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EC number: 422-630-9 | CAS number: 22208-25-9
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- fertility, other
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 06 January 2023 – 28 January 2023
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 023
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 407
- Deviations:
- yes
- Remarks:
- (The study period was only 14 days as it was conducted as a dose range finding study for a subsequent more extensive toxicity study)
- GLP compliance:
- no
- Remarks:
- DRF study performed without GLP
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 422-630-9
- EC Name:
- -
- Cas Number:
- 22208-25-9
- Molecular formula:
- C18H26O9
- IUPAC Name:
- 2,2-bis({[(3-oxobutanoyl)oxy]methyl})butyl 3-oxobutanoate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-house bred animals.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks (at receipt)
- Weight at study initiation: 213.78-217.06 g (range of average values of each group of males); 179.99-183.89 g (range of average values of each group of females)
- Fasting period before study: No
- Housing: Maximum of three animals of same sex were housed in a standard polycarbonate cage (Size: L 43 X B 28 X H 21 cm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized corn cob was provided as bedding material.
- Diet (e.g. ad libitum): Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG) was provided ad libitum to the animals throughout the acclimatization and experimental period.
- Water (e.g. ad libitum): Water was provided ad libitum throughout the acclimatization and experimental period. Deep bore-well water passed through a Reverse Osmosis Unit was provided in plastic water bottles with stainless-steel sipper tubes.
- Acclimation period: 8 days
DETAILS OF FOOD AND WATER QUALITY:
Analyses of feed and water were performed before starting the study. The corresponding certificates are annexed to the test report.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1-22.9 ºC
- Humidity (%): 46-66 %
- Air changes (per hr): 12-15
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: From: 06 January 2023 To: 28 January 2023
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
The test item formulations were freshly prepared before dose administration and homogeneity was achieved by thorough stirring using a magnetic stirrer during administration. The required quantity of test item was weighed separately and transferred, mixed and stirred using glass rod and thereafter the entire quantity of the formulation was transferred into measuring cylinder. The rinsing procedure was repeated (many times). Finally, the volume was adjusted to required mark in measuring cylinder with vehicle to get a desired concentration.
VEHICLE
- Justification for use and choice of vehicle (if other than water): In a solubility test, the test item formed suspension in corn oil. Hence, corn oil was selected as vehicle to prepare test item formulations in this study. Corn oil is one of the commonly used vehicles in toxicology studies.
- Concentration in vehicle: 10, 30 and 100 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): not reported.
- Purity: N/A - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- The stability and homogeneity of the test item in dose formulations was not established under this dose range finding study. However, freshly prepared test item formulations were administered to the animals and homogeneity was achieved by thorough stirring using magnetic stirrer. The actual dose volume for each animal was calculated based on the most recent body weight.
- Duration of treatment / exposure:
- 14 days
- Frequency of treatment:
- Once a day
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- G1 - Vehicle control
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- G2 - Low dose
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- G3 - Mid dose
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- G4 - High dose
- No. of animals per sex per dose:
- 3
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The doses of 0, 100, 300 and 1000 mg/kg bw/day have been selected for dose range finding study as no literature is available for the test item.
- Fasting period before blood sampling for clinical biochemistry: The animals were fasted overnight before blood collection. Water was provided ad libitum during fasting period. - Positive control:
- None
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily for clinical signs of toxicity and twice daily for mortality and morbidity.
DETAILED CLINICAL OBSERVATIONS: Yes
BODY WEIGHT: Yes
- Time schedule for examinations: Individual animal body weight was recorded on the day of randomization, on day of treatment (Day 1) prior to treatment and weekly thereafter.
FOOD CONSUMPTION: yes
-feed consumption was measured at weekly intervals. Average feed intake per rat (g/rat/day) was calculated using the amount of feed given and left over in each cage and the number of rats surviving in each cage.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: On the day of necropsy (day 15)
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes (water provided ad libitum)
- How many animals: all animals
- Parameters checked: Haemoglobin concentration (HGB), Haematocrit (HCT), Erythrocyte count (RBC), Total leukocyte count (WBC), Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular haemoglobin concentration (MCHC), Platelet count (PLT), Mean platelet volume (MPV), Reticulocyte count (Retic), Absolute reticulocyte count, Differential leucocytes count (DLC), Absolute differential leucocytes count (DLC). Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) were estimated by coagulation analyzer.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on the day of necropsy (day 15)
- Animals fasted: Yes (water provided ad libitum)
- How many animals: all animals
- Parameters checked: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Cholinesterase, Total Protein, Albumin, Total bilirubin, Glucose, Total Cholesterol, Creatinine, Urea, Triglycerides, Phosphorous, Calcium, Blood Urea Nitrogen, Globulin, Albumin/Globulin ratio. Sodium (mmol/L), Potassium (mmol/L) and Chloride (mmol/L) were estimated using Prolyte Na/K/Cl analyzer (Medica Corporation).
URINALYSIS: Yes
- Time schedule for collection of urine: on the day of necropsy (day 15)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked: Blood, Bilirubin, Urobilinogen, Ketones, Protein, Glucose, Leucocytes. In addition pH, nitrite and specific gravity were also analyzed. After analysis of the above parameters, the urine was subjected for centrifugation at 1500 rpm for 3 minutes. Then the urine was subjected for microscopic examination for urine sediments. - Sperm parameters (parental animals):
- Testes and epididymides were subjected to necropsy and detailed gross pathological examination. These organs were weighed and weight ratios as percentage of body weight were determined.
- Postmortem examinations (parental animals):
- SACRIFICE
-On day15, all animals of Group G1, G2, G3 and G4 were subjected to necropsy and detailed gross pathological examination
GROSS NECROPSY
-Gross pathological examination of external surfaces, external orifices, abdominal, thoracic and cranial cavities, as well as organs and tissues of each animal with special emphasis on reproductive organs.
The following organs from all animals at the scheduled sacrifices were weighed wet as soon as possible to avoid drying: Kidneys, Adrenals, Spleen, Heart, Liver, Thymus, Brain, Lungs Testes/Ovaries, Epididymides/Uterus, Prostate along with seminal vesicles with coagulating gland.
HISTOPATHOLOGY / ORGAN WEIGHTS
-The above mentioned organs from all animals were collected, weighed and preserved. The organ weight ratios as percentage of body weight were determined. - Statistics:
- After verification, the data was subjected to statistical analysis using SPSS software, version 27. Body weight, percent change in body weight with respect to day 1, haematological, clinical chemistry estimations parameters absolute and relative organ weights were subjected to statistical analysis. One way ANOVA followed by Dunnett’s post test was done for different treatment groups comparing with the control group data. All analysis and comparisons were evaluated at the 95% level of confidence (P<0.05).
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs of toxicity were seen in all the tested dose group animals in either sex.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- There were no mortality/morbidity observed at any dose group during the experimental period.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No test item related variations in mean body weight and percent body weight change were noted, when compared to vehicle control group.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There was not any impact of test item on feed consumption in any of the tested group in either sex.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no adverse test item related changes in the haematology and coagulation parameters. However, in males statistically significant (p<0.05) increases in Erythrocyte count (RBC), Haemoglobin concentration (HGB), Haematocrit (HCT) Eosinophils in G4 was noted and in females decrease in Prothrombin Time (PT) in G2 and G4 was noted. The observed variation is considered incidental in the absence of dose responsiveness and similar changes were not noted in other sex.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item related adverse changes were observed in any of the clinical chemistry parameters, in both sexes when compared to the vehicle control.
However, in G2 female statistically significant (p<0.05) increase in glucose was noted. The noted variation lacked dose responsiveness, hence is considered incidental. - Endocrine findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- No gross pathological changes or effects in absolute and relative weights were noted in testes or epididymides at any dose tested.
- Reproductive performance:
- not examined
Details on results (P0)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No treatment related effects found up to highest tested dose of 1000 mg/kg bw/d.
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
Effect levels (F1)
- Remarks on result:
- other: F1 was not assessed as this study was conducted as a dose range finding study for a subsequent more extensive toxicity study
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 1. Summary of clinical signs of toxicity, detailed clinical examination and mortality record
Group, Sex & Dose (mg/kg body weight/day) | No. of Animals | Clinical Signs of Toxicity (No of animals exhibiting signs/Total no. of animals) | Mortality No. of Animals) |
G1, M & 0 | 3 | N | 0/3 |
G2, M & 100 | 3 | N | 0/3 |
G3, M & 300 | 3 | N | 0/3 |
G4, M & 1000 | 3 | N | 0/3 |
G1, F & 0 | 3 | N | 0/3 |
G2, F & 100 | 3 | N | 0/3 |
G3, F & 300 | 3 | N | 0/3 |
G4, F & 1000 | 3 | N | 0/3 |
Table 2. Summary of body weight (g) record
Group, Sex & Dose (mg/kg body weight/day) | Body Weight (g) on Days | ||||
1 | 8 | 14 | |||
G1, M & 0 | Mean | 215.52 | 236.13 | 258.22 | |
±SD | 27.54 | 33.11 | 34.05 | ||
n | 3 | 3 | 3 | ||
G2, M & 100 | Mean | 215.55 | 241.01 | 264.64 | |
±SD | 13.93 | 17.21 | 20.88 | ||
n | 3 | 3 | 3 | ||
G3, M & 300 | Mean | 213.78 | 237.88 | 257.62 | |
±SD | 11.77 | 13.98 | 25.67 | ||
n | 3 | 3 | 3 | ||
G4, M & 1000 | Mean | 217.06 | 240.54 | 259.24 | |
±SD | 5.56 | 6.47 | 10.16 | ||
n | 3 | 3 | 3 | ||
G1, F & 0 | Mean | 180.83 | 193.18 | 207.07 | |
±SD | 11.46 | 9.00 | 6.98 | ||
n | 3 | 3 | 3 | ||
G2, F & 100 | Mean | 183.89 | 193.86 | 210.85 | |
±SD | 13.30 | 15.13 | 15.73 | ||
n | 3 | 3 | 3 | ||
G3, F & 300 | Mean | 179.99 | 193.78 | 202.25 | |
±SD | 5.34 | 3.54 | 3.17 | ||
n | 3 | 3 | 3 | ||
G4, F & 1000 | Mean | 183.35 | 197.98 | 211.12 | |
±SD | 5.14 | 2.66 | 9.26 | ||
n | 3 | 3 | 3 |
Table 3. Summary of percent change in body weight (%) with respect to day 1 record
Group, Sex & Dose (mg/kg body weight/day) |
| Percent Change in Body Weight (%) during Days | ||
1 to 8 | 1 to 14 | |||
G1, M & 0 | Mean | 9.44 | 19.77 | |
±SD | 2.03 | 0.50 | ||
n | 3 | 3 | ||
G2, M & 100 | Mean | 11.81 | 22.75 | |
±SD | 2.66 | 4.23 | ||
n | 3 | 3 | ||
G3, M & 300 | Mean | 11.30 | 20.53 | |
±SD | 3.72 | 10.27 | ||
n | 3 | 3 | ||
G4, M & 1000 | Mean | 10.86 | 19.52 | |
±SD | 4.18 | 6.62 | ||
n | 3 | 3 | ||
G1, F & 0 | Mean | 6.91 | 14.66 | |
±SD | 2.02 | 3.72 | ||
n | 3 | 3 | ||
G2, F & 100 | Mean | 5.39 | 14.75 | |
±SD | 0.60 | 6.28 | ||
n | 3 | 3 | ||
G3, F & 300 | Mean | 7.75 | 12.47 | |
±SD | 4.86 | 5.07 | ||
n | 3 | 3 | ||
G4, F & 1000 | Mean | 8.02 | 15.18 | |
±SD | 2.45 | 5.08 | ||
n | 3 | 3 |
Table 4. Summary of feed consumption (g/rat/day) record
Group, Sex & Dose (mg/kg body weight/day) |
| Week 1 | Week 2 | |
G1, M & 0 | Mean | 19.01 | 19.59 | |
±SD | - | - | ||
n | 1 | 1 | ||
G2, M & 100 | Mean | 19.64 | 22.03 | |
±SD | - | - | ||
n | 1 | 1 | ||
G3, M & 300 | Mean | 20.34 | 20.40 | |
±SD | - | - | ||
n | 1 | 1 | ||
G4, M & 1000 | Mean | 21.02 | 20.49 | |
±SD | - | - | ||
n | 1 | 1 | ||
G1, F & 0 | Mean | 16.99 | 16.83 | |
±SD | - | - | ||
n | 1 | 1 | ||
G2, F & 100 | Mean | 15.12 | 15.99 | |
±SD | - | - | ||
n | 1 | 1 | ||
G3, F & 300 | Mean | 16.82 | 17.44 | |
±SD | - | - | ||
n | 1 | 1 | ||
G4, F & 1000 | Mean | 16.64 | 17.46 | |
±SD | - | - | ||
n | 1 | 1 |
Table 5. Summary of gross pathology findings
Sex | Male | Female | ||||||
Group | G1 | G2 | G3 | G4 | G1 | G2 | G3 | G4 |
Dose (mg/kg body weight/day) | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Number of animals | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
No. of dead rats during treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
No. of moribund sacrificed rats | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
No. of terminally sacrificed rats | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
No of rats showing gross pathology | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 6. Summary of haematology record
Group, Sex & Dose (mg/kg body weight/day) |
| Total Leucocyte Count | Total Erythrocyte Count | Hemoglobin | Haematocrit | Mean Corpuscular Volume | Mean Corpuscular Hemoglobin | Mean Corpuscular Hemoglobin Concentration |
(WBC) | (RBC) | (HGB) | (HCT) | (MCV) | (MCH) | (MCHC) | ||
(103 cells/µL) | (106 cells/µL) | (g/dL) | (%) | (fL) | (pg) | (g/dL) | ||
G1, M & 0 | Mean | 15.41 | 7.66 | 15.03 | 44.63 | 58.30 | 19.63 | 33.63 |
±SD | 3.40 | 0.18 | 0.58 | 2.12 | 2.84 | 0.95 | 0.49 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 20.59 | 7.85 | 15.50 | 47.43 | 60.53 | 19.83 | 32.73 |
±SD | 3.47 | 0.31 | 0.46 | 0.50 | 2.85 | 1.24 | 0.60 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 11.31 | 7.88 | 15.53 | 47.27 | 59.93 | 19.70 | 32.87 |
±SD | 3.65 | 0.11 | 0.45 | 2.15 | 2.28 | 0.36 | 0.64 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 13.96 | 8.61* | 16.37* | 49.90* | 57.97 | 19.00 | 32.77 |
±SD | 2.38 | 0.14 | 0.51 | 1.25 | 0.61 | 0.46 | 0.57 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G1, F & 0 | Mean | 14.09 | 7.75 | 14.87 | 43.47 | 56.10 | 19.20 | 34.23 |
±SD | 2.26 | 0.80 | 1.25 | 4.44 | 0.35 | 0.44 | 0.85 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 14.20 | 7.76 | 15.57 | 43.93 | 56.73 | 20.20 | 35.63 |
±SD | 5.77 | 0.93 | 0.58 | 4.95 | 3.25 | 1.81 | 2.89 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 13.26 | 7.26 | 14.77 | 41.33 | 56.90 | 20.43 | 35.93 |
±SD | 5.42 | 0.75 | 0.59 | 4.48 | 1.11 | 1.36 | 2.55 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 12.50 | 7.65 | 14.93 | 44.07 | 57.63 | 19.47 | 33.83 |
±SD | 1.75 | 0.41 | 0.57 | 2.06 | 1.17 | 0.31 | 0.55 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Group, Sex & Dose (mg/kg body weight/day) |
| Platelet Count | Mean Platelet Volume | Reticulocyte Count | Neutrophils | Lymphocytes | Monocytes | Eosinophils | Basophils |
(PLT) | (MPV) | (Retic) | (Neut) | (Lymph) | (Mono) | (Eos) | (Baso) | ||
(103 cells/µL) | (fL) | (%) | (%) | (%) | (%) | (%) | (%) | ||
G1, M & 0 | Mean | 713.00 | 7.47 | 4.04 | 15.50 | 78.80 | 3.10 | 1.00 | 0.40 |
±SD | 464.46 | 0.38 | 1.21 | 5.30 | 6.46 | 1.30 | 0.50 | 0.10 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 946.00 | 7.53 | 4.37 | 18.50 | 75.77 | 2.43 | 1.17 | 0.47 |
±SD | 239.95 | 0.21 | 0.71 | 14.04 | 14.26 | 0.75 | 1.24 | 0.15 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 913.33 | 7.73 | 2.96 | 18.10 | 71.87 | 5.80 | 2.23 | 0.30 |
±SD | 88.64 | 0.21 | 0.61 | 0.60 | 0.38 | 1.31 | 1.02 | 0.00 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 994.67 | 7.53 | 3.23 | 24.10 | 65.77 | 4.53 | 4.00* | 0.33 |
±SD | 104.27 | 0.21 | 0.86 | 2.46 | 2.21 | 1.89 | 1.01 | 0.06 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G1, F & 0 | Mean | 937.00 | 7.60 | 3.42 | 19.10 | 74.00 | 3.77 | 1.20 | 0.33 |
±SD | 307.15 | 0.20 | 2.00 | 3.89 | 2.89 | 1.21 | 0.46 | 0.06 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 764.67 | 8.20 | 3.40 | 16.30 | 75.63 | 2.87 | 3.20 | 0.43 |
±SD | 361.51 | 0.50 | 1.52 | 7.47 | 10.83 | 1.65 | 2.31 | 0.06 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 896.00 | 7.93 | 4.09 | 19.03 | 72.40 | 3.87 | 2.13 | 0.40 |
±SD | 162.86 | 0.25 | 1.84 | 5.69 | 5.96 | 0.50 | 1.33 | 0.17 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 985.67 | 8.13 | 3.85 | 22.40 | 71.70 | 3.13 | 1.53 | 0.27 |
±SD | 65.52 | 0.15 | 0.28 | 4.26 | 4.79 | 0.75 | 0.59 | 0.06 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Group, Sex & Dose (mg/kg body weight/day) |
| Absolute Reticulocyte Count | Absolute Neutrophils | Absolute Lymphocytes | Absolute Monocytes | Absolute Eosinophils | Absolute Basophils | Prothrombin Time | Activated Prothrombin Time |
(Retic) | (Neut) | (Lymph) | (Mono) | (Eos) | (Baso) | (PT) | (APTT) | ||
(109 cells/L) | (103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (103 cells/µL) | (Seconds) | (Seconds) | ||
G1, M & 0 | Mean | 308.97 | 2.30 | 12.24 | 0.48 | 0.14 | 0.06 | 17.33 | 17.37 |
±SD | 90.40 | 0.51 | 3.50 | 0.21 | 0.06 | 0.04 | 1.25 | 0.84 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 343.43 | 3.53 | 15.89 | 0.50 | 0.21 | 0.10 | 16.36 | 20.59 |
±SD | 62.23 | 2.11 | 5.20 | 0.15 | 0.21 | 0.04 | 0.57 | 1.98 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 233.13 | 2.06 | 8.12 | 0.62 | 0.28 | 0.03 | 16.27 | 18.77 |
±SD | 49.68 | 0.73 | 2.60 | 0.04 | 0.22 | 0.02 | 0.77 | 2.34 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 277.90 | 3.33 | 9.21 | 0.63 | 0.57 | 0.05 | 16.61 | 16.25 |
±SD | 75.02 | 0.32 | 1.76 | 0.30 | 0.23 | 0.01 | 1.36 | 1.57 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G1, F & 0 | Mean | 254.47 | 2.71 | 10.41 | 0.51 | 0.17 | 0.05 | 17.62 | 19.53 |
±SD | 122.89 | 0.86 | 1.54 | 0.13 | 0.05 | 0.02 | 0.61 | 4.33 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 261.13 | 2.07 | 11.05 | 0.39 | 0.39 | 0.06 | 15.72* | 17.88 |
±SD | 118.33 | 0.40 | 5.73 | 0.19 | 0.18 | 0.02 | 0.42 | 5.81 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 297.23 | 2.39 | 9.70 | 0.53 | 0.28 | 0.06 | 16.50 | 18.70 |
±SD | 145.43 | 0.64 | 4.50 | 0.29 | 0.17 | 0.05 | 0.82 | 3.98 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 294.43 | 2.75 | 9.02 | 0.38 | 0.18 | 0.03 | 16.09* | 21.79 |
±SD | 18.86 | 0.12 | 1.84 | 0.09 | 0.05 | 0.02 | 0.36 | 0.81 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
*: Statistically significant (P<0.05)
Table 7. Summary of clinical chemistry record
Group, Sex & Dose (mg/kg body weight/day) |
| Glucose | Urea | Creatinine | Total Cholesterol | Triglycerides | Total Protein | Albumin | Alanine aminotransferase | Aspartate aminotransferase | Alkaline phosphatase |
(GLU) | (CRE) | (CHO) | (TRI) | (TPR) | (ALB) | (ALT) | (AST) | (ALP) | |||
(mg/dL) | (mg/dL) | (mg/dL) | (mg/dL) | (mg/dL) | g/dL) | (g/dL) | (U/L) | (U/L) | (U/L) | ||
G1, M & 0 | Mean | 101.67 | 29.37 | 0.55 | 58.33 | 66.67 | 7.20 | 3.22 | 53.33 | 121.67 | 221.33 |
±SD | 10.60 | 5.35 | 0.02 | 4.93 | 17.04 | 0.20 | 0.10 | 4.93 | 24.19 | 74.10 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 96.33 | 29.53 | 0.57 | 62.00 | 55.33 | 7.50 | 3.30 | 68.33 | 129.67 | 236.33 |
±SD | 7.64 | 5.85 | 0.02 | 12.77 | 13.87 | 0.30 | 0.17 | 3.21 | 7.23 | 54.50 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 89.67 | 29.80 | 0.52 | 51.67 | 101.33 | 7.03 | 3.33 | 61.67 | 122.33 | 341.67 |
±SD | 4.16 | 5.20 | 0.01 | 6.43 | 65.96 | 0.21 | 0.16 | 9.07 | 20.55 | 89.40 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 97.00 | 29.00 | 0.54 | 55.67 | 59.33 | 7.33 | 3.45 | 58.33 | 113.33 | 328.33 |
±SD | 4.36 | 5.55 | 0.04 | 8.50 | 35.73 | 0.49 | 0.17 | 9.07 | 6.03 | 32.65 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G1, F & 0 | Mean | 86.33 | 39.23 | 0.57 | 62.00 | 72.67 | 7.67 | 3.38 | 55.00 | 127.00 | 247.00 |
±SD | 4.16 | 6.38 | 0.04 | 7.81 | 33.65 | 0.06 | 0.09 | 9.00 | 17.78 | 90.54 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 104.67* | 35.70 | 0.60 | 65.67 | 61.67 | 7.70 | 3.46 | 99.33 | 181.33 | 182.33 |
±SD | 4.51 | 10.36 | 0.03 | 16.44 | 32.13 | 0.35 | 0.24 | 68.07 | 58.14 | 60.34 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 95.33 | 29.93 | 0.54 | 54.67 | 75.33 | 7.37 | 3.26 | 57.00 | 139.33 | 232.00 |
±SD | 8.08 | 4.66 | 0.03 | 5.13 | 39.88 | 0.25 | 0.20 | 4.58 | 17.39 | 164.79 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 98.67 | 24.57 | 0.53 | 73.00 | 66.67 | 7.33 | 3.52 | 55.00 | 106.33 | 204.33 |
±SD | 5.86 | 0.90 | 0.01 | 22.65 | 23.86 | 0.50 | 0.22 | 2.65 | 11.02 | 55.37 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Group, Sex & Dose (mg/kg body weight/day) |
| Total Bilirubin | Calcium | Phosphorous | Cholinesterase | Globulin | Albumin/Globulin ratio | Blood Urea Nitrogen | Sodium | Potassium | Chloride |
(BIT) | (CAL) | (PHO) | (CHE) | (GLO) | (A/G Ratio) | (BUN) | (Na) | (K) | (CLO) | ||
(mg/dL) | (mg/dL) | (mg/dL) | (U/L) | (g/dL) | - | (mg/dL) | (mmol/L) | (mmol/L) | (mmol/L) | ||
G1, M & 0 | Mean | 0.11 | 10.03 | 6.13 | 154.67 | 3.98 | 0.81 | 13.73 | 139.60 | 3.71 | 105.57 |
±SD | 0.02 | 0.12 | 0.60 | 16.17 | 0.27 | 0.08 | 2.50 | 1.71 | 0.37 | 2.20 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 0.07 | 10.10 | 6.05 | 121.00 | 4.20 | 0.79 | 13.80 | 141.87 | 3.93 | 107.47 |
±SD | 0.01 | 0.46 | 0.34 | 37.64 | 0.14 | 0.03 | 2.73 | 0.15 | 0.56 | 1.00 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 0.11 | 10.13 | 6.12 | 101.00 | 3.71 | 0.90 | 13.92 | 140.10 | 3.65 | 104.30 |
±SD | 0.04 | 0.49 | 0.64 | 42.53 | 0.09 | 0.04 | 2.43 | 0.46 | 0.18 | 4.06 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 0.10 | 10.27 | 5.98 | 115.33 | 3.88 | 0.89 | 13.55 | 139.23 | 3.66 | 102.63 |
±SD | 0.02 | 0.25 | 0.12 | 11.59 | 0.34 | 0.05 | 2.59 | 2.25 | 0.10 | 3.91 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G1, F & 0 | Mean | 0.09 | 10.20 | 5.69 | 448.67 | 4.29 | 0.79 | 18.34 | 139.53 | 3.81 | 106.87 |
±SD | 0.04 | 0.10 | 0.34 | 218.60 | 0.12 | 0.04 | 2.98 | 1.70 | 0.14 | 1.78 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 0.06 | 10.03 | 4.96 | 488.33 | 4.24 | 0.82 | 16.68 | 141.23 | 3.73 | 108.33 |
±SD | 0.01 | 0.31 | 1.52 | 401.85 | 0.46 | 0.14 | 4.84 | 1.27 | 0.43 | 1.08 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 0.08 | 9.87 | 5.18 | 415.33 | 4.11 | 0.79 | 13.99 | 139.63 | 3.74 | 107.10 |
±SD | 0.02 | 0.15 | 0.31 | 199.14 | 0.07 | 0.04 | 2.18 | 1.25 | 0.07 | 1.75 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 0.08 | 9.97 | 5.28 | 362.67 | 3.81 | 0.93 | 11.48 | 140.93 | 3.72 | 105.77 |
±SD | 0.01 | 0.35 | 0.47 | 208.41 | 0.29 | 0.02 | 0.43 | 0.84 | 0.12 | 2.20 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
*: Statistically significant (P<0.05)
Table 8. Summary of urinalysis record
Examination | Group, Sex & Dose (mg/kg/day) | G1, M & 0 | G2, M & 100 | G3, M & 300 | G4, M & 1000 | |
Number of Animals | 3 | 3 | 3 | 3 | ||
Physical Examination | Color | Pale Yellow | 3 | - | 3 | 3 |
Yellow | - | 3 | - | - | ||
Apperance | Clear | 3 | 1 | 3 | 3 | |
Turbidity | - | 2 | - | - | ||
Volume (mL) | Mean | 2.2 | 2.7 | 1.2 | 3.0 | |
±SD | 0.8 | 0.3 | 0.3 | 0.5 | ||
Chemical Examination | pH | Mean | 5.8 | 6.3 | 5.7 | 5.8 |
±SD | 0.3 | 0.3 | 0.3 | 0.3 | ||
Specific gravity (SG) | Mean | 1.030 | 1.030 | 1.030 | 1.030 | |
±SD | 0.000 | 0.000 | 0.000 | 0.000 | ||
Urobilinogen (UBG) (mg/dL) | Mean | 0.7 | 0.2 | 1.0 | 0.7 | |
±SD | 0.5 | 0.0 | 0.0 | 0.5 | ||
Bilirubin (BIL) (mg/dL) | 1 | 3 | 3 | 3 | 3 | |
Ketones (KET) (mg/dL) | 5 | 3 | 3 | 3 | 2 | |
15 | - | - | - | 1 | ||
Blood (BLD) (Ery/µL) | Neg | 2 | 2 | - | - | |
Ca80 | - | - | - | 1 | ||
Ca10 | - | 1 | 1 | - | ||
Ca25 | - | - | 2 | 2 | ||
>=Ca200 | 1 | - | - | - | ||
Protein (PRO) (mg/dL) | 30 | 3 | 3 | 3 | 3 | |
Nitrite (NIT) | Neg | 2 | - | 1 | 2 | |
Pos | 1 | 3 | 2 | 1 | ||
Leucocytes (LEU) (Leu/µL) | Ca70 | 2 | 3 | - | - | |
Ca15 | 1 | - | 3 | 3 | ||
Glucose (GLU) (mg/dL) | Neg | 3 | 3 | 3 | 3 | |
Microscopic Examination | Epi Cells | 0 | 2 | 1 | 3 | 2 |
0-1 | 1 | 1 | - | 1 | ||
1-2 | - | 1 | - | - | ||
Casts | Absent | 3 | 3 | 3 | 3 | |
Crystals | Present | 3 | 3 | 3 | 3 |
Examination | Group, Sex & Dose (mg/kg/day) | G1, F & 0 | G2, F & 100 | G3, F & 300 | G4, F & 1000 | |
Number of Animals | 3 | 3 | 3 | 3 | ||
Physical Examination | Color | Pale Yellow | 3 | 3 | 2 | 3 |
Yellow | - | - | 1 | - | ||
Apperance | Clear | 3 | 3 | 2 | 3 | |
Turbidity | - | - | 1 | - | ||
Volume (mL) | Mean | 1.2 | 2.7 | 2.2 | 4.3 | |
±SD | 0.3 | 0.8 | 0.8 | 1.8 | ||
Chemical Examination | pH | Mean | 6.0 | 5.8 | 7.3 | 5.8 |
±SD | 0.0 | 0.3 | 1.6 | 0.3 | ||
Specific gravity (SG) | Mean | 1.030 | 1.030 | 1.017 | 1.025 | |
±SD | 0.000 | 0.000 | 0.012 | 0.005 | ||
Urobilinogen (UBG) (mg/dL) | Mean | 0.7 | 0.2 | 0.7 | 0.2 | |
±SD | 0.5 | 0.0 | 0.5 | 0.0 | ||
Bilirubin (BIL) (mg/dL) | Neg | - | 1 | - | 2 | |
1 | 3 | 2 | 3 | 1 | ||
Ketones (KET) (mg/dL) | 5 | 3 | 2 | 3 | 1 | |
Neg | - | 1 | - | 2 | ||
Blood (BLD) (Ery/µL) | Neg | 3 | 1 | 3 | 3 | |
Ca10 | - | 2 | - | - | ||
Protein (PRO) (mg/dL) | Neg | - | - | - | 3 | |
Trace | - | 3 | 1 | - | ||
>=300 | - | - | 1 | - | ||
100 | - | - | 1 | - | ||
30 | 3 | - | - | - | ||
Nitrite (NIT) | Neg | - | 2 | 1 | 3 | |
Pos | 3 | 1 | 2 | - | ||
Leucocytes (LEU) (Leu/µL) | Neg | - | 1 | 1 | 3 | |
Ca70 | - | - | 2 | - | ||
Ca15 | 3 | 2 | - | - | ||
Glucose (GLU) (mg/dL) | Neg | 3 | 3 | 3 | 3 | |
Microscopic Examination | Epi Cells | 0 | 2 | 3 | 2 | 2 |
0-1 | 1 | - | 1 | 1 | ||
Casts | Absent | 3 | 3 | 3 | 3 | |
Crystals | Present | 3 | 3 | 3 | 3 |
Table 9. Summary of absolute organ weights (g) record
Group, Sex & Dose (mg/kg body weight/day) |
| Adrenals | Thymus | Spleen | Testes | Epididymides | Heart | Kidneys | Brain | Liver | Prostate+Seminal vesicles with coagulating glands (PSC) |
G1, M & 0 | Mean | 0.0569 | 0.3161 | 1.1578 | 2.9419 | 0.8424 | 0.8946 | 1.7430 | 1.6811 | 7.8730 | 1.4337 |
±SD | 0.0141 | 0.0269 | 0.2774 | 0.0317 | 0.1045 | 0.1037 | 0.2386 | 0.0548 | 0.9084 | 0.4801 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 0.0434 | 0.3843 | 1.3946 | 2.8097 | 0.7433 | 0.9793 | 1.7929 | 1.8006 | 8.6424 | 1.4464 |
±SD | 0.0063 | 0.0561 | 0.4100 | 0.1846 | 0.0476 | 0.0701 | 0.0379 | 0.0975 | 1.0011 | 0.1312 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 0.0471 | 0.2860 | 1.4546 | 3.2638 | 0.8225 | 0.9156 | 1.7204 | 1.8688 | 8.2005 | 1.4351 |
±SD | 0.0137 | 0.0853 | 0.6647 | 0.1690 | 0.0939 | 0.1069 | 0.1870 | 0.1451 | 1.4470 | 0.1714 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 0.0502 | 0.3586 | 1.0628 | 3.2475 | 0.8604 | 0.9275 | 1.7705 | 1.8239 | 7.9500 | 1.5484 |
±SD | 0.0118 | 0.0728 | 0.2475 | 0.3785 | 0.1349 | 0.0234 | 0.0264 | 0.0664 | 0.5808 | 0.1829 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Group, Sex & Dose (mg/kg body weight/day) |
| Adrenals | Thymus | Spleen | Ovaries with Oviduct | Uterus with cervix | Heart | Kidneys | Brain | Liver |
G1, F & 0 | Mean | 0.0653 | 0.3518 | 1.3109 | 0.1014 | 0.5245 | 0.7561 | 1.4506 | 1.6489 | 6.9631 |
±SD | 0.0155 | 0.0988 | 0.5494 | 0.0221 | 0.3749 | 0.0214 | 0.1304 | 0.0324 | 0.6644 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 0.0633 | 0.2851 | 1.0969 | 0.1151 | 0.4561 | 0.8306 | 1.4629 | 1.7280 | 6.8227 |
±SD | 0.0083 | 0.0685 | 0.1513 | 0.0116 | 0.0940 | 0.1027 | 0.0496 | 0.0323 | 0.4436 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 0.0643 | 0.3018 | 1.0642 | 0.1184 | 0.4597 | 0.8005 | 1.4591 | 1.7184 | 6.7091 |
±SD | 0.0019 | 0.0199 | 0.3251 | 0.0298 | 0.1173 | 0.0900 | 0.0930 | 0.0377 | 0.4766 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 0.0762 | 0.3893 | 0.9916 | 0.1098 | 0.4997 | 0.8543 | 1.4356 | 1.7151 | 7.4837 |
±SD | 0.0182 | 0.1208 | 0.1645 | 0.0163 | 0.2168 | 0.0489 | 0.1095 | 0.0883 | 0.1878 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Table 10. Summary of organ weight relative to fasting body weight (%) record
Group, Sex & Dose (mg/kg body weight/day) | Fasting Body Weight (g) | Adrenals | Thymus | Spleen | Testes | Epididymides | Heart | Kidneys | Brain | Liver | Prostate+Seminal vesicles with coagulating glands (PSC) | |
G1, M & 0 | Mean | 236.92 | 0.0241 | 0.1343 | 0.4901 | 1.2518 | 0.3581 | 0.3783 | 0.7343 | 0.7169 | 3.3246 | 0.5969 |
±SD | 26.27 | 0.0058 | 0.0161 | 0.1172 | 0.1354 | 0.0555 | 0.0327 | 0.0185 | 0.0990 | 0.1533 | 0.1560 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, M & 100 | Mean | 237.31 | 0.0183 | 0.1614 | 0.5973 | 1.1845 | 0.3137 | 0.4127 | 0.7574 | 0.7599 | 3.6472 | 0.6141 |
±SD | 16.88 | 0.0019 | 0.0130 | 0.2070 | 0.0292 | 0.0193 | 0.0073 | 0.0408 | 0.0385 | 0.4241 | 0.0962 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, M & 300 | Mean | 235.95 | 0.0199 | 0.1200 | 0.6028 | 1.3875 | 0.3533 | 0.3876 | 0.7303 | 0.7931 | 3.4581 | 0.6079 |
±SD | 22.99 | 0.0056 | 0.0249 | 0.2143 | 0.0692 | 0.0726 | 0.0121 | 0.0612 | 0.0171 | 0.2692 | 0.0328 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, M & 1000 | Mean | 238.03 | 0.0210 | 0.1501 | 0.4493 | 1.3677 | 0.3617 | 0.3902 | 0.7446 | 0.7676 | 3.3412 | 0.6493 |
±SD | 8.58 | 0.0045 | 0.0249 | 0.1199 | 0.1890 | 0.0577 | 0.0225 | 0.0342 | 0.0545 | 0.2420 | 0.0561 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Group, Sex & Dose (mg/kg/day) |
| Fasting Body Weight (g) | Adrenals | Thymus | Spleen | Ovaries with Oviduct | Uterus with Cervix | Heart | Kidneys | Brain | Liver |
G1, F & 0 | Mean | 181.39 | 0.0361 | 0.1930 | 0.7193 | 0.0557 | 0.2860 | 0.4168 | 0.7996 | 0.9098 | 3.8379 |
±SD | 5.09 | 0.0088 | 0.0496 | 0.2853 | 0.0110 | 0.1975 | 0.0013 | 0.0665 | 0.0434 | 0.3318 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G2, F & 100 | Mean | 192.11 | 0.0330 | 0.1498 | 0.5757 | 0.0598 | 0.2360 | 0.4313 | 0.7644 | 0.9024 | 3.5547 |
±SD | 11.58 | 0.0044 | 0.0423 | 0.1166 | 0.0025 | 0.0358 | 0.0288 | 0.0734 | 0.0730 | 0.2006 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G3, F & 300 | Mean | 182.68 | 0.0352 | 0.1651 | 0.5841 | 0.0647 | 0.2526 | 0.4388 | 0.7994 | 0.9410 | 3.6751 |
±SD | 3.97 | 0.0009 | 0.0076 | 0.1854 | 0.0152 | 0.0701 | 0.0553 | 0.0625 | 0.0302 | 0.2961 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | |
G4, F & 1000 | Mean | 192.63 | 0.0393 | 0.1997 | 0.5158 | 0.0568 | 0.2547 | 0.4455 | 0.7456 | 0.8953 | 3.9044 |
±SD | 15.88 | 0.0070 | 0.0447 | 0.0882 | 0.0039 | 0.0876 | 0.0458 | 0.0109 | 0.0995 | 0.3622 | |
n | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Applicant's summary and conclusion
- Conclusions:
- The NOAEL was determined to be at 1000 mg/kg bw/day in rats after 14 days of oral exposure.
- Executive summary:
A dose range finding study was performed for the test substance in accordance with OECD guideline 407 in order to evaluate its toxic potential after repeated exposure and select the appropriate doses for a subsequent toxicity study. The test item was diluted in corn oil (vehicle) and added to Sprague-Dawley rats (3 per sex per dose) at doses of 0 (vehicle only), 100, 300 and 1000 mg/kg bw/day for a period of 14 days. The vehicle and test item formulations were administered orally (gavage) at a dose volume of 10 mL/kg body weight. Freshly prepared test item formulations were administered to the animals as soon as possible after preparation.
All animals for each group were observed for clinical signs of toxicity once daily, mortality and morbidity twice daily, and body weight and feed consumption weekly. Clinical pathology (haematology, clinical chemistry analysis and urinalysis) was conducted for all the animals sacrificed at termination. All animals were subjected to gross pathological examination and the organs were weighed, collected and preserved.
No clinical signs of toxicity or mortality were observed. No treatment related changes in mean body weight and percent change in body weight (%) with respect to day 1 and feed consumption were observed. No treatment related changes were observed in haematology, coagulation, clinical chemistry and urinalysis parameters. No treatment related changes in fasting body weights, organ weights and its ratios were noted. No gross pathological changes were observed. Specifically, no gross pathological changes or effects in absolute and relative weights were noted in reproductive organs at any dose tested.
Based on these results, the NOAEL was determined to be at 1000 mg/kg bw/day.
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