Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 203-212-3 | CAS number: 104-54-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Feb 2020 to Jul 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- 2008
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Cinnamyl alcohol
- EC Number:
- 203-212-3
- EC Name:
- Cinnamyl alcohol
- Cas Number:
- 104-54-1
- Molecular formula:
- C9H10O
- IUPAC Name:
- 3-phenylpropan-1-ol
- Test material form:
- solid
- Details on test material:
- Name: Cinnamyl Alcohol
CAS No. 104-54-1
IUPAC Name: 3-Phenyl-2-propen-1-ol
Molecular Formula: C9-H10-O
Molecular Weight: 134.177 g/mol
SMILES: OC\C=C\c1ccccc1
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Rats are the standard laboratory rodent species used as a reliable test model to assess the Toxicity of the test item and recommended by the guidelines The strain Wistar was chosen on account of available historical data.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Sipra Labs Limited, Plot No.13, IDA, Balanagar, Hyderabad, India.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6-7 Weeks
- Weight at study initiation:
Male: 128.1g -136.9 g
Female: 125.7 g -134.4 g
- Fasting period before study: No Data Available
- Housing: Animals were housed in an autoclaved polycarbonate cages with stainless steel top grill having facilities for holding pellet feed and drinking water in polycarbonate bottle. Autoclaved corn cob was used as bedding material and it was changed at least once in a week.
- Diet (e.g. ad libitum): Rodent feed from a certified vendor was provided as ad libitum.
- Water (e.g. ad libitum): Aquaguard purified water was provided ad libitum by a water dispensing bottle.
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1°C – 23.4°C.
- Humidity (%): 51 – 61 %.
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle per day
IN-LIFE DATES: From: To: No Data Available
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- Distilled water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test chemical was weighed in pre-weighed glass beakers on an appropriate weighing balance. The test chemical was transferred to mortar and triturated with pestle. 10 mL of the vehicle was added to mortar and again triturated. This was transferred to a measuring cylinder. Sufficient quantity of vehicle was added to make up the required volume of formulation. This was transferred back to beaker. Homogeneity of the test chemical in the vehicle was maintained during administration using a magnetic stirrer.
DIET PREPARATION
- Rate of preparation of diet (frequency): No Data Available
- Mixing appropriate amounts with (Type of food): No Data Available
- Storage temperature of food: No Data Available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water was used as a vehicle.
- Concentration in vehicle: 0 mg/ml, 25 mg/ml, 50 mg/ml and 100 mg/ml for control, low dose, mid dose and high dose groups, respectively.
- Amount of vehicle (if gavage): 10 ml/kg
- Lot/batch no. (if required): No Data Available
- Purity: No Data Available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability of dose formulation was checked before treatment start day at 0 and 6 hours. Test item was checked for its stability in the dose formulation with samples collected immediately (0 hours) and 6 hours post dose formulation preparation. Samples of the dose formulations were taken immediately after dilution of the concentrates with the diluents (vehicle) on treatment start date and treatment end date for homogeneity (mean of homogeneity was given as dose concentration) analyses. On week 3, samples of all dose formulations were taken for dose concentration analysis.
Linearity: Linearity was carried out by injecting a minimum of 5 different test concentrations (three replications from each concentration).The correlation coefficient and regression was calculated (r=0.9982).
Accuracy: Accuracy was performed at three levels ie., 50, 100, 150%. The mean recovery values of samples for 50% level is 102.35% , for 100% level is 100.18% and for 150% level is 97.14%.
Precision: The relative standard deviation of analysis of five independent fortifications samples were not exceed ±20% of the mean value.
Specificity: No interference was observed above 30 % of total peak area for target analyte.
The dose concentration verification was carried out for test item fortified in Distilled water pertaining to low dose (25mg/mL), mid dose (50mg/mL) and high dose (100mg/mL). The recovery of test item in the prepared dose formulation was within the guideline specification.
The test item was found to be homogeneously dispersed in Distilled water, which was evinced from the recovery of test item from different layers (Top, middle and bottom layers of Distilled water). - Duration of treatment / exposure:
- 28 days consecutively.
- Frequency of treatment:
- Once Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Control Group (G1)
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- Control Group (Recovery) (G1R)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Remarks:
- Low Dose Group (G2)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Remarks:
- Intermediate Dose Group (G3)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- High Dose Group (G4)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- High Dose Group (Recovery) (G4R)
- No. of animals per sex per dose:
- 5 animals per sex per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The doses for the study were selected based on the dose range finding study.
- Rationale for animal assignment (if not random): Animals were selected and grouped based on stratified randomization by using body weights taken before start of treatment. Computerized statistical analysis was used for randomization.
- Fasting period before blood sampling for clinical biochemistry: Yes, the animals were fasted before the blood sampling.
- Rationale for selecting satellite groups: Recovery groups for vehicle control and high dose were included to know the reversibility of treatment related effects.
- Post-exposure recovery period in satellite groups: 2 weeks
- Section schedule rationale (if not random): No Data Available
- Other: No Data Available - Positive control:
- None
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily on first 3 days of treatment; once daily thereafter
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once prior to the first exposure and weekly thereafter.
BODY WEIGHT: Yes
- Time schedule for examinations: Once weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, Once weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: During week 4
- Dose groups that were examined: All dose groups were examined.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Week 4 for main groups and Week 6 for recovery group
- Anaesthetic used for blood collection: Yes (isofluorane)
- Animals fasted: Yes
- How many animals: All animals were fasted.
The following hematology parameters were determined:
Erythrocyte count (RBC)
Hemoglobin (Hb)
Hematocrit (PCV)
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin (MCH)
Mean corpuscular hemoglobin concentration
(MCHC)
Platelet (thrombocyte) count (PLT)
Total leukocyte count (WBC)
Differential leukocyte count (DC)
Prothrombin time (PT)
Activated Partial Thromboplastin time (APTT)
Reticulocyte count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Week 4 for main groups and Week 6 for recovery group
- Animals fasted: Yes
The following clinical biochemistry parameters were determined:
Glucose
Urea
Creatinine
Cholesterol, total
Triglycerides
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
Alkaline phosphatase (ALP)
γ-glutamyl transferase
Bilirubin
Sodium (Na)
Potassium (K)
Chloride (Cl)
Protein, total
Albumin
Globulin
A G ratio
URINALYSIS: Yes
- Time schedule for collection of urine: Week 4 for main groups and Week 6 for recovery group
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
The following urinalysis parameters were determined: Volume, specific gravity, colour, clarity, pH, urobilinogen, bilirubin, ketone bodies, proteins and glucose. Urine analysis was done using Test Strips with urine analyzer.
Microscopic examination of urine was done for epithelial cells, pus cells, RBC, cast and crystals.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Before sacrifice
- Dose groups that were examined: All the dose groups
- Battery of functions tested: sensory activity / grip strength / motor activity / - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, All animals in main study (Group 1 to Group 4) was sacrificed at the end of week 4 and animals in recovery group (Group 1R and Group 4R) were sacrificed at the end of week 6 of experimental period by Carbon dioxide asphyxiation. All animals were weighed and sent to necropsy.
Samples of the following tissues and organs were collected from Allocation A & B Animals at necropsy and fixed in 10% Neutral Buffered Formalin solution (NBF) except testes and eyes, which were fixed in Modified Davidson’s fixative for 24 hours and then transferred to NBF. Adrenal glands, Aorta, Bone marrow (Sternum), Brain (3 levels), Cecum Cervix, Colon, Duodenum, Epididymides, Eye, Heart, Ileum, with Peyer's patches Jejunum, Kidneys, Liver, Lungs (inflated with NBF at necropsy), Lymph nodes (mesenteric, axillary), Oesophagus, Ovaries, Pancreas, Rectum, Prostate + Seminal vesical with coagulating glands, Pituitary, Sciatic nerve, Skeletal muscle, Spinal cord (cervical, mid-thoracic, lumbar), Spleen, Stomach, Testes, Thymus, Thyroid, Trachea, Urinary bladder (inflated with NBF at necropsy), Uterus, Vagina, All Gross lesions
The following organs were weighed and recorded on the scheduled dates of necropsy. Wet weight was taken after dissection to avoid drying.
Brain Spleen Thymus Epididymides
Heart Kidneys Testes Ovaries
Liver Adrenals Uterus
Prostate + Seminal vesical with coagulating glands
HISTOPATHOLOGY: Yes, full histopathology was performed on the preserved organs and tissues of all animals in the control and high dose groups. Histopathology examination was extended to the organs such as liver, testes and epididymides in low dose and intermediate dose group. - Statistics:
- The following statistical methods were used to analyze the body weight, feed consumption, organ weights as well as clinical pathology data.
• Data was summarized in tabular form. Statistical analysis was performed using SAS/STAT® Software (Version 9.3).
• All the data were analysed for homogeneity using Levene’s test
• The difference between the means was analyzed using Dunnet’s t- test
• Significant differences between control and treated groups analyzed using one-way ANOVA statistics
• Values were summarized as mean ± standard deviation (SD)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs of toxicity were observed in the study.
- Mortality:
- no mortality observed
- Description (incidence):
- All animals survived to scheduled sacrifice.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No significant changes in body weight or body weight gain were observed.
For tabular data, please refer to Table 1-2 below. - Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No significant changes in food intake were observed. For tabular data, please refer to pp. 27-30 in the attached report).
- Food efficiency:
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- No eye abnormalities were observed in the study.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Treatment with cinnamyl alcohol had no effect on both male and female animals with respect to haematological parameters viz RBC, Hb, MCV, MCHC, PCV, PLT, PT and APTT when compared with control group. However, in males, WBC count was decreased in the high dose (G4) group, when compared with control group, was observed and in females, WBC values were comparable with control. This significance may not be attributed to treatment since all the haematological values fall within the normal biological range and no biological significance was noted.
For tabular data, please refer to Table 3 and 4 below. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Clinical biochemistry parameters revealed no significant changes in the test item treated and recovery males and female animals with an exception of Bilirubin, ALT, Total proteins, ALB, GLB and Cholesterol in males, glucose, creatinine, Bilirubin, triglycerides in females of treatment groups. There was no dose-related effect on any of the biochemical parameters. In males, when compared with control group, bilirubin levels increased in low dose group (G2), ALT levels decreased in high dose (G4), total protein levels decreased in low dose (G2) and intermediate dose (G3) compared to control, albumin levels increased in low (G2), intermediate and high dose, Globulin levels decreased in low dose (G2), intermediate (G3) and high dose (G4), cholesterol levels increased in low dose (G2) and high dose (G4). In females, when compared with control group, creatinine levels decreased in intermediate dose group (G3), bilirubin levels decreased in high dose (G4), triglyceride levels increased in intermediate dose (G3). All the recovery group male and female animals showed no effect on biochemical parameters. This change in the biochemical parameters is considered to have arisen by chance or caused by slightly higher/lower control values and not to represent a change of any biological significance.
For tabular data, please refer to Table 5 and 6 below. - Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No significant changes in urinalysis were observed in the study.
For tabular data, please refer to pp. 65-67 in the attached report. - Behaviour (functional findings):
- no effects observed
- Description (incidence and severity):
- No significant changes in the functional observatory battery were observed. For tabular data, please refer to pp. 49-54 in the attached report.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- No significant changes in absolute or relative organ weight were observed.
For tabular data, please refer to Table 7-10 below. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No gross findings were observed in the study.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Observed microscopic lesions in G1 and G4 occured at comparable incidences and were considered to be common background findings in Wistar rats.
For tabular data, please refer to Table 11 below. - Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- clinical signs
- food consumption and compound intake
- gross pathology
- haematology
- histopathology: non-neoplastic
- mortality
- ophthalmological examination
- organ weights and organ / body weight ratios
- urinalysis
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1. BODY WEIGHTS (G) – SUMMARY MALES
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 1 | Mean | 130.6 | 132.2 | 133.3 | 132.0 |
SD | 1.63 | 2.00 | 2.48 | 2.85 | |
Min | 128.4 | 130.7 | 130.9 | 128.3 | |
Max | 131.7 | 135.4 | 136.8 | 136.3 | |
N | 5 | 5 | 5 | 5 | |
Day 8 | Mean | 146.9 | 148.5 | 148.5 | 148.3 |
SD | 2.20 | 2.75 | 1.50 | 3.33 | |
Min | 144.3 | 147.0 | 146.7 | 143.3 | |
Max | 148.8 | 153.4 | 150.8 | 152.4 | |
N | 5 | 5 | 5 | 5 | |
Day 15 | Mean | 161.7 | 163.8 | 163.9 | 163.9 |
SD | 1.38 | 3.51 | 1.29 | 2.96 | |
Min | 159.9 | 161.4 | 162.1 | 159.2 | |
Max | 163.3 | 169.9 | 165.4 | 167.2 | |
N | 5 | 5 | 5 | 5 |
Table 1.BODY WEIGHTS (G) – SUMMARY (CONTD.) MALES
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 22 | Mean | 176.8 | 178.2 | 179.2 | 179.1 |
SD | 1.48 | 3.29 | 1.98 | 3.12 | |
Min | 175.1 | 175.9 | 176.7 | 174.0 | |
Max | 178.8 | 184.0 | 181.5 | 182.4 | |
N | 5 | 5 | 5 | 5 | |
Day 28 | Mean | 190.2 | 190.5 | 192.6 | 192.5 |
SD | 1.59 | 2.53 | 2.72 | 3.41 | |
Min | 187.8 | 188.3 | 189.5 | 188.6 | |
Max | 192.1 | 194.6 | 196.0 | 196.1 | |
N | 5 | 5 | 5 | 5 |
Table 2. BODY WEIGHTS (G) – SUMMARY FEMALES
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 1 | Mean | 130.1 | 129.7 | 129.9 | 129.8 |
SD | 2.91 | 2.93 | 2.83 | 2.84 | |
Min | 125.7 | 126.5 | 126.6 | 127.2 | |
Max | 133.4 | 133.7 | 133.7 | 134.4 | |
N | 5 | 5 | 5 | 5 | |
Day 8 | Mean | 145.0 | 145.8 | 146.6 | 145.6 |
SD | 3.30 | 3.76 | 3.09 | 3.62 | |
Min | 140.1 | 141.2 | 143.4 | 141.1 | |
Max | 149.3 | 151.1 | 151.1 | 150.2 | |
N | 5 | 5 | 5 | 5 | |
Day 15 | Mean | 160.2 | 161.4 | 162.7 | 161.4 |
SD | 3.08 | 3.97 | 3.68 | 4.11 | |
Min | 156.4 | 156.3 | 158.6 | 156.8 | |
Max | 164.8 | 167.3 | 167.0 | 166.7 | |
N | 5 | 5 | 5 | 5 |
Table 2. BODY WEIGHTS (G) – SUMMARY (CONTD.) FEMALES
| Group 1 | Group 2 | Group 3 | Group 4 | |
Day 22 | Mean | 175.0 | 175.8 | 177.1 | 175.9 |
SD | 2.69 | 4.10 | 3.98 | 4.27 | |
Min | 171.1 | 170.0 | 173.2 | 171.1 | |
Max | 178.6 | 181.5 | 182.6 | 180.4 | |
N | 5 | 5 | 5 | 5 | |
Day 28 | Mean | 185.9 | 185.8 | 188.0 | 187.1 |
SD | 3.03 | 3.70 | 3.50 | 3.84 | |
Min | 182.7 | 180.6 | 184.8 | 182.6 | |
Max | 190.6 | 190.6 | 193.2 | 191.3 | |
N | 5 | 5 | 5 | 5 |
Table 3. HEMATOLOGY SUMMARY – MALES
Week -04 | |||||||||||||||||
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocyte | ||||||||||
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | |||||||||||
Group 1 | Mean | 8.12 | 14.78 | 45.44 | 56.02 | 32.54 | 32.54 | 1.84 | |||||||||
SD | 0.299 | 0.335 | 1.504 | 2.150 | 0.989 | 0.989 | 0.039 | ||||||||||
Group 2 | Mean | 8.02 | 15.10 | 47.86 | 59.80 | 18.84 | 31.54 | 1.86 | |||||||||
SD | 0.647 | 0.787 | 1.858 | 2.781 | 0.541 | 0.654 | 0.049 | ||||||||||
Group 3 | Mean | 8.41 | 14.50 | 48.92 | 58.22 | 17.26 | 29.78 | 1.87 | |||||||||
SD | 0.441 | 2.190 | 3.044 | 3.072 | 2.543 | 5.094 | 0.049 | ||||||||||
Group 4 | Mean | 8.11 | 15.24 | 47.60 | 58.74 | 18.78 | 32.04 | 1.88 | |||||||||
SD | 0.360 | 0.336 | 2.021 | 1.050 | 0.502 | 0.808 | 0.059 | ||||||||||
| PLT | WBC | DC (%) | PT | APT T | ||||||||||||
X103cel ls/µl | X103c ells/ µl |
Neut |
Lymph |
Mono |
Eos |
Baso |
Sec |
Sec | |||||||||
Group 1 | Mean | 882.80 | 21.54 | 10.60 | 84.00 | 3.60 | 1.80 | 0.00 | 17.20 | 43.00 | |||||||
SD | 94.896 | 2.644 | 2.191 | 2.345 | 0.548 | 0.447 | 0.000 | 1.095 | 3.464 | ||||||||
Group 2 | Mean | 824.80 | 20.54 | 11.20 | 84.60 | 2.80 | 1.40 | 0.00 | 17.20 | 41.80 | |||||||
SD | 106.251 | 4.239 | 2.490 | 3.647 | 0.837 | 0.548 | 0.000 | 1.095 | 1.095 | ||||||||
Group 3 | Mean | 901.60 | 16.06 | 13.40 | 81.60 | 3.20 | 1.80 | 0.00 | 17.20 | 41.40 | |||||||
SD | 155.191 | 6.491 | 4.336 | 6.025 | 1.643 | 0.447 | 0.000 | 1.095 | 1.342 | ||||||||
Group 4 | Mean | 678.50 | 13.78* | 15.80 | 79.60 | 3.20 | 1.40 | 0.00 | 17.20 | 42.80 | |||||||
SD | 327.366 | 2.266 | 5.167 | 3.782 | 0.837 | 0.894 | 0.000 | 1.095 | 1.304 | ||||||||
*Significant at p ≤ 0.05 level with group 1 | |||||||||||||||||
Week -06 |
| ||||||||||||||||
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocyte | ||||||||||
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | |||||||||||
Group 1R | Mean | 8.63 | 15.54 | 49.04 | 56.88 | 31.64 | 31.64 | 1.85 | |||||||||
SD | 0.226 | 0.498 | 1.616 | 2.241 | 0.428 | 0.428 | 0.073 | ||||||||||
Group 4R | Mean | 8.90 | 16.16 | 51.36 | 57.70 | 18.16 | 31.48 | 1.87 | |||||||||
SD | 0.389 | 0.680 | 2.502 | 0.579 | 0.321 | 0.497 | 0.082 | ||||||||||
| PLT | WBC | DC (%) | PT | AP TT | ||||||||||||
x103cells /µL | x103cells / µL | Neut | Lymph | Mono | Eos | Baso | Sec | Sec | |||||||||
Group 1R | Mean |
784.00 |
15.06 |
15.20 |
79.00 |
3.60 |
2.20 |
0.00 | 16.4 0 | 42.2 0 | |||||||
SD |
87.227 |
4.194 |
2.490 |
3.391 |
0.894 |
0.447 |
0.000 | 1.14 0 | 2.77 5 | ||||||||
Group 4R | Mean |
805.40 |
17.12 |
14.20 |
80.40 |
3.40 |
2.00 |
0.00 | 16.8 0 | 42.4 0 | |||||||
SD |
147.025 |
3.432 |
1.643 |
1.140 |
0.548 |
0.000 |
0.000 | 1.09 5 | 2.79 3 |
Table 4. HEMATOLOGY SUMMARY – FEMALES
Week -04 | ||||||||||||||||||||||||||||||||||||||
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocyte | |||||||||||||||||||||||||||||||
x106Cells/µL | g/dL | % | fL | pg | g/dL | % | ||||||||||||||||||||||||||||||||
Group 1 | Mean | 7.67 | 15.40 | 46.22 | 60.30 | 20.10 | 35.34 | 1.84 | ||||||||||||||||||||||||||||||
SD | 0.520 | 0.778 | 2.600 | 1.471 | 0.632 | 4.286 | 0.055 | |||||||||||||||||||||||||||||||
Group 2 | Mean | 7.41 | 14.38 | 43.20 | 58.36 | 19.44 | 33.34 | 1.85 | ||||||||||||||||||||||||||||||
SD | 0.640 | 1.013 | 3.652 | 0.817 | 0.550 | 0.723 | 0.056 | |||||||||||||||||||||||||||||||
Group 3 | Mean | 7.45 | 14.74 | 45.04 | 60.54 | 19.80 | 30.72 | 1.95 | ||||||||||||||||||||||||||||||
SD | 0.382 | 0.351 | 0.921 | 2.454 | 0.570 | 4.803 | 0.099 | |||||||||||||||||||||||||||||||
Group 4 | Mean | 7.24 | 14.50 | 43.30 | 59.90 | 20.06 | 33.48 | 7.24 | ||||||||||||||||||||||||||||||
SD | 0.578 | 0.831 | 2.788 | 1.134 | 0.594 | 0.729 | 0.578 | |||||||||||||||||||||||||||||||
| PLT | WBC | DC (%) | PT | AP TT | |||||||||||||||||||||||||||||||||
X103cel ls/µl | X103cel ls/ µl | Neut | Lymp h | Mono | Eos | Baso | Sec | Sec | ||||||||||||||||||||||||||||||
Group 1 | Mean |
784.20 |
12.44 |
15.80 |
83.00 |
3.20 |
1.40 |
0.00 |
17.20 | 42.6 0 | ||||||||||||||||||||||||||||
SD |
89.926 |
3.197 |
8.871 |
5.431 |
1.095 |
0.548 |
0.000 |
1.095 | 3.71 5 | |||||||||||||||||||||||||||||
Group 2 | Mean |
857.40 |
19.94 |
13.40 |
82.40 |
2.80 |
1.40 |
0.00 |
17.60 | 41.8 0 | ||||||||||||||||||||||||||||
SD |
65.416 |
6.303 |
1.817 |
2.881 |
0.837 |
0.548 |
0.000 |
0.894 | 1.09 5 | |||||||||||||||||||||||||||||
Group 3 | Mean |
883.60 |
15.04 |
12.40 |
83.20 |
2.80 |
1.60 |
0.00 |
16.80 | 41.8 0 | ||||||||||||||||||||||||||||
SD | 138.14 8 |
5.772 |
2.510 |
3.271 |
0.447 |
0.548 |
0.000 |
1.095 | 1.09 5 | |||||||||||||||||||||||||||||
Group 4 | Mean |
863.60 |
12.46 |
12.60 |
83.40 |
2.40 |
1.60 |
0.00 |
17.20 | 42.4 0 |
| |||||||||||||||||||||||||||
SD |
87.048 |
3.446 |
2.881 |
4.336 |
1.140 |
0.548 |
0.000 |
1.095 | 2.51 0 |
| ||||||||||||||||||||||||||||
Week -06 |
| |||||||||||||||||||||||||||||||||||||
| RBC | Hb | PCV | MCV | MCH | MCHC | Reticulocytes |
| ||||||||||||||||||||||||||||||
x106Cells/µL | g/dL | % | fL | pg | g/dL | % |
| |||||||||||||||||||||||||||||||
Group 1R | Mean | 8.20 | 15.48 | 47.76 | 58.32 | 18.92 | 32.44 | 1.87 |
| |||||||||||||||||||||||||||||
SD | 0.425 | 0.585 | 2.089 | 2.203 | 1.083 | 0.820 | 0.036 |
| ||||||||||||||||||||||||||||||
Group 4R | Mean | 8.26 | 15.64 | 48.92 | 59.28 | 18.96 | 32.00 | 1.87 |
| |||||||||||||||||||||||||||||
SD | 0.455 | 0.472 | 2.321 | 1.791 | 0.680 | 0.620 | 0.036 |
| ||||||||||||||||||||||||||||||
| PLT | WBC | DC (%) | PT | AP TT |
| ||||||||||||||||||||||||||||||||
x103cells/ µL | x103cell s/ µL | Neut | Lymph | Mono | Eos | Baso | Sec | Sec |
| |||||||||||||||||||||||||||||
Group 1R | Mean |
783.40 |
15.44 |
12.40 |
82.80 |
3.20 |
1.60 |
0.00 | 16.4 0 | 41. 80 |
| |||||||||||||||||||||||||||
SD |
63.885 |
3.523 |
3.050 |
3.564 |
0.447 | 0.54 8 |
0.000 | 1.14 0 | 3.4 21 |
| ||||||||||||||||||||||||||||
Group 4R | Mean |
867.60 |
13.56 |
11.20 |
84.80 |
2.60 |
1.40 |
0.00 | 16.2 0 | 40. 80 |
| |||||||||||||||||||||||||||
SD |
104.333 |
2.651 |
1.924 |
2.683 |
0.548 | 0.54 8 |
0.000 | 0.83 7 | 3.1 14 |
|
Table 5. CLINICAL BIOCHEMISTRY SUMMARY – MALES
|
GLU |
UREA |
CREA |
BLI |
ALT |
AST |
ALP | TPO | ||||||||||
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | |||||||||||
Group 1 | Mean | 78.80 | 47.60 | 0.70 | 0.07 | 59.20 | 147.80 | 427.00 | 7.52 | |||||||||
SD | 24.160 | 10.550 | 0.000 | 0.012 | 15.627 | 15.450 | 82.592 | 0.342 | ||||||||||
Group 2 | Mean | 77.20 | 46.00 | 0.78 | 0.09! | 55.00 | 162.00 | 308.00 | 6.96! | |||||||||
SD | 8.044 | 12.708 | 0.084 | 0.011 | 7.141 | 26.739 | 155.816 | 0.097 | ||||||||||
Group 3 | Mean | 90.40 | 36.00 | 0.74 | 0.07 | 46.20 | 155.60 | 312.60 | 6.76# | |||||||||
SD | 10.502 | 14.782 | 0.055 | 0.010 | 5.718 | 17.387 | 150.324 | 0.152 | ||||||||||
Group 4 | Mean | 72.80 | 56.60 | 0.74 | 0.08 | 37.40* | 162.20 | 321.00 | 7.14 | |||||||||
SD | 14.822 | 7.057 | 0.055 | 0.008 | 3.507 | 16.858 | 162.691 | 0.404 | ||||||||||
| ||||||||||||||||||
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |||||||||
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||||||||||
Group 1 | Mean | 2.61 | 4.92 | 41.80 | 95.20 | 139.28 | 5.27 | 99.14 | 1.38 | 0.53 | ||||||||
SD | 0.222 | 0.466 | 3.633 | 27.289 | 1.018 | 0.880 | 1.141 | 0.779 | 0.086 | |||||||||
Group 2 | Mean | 3.01! | 3.84! | 57.20! | 70.20 | 140.58 | 4.99 | 100.66 | 2.32 | 0.78 | ||||||||
SD | 0.244 | 0.313 | 8.786 | 6.943 | 0.722 | 0.358 | 1.301 | 1.639 | 0.088 | |||||||||
Group 3 | Mean | 3.12# | 3.64# | 49.40 | 73.80 | 143.90 | 4.89 | 102.60 | 1.58 | 0.86 | ||||||||
SD | 0.175 | 0.207 | 10.644 | 36.602 | 8.514 | 0.977 | 3.574 | 0.383 | 0.092 | |||||||||
Group 4 | Mean | 3.04* | 4.10* | 57.00* | 96.20 | 140.80 | 5.14 | 100.84 | 2.36 | 0.74 | ||||||||
SD | 0.213 | 0.308 | 7.681 | 49.877 | 1.693 | 0.328 | 1.950 | 0.760 | 0.065 | |||||||||
#Significant at p ≥ 0.05 level with group 1,* Significant at p ≥ 0.05 level with group 1 |
Table 5. CLINICAL BIOCHEMISTRY SUMMARY – MALES (CONTD.)
WEEK -06 | ||||||||||
|
GLU |
UREA |
CREA |
BLI |
ALT |
AST |
ALP | TPO | ||
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | |||
Group 1R | Mean | 106.40 | 42.60 | 0.70 | 0.09 | 42.20 | 147.00 | 433.20 | 6.64 | |
SD | 18.229 | 4.615 | 0.000 | 0.018 | 10.010 | 16.000 | 115.818 | 0.251 | ||
Group 4R | Mean | 94.80 | 47.20 | 0.74 | 0.08 | 42.60 | 146.20 | 224.00 | 6.90 | |
SD | 9.524 | 3.114 | 0.055 | 0.015 | 8.081 | 19.992 | 78.026 | 0.187 | ||
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||
Group 1R | Mean | 3.02 | 3.64 | 44.80 | 122.80 | 140.82 | 5.36 | 101.04 | 1.90 | 0.83 |
SD | 0.104 | 0.270 | 13.368 | 43.797 | 0.680 | 0.129 | 2.257 | 1.020 | 0.080 | |
Group 4R | Mean | 2.96 | 3.94 | 57.80 | 109.80 | 140.90 | 5.05 | 103.02 | 1.58 | 0.75 |
SD | 0.148 | 0.207 | 10.640 | 37.930 | 0.721 | 0.516 | 1.514 | 0.988 | 0.066 |
Table 6. CLINICAL BIOCHEMISTRY SUMMARY – FEMALES
WEEK -04 | |||||||||||||||||
|
GLU |
UREA |
CREA |
BLI |
ALT |
AST |
ALP | TPO | |||||||||
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | ||||||||||
Group 1 | Mean | 88.20 | 50.20 | 0.84 | 0.12 | 41.00 | 145.60 | 190.40 | 7.00 | ||||||||
SD | 9.121 | 3.962 | 0.055 | 0.035 | 5.385 | 16.920 | 70.769 | 0.224 | |||||||||
Group 2 | Mean | 78.40 | 43.00 | 0.80 | 0.11 | 44.80 | 153.60 | 221.80 | 7.36 | ||||||||
SD | 6.804 | 9.539 | 0.000 | 0.023 | 2.280 | 10.431 | 98.609 | 0.428 | |||||||||
Group 3 | Mean | 75.40 | 53.00 | 0.74# | 0.09 | 53.80 | 152.00 | 284.40 | 7.24 | ||||||||
SD | 18.447 | 11.726 | 0.055 | 0.027 | 13.936 | 18.069 | 97.999 | 0.089 | |||||||||
Group 4 | Mean | 114.60! | 59.00 | 0.82 | 0.07* | 33.60 | 165.60 | 182.00 | 7.02 | ||||||||
SD | 7.701 | 5.431 | 0.045 | 0.007 | 8.849 | 10.574 | 47.911 | 0.319 | |||||||||
| |||||||||||||||||
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | ||||||||
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | |||||||||
Group 1 | Mean | 3.18 | 3.82 | 48.58 | 63.40 | 139.10 | 4.58 | 100.48 | 2.12 | 0.83 | |||||||
SD | 0.114 | 0.277 | 24.039 | 15.258 | 0.308 | 0.160 | 0.986 | 0.915 | 0.086 | ||||||||
Group 2 | Mean | 3.01 | 4.36 | 62.80 | 82.20 | 151.72 | 4.83 | 102.18 | 1.64 | 0.70 | |||||||
SD | 0.214 | 0.550 | 13.535 | 20.389 | 26.888 | 0.065 | 0.680 | 0.835 | 0.127 | ||||||||
Group 3 | Mean | 3.09 | 4.16 | 62.60 | 121.60# | 139.52 | 5.25 | 101.14 | 1.96 | 0.74 | |||||||
SD | 0.203 | 0.288 | 14.363 | 54.998 | 1.165 | 0.946 | 1.665 | 0.971 | 0.099 | ||||||||
Group 4 | Mean | 3.03 | 3.98 | 60.40 | 70.60 | 140.62 | 4.70 | 102.32 | 1.30 | 0.76 | |||||||
SD | 0.112 | 0.396 | 7.021 | 32.708 | 1.411 | 0.136 | 1.399 | 1.356 | 0.095 | ||||||||
!#* Significant at p ≤0.05 level with group 1 |
Table 6. CLINICAL BIOCHEMISTRY SUMMARY – FEMALES (CONTD.)
WEEK -06 |
|
|
|
|
|
|
|
| ||
|
GLU |
UREA |
CREA |
BLI |
ALT |
AST |
ALP | TPO | ||
mmol /L | mmol /L | µmol /L | µmol /L | U/L | U/L | U/L | g/L | |||
Group 1R | Mean | 84.00 | 47.40 | 0.82 | 0.11 | 43.40 | 156.20 | 232.00 | 7.18 | |
SD | 6.519 | 7.701 | 0.045 | 0.023 | 2.302 | 13.882 | 101.993 | 0.295 | ||
Group 4R | Mean | 109.40 | 51.60 | 0.86 | 0.09 | 35.00 | 154.80 | 180.00 | 7.40 | |
SD | 15.043 | 9.072 | 0.055 | 0.008 | 5.244 | 12.194 | 30.927 | 0.367 | ||
| ALB | GLB | CHOL | TRIGL | Na | K | Cl | GGT | A/G | |
g/L | g/L | mmol /L | mmol /L | mmol /L | mmol /L | mmol /L | U/L | _ | ||
Group 1R | Mean | 3.21 | 3.98 | 61.00 | 68.00 | 140.00 | 4.90 | 102.38 | 2.58 | 0.81 |
SD | 0.067 | 0.268 | 4.528 | 28.169 | 0.791 | 0.174 | 1.057 | 0.460 | 0.050 | |
Group 4R | Mean | 3.47 | 3.94 | 62.00 | 73.20 | 140.08 | 4.83 | 102.52 | 1.74 | 0.88 |
SD | 0.185 | 0.371 | 7.583 | 23.091 | 1.092 | 0.319 | 0.726 | 1.680 | 0.102 |
Table 7. ORGAN WEIGHTS (GRAM) – SUMMARY MALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 188.0 | 187.8 | 190.0 | 190.0 | 225.5 | 226.6 |
SD | 1.98 | 1.75 | 2.94 | 2.94 | 2.64 | 2.25 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain | Mean | 1.5430 | 1.7382 | 1.7330 | 1.4304 | 1.7530 | 1.6732 |
SD | 0.04971 | 0.06478 | 0.15706 | 0.47356 | 0.22155 | 0.05758 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.8344 | 0.9568 | 0.9258 | 0.8464 | 1.1662 | 0.9258 |
SD | 0.17248 | 0.15895 | 0.20795 | 0.08252 | 0.14443 | 0.18871 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 8.1652 | 8.7424 | 8.7168 | 8.0322 | 11.8724 | 8.4078 |
SD | 1.15197 | 1.56685 | 1.48162 | 0.57004 | 3.58843 | 1.77379 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 1.0728 | 1.2652 | 0.9974 | 0.8522 | 1.0582 | 2.0620 |
SD | 0.08228 | 0.30047 | 0.30545 | 0.12619 | 0.08389 | 2.57129 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Kidneys | Mean | 1.5832 | 1.5464 | 1.6710 | 1.4906 | 2.0448 | 1.6392 |
SD | 0.18549 | 0.17077 | 0.38220 | 0.10094 | 0.26631 | 0.30563 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 7. ORGAN WEIGHTS (GRAM) – SUMMARY MALES (CONTD.)
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Adrenals | Mean | 0.0566 | 0.0776 | 0.0672 | 0.0544 | 0.0482 | 0.0668 |
SD | 0.02176 | 0.02492 | 0.02007 | 0.00777 | 0.00712 | 0.00705 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Testes | Mean | 2.0332 | 0.7208 | 2.4070 | 2.0160 | 2.6044 | 2.5612 |
SD | 1.05259 | 0.93357 | 0.36166 | 0.89828 | 0.12315 | 0.29673 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Epididymes | Mean | 0.3388 | 0.3450 | 0.3526 | 0.4338 | 0.6208 | 0.3088 |
SD | 0.09377 | 0.04554 | 0.08898 | 0.09132 | 0.43014 | 0.11852 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.9638 | 1.2862 | 1.2254 | 1.0340 | 1.3868 | 1.0706 |
SD | 0.36533 | 1.02182 | 0.61066 | 0.15234 | 0.39887 | 0.46435 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Pro + Sem. Vesical with Coagulating glands | Mean | 1.1048 | 1.0556 | 1.2926 | 0.9480 | 1.2198 | 1.3300 |
SD | 0.44539 | 0.54158 | 0.37314 | 0.49306 | 0.63471 | 0.40374 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 8. ORGAN WEIGHTS (GRAM) – SUMMARY FEMALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 183.6 | 183.6 | 185.9 | 184.7 | 222.7 | 227.2 |
SD | 3.08 | 3.53 | 3.75 | 3.86 | 2.60 | 2.61 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain | Mean | 1.6490 | 1.6490 | 1.6518 | 1.7262 | 1.6706 | 1.7658 |
SD | 0.28800 | 0.10695 | 0.09125 | 0.04262 | 0.12188 | 0.08867 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.7794 | 0.7518 | 0.8738 | 0.7846 | 0.7848 | 0.7976 |
SD | 0.08175 | 0.09130 | 0.47131 | 0.03816 | 0.14482 | 0.09502 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 7.4798 | 6.9852 | 6.7412 | 6.4838 | 6.4204 | 6.8684 |
SD | 0.63619 | 0.49866 | 0.81772 | 0.57539 | 0.28058 | 1.25711 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 0.9762 | 1.0416 | 0.9322 | 0.8784 | 0.8114 | 0.7872 |
SD | 0.18277 | 0.19668 | 0.07474 | 0.22041 | 0.07522 | 0.15867 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Kidneys | Mean | 1.4362 | 1.3130 | 1.3230 | 1.2294 | 1.3412 | 1.4292 |
SD | 0.09410 | 0.12204 | 0.18534 | 0.07887 | 0.16524 | 0.17327 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 8. ORGAN WEIGHTS (GRAM) – SUMMARY FEMALES (CONTD.)
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Adrenals | Mean | 0.0626 | 0.0768 | 0.0712 | 0.0692 | 0.0906 | 0.0778 |
SD | 0.01337 | 0.03611 | 0.01686 | 0.01585 | 0.05127 | 0.01457 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Ovaries | Mean | 0.7036 | 0.6836 | 0.2088 | 0.1798 | 0.2632 | 0.3420 |
SD | 1.03313 | 0.91919 | 0.07944 | 0.06956 | 0.13995 | 0.44364 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Uterus | Mean | 0.4514 | 0.5074 | 0.2090 | 0.3390 | 0.3394 | 0.3248 |
SD | 0.11485 | 0.53257 | 0.08184 | 0.08909 | 0.27956 | 0.16199 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.4582 | 0.5594 | 0.4322 | 0.3574 | 0.3838 | 0.3694 |
SD | 0.21840 | 0.35996 | 0.20254 | 0.12132 | 0.31577 | 0.06308 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 9. ORGAN WEIGHTS RATIO (%) – SUMMARY MALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 188.0 | 187.8 | 190.0 | 190.4 | 225.5 | 226.6 |
SD | 1.98 | 1.75 | 2.94 | 3.41 | 2.64 | 2.25 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain | Mean | 0.8207 | 0.9258 | 0.9122 | 0.7496 | 0.7780 | 0.7385 |
SD | 0.02740 | 0.03976 | 0.08319 | 0.24591 | 0.10199 | 0.03021 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.4444 | 0.5090 | 0.4868 | 0.4443 | 0.5171 | 0.4086 |
SD | 0.09613 | 0.08011 | 0.10691 | 0.03796 | 0.06335 | 0.08436 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 4.3427 | 4.6518 | 4.5857 | 4.2171 | 5.2691 | 3.7113 |
SD | 0.63238 | 0.80538 | 0.76966 | 0.24423 | 1.61179 | 0.78835 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 0.5704 | 0.6728 | 0.5240 | 0.4478 | 0.4693 | 0.9089 |
SD | 0.04130 | 0.15404 | 0.15559 | 0.06641 | 0.03585 | 1.13188 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 9. ORGAN WEIGHTS RATIO (%) – SUMMARY MALES (CONTD.)
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Kidneys | Mean | 0.8426 | 0.8230 | 0.8791 | 0.7832 | 0.9068 | 0.7236 |
SD | 0.10575 | 0.08447 | 0.20039 | 0.05407 | 0.11811 | 0.13762 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Adrenals | Mean | 0.0301 | 0.0414 | 0.0353 | 0.0286 | 0.0214 | 0.0295 |
SD | 0.01158 | 0.01342 | 0.01020 | 0.00442 | 0.00318 | 0.00330 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Testes | Mean | 1.0838 | 0.3852 | 1.2662 | 1.0603 | 1.1549 | 1.1303 |
SD | 0.56357 | 0.50072 | 0.18394 | 0.47313 | 0.04812 | 0.13338 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Epididymes | Mean | 0.1806 | 0.1836 | 0.1854 | 0.2273 | 0.2213 | 0.1365 |
SD | 0.05174 | 0.02314 | 0.04612 | 0.04421 | 0.22054 | 0.05340 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.5140 | 0.6813 | 0.6473 | 0.5436 | 0.6159 | 0.4719 |
SD | 0.19857 | 0.53443 | 0.32900 | 0.08214 | 0.18016 | 0.20480 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Pro + Sem. Vesical with Coagulating glands | Mean | 0.5875 | 0.5608 | 0.6813 | 0.5007 | 0.5421 | 0.5857 |
SD | 0.23452 | 0.28481 | 0.20256 | 0.26528 | 0.28509 | 0.17395 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 10. ORGAN WEIGHTS RATIO (%) – SUMMARY FEMALES
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Body Weight (G) | Mean | 183.6 | 183.6 | 185.9 | 184.7 | 222.7 | 227.2 |
SD | 3.08 | 3.53 | 3.75 | 3.86 | 2.60 | 2.61 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Brain | Mean | 0.8979 | 0.8990 | 0.8884 | 0.9350 | 0.7504 | 0.7774 |
SD | 0.15129 | 0.06615 | 0.04569 | 0.03864 | 0.05824 | 0.04080 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Heart | Mean | 0.4247 | 0.4102 | 0.4716 | 0.4250 | 0.3521 | 0.3513 |
SD | 0.04570 | 0.05469 | 0.25812 | 0.02442 | 0.06263 | 0.04372 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Liver | Mean | 4.0724 | 3.8064 | 3.6250 | 3.5092 | 2.8833 | 3.0245 |
SD | 0.29584 | 0.27864 | 0.41819 | 0.29140 | 0.13552 | 0.55605 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Spleen | Mean | 0.5313 | 0.5674 | 0.5017 | 0.4761 | 0.3647 | 0.3464 |
SD | 0.09671 | 0.10625 | 0.04320 | 0.12289 | 0.03784 | 0.06855 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Kidneys | Mean | 0.2043 | 0.2253 | 0.2303 | 0.6657 | 0.6028 | 0.6296 |
SD | 0.02841 | 0.03481 | 0.03571 | 0.04328 | 0.08087 | 0.08059 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 10. ORGAN WEIGHTS RATIO (%) – SUMMARY FEMALES (CONTD.)
| Group 1 | Group 2 | Group 3 | Group 4 | Group 1R | Group 4R | |
Adrenals | Mean | 0.3576 | 0.3653 | 0.3559 | 0.0375 | 0.0409 | 0.0342 |
SD | 0.02979 | 0.02776 | 0.03506 | 0.00876 | 0.02375 | 0.00605 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
ovaries | Mean | 0.0882 | 0.0913 | 0.1025 | 0.0974 | 0.1185 | 0.1510 |
SD | 0.01530 | 0.02638 | 0.02438 | 0.03789 | 0.06409 | 0.19642 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Uterus | Mean | 0.3496 | 0.3715 | 0.4139 | 0.1841 | 0.1523 | 0.1432 |
SD | 0.06959 | 0.14679 | 0.18006 | 0.05147 | 0.12629 | 0.07161 | |
N | 5 | 5 | 5 | 5 | 5 | 5 | |
Thymus | Mean | 0.9552 | 0.9515 | 1.0181 | 0.1928 | 0.1734 | 0.1625 |
SD | 0.09352 | 0.08186 | 0.05783 | 0.06338 | 0.14280 | 0.02663 | |
N | 5 | 5 | 5 | 5 | 5 | 5 |
Table 11. SUMMARY OF INCIDENCE OF MICROSCOPIC FINDINGS
| ||||
Organs/Microscopic findings | G1 | G4 | ||
Male 0 mg/kg bw (Vehicle control) | Female 1000 mg/kg bw (High dose) | Male 0 mg/kg bw (Vehicle control) | Female 1000 mg/kg bw (High dose) | |
Liver |
|
|
|
|
Vacoular degeneration | 0/5 | 1/5 | 0/5 | 0/5 |
Foci of inflammation/ Necrosis in Perfortal/ Centrilobular region |
4/5 |
1/5 |
2/5 |
1/5 |
NAD | 1/5 | 4/5 | 3/5 | 4/5 |
Spleen |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Lungs |
|
|
|
|
Alveolar Hemorrhage | 1/5 | 0/5 | 0/5 | 1/5 |
Alveolar Inflammation/Peribrancheolar Lymphoid Hyperplesia |
3/5 |
2/5 |
3/5 |
3/5 |
NAD | 1/5 | 3/5 | 2/5 | 1/5 |
Heart |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Aorta |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Kidney |
|
|
|
|
Tubular/Interptitial inflammation/Infilteration of inflammatory cells |
2/5 |
1/5 |
2/5 |
3/5 |
NAD | 3/5 | 4/5 | 3/5 | 2/5 |
Adrenals |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Brain |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Pituitary |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Thyroid |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Trachea |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Oesophagus |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Duodenum |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Jejunum |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Ileum |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Colon |
|
|
|
|
Sub mucosal Lymphoid tissue Hyperplasia | 1/5 | 1/5 | 0/5 | 1/5 |
NAD | 4/5 | 4/5 | 5/5 | 4/5 |
Rectum |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Caecum |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Lymph Node |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Pancreas |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Thymus |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Urinary Bladder |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Testes |
|
|
|
|
NAD | 5/5 | - | 5/5 | - |
Prostate |
|
|
|
|
Submucosal Inflammation | 1/5 | - | 0/5 | - |
NAD | 4/5 | - | 5/5 | - |
Seminal Vesicles with Coagulating Glands |
|
|
|
|
NAD | 5/5 | - | 5/5 | - |
Epididymes |
|
|
|
|
NAD | 5/5 | - | 5/5 | - |
Ovary |
|
|
|
|
NAD | - | 5/5 | - | 5/5 |
Uterus |
|
|
|
|
NAD | - | 5/5 | - | 5/5 |
Cervix + Vagina |
|
|
|
|
NAD | - | 5/5 | - | 5/5 |
Stomach |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Skeletal Muscle |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Eye |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Spinal Cord |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Bone Marrow (Sternum) |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Sciatic Nerve |
|
|
|
|
NAD | 5/5 | 5/5 | 5/5 | 5/5 |
Key- NAD: No Abnormality Detected
Applicant's summary and conclusion
- Conclusions:
- NOAEL was determined to be 1000 mg/kg bw/day in both sexes.
- Executive summary:
A 28 days repeated dose toxicity study was performed in accordance with the OECD TG 407 under GLP conditions using male and female Wistar rats. In this study, the animals of age 6 -7 weeks were used. 5 animals per sex per dose were used in the study. A total of 6 dose groups were selected for the study viz. 0 mg/kg bw/day (control group), 250 mg/kg bw (Low Dose Group), 500 mg/kg bw (Intermediate Dose Group) and 1000 mg/kg bw (High Dose Group). Further, two recovery groups were also included in the study in order to check the reversibility of the effects that are observed due to the administration of the test chemical, namely, Control Group Recovery (0 mg/kg bw/day) and High Dose Recovery (1000 mg/kg bw/day). 5 animals per sex per dose were used in the study. The animals were treated daily once via oral gavage route. The vehicle used for the study was distilled water. The parameters that were checked in the study were clincal signs, clinical observations (behavioral parameters), body weight and feed consumption, hematological and clinical biochemistry parameters, urinalysis, absolute and relative organ weights, gross pathology and histopathology. The animals of main groups were dosed consecutively for 28 days and on day 29, they were sacrificed. The animals were kept in metabolic cages a day prior to sacrifice in order to collect urine for urinalysis. Before sacrifice, blood was collected from all the animals from all the dose groups, using isofluorane anesthesia for hematological and biochemistry parameters. The same procedure was followed for recovery group animals before sacrifice on day 43. The in-life observations showed that No clinical signs were observed in any of the vehicle control(G1), low(G2), intermediate (G3), high dose(G4), vehicle control recovery (G1R) and recovery high dose (G4R) group animals. No mortality was observed in vehicle control (G1), low (G2), intermediate (G3), high dose (G4), recovery control (G1R) and recovery high dose (G4R) group animals. No adverse effect on body weight was observed for treated groups when compared with control group. No significant and toxicologically relevant changes in the body weight between treated and control group were observed. No significant changes related to the test chemical in the feed consumption was observed in any of the treated and recovery groups when compared with vehicle control (G1) group. No adverse effects on opthalmological findings were observed during the study. In hematological parameters, males in high dose group (G4) were showed decrease in WBC count when compared with control group. However, no changes in the females were observed. Treatment with the test chemical had no effects on both male and female animals with respect to hematological parameters viz RBC, Hb, MCV, MCHC, PCV, PLT, PT and APTT. In males, when compared with control group, bilirubin levels increased in low dose group (G2), ALT levels decreased in high dose, total protein levels decreased in low dose and intermediate dose compared to control, albumin levels increased in low, intermediate and high dose, Globulin levels decreased in low dose, intermediate and high dose, cholesterol levels increased in low dose and high dose. In females, when compared with control group, creatinine levels decreased in intermediate dose group (G3), bilirubin levels decreased in high dose (G4), triglyceride levels increased in intermediate dose (G3). All the recovery group male and female animals showed no effect on biochemical parameters. This change in the biochemical parameters is considered to have arisen by chance or caused by slightly higher/lower control values and not to represent a change of any biological significance. No significant changes in any of the treated groups and recovery groups were observed in urinalysis findings. No significant and test chemical related findings were observed during functional observation battery. There were no test chemical related changes in the in absolute and relative organ weights in both sexes in main group and recovery group animals. No test chemical related effects were observed during the necropsy of the animals in any organs in main groups or also in the recovery group. No test chemical related changes in the histopathology was observed in the animals of all dose groups in main groups or also in the recovery group. Therefore, based on all the available data, it was observed that the test chemical did not induce any systemic and local toxicity in the tested animals in main groups and recovery groups, respectively. Therefore, on the basis of all the observations and results, it was concluded that the NOAEL for the test chemical was 1000 mg/kg bw/day.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.