVARIES, UTERUS, UTERINE CERVIX, CLITORAL GLANDS. 

—————————————————————————————————————————————————————————————————————————

Final Report - Page 265 of 272 -
PATHOLOGY REPORT PAGE : 90/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

—————————————————————————————————————————————————————————————————————————

TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

—————————————————————————————————————————————————————————————————————————

TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

—————————————————————————————————————————————————————————————————————————

* STATE AT NECROPSY: K0 

 DAYS ON TEST : 43 * ANIMAL NO. : 80

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

* NECROPSY FINDINGS

 NO NECROPSY OBSERVATIONS NOTED.

* MICROSCOPIC FINDINGS

 LUNG:

 —Alveolar inflammation, mixed, grade 1 

 with free and phagocytosed erythrocytes. 

 LIVER:

 —Hemopoietic cell foci, grade 1 

 —Inflammatory cell foci, lymphocytic, grade 1 

 KIDNEYS:

 —Inflammation, interstitial lymphocytic, unilateral, grade 1 

 —Basophilia, tubular, corticomedullary, unilateral, grade 1 

 UTERUS:

 —Implantation site(s) 

 VAGINA:

 —Parturition debris 

 ADRENAL GLANDS:

 —Vacuolation, zona glomerulosa, bilateral, grade 1 

 SPLEEN:

 —Hemopoietic foci, primarily erythropoiesis, grade 3 

 FEMALE MAMMARY GLAND AREA:

 —Glandular development 

 SKELETAL MUSCLE:

 —Myofiber degeneration, focal, grade 1 

 —Inflammation, mononuclear, focal, grade 1 

 ALL OTHER PROTOCOL TISSUES WITHOUT PATHOLOGIC FINDINGS.

Final Report - Page 266 of 272 -
PATHOLOGY REPORT PAGE : 91/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

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TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LAA

TEST SYSTEM : RAT, Combined 28—day, Gavage DATE : 17—MAR—14

SPONSOR : SCOC, SOCMA PathData©System V6.2d1

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TEXT OF GROSS AND MICROSCOPIC FINDINGS 

DOSE GROUP : 04, 1000 MG/KG FEMALE

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 CONT./FF. ANIMAL NO. : 80

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

* ORGANS WITHOUT ABNORMALITIES

— BRAIN, SPINAL CORD — CERVICAL SEGMENT, SPINAL CORD — THORACIC 

 SEGMENT, SPINAL CORD — LUMBAR SEGMENT, SCIATIC NERVE, HEART, 

 TRACHEA, STOMACH, DUODENUM, JEJUNUM, ILEUM, PEYER'S PATCHES, 

 CECUM, COLON, RECTUM, URINARY BLADDER, OVARIES, UTERINE CERVIX, 

 CLITORAL GLANDS, PITUITARY GLAND, THYROID GLANDS, PARATHYROID 

 GLANDS, BONE MARROW — STERNAL, THYMUS, MESENTERIC LYMPH NODE, 

 MANDIBULAR LYMPH NODES, BONE (STERNUM), FEMOROTIBIAL JOINT, EYES,

 FEMUR. 

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 — ALL OTHER ANIMALS IN DOSE GROUP WITHOUT PATHOLOGICAL FINDINGS —

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Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

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APPENDIX 5 CERTIFICATE OF ANALYSIS

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APPENDIX 5

Final Report

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APPENDIX 6 SUMMARY OF DOSE RANGE FINDING STUDY

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APPENDIX 6

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Summary of Dose Range Finding Study

Study Plan Treatment: 02-11 September 2013

Necropsy: 11 September 2013

Aim of the study

In order to set the dose levels for the main study (Project 503342), and to determine the peak effect of 

occurrence of clinical signs after dosing, a dose range finding study was performed (Project 503343).

Guidelines

No guidelines were applicable as this study was intended for dose level selection purposes only.

Materials and methods

If not mentioned otherwise, test system, procedures and techniques were identical to those used 

during the main study.

Test System/Animal husbandry

Number of rats/group 3 females (allocated at random and identified by ear- and tailmark).

Treatment

Duration of treatment 10 days. 

Dose levels 500 and 1000 mg/kg.

Dose levels were based on the results of the acute oral toxicity 

study (project 503339).

No chemical analyses of dose preparations were conducted.

Observations

Mortality At least twice daily. 

Clinical signs Days 1-10: Detailed clinical observations were made in all animals at 0-15 

minutes, 1 hour (±15 minutes) and 3 hours (± 30 minutes) after dosing.

Body weights Days 1, 5 and 10.

Food consumption Days 1-5 and 5-10.

Pathology

Necropsy All animals were subjected to an external, thoracic and abdominal 

examination on Day 10 after the last observation of clinical signs 

(scheduled necropsy). No organs were fixed. Animals were not deprived of 

food prior to necropsy. 

Organ weights Terminal body weight, kidney and liver weight.

List of protocol deviations

1. Temporary deviations from the maximum level of relative humidity occurred.

Evaluation: Laboratory historical data do not indicate an effect of the deviations.

2. During clinical observations on Day 7, the actual time instead of the nominal time of 07.00 hrs 

was used for the 0 hour observation. 

Evaluation: All clinical observations were conducted and recorded online on the time points after 

dosing as per protocol. The use of nominal times was for computer registration purposes only. 

The study integrity was not adversely affected by the deviations.

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APPENDIX 6

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Results

Parameter 500 mg/kg 1000 mg/kg

Mortality No mortality. No mortality.

Clinical appearance Rales was noted for one animal. Hunched posture and piloerection were noted 

for one animal. 

Body weight

Mean body weights and body weight gains 

were normal. One animal only gained 2 

grams over the treatment period. The other 

two had normal gains. 

Mean body weights and body weight gains 

were normal. One animal lost a slight amount 

of weight from Days 5-10. The other two had 

normal gains. 

Food consumption Normal. Normal.

Macroscopic examination No abnormalities noted. No abnormalities noted.

Organ weights

Absolute liver weights were slightly 

increased. Kidney weights were considered 

to be normal.

Liver weights and liver to body weight ratios 

were slightly increased. Kidney weights 

considered to be normal.

Conclusion

Based on the results of this range finding study, dose levels for the main study were: 100, 300 and 

1000 mg/kg.

The peak effect of occurrence of clinical signs occurred at 1 hour after dosing. This time point was 

taken into account to set a time range within which clinical observations and functional observation 

tests are to be conducted after dosing in the main study.

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