# FINAL REPORT

Study Title 

# COMBINED 28 - DAY REPEATED DOSE TO XICITY STUDY WITH TH E REPRODUCTION/DEVELOP MENTAL TOXICITY SCREENING TEST OF CASTOR OIL, SULFATED , SODIUM SALT, 75% IN RATS BY ORAL GAVAGE

Author M.E.W. de Raaf - Beekhuijzen, M Sc. 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 COM PLIANCE ............................................................................................. 4 3. QUALITY ASSURANCE ST ATEMENT ............................................................................................ 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 METHOD S ........................................................................................................ 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. Cli nical 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. H istotechnology .......................................................................................................... 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. Cli nical 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 CONCL USION ................................................................................................ 25 9. REFERENCES ............................................................................................................................... 26 APPENDICES APPENDIX 1 SUMMARY TABLES APPENDIX 2 INDIVIDUAL TABLES APPENDIX 3 PHASE REPORT FORMULATION ANALYSIS APPENDIX 4 PHASE REPORT HI STOPATHOLOGY 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 guideline s: 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 4 21, 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 APPENDI X 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 ac climatization , 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 w ere 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 terminat ion, 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 we re 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 ( P roject 503343 ) is given in APPENDIX 6 . Two project numbers were used to collect online data (project 503342 and 5 03344 ). 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 Eur ope 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. S tudy 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 w as 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 behavi our, conception, parturition and early postnatal development. P arental, reproduction (up to and including implantation) and developmental (from implantation onwards) No Observed Adverse Effect Level s (NOAEL s ) w ere evaluated. This study should provide part of a rational basis for toxicological risk assessment in man. 5.4. Guidelines Th e 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 we re 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 Guideline s 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 s pecimens 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 METHOD S 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: T he 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. 7 0.7 %] . 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) w ere prepared daily within 4 hours prior to dosing and w ere homogenized to a visually acceptable level. Adjustment w as made for specific gravity/density of the test substance (1.049) . A correction w as made for the purity/composition of the test substance. A correction factor of 1.41 w as 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 meth od was not suited to measure the test substance in the se frozen samples, additional samples were collected after the in - life phase ( 19 December 2013 ) . These formulations w ere 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 co uld 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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### A ccuracy 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 s ystem Rat: Crl:WI(Han) (outbred, SPF - Quality). Nulliparous and non - pregnant females and untreated animals w ere 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 sp ecies from the same strain and source. This animal model has been proven to be susceptible to the effects of reproductive toxicants. Source F 0 

### Charles River Deutschland, Sulzfeld, Germany. Age at start F 0 

### - treatment Approximately 11 weeks. Number of F 0 

### - animals 40 females and 40 males. Acclimatization F 0 

### At least 5 days prior to start of treatment. Health inspection F 0 

### Upon receipt of the animals . Randomization F 0 

### Prior to commencement of treatment, by computer - generated random algorithm according to body weight, with all animals within ± 20% of the sex mean. Identification F 0 

### Earmark and tattoo. Mating procedures Following a minimum of 14 days of exposure for the males and females, one female w as cohabitated with one male of the same treatment group , avoiding sibling mating. Detection of mating w as confirmed by evidence of sperm in the vaginal lavage or by the appearance of an intravaginal copulatory plug. This day w as designated Day 0 post - coitum. Once mating occurred, the males and females w ere separated. Parturition The females w ere allowed to litter normally. Day 1 of lactation wa s defined as the day when a litter wa s found completed (i.e. membranes and placentas cleaned up, nest build up and/or feeding of pups started). Females that wer e li ttering w ere left undisturbed. Number of pups 430 pups. Identification of pups On Day 1 of lactation, all pups w ere individually identified by means of subcutaneous injection of Indian ink. 6.3. Allocation Group Dose level 1 

### 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 

### D ose 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 woul d result in dose levels of 105, 316 and 1052 mg/kg.

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### The following 5 animals/sex/group we re 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, 6 8, 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 m otor 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 w ere housed in groups of 5 animals/sex/cage in Macrolon plastic cages (MIV type, height 18 cm). Mating Females w ere caged together with males on a one - to - one - basis in Macrolon plastic cages (MIII type, height 18 cm). Post - mating Males w ere housed in their home cage ( Macrolon plastic cages, MIV type, height 18 cm) with a maximum of 5 animals/cage. Females w ere individually housed in Ma crolon plastic cages (MIII type, height 18 cm). Lactation Pups w ere 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 b ottles 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) w ere 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 w ere placed on a magnetic stirrer during dosing. Dose volume 5 mL/kg body weight. Actual dose volumes w ere 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 necro psy) . Female no. 47 (Group 1 ) w as not dosed during littering. 6.5.2. Pups Pups w ere 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 t he treatment period this w as also performed outside the home cage in a standard arena. The time of onset, grade and duration of any observed sign w as recorded. Signs w ere graded for severity and the maximum grade w as predefined at 3 or 4. Grades w ere 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) w as scored. In the data tables, the scored grades w ere reported, as well as the percentage of animals affected in summary tables. Functional Observations The following tests w ere 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 we re 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 w ere teste d 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 w ere weighed on the first day of exposure and weekly thereafter. Mated females w ere 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 we re housed together for mating and for females without evidence of mating. Food consumption of mated females w as measured on Days 0, 4, 7, 11, 14, 17 and 20 pos tcoitum 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 w as exa mined to determine the following, if practically possible: Mortality / Viability The numbers of live and dead pups on Day 1 of lactation and daily thereafter w ere determined. If possible, defects or cause of death w ere evaluated. Clinical signs At least once daily, detailed clinical observations w ere made for all animals. Body weights Live pups w ere weighed on Days 1 and 4 of lactation. Sex Sex w as 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 w ere deprived of food overnight (with a maximum of 24 hours) before blood sampling, but water w as available . Blood samples w ere drawn from the retro - orbital sinus and collected into tubes ( Greiner Bio - One GmbH, Kremsmünster, Austria ) prepared with K 3 

### - EDTA for haematologic al 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) w as collected into serum tubes for determination of bile acids. The following parameters w ere determined: 6.7.1. Haematology The following haematology parameters were determined in blood prepared with K 3 

### - EDTA as an anti coagulant, using the ADVIA ® 120 Hematology System ( Siemens Healthcare Diagnostics B.V., Breda, The Netherlands) :

Parameter (Abbreviation) Unit White blood cells (WBC) 10 9 

### /L Differential leucocyte count: Neutrophils %WBC Lymphocytes %WBC Monocytes %WBC Eosinophils %WBC Basophils %WBC Red blood cells 10 12 

### /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 10 9 

### /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, e x cept for bile acids which w ere determined in seru m:

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 w ere 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 w as conducted on the following days: Condition Day of necropsy Females which deliver ed Lactation Days 5 - 7. Females which fail ed to deliver (nos. 46, 59, 61, 62, 79 ) Post - coitum Days 25 - 27 (females with evidence of mating) Males Following completion of th e mating period (a minimum of 28 days of dose administration). The number s of former implantation sites and corpora lutea w ere recorded for all paired females.

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### Samples of the following tissues and organs w ere 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 fail ed to deliver 2 

### : 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.

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### 6.8.2. Necropsy pups Pups surviving to planned termination w ere killed by decapitation on Days 5 - 7 of lactation. All pups w ere sexed and descriptions of all external abnormalities w ere recorded. 6.8.3. Organ weights Terminal body weight w ere 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 Prostate 1 

### Liver Seminal vesicles including coagulating glands 1 

### 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 ), w ere processed, embedded and cut at a thickness of 2 - 4 micrometers and stained with haematoxylin and eosin (Klinip ath, 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 w ere prepared to examine staging of spermatogenesis. The testes w ere processed, sectioned at 3 - 4 micrometers, and stained with PAS/haematoxylin (Klinipath, Duiven, The Netherlands). 6.8.5. Histopathology T he following slides w ere 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 include d the cervix, clitoral gland, coagulation gland, epididymides,

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

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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/m easurements in the study w ere 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): Haematolo gy.

- 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.

- Shimad zu TOC - Control V version 2.10 (Shimadzu, Kyoto, Japan): Carbon analysis of formulations . T wo 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 w ere performed: M ating 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

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### 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 w ere used to analy z e the data:

- If the variables could be assumed to follow a normal distribution, the Dunnett -t est ( Ref. 2 ; many - to one 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 , s ince 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 formulat ions (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 Shimad zu 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 deviatio ns 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.

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### 7. RESULTS 7.1. Analysis of d ose p reparations 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 s igns 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 ran ge 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 w eights 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 c onsumption Food consumption before or after allowance for body weight was similar between treated and control anim als.

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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 th is 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 b iochemistry Clinical biochemistry parameters of treated rats were considered not to have been affected by treatment up to 1000 mg/kg. 7.2.8. Macroscopic e xamination 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 dose related 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 singl e occurrence, it was not considered toxicologically significant. 7.2.9. Organ w eights 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 1 00 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 e xamination 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 recor ded, were within the normal range of background pathology encountered in Wistar (Han) rats of this age. In each g roup one or two females were not pregnant. No treatment - related findings were recorded in the reproductive organs of those females and their matching males.

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### The spermatogenic staging profiles were normal for all males examined. For further details, see APPENDIX 4 . 7.3. Reproduction/ d evelopmental 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 ind ices , 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 n umbers 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/ m aternal 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 cannibalis ed. 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 consist ed 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.

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### 8. DISCUSSION AND CONCL USION 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 (f or 41 - 47 d ays). Formula tion 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 we re 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 a drenal glands was noted. 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. 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 f or 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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### 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).

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### APPENDIX 1 SUMMARY TABLES05Nov13 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. . . . . .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 .

.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 MEAN 1 3030 4072 3711 2788 ST.DEV 1041 893 1003 507 N 5 5 5 5 Ambulations MEAN 1 595 951 * 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 12Counts

Interval (5 min.) Total Movements Males 2 

### 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 12Counts

Interval (5 min.) Ambulations Males 2 

### Group 1 Group 2 Group 3 Group 4CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 503342

APPENDIX 1 1.3 MOTOR ACTIVITY TEST SUMMARY FEMALES AT LACTATION GROUP 1 CONTROL MEAN 1 3608 3515 3992 3789 ST.DEV 1042 711 776 820 N 5 5 5 5 Ambulations MEAN 1 789 743 752 835 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 12Counts

Interval (5 min.) Total Movements Females 2 

### 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 12Counts

Interval (5 min.) Ambulations Females 2 

### Group 1 Group 2 Group 3 Group 405Nov13 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 .

.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 .

.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 .

.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 .

.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 .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 .

.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 .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 .

.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 .

.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 .

.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 .

.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 .

.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 .

.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 .

.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 .

.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 .

.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 .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 .02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .

.02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .

.02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .

.02Dec13 08h02

*/** Dunnett-test based on pooled variance significant at 5% (*) or 1% (**) level CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .

.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) * 10005Nov13 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 .07Nov13 07h53

+/++ Steel-test significant at 5% (+) or 1% (++) level CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .

.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 .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 .

.

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

### APPENDIX 2 INDIVIDUAL TABLES05Nov13 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 .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 .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 .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 .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 .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 .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 .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 .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)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)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)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)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 .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 .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 .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 .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 .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 .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 .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 .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 .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 .13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 11.513Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .13Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 9.113Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 129913Mar14 11h44

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 .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 1.7705Nov13 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 .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 2.2905Nov13 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 2.7605Nov13 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 .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 .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 .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 1.09302Dec13 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 --- .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 --- .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 0.30402Dec13 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 --- .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 --- .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 .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 .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 .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 .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 .07Nov13 07h54

CASTOR OIL, SULFATED, SODIUM SALT, 75% Project 50334 2 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 sites05Nov13 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 .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 .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 .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 .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 .

.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 .

.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 .

.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 .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 .

.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 .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 .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 .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 .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 .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 .

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

### 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 μ mol/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

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

### APPENDIX 3 PHASE REPORT FORMULATION ANALYSI S

### 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 METHOD S .......................................................................................................... 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

### 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 formula tions of Group 2 and Group 4 were homogeneous (i.e. coefficient of variation ≤ 10%).

### 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 produ ct(s). 5. MATERIALS AND METHOD S 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 formu lations.

### 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 TO C-V cph 

### 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 s tock 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:

- Shimad zu TOC - Control V version 2.10 (Shimadzu, Kyoto, Japan): Carbon an alysis. 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) .

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 7 - 5.4.1. Formulas T he concentration test substance was calculated based on the purity determined in project 50333 5 [i.e. 74.4%] . Th is information was not available when the targ et concentrations were calculated. The target concentrations were based on the purity supplied by the sponsor [i.e. 7 0.7 %] . Response (R) mean concentration organic carbon in solution [mg C /l] Analysed concentration (C A 

### ) 

## /g][mg 100 %purity w V d %C 100 RC

A 

## ××××= where: %C = organic carbon content of the test substance [i.e. 54.48%, determined in P roject 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 P roject 503335] Recovery 

## [%] 100 C C N

A 

## × where: C N 

### = nominal concentration [mg/g] Accuracy 

## [%] 100 C C T

A 

## × where: C T 

### = target concentration [mg/g] Relative difference (relative diff.) 

## [%] 100 C CC 0 0t 

## ×

− where: C t 

### = mean concentration of stored samples [mg/g] C 0 

### = 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%.

### 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%).

### 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.

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

### APPENDIX 4 PHASE REPORT HISTOPATHOLOGY

### 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

### 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 p ups 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 in crease 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.

### 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 r ecorded. 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 glands mandibular and sublingual], sciatic nerve(1), seminal vesicles (2) with

### 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 mi croscopic findings were recorded by the undersigned pathologist using on -line input under pathology number: 31316LAA.

### 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 a re 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 Micros copic 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.

### 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 recor ded 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 incr ease 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 .

### 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 backgroun d 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.

### 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

### 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

————————

—————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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 — — —

——————————

———————————————————————————————————————————————————————————————

### 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 V6.2d 1

————————————————————————————————————————————————————————————————————————— 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

—————————————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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

———————————————————————————————————————————————————————————————————————— —

### 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

—————————————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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 —

—————————————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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

—————————————————————————————————————————————————————————————————————————

### 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 — — — — — ' ' ' ' '

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

### 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. . .

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

### 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 — — — — — ' ' ' ' '

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

### 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 ' — — — — ' —

' ' '

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

### 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. ' — — — — ' —

' ' '

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

### 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 ' — — — — ' —

' ' '

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

### 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.

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

### 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. . . .

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

### 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.

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

### PATHOLOGY REPORT PAGE : 33/ 91

INDIVIDUAL ANIMAL DATA TOX : 503342

————————————————————————————————————————————————————————————————————————— TEST ITEM : Castor Oil, Sulfated, Sodium Salt PATHOL. NO.: 31316 LA A 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.

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

### 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 — — — — — ' ' ' ' '

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

### 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.

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

### 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 — — — — — ' ' ' ' '

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

### 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 ' ' — ' — —

' —

' —

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

### 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.

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

### 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 ' ' — ' — —

' —

' —

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

### 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 1 6 — 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

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

### 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.

### 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.

—————————————————————————————————————————————————————————————————————————

### 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.

### 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

### 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.

### 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.

### 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

### 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 2 8 — 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.

### 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).

—————————————————————————————————————————————————————————————————————————

### 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.

### 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

### 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 T HYMUS:

— 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.

—————————————————————————————————————————————————————————————————————————

### 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.

### 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

### 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.

### 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

### 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 —

—————————————————————————————————————————————————————————————————————————

### 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 — O CT — 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

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

### 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

### 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

### 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.

### 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).

—————————————————————————————————————————————————————————————————————————

### 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 ABNORMALITIE S

— OVIDUCTS, ADRENAL GLANDS.

————————————————————————————————————————————————————————————————————————— * STATE AT NECROPSY: K0 DAYS ON TEST : 43 * ANIMAL NO. : 52

......................................................................... * NECROPSY FINDINGS NO NECROPSY OBSERVATIONS NOTED.

### 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.

—————————————————————————————————————————————————————————————————————————

### 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 —

—————————————————————————————————————————————————————————————————————————

### 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

......................................................................... 2 1 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 — NO V — 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

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

### 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.

—————————————————————————————————————————————————————————————————————————

### 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).

—————————————————————————————————————————————————————————————————————————

### 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.

—————————————————————————————————————————————————————————————————————————

### 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.

### 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

### 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 — d ay, 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 —

—————————————————————————————————————————————————————————————————————————

### 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

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

### 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 H EART:

— 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.

### 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

### 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.

—————————————————————————————————————————————————————————————————————————

### 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.

### 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

### PATHOLOGY REPORT PAGE : 79/ 9 1

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.

————————————————————————————————————————————————————————————————————— ————

### 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

### 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.

### 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).

—————————————————————————————————————————————————————————————————————————

### 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

### 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

### 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.

—————————————————————————————————————————————————————————————————————————

### 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:

— H emopoietic 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.

### 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.

—————————————————————————————————————————————————————————————————————————

### 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.

### 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.

—————————————————————————————————————————————————————————————————————————

### 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.

### PATHOLOGY REPORT PAGE : 91/ 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. : 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.

————————————————— ————————————————————————————————————————————————————————

— ALL OTHER ANIMALS IN DOSE GROUP WITHOUT PATHOLOGICAL FINDINGS —

—————————————————————————————————————————————————————————————————————————

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

### APPENDIX 5 CERTIFICATE OF ANALYSIS

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342 APPENDIX 5

- Page 2 -

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342

- Page 1 - 

### APPENDIX 6 SUMMARY OF DOSE RANGE FINDING STUDY

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342 APPENDIX 6

- Page 2 - 

## 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 stu dy 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 bo dy weight, kidney and liver weight. List of protocol deviations 1 . Temporary d eviations from the maximum le vel of relative humidity occurred. Evaluation: Laboratory historical data do not indicate an effect of the deviations. 2 . During clinical observati ons on Day 7 , the actual time instead of the nominal time of 0 7 .00 hrs was used f or the 0 hour observatio n . 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 deviati ons.

### Castor Oil, Sulfated, Sodium Salt, 75% Project 503342 APPENDIX 6

- Page 3 - 

### 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 stu dy.