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EC number: 941-303-6 | CAS number: 1689576-55-3
- 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
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 2017-05-18 to 2017-09-21
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- Adopted 1998-09-21
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Trioctyl benzene-1,2,4-tricarboxylate
- EC Number:
- 201-877-4
- EC Name:
- Trioctyl benzene-1,2,4-tricarboxylate
- Cas Number:
- 89-04-3
- Molecular formula:
- C33H54O6
- IUPAC Name:
- trioctyl benzene-1,2,4-tricarboxylate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Polynt Lot No. 3606217009
- Expiration date of the lot/batch: 09 Jan 2018
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient conditions
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: Soluble/miscible and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: None
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Envigo RMS srl, San Pietro al Natisone, Italy
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 42 - 44 days
- Weight at study initiation: Males: 181-226 g; Females: 144-177 g
- Fasting period before study: None
- Housing: Group caged
- Diet (e.g. ad libitum): Commercial laboratory rodent dient, ad-libitum
- Water (e.g. ad libitum): Municipal drinking water, ad-libitum
- Acclimation period: 15 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 deg C
- Humidity (%): 40 - 70 %
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 2017-05-25 To: 2017-09-21
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- - PREPARATION OF DOSING SOLUTIONS:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): Commonly used vehicle for non-water miscible materials
- Concentration in vehicle: 0, 10, 40 and 160 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The formulation procedure was checked in the range from 1 to 250 mg/mL by chemical analysis for concentration and homogeneity to confirm that the method was suitable.
Samples of the formulations prepared on Week 1 and last week (Week 13) of the dosing phase were analysed to check the homogeneity and concentration. - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Remarks:
- Vehicle control
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Dose / conc.:
- 800 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10 males/10 females per dose
Additional 5 males/5 females in control and high dose groups to examine recovery from treatment - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on data from shorter-term studies
- Rationale for animal assignment: Random
- Rationale for selecting satellite groups: Groups pre-assigned, animal assignment with groups random as for main study groups
- Post-exposure recovery period in satellite groups: 4 weeks
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: At least daily, at same time interval
- Cage side observations included. Mortality/morbidity, gross clinical signs/response to treatment
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
- Observations included: Detailed clinical examination in an open arena for changes in gait and posture, reactivity to handling, presence of clonic or tonic movements, stereotypies or bizarre behaviour
and effects on the autonomic nervous system (e.g. lachrymation, piloerection, unusual respiratory pattern). Changes in fur, skin, eyes, mucous membranes, occurrences of secretions and excretions.
BODY WEIGHT: Yes
- Time schedule for examinations: On the day of allocation to treatment, on the day before treatment commenced, weekly thereafter and just prior to necropsy.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes - Weight of food consumed by each cage of rats recorded at weekly
intervals following allocation. Group mean daily intake per rat calculated.
WATER CONSUMPTION AND COMPOUND INTAKE: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Pre-dose and during Week 13 of treatment.
- Dose groups that were examined: All animals pre-dose. Control and high-dose animals during Week 13 of treatment.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: During Week 13 of treatment and Week 4 of recovery
- Anaesthetic used for blood collection: Yes (isofluorane)
- Animals fasted: Yes
- How many animals: All animals
- Parameters examined: Haematocrit, Haemoglobin, Red blood cell count, Reticulocyte count, Mean red blood cell volume, Mean corpuscular haemoglobin, Mean corpuscular haemoglobin concentration,
White blood cell count , Differential leucocyte count, Platelets, Prothrombin time.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: During Week 13 of treatment and Week 4 of recovery
- Anaesthetic used for blood collection: Yes (isofluorane)
- Animals fasted: Yes
- How many animals: All animals
- Parameters examined: Alkaline phosphatase, Alanine aminotransferase, Aspartate aminotransferase, Gamma –glutamyltransferase, Urea, Creatinine, Glucose, Triglycerides, Phosphorus,
Total bilirubin, Total cholesterol, Total protein, Albumin, Globulin, A/G Ratio, Sodium, Potassium, Calcium, Chloride
URINALYSIS: Yes
- Time schedule for collection of blood: During Week 13 of treatment and Week 4 of recovery
- Animals fasted: Yes
- How many animals: All animals
- Parameters examined: Appearance, Volume, Specific gravity, pH, Protein, Glucose, Ketones, Bilirubin, Urobilinogen, Blood, sediment obtained from centrifugation examined microscopically for
epithelial cells, leucocytes, erythrocytes, crystals, spermatozoa and precursors, other abnormal components
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Once during Week 12 of treatment and once during Week 4 of recovery
- Dose groups that were examined: All groups at end of treatment phase, Control and high-dose animals at end of recovery phase.
- Battery of functions tested: Evaluation of sensory reactivity to stimuli of different modalities (e.g. auditory, visual and proprioceptive stimuli) and an assessment of grip strength. Motor activity
assessed using an automated activity recorder. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Detailed post mortem examination including examination of the external surface and orifices. Changes noted, the requisite organs weighed and the required tissue samples preserved in fixative.
Organ weights - Adrenal glands, Brain, Coagulating glands, Epididymides, Heart, Kidneys, Liver, Ovaries, Parathyroid glands, Prostate gland, Seminal vesicles, Spleen, Testes, Thymus (where
present), Thyroid, Uterus – cervix.
Tissues fixed and preserved – Abnormalities, Adrenal glands, Aorta, Bone marrow (from sternum), Brain (cerebrum, cerebellum, medullalpons), Caecum, Coagulating glands, Colon, Duodenum,
Epididymides, Eyes, Femur with joint, Heart, Ileum, Jejunum (including Peyer’s patches), Kidneys, Larynx, Liver, Lungs (including mainstem bronchi), Lymph nodes — cervical, Lymph nodes — mesenteric,
Mammary area, Nasopharynx, Oesophagus, Optic nerves, Ovaries, Oviducts, Pancreas, Parathyroid glands, Pituitary gland, Prostate gland, Rectum, Salivary glands, Sciatic nerve, Seminal vesicles,
Skeletal muscle, Skin, Spinal column, Spinal cord (cervical, mid-thoracic, lumbar), Spleen, Stomach, Testes, Thymus (where present), Thyroid, Trachea, Urinary bladder, Uterus – cervix, Vagina
HISTOPATHOLOGY: Yes
Tissues examined - Abnormalities, Adrenal glands, Aorta, Bone marrow (from sternum), Brain (cerebrum, cerebellum, medullalpons), Caecum, Coagulating glands, Colon, Duodenum,
Epididymides, Eyes, Femur with joint, Heart, Ileum, Jejunum (including Peyer’s patches), Kidneys, Larynx, Liver, Lungs (including mainstem bronchi), Lymph nodes — cervical, Lymph nodes — mesenteric,
Mammary area, Nasopharynx, Oesophagus, Optic nerves, Ovaries, Oviducts, Pancreas, Parathyroid glands, Pituitary gland, Prostate gland, Rectum, Salivary glands, Sciatic nerve, Seminal vesicles,
Skeletal muscle, Skin, Spinal cord (cervical, mid-thoracic, lumbar), Spleen, Stomach, Testes, Thymus (where present), Thyroid, Trachea, Urinary bladder, Uterus – cervix, Vagina
After dehydration and embedding in paraffin wax, sections were cut at 5 micrometre thickness and stained with haematoxylin and eosin. In the first instance the examination was limited to: All abnormalities in all main
phase groups and tissues listed above from all animals in the control and high dose groups at the end of the 13 weeks of treatment. Examination of the liver and spleen was extended to intermediate groups and
recovery animals. In addition, the testes and epididymides of main group animals were cut at 2-3 micrometre thickness and stained with Periodic Acid Schiff (PAS). The morphological evaluation of the seminiferous
epithelium (staging of spermatogenic cycle) was performed in all animals of the control and high dose groups at the end of the 13 weeks of treatment. - Other examinations:
- The testes and epididymides of main group animals were cut at 2-3 micrometre thickness and stained with Periodic Acid Schiff (PAS). A morphological evaluation of the seminiferous epithelium (staging of
spermatogenic cycle) was performed on all animals in the control and high dose groups killed at the end of the 13 weeks of treatment. Should effects have been observed, examination would have been
extended to animals of intermediate groups and recovery groups. - Statistics:
- For continuous variables the significance of the differences amongst group means was assessed by Dunnett’s test or a modified t test, depending on the homogeneity of data.
Statistical analysis of histopathological findings was carried out by means of the non parametric Kolmogorov Smirnov test.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Leucocytosis, mainly represented by increased lymphocytes and monocytes, was noted in a number of animals from all treated groups.
Changes were with no dose-relation and males were more sensitive than females - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Fluctuations of some parameters (alkaline phosphatase, total bilirubin, triglycerides) were recorded in treated animals.
Due to the slight severity and/or absence of dose-relation, the severity of these findings was not considered to be suggestive of tissue/organ injury. - Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Absolute and relative liver weights were increased approximately 25% in high dose (800 mg/kg bw/day males and females.
The relative weight (to terminal body weight) of the liver was also increased in Group 3 animals (200 mg/kg bw/day). - Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment-related findings were only seen in the liver of most males and females treated at 800 mg/kg bw/day.
Minimal, hepatocellular hypertrophy with centrilobular distribution, morphologically represented by a minimal increase in liver cell size, accompanied by an increase in liver weight,
when compared with controls, was commonly associated with microsomal enzyme induction and considered in this case as an adaptive response - Other effects:
- no effects observed
- Description (incidence and severity):
- Seminiferous tubules were evaluated with respect to their stage in the spermatogenic cycle and to the integrity of the various cell types within the different stages.
Regular layering in the germinal epithelium was noted and the cycle of spermatogenesis in the high dose males was regarded as normal with no treatment-related effect apparent.
Normal physiology of the oestrous cycle (oestrus, metestrus, diestrus and proestrus) was noted in control and treated females. The morphological changes seen were normal when
compared to each “oestrus phase” in the ovaries, uterus/cervix and vagina.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 800 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- no
- Lowest effective dose / conc.:
- 800 mg/kg bw/day (nominal)
- System:
- hepatobiliary
- Organ:
- liver
Any other information on results incl. tables
Body weight (g) - Group mean data
Males |
|
|
|
|
|
|
|
Treatment Day |
|
|
|
|
|
|
|
|
|
1 |
8 |
15 |
22 |
29 |
36 |
43 |
50 |
57 |
64 |
71 |
78 |
85 |
92 |
|
(n) |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
Control |
Mean |
206.10 |
257.26 |
297.97 |
330.65 |
354.21 |
375.46 |
391.38 |
407.69 |
417.38 |
426.77 |
434.11 |
444.59 |
452.85 |
443.87 |
|
SD |
9.186 |
12.573 |
16.945 |
18.495 |
21.101 |
23.511 |
25.325 |
26.277 |
27.477 |
29.018 |
30.732 |
31.424 |
33.114 |
37.744 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
205.66 |
257.19 |
301.54 |
332.12 |
354.93 |
376.75 |
394.49 |
411.29 |
420.31 |
430.56 |
439.41 |
448.09 |
456.96 |
442.66 |
|
SD |
8.035 |
14.045 |
21.965 |
25.789 |
26.152 |
28.406 |
29.724 |
30.992 |
32.992 |
33.890 |
35.674 |
37.576 |
39.497 |
40.577 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
207.75 |
261.09 |
305.55 |
336.02 |
358.37 |
378.18 |
394.96 |
412.41 |
420.61 |
430.64 |
438.59 |
449.21 |
456.70 |
438.66 |
|
SD |
10.601 |
15.130 |
19.735 |
23.387 |
27.611 |
30.222 |
32.541 |
34.286 |
32.617 |
33.558 |
37.864 |
41.566 |
38.985 |
39.664 |
|
(n) |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
800 mg/kg |
Mean |
206.79 |
256.69 |
297.54 |
326.23 |
345.90 |
364.95 |
378.73 |
391.86 |
400.69 |
408.26 |
415.77 |
421.59 |
429.58 |
417.81 |
|
SD |
13.059 |
17.097 |
19.175 |
21.858 |
23.728 |
24.501 |
24.476 |
25.001 |
27.528 |
27.927 |
26.854 |
28.853 |
29.291 |
33.514 |
Males |
|
|
Recovery Day |
|
|
|
|
8 |
15 |
22 |
29 |
|
(n) |
5 |
5 |
5 |
5 |
Control |
Mean |
478.40 |
487.86 |
493.92 |
475.86 |
|
SD |
41.003 |
46.580 |
55.650 |
54.009 |
|
(n) |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
442.90 |
451.70 |
458.62 |
446.44 |
|
SD |
41.771 |
38.104 |
40.245 |
37.303 |
Females |
|
|
|
|
|
|
|
Treatment Day |
|
|
|
|
|
|
|
|
|
1 |
8 |
15 |
22 |
29 |
36 |
43 |
50 |
57 |
64 |
71 |
78 |
85 |
92 |
|
(n) |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
Control |
Mean |
159.50 |
181.24 |
194.11 |
210.43 |
220.31 |
229.25 |
239.47 |
244.41 |
249.87 |
253.57 |
255.67 |
264.56 |
268.06 |
265.77 |
|
SD |
7.993 |
7.875 |
9.302 |
11.329 |
13.014 |
12.911 |
13.028 |
13.157 |
15.413 |
15.064 |
13.315 |
15.595 |
18.342 |
16.741 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
160.13 |
180.02 |
193.70 |
209.24 |
222.45 |
230.78 |
236.94 |
243.94 |
248.02 |
251.94 |
255.20 |
265.59 |
271.77 |
264.01 |
|
SD |
6.158 |
7.218 |
9.808 |
12.724 |
13.319 |
14.007 |
12.756 |
14.412 |
15.970 |
14.168 |
17.436 |
11.912 |
12.745 |
14.810 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
158.94 |
177.94 |
187.39 |
201.06 |
214.10 |
221.05 |
229.99 |
236.13 |
239.18 |
242.74 |
245.50 |
261.86 |
265.89 |
258.18 |
|
SD |
7.389 |
14.173 |
18.364 |
20.167 |
23.240 |
20.702 |
22.514 |
22.849 |
21.424 |
21.844 |
20.503 |
22.838 |
20.176 |
20.051 |
|
(n) |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
15 |
800 mg/kg |
Mean |
159.35 |
179.51 |
192.91 |
205.89 |
217.01 |
225.83 |
234.09 |
241.49 |
245.33 |
247.59 |
250.87 |
258.26 |
262.08 |
258.97 |
|
SD |
7.415 |
8.743 |
11.766 |
14.402 |
14.231 |
13.939 |
15.163 |
15.089 |
14.991 |
14.613 |
16.792 |
16.396 |
17.949 |
18.740 |
Females |
|
|
Recovery Day |
|
|
|
|
8 |
15 |
22 |
29 |
|
(n) |
5 |
5 |
5 |
5 |
Control |
Mean |
261.52 |
263.24 |
266.16 |
260.64 |
|
SD |
19.520 |
22.964 |
24.209 |
24.966 |
|
(n) |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
265.18 |
270.14 |
269.10 |
252.90 |
|
SD |
17.092 |
17.966 |
16.195 |
15.697 |
Food consumption (g) - Group mean data
Males |
|
|
|
|
|
|
|
Treatment Day |
|
|
|
|
|
|
|
|
8 |
15 |
22 |
29 |
36 |
43 |
50 |
57 |
64 |
71 |
78 |
85 |
92 |
|
(n) |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
Control |
Mean |
23.02 |
23.10 |
22.82 |
22.13 |
21.56 |
21.22 |
20.67 |
19.78 |
19.49 |
18.97 |
18.48 |
18.86 |
15.54 |
|
SD |
0.762 |
1.209 |
1.108 |
0.814 |
0.760 |
0.430 |
0.663 |
0.577 |
0.610 |
0.862 |
1.009 |
0.721 |
2.160 |
|
(n) |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
50 mg/kg |
Mean |
22.87 |
23.06 |
22.40 |
23.02 |
21.76 |
21.54 |
20.48 |
20.40 |
20.06 |
19.75 |
19.23 |
19.77 |
15.65 |
|
SD |
1.299 |
0.867 |
0.579 |
1.044 |
0.604 |
0.941 |
1.179 |
0.995 |
0.731 |
0.807 |
0.936 |
0.724 |
0.876 |
|
(n) |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
200 mg/kg |
Mean |
23.15 |
23.80 |
23.28 |
22.30 |
21.96 |
21.69 |
20.72 |
20.44 |
20.12 |
19.98 |
19.64 |
19.66 |
14.97 |
|
SD |
0.896 |
1.056 |
1.323 |
1.126 |
5.570 |
1.103 |
0.798 |
1.113 |
0.871 |
0.926 |
0.837 |
0.436 |
0.163 |
|
(n) |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
800 mg/kg |
Mean |
21.37*D |
22.45 |
22.79 |
22.31 |
21.75 |
21.81 |
20.25 |
20.50 |
19.63 |
19.45 |
17.98 |
19.18 |
16.13 |
|
SD |
1.020 |
1.343 |
1.205 |
1.232 |
1.049 |
1.100 |
1.450 |
1.510 |
1.085 |
1.276 |
2.972 |
1.336 |
2.283 |
Males |
|
|
Recovery Day |
|
|
|
|
8 |
15 |
22 |
29 |
|
(n) |
2 |
2 |
2 |
2 |
Control |
Mean |
34.35 |
23.17 |
26.88 |
22.30 |
|
SD |
2.133 |
3.357 |
2.234 |
1.414 |
|
(n) |
2 |
2 |
2 |
2 |
800 mg/kg |
Mean |
15.21 |
24.79 |
25.45 |
21.58 |
|
SD |
8.656 |
1.057 |
0.422 |
1.156 |
Females |
|
|
|
|
|
|
|
Treatment Day |
|
|
|
|
|
|
|
|
8 |
15 |
22 |
29 |
36 |
43 |
50 |
57 |
64 |
71 |
78 |
85 |
92 |
|
(n) |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
Control |
Mean |
16.05 |
16.27 |
15.51 |
15.61 |
15.12 |
15.66 |
14.53 |
14.41 |
14.83 |
13.32 |
13.82 |
14.30 |
11.87 |
|
SD |
0.578 |
2.389 |
0.368 |
0.662 |
0.536 |
0.715 |
0.391 |
0.864 |
1.300 |
0.509 |
0.694 |
1.070 |
0.422 |
|
(n) |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
50 mg/kg |
Mean |
15.47 |
15.11 |
15.64 |
16.17 |
15.82 |
15.44 |
14.14 |
14.13 |
14.60 |
14.02 |
14.24 |
14.50 |
11.97 |
|
SD |
0.555 |
0.466 |
0.664 |
0.468 |
0.745 |
0.760 |
0.500 |
0.642 |
0.915 |
0.559 |
1.399 |
0.616 |
1.095 |
|
(n) |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
200 mg/kg |
Mean |
15.24 |
14.45 |
15.12 |
15.58 |
14.13 |
15.17 |
13.65 |
13.52 |
12.94 |
13.21 |
14.16 |
14.04 |
10.75 |
|
SD |
1.056 |
1.546 |
1.091 |
1.168 |
0.758 |
2.345 |
0.559 |
0.489 |
1.958 |
0.679 |
0.662 |
0.914 |
0.532 |
|
(n) |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
6 |
800 mg/kg |
Mean |
15.34 |
15.21 |
15.68 |
15.88 |
15.42 |
15.43 |
15.20 |
14.27 |
14.76 |
13.74 |
13.49 |
14.27 |
12.28 |
|
SD |
0.677 |
0.990 |
0.854 |
0.673 |
1.603 |
1.504 |
2.139 |
0.790 |
1.049 |
1.131 |
1.156 |
1.140 |
1.104 |
Females |
|
|
Recovery Day |
|
|
|
|
8 |
15 |
22 |
29 |
|
(n) |
2 |
2 |
2 |
2 |
Control |
Mean |
16.40 |
16.67 |
16.98 |
14.97 |
|
SD |
0.406 |
0.375 |
0.031 |
0.211 |
|
(n) |
2 |
2 |
2 |
2 |
800 mg/kg |
Mean |
16.82 |
18.22 |
17.59 |
14.00 |
|
SD |
1.643 |
1.350 |
0.883 |
0.897 |
Haematology - Terminal sacrifice - Group mean data
Males |
|
RBC |
HGB |
HCT |
MCV |
MCH |
MCHC |
RET |
RETR |
WBC |
|
|
(x10E6/μL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(x10E9/L) |
(%) |
(x10E3/μL) |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
8.257 |
14.54 |
44.52 |
53.91 |
17.61 |
32.70 |
158.62 |
1.921 |
7.217 |
|
SD |
0.2502 |
0.276 |
1.401 |
1.006 |
0.398 |
0.632 |
13.180 |
0.1500 |
1.6226 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
8.201 |
14.68 |
45.13 |
55.03 |
17.91 |
32.58 |
164.10 |
2.000 |
9.510+D |
|
SD |
0.1962 |
0.365 |
1.538 |
1.396 |
0.325 |
0.561 |
17.706 |
0.1988 |
1.2913 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
8.520 |
14.98 |
46.09 |
54.08 |
17.60 |
32.51 |
164.63 |
1.925 |
9.637+D |
|
SD |
0.5238 |
0.764 |
2.799 |
0.992 |
0.527 |
0.669 |
28.522 |
0.2449 |
1.1377 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
8.334 |
14.73 |
45.09 |
54.09 |
17.67 |
32.66 |
147.61 |
1.768 |
9.169+D |
|
SD |
0.2876 |
0.604 |
1.806 |
1.003 |
0.337 |
0.288 |
21.134 |
0.2301 |
1.4721 |
Males |
|
NEU |
LYM |
MON |
EOS |
BAS |
LUC |
NEUR |
LYMR |
MONR |
EOSR |
BASR |
LUCR |
PLT |
PT |
|
|
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(x10E3/μL) |
(sec) |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
1.078 |
5.735 |
0.204 |
0.091 |
0.056 |
0.053 |
14.80 |
79.54 |
2.87 |
1.29 |
0.76 |
0.74 |
873.1 |
19.98 |
|
SD |
0.6394 |
1.3202 |
0.0554 |
0.0281 |
0.0196 |
0.0216 |
6.455 |
6.255 |
0.615 |
0.370 |
0.151 |
0.190 |
61.10 |
0.594 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
1.133 |
7.821+D |
0.281*D |
0.105 |
0.093+D |
0.077*C |
11.65 |
82.42 |
3.00 |
1.12 |
0.98*D |
0.81 |
863.8 |
19.66 |
|
SD |
0.4925 |
0.9709 |
0.0536 |
0.0378 |
0.0216 |
0.0149 |
3.686 |
3.924 |
0.741 |
0.343 |
0.132 |
0.173 |
102.29 |
0.440 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
1.216 |
7.816+D |
0.332+D |
0.083 |
0.097+D |
0.087*C |
12.72 |
81.05 |
3.43 |
0.89*D |
1.01*D |
0.89 |
836.0 |
19.55 |
|
SD |
0.2718 |
1.0413 |
0.0846 |
0.0200 |
0.0275 |
0.0340 |
2.945 |
3.153 |
0.682 |
0.26 |
0.238 |
0.311 |
46.44 |
0.544 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
0.959 |
7.637+D |
0.316+D |
0.063 |
0.083 |
0.113+C |
10.47 |
83.32 |
3.45 |
0.66+D |
0.88 |
1.22*C |
865.5 |
20.41 |
|
SD |
0.2335 |
1.2057 |
0.0793 |
0.0283 |
0.0323 |
0.0531 |
2.110 |
2.478 |
0.615 |
0.222 |
0.193 |
0.437 |
57.09 |
0.808 |
Females |
|
RBC |
HGB |
HCT |
MCV |
MCH |
MCHC |
RET |
RETR |
WBC |
|
|
(x10E6/μL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(x10E9/L) |
(%) |
(x10E3/μL) |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
7.426 |
13.83 |
42.63 |
57.42 |
18.63 |
32.42 |
174.78 |
2.353 |
4.966 |
|
SD |
0.2726 |
0.523 |
1.758 |
1.225 |
0.350 |
0.361 |
32.840 |
0.4335 |
1.0897 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
7.523 |
13.91 |
42.53 |
56.56 |
18.50 |
32.73 |
145.89 |
1.943 |
5.946 |
|
SD |
0.2931 |
0.479 |
1.748 |
0.906 |
0.383 |
0.356 |
20.732 |
0.2886 |
1.4523 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
7.349 |
13.58 |
41.80 |
56.92 |
18.50 |
32.51 |
148.03 |
2.015 |
6.169 |
|
SD |
0.3193 |
0.365 |
1.473 |
1.737 |
0.577 |
0.345 |
28.280 |
0.3853 |
1.0246 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
7.500 |
13.83 |
42.54 |
56.74 |
18.43 |
32.53 |
158.59 |
2.123 |
5.924 |
|
SD |
0.3016 |
0.521 |
1.833 |
1.326 |
0.350 |
0.347 |
29.226 |
0.4272 |
0.7587 |
Females |
|
NEU |
LYM |
MON |
EOS |
BAS |
LUC |
NEUR |
LYMR |
MONR |
EOSR |
BASR |
LUCR |
PLT |
PT |
|
|
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(x10E3/μL) |
(sec) |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
0.448 |
4.305 |
0.089 |
0.079 |
0.024 |
0.021 |
9.18 |
86.48 |
1.81 |
1.62 |
0.45 |
0.44 |
985.9 |
23.44 |
|
SD |
0.1440 |
1.0019 |
0.0360 |
0.0208 |
0.0117 |
0.0099 |
2.296 |
2.409 |
0.656 |
0.478 |
0.158 |
0.143 |
89.05 |
0.908 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
0.461 |
5.168 |
0.145*D |
0.112 |
0.033 |
0.028 |
7.94 |
86.75 |
2.54 |
1.80 |
0.50 |
0.47 |
965.3 |
22.73 |
|
SD |
0.1225 |
1.3316 |
0.0438 |
0.1203 |
0.0170 |
0.0140 |
1.731 |
2.848 |
0.844 |
1.702 |
0.183 |
0.134 |
117.68 |
1.106 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
0.440 |
5.464 |
0.127 |
0.072 |
0.029 |
0.036 |
7.10 |
88.58 |
2.12 |
1.18 |
0.45 |
0.58 |
935.7 |
22.98 |
|
SD |
0.1438 |
0.9283 |
0.0469 |
0.0270 |
0.0088 |
0.0126 |
1.573 |
2.134 |
0.761 |
0.405 |
0.071 |
0.193 |
188.66 |
1.583 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
0.510 |
5.121 |
0.146*D |
0.071 |
0.032 |
0.043+D |
8.67 |
86.41 |
2.46 |
1.24 |
0.51 |
0.73+D |
965.4 |
22.70 |
|
SD |
0.2047 |
0.7039 |
0.0386 |
0.0264 |
0.0140 |
0.0195 |
3.666 |
3.266 |
0.638 |
0.357 |
0.179 |
0.271 |
106.27 |
1.347 |
Haematology - Recovery sacrifice - Group mean data
Males |
|
RBC |
HGB |
HCT |
MCV |
MCH |
MCHC |
RET |
RETR |
WBC |
|
|
(x10E6/μL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(x10E9/L) |
(%) |
(x10E3/μL) |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
9.348 |
15.82 |
51.04 |
54.60 |
16.94 |
31.02 |
171.30 |
1.828 |
7.022 |
|
SD |
0.1883 |
0.148 |
1.210 |
1.334 |
0.251 |
0.531 |
27.001 |
0.2621 |
1.2996 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
8.882 |
15.52 |
49.34 |
55.58 |
17.48*D |
31.42 |
197.68 |
2.238 |
6.442 |
|
SD |
0.4775 |
0.716 |
2.082 |
1.904 |
0.444 |
0.522 |
46.671 |
0.5832 |
0.5558 |
Males |
|
NEU |
LYM |
MON |
EOS |
BAS |
LUC |
NEUR |
LYMR |
MONR |
EOSR |
BASR |
LUCR |
PLT |
|
|
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(x10E3/μL) |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
0.746 |
5.738 |
0.274 |
0.144 |
0.080 |
0.046 |
10.78 |
81.28 |
3.94 |
2.22 |
1.08 |
0.64 |
942.6 |
|
SD |
0.1623 |
1.2240 |
0.0472 |
0.0650 |
0.0224 |
0.0134 |
2.286 |
3.761 |
0.760 |
1.472 |
0.110 |
0.089 |
100.50 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
0.808 |
5.172 |
0.238 |
0.124 |
0.054*D |
0.046 |
12.50 |
80.28 |
3.66 |
1.98 |
0.88*D |
0.74 |
932.4 |
|
SD |
0.1344 |
0.4123 |
0.0978 |
0.0635 |
0.0089 |
0.0089 |
1.505 |
1.424 |
1.246 |
1.123 |
0.084 |
0.114 |
56.64 |
Females |
|
RBC |
HGB |
HCT |
MCV |
MCH |
MCHC |
RET |
RETR |
WBC |
|
|
(x10E6/μL) |
(g/dL) |
(%) |
(fL) |
(pg) |
(g/dL) |
(x10E9/L) |
(%) |
(x10E3/μL) |
|
(n) |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
Control |
Mean |
8.438 |
15.15 |
46.18 |
54.73 |
17.98 |
32.80 |
148.98 |
1.765 |
4.293 |
|
SD |
0.2534 |
0.480 |
1.576 |
0.670 |
0.250 |
0.082 |
16.391 |
0.1686 |
0.4586 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
8.420 |
15.20 |
46.20 |
54.86 |
18.04 |
32.86 |
136.50 |
1.622 |
4.380 |
|
SD |
0.1719 |
0.485 |
1.263 |
0.416 |
0.336 |
0.428 |
28.175 |
0.3432 |
1.2468 |
Females |
|
NEU |
LYM |
MON |
EOS |
BAS |
LUC |
NEUR |
LYMR |
MONR |
EOSR |
BASR |
LUCR |
PLT |
|
|
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(x10E3/μL) |
(%) |
(%) |
(%) |
(%) |
(%) |
(%) |
(x10E3/μL) |
|
(n) |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
Control |
Mean |
0.493 |
3.488 |
0.148 |
0.105 |
0.033 |
0.028 |
11.38 |
81.38 |
3.43 |
2.48 |
0.70 |
0.63 |
1060.3 |
|
SD |
0.1320 |
0.3457 |
0.0403 |
0.0191 |
0.0096 |
0.0050 |
2.398 |
2.484 |
0.814 |
0.492 |
0.216 |
0.126 |
46.29 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
0.422 |
3.654 |
0.146 |
0.082 |
0.042 |
0.036 |
9.54 |
83.64 |
3.32 |
1.86 |
0.90 |
0.74 |
997.6 |
|
SD |
0.1452 |
1.0038 |
0.0573 |
0.0286 |
0.0239 |
0.0182 |
1.274 |
1.942 |
0.476 |
0.483 |
0.255 |
0.251 |
116.77 |
Clinical chemistry - Terminal sacrifice - Group mean data
Males |
|
ALP |
ALT |
AST |
GGT |
TBIL |
CHOL |
TRIG |
GLU |
UREA |
|
|
(U/L) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
|
(n) |
10 |
10 |
10 |
0@ |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
185.54 |
38.76 |
77.68 |
- |
0.057 |
72.59 |
29.49 |
120.51 |
28.01 |
|
SD |
21.942 |
15.476 |
15.759 |
- |
0.0170 |
3.566 |
9.029 |
18.760 |
5.368 |
|
(n) |
10 |
10 |
10 |
0@ |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
192.63 |
37.07 |
75.02 |
- |
0.053 |
76.57 |
49.09+D |
156.00*D |
29.74 |
|
SD |
37.139 |
9.523 |
22.362 |
- |
0.0164 |
10.797 |
16.901 |
36.559 |
6.259 |
|
(n) |
10 |
10 |
10 |
1@ |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
214.29 |
37.25 |
67.29 |
0.90 |
0.041 |
81.56 |
55.40+D |
125.83 |
26.07 |
|
SD |
43.789 |
3.955 |
6.330 |
- |
0.0137 |
12.757 |
9.497 |
18.217 |
4.781 |
|
(n) |
10 |
10 |
10 |
4@ |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
358.20+C |
47.34 |
64.72 |
0.45 |
0.022+D |
94.77#C |
59.07+D |
150.54 |
26.73 |
|
SD |
139.244 |
10.907 |
7.801 |
0.412 |
0.0123 |
10.482 |
15.711 |
35.365 |
4.719 |
Males |
|
CREA |
Cl |
Ca |
Na |
K |
IP |
PROT |
ALB |
GLO |
AG |
|
|
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mg/dL) |
(g/dL) |
(g/dL) |
(g/dL) |
|
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
0.391 |
101.05 |
2.651 |
144.54 |
4.010 |
6.095 |
6.45 |
3.72 |
2.73 |
1.36 |
|
SD |
0.0357 |
1.099 |
0.0924 |
0.769 |
0.2593 |
0.6497 |
0.201 |
0.140 |
0.082 |
0.052 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
0.412 |
100.50 |
2.650 |
144.41 |
4.097 |
6.137 |
6.31 |
3.66 |
2.65 |
1.38 |
|
SD |
0.0605 |
1.101 |
0.0478 |
0.610 |
0.2863 |
0.4611 |
0.238 |
0.158 |
0.118 |
0.063 |
|
(n) |
10 |
10 |
2.733 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
0.401 |
100.81 |
0.0887 |
144.41 |
4.049 |
6.244 |
6.32 |
3.70 |
2.62 |
1.42 |
|
SD |
0.0626 |
1.009 |
|
0.610 |
0.2465 |
0.4127 |
0.215 |
0.156 |
0.103 |
0.079 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
0.394 |
102.46*D |
2.709 |
144.78 |
3.904 |
6.732*D |
5.73+D |
3.43+D |
2.30+D |
1.50+D |
|
SD |
0.0749 |
0.9950 |
0.0755 |
0.691 |
0.2738 |
0.4101 |
0.323 |
0.183 |
0.156 |
0.047 |
Females |
|
ALP |
ALT |
AST |
GGT |
TBIL |
CHOL |
TRIG |
GLU |
UREA |
|
|
(U/L) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
|
(n) |
10 |
10 |
10 |
8@ |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
136.06 |
25.92 |
58.13 |
0.78 |
0.056 |
78.36 |
37.50 |
131.20 |
31.54 |
|
SD |
25.430 |
3.469 |
6.285 |
0.453 |
0.0158 |
13.220 |
6.846 |
15.874 |
4.913 |
|
(n) |
10 |
10 |
10 |
8@ |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
140.90 |
26.81 |
66.69*C |
0.79 |
0.041 |
72.34 |
36.55 |
118.08 |
35.19 |
|
SD |
42.704 |
3.542 |
7.029 |
0.795 |
0.0120 |
12.370 |
6.196 |
16.967 |
6.686 |
|
(n) |
10 |
10 |
10 |
8@ |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
140.08 |
23.06 |
50.26+C |
0.53 |
0.050 |
64.30*D |
41.05 |
157.42 |
29.42 |
|
SD |
39.369 |
4.656 |
4.093 |
0.486 |
0.0271 |
9.302 |
10.554 |
39.192 |
2.929 |
|
(n) |
9 |
9 |
9 |
8@ |
9 |
9 |
9 |
9 |
9 |
800 mg/kg |
Mean |
179.60 |
34.08 |
65.94 |
0.70 |
0.034 |
76.93 |
45.07 |
169.66*C |
29.60 |
|
SD |
39.862 |
11.452 |
25.231 |
0.457 |
0.0188 |
5.754 |
7.744 |
31.189 |
4.677 |
Females |
|
CREA |
Cl |
Ca |
Na |
K |
IP |
PROT |
ALB |
GLO |
AG |
|
|
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mg/dL) |
(g/dL) |
(g/dL) |
(g/dL) |
|
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
0.377 |
100.90 |
2.604 |
141.85 |
3.300 |
5.465 |
5.95 |
3.59 |
2.36 |
1.52 |
|
SD |
0.0254 |
1.757 |
0.1230 |
1.628 |
0.1719 |
0.6427 |
0.443 |
0.288 |
0.165 |
0.063 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
0.414 |
102.27 |
2.718*D |
143.20 |
3.635*D |
6.314+D |
5.96 |
3.60 |
2.36 |
1.51 |
|
SD |
0.0718 |
1.061 |
0.0787 |
1.566 |
0.2331 |
0.4998 |
0.357 |
0.221 |
0.151 |
0.057 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
0.393 |
101.72 |
2.627 |
141.90 |
3.781+D |
6.285+D |
5.48*D |
3.33*D |
2.15*D |
1.55 |
|
SD |
0.0330 |
1.062 |
0.0595 |
0.751 |
0.2824 |
0.6196 |
0.358 |
0.221 |
0.172 |
0.108 |
|
(n) |
9 |
9 |
9 |
9 |
9 |
9 |
9 |
9 |
9 |
9 |
800 mg/kg |
Mean |
0.394 |
101.060 |
2.616 |
142.40 |
3.740+D |
5.999 |
5.49*D |
3.36 |
2.13*D |
1.58 |
|
SD |
0.0482 |
1.788 |
0.0930 |
1.663 |
0.2844 |
0.4411 |
3.48 |
0.188 |
0.173 |
0.067 |
Clinical chemistry - Recovery sacrifice - Group mean data
Males |
|
ALP |
ALT |
AST |
GGT |
TBIL |
CHOL |
TRIG |
GLU |
UREA |
|
|
(U/L) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
|
(n) |
5 |
5 |
5 |
1@ |
4@ |
5 |
5 |
5 |
5 |
Control |
Mean |
168.08 |
42.68 |
56.28 |
0.90 |
0.045 |
112.74 |
131.74 |
133.42 |
32.10 |
|
SD |
19.615 |
2.739 |
8.854 |
- |
0.0311 |
24.430 |
98.531 |
38.102 |
4.027 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
161.76 |
37.82 |
55.00 |
1.16 |
0.046 |
95.42 |
102.46 |
171.88 |
33.48 |
|
SD |
30.229 |
5.136 |
14.137 |
0.594 |
0.0241 |
11.540 |
32.405 |
59.304 |
2.587 |
Males |
|
CREA |
Cl |
Ca |
Na |
K |
IP |
PROT |
ALB |
GLO |
AG |
|
|
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mg/dL) |
(g/dL) |
(g/dL) |
(g/dL) |
|
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
0.328 |
99.16 |
2.780 |
142.70 |
4.058 |
4.838 |
6.80 |
3.94 |
2.86 |
1.36 |
|
SD |
0.0460 |
2.392 |
0.0469 |
1.907 |
0.5964 |
0.6305 |
0.141 |
0.152 |
0.114 |
0.089 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
0.304 |
99.80 |
2.774 |
141.96 |
4.112 |
5.930*D |
6.52 |
3.78 |
2.74 |
1.38 |
|
SD |
0.0288 |
2.113 |
0.0856 |
1.616 |
0.2872 |
0.7296 |
0.432 |
0.239 |
0.207 |
0.045 |
Females |
|
ALP |
ALT |
AST |
GGT |
TBIL |
CHOL |
TRIG |
GLU |
UREA |
|
|
(U/L) |
(U/L) |
(U/L) |
(U/L) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
(mg/dL) |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
112.24 |
43.92 |
65.06 |
0.68 |
0.058 |
101.24 |
64.16 |
97.00 |
42.42 |
|
SD |
16.131 |
4.853 |
7.996 |
0.421 |
0.0084 |
26.033 |
9.259 |
13.258 |
4.209 |
|
(n) |
5 |
5 |
5 |
3@ |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
106.56 |
30.54+D |
61.24 |
1.33 |
0.066 |
116.52 |
58.78 |
99.00 |
29.50+D |
|
SD |
12.195 |
4.229 |
5.693 |
0.896 |
0.0261 |
24.905 |
12.857 |
4.995 |
3.236 |
Females |
|
CREA |
Cl |
Ca |
Na |
K |
IP |
PROT |
ALB |
GLO |
AG |
|
|
(mg/dL) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mmol/L) |
(mg/dL) |
(g/dL) |
(g/dL) |
(g/dL) |
|
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
0.360 |
100.68 |
2.704 |
141.36 |
3.370 |
4.608 |
6.78 |
4.04 |
2.74 |
1.46 |
|
SD |
0.0316 |
1.469 |
0.0391 |
1.193 |
0.3338 |
0.4456 |
0.311 |
0.152 |
0.167 |
0.055 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
0.330 |
101.86 |
2.716 |
141.36 |
3.564 |
5.290 |
6.48 |
3.88 |
2.60 |
1.50 |
|
SD |
0.0480 |
1.798 |
0.0654 |
1.471 |
0.3378 |
0.8643 |
0.164 |
0.148 |
0.071 |
0.100 |
Absolute organ weight - Terminal sacrifice - Group mean data
Males |
|
Body weight |
Adrenals |
Brain |
Epididymides |
Heart |
Kidneys |
Liver |
Spleen |
Testes |
Thymus |
Thyroid |
|
|
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
427.89 |
0.0590 |
1.862 |
1.3769 |
1.442 |
2.721 |
11.433 |
0.7690 |
3.9619 |
0.3236 |
0.0253 |
|
SD |
32.077 |
0.01232 |
0.0552 |
0.10262 |
0.0952 |
0.2481 |
1.2470 |
0.10846 |
0.20651 |
0.04725 |
0.00957 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
440.59 |
0.0608 |
1.891 |
1.4550 |
1.499 |
2.783 |
12.235 |
0.8295 |
3.9352 |
0.3813 |
0.0210 |
|
SD |
40.093 |
0.01069 |
0.0860 |
0.09291 |
0.1611 |
0.3009 |
1.3782 |
0.08300 |
0.21285 |
0.09731 |
0.00455 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
436.84 |
0.0554 |
1.900 |
1.3520 |
1.431 |
2.685 |
12.571 |
0.7816 |
3.6699 |
0.3447 |
0.0236 |
|
SD |
40.037 |
0.00698 |
0.0910 |
0.20774 |
0.1081 |
0.2733 |
1.4254 |
0.07942 |
0.89508 |
0.09736 |
0.00591 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
404.34 |
0.0570 |
1.834 |
1.3379 |
1.346 |
2.568 |
13.490+D |
0.7262 |
4.0157 |
0.3054 |
0.0195 |
|
SD |
21.486 |
0.00920 |
0.0837 |
0.06782 |
0.1192 |
0.4162 |
0.6409 |
0.08242 |
0.28532 |
0.03642 |
0.00584 |
Females |
|
Body weight |
Adrenals |
Brain |
Heart |
Kidneys |
Liver |
Ovaries |
Spleen |
Thymus |
Thyroid |
Uterus |
|
|
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
253.73 |
0.0585 |
1.762 |
0.959 |
1.557 |
6.897 |
0.1323 |
0.6248 |
0.2409 |
0.0264 |
1.0999 |
|
SD |
11.839 |
0.00829 |
0.0770 |
0.0558 |
0.1198 |
0.5130 |
0.02362 |
0.10721 |
0.05145 |
0.00272 |
0.53173 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
249.08 |
0.0598 |
1.763 |
0.932 |
1.577 |
7.098 |
0.1319 |
0.6015 |
0.2374 |
0.0244 |
0.5784*D |
|
SD |
13.140 |
0.00779 |
0.1084 |
0.0623 |
0.0886 |
0.6474 |
0.02185 |
0.07545 |
0.04729 |
0.00363 |
0.21805 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
242.72 |
0.0559 |
1.741 |
0.917 |
1.504 |
7.298 |
0.1310 |
0.6123 |
0.2723 |
0.0261 |
0.8027 |
|
SD |
19.348 |
0.00808 |
0.1010 |
0.0964 |
0.1732 |
0.6378 |
0.01500 |
0.05412 |
0.04361 |
0.00375 |
0.39748 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
240.31 |
0.0605 |
1.746 |
0.908 |
1.504 |
8.235+D |
0.1133 |
0.5864 |
0.2223 |
0.0280 |
0.6016*C |
|
SD |
19.257 |
0.01318 |
0.0434 |
0.0814 |
0.1030 |
0.9561 |
0.01256 |
0.06275 |
0.03579 |
0.00386 |
0.2180 |
Absolute organ weight - Recovery sacrifice - Group mean data
Males |
|
Body weight |
Adrenals |
Brain |
Epididymides |
Heart |
Kidneys |
Liver |
Spleen |
Testes |
Thymus |
Thyroid |
|
|
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
472.18 |
0.0552 |
1.826 |
1.3678 |
1.507 |
3.204 |
13.349 |
0.7900 |
3.9638 |
0.3148 |
0.0270 |
|
SD |
57.045 |
0.00554 |
0.1223 |
0.09981 |
0.1462 |
0.3125 |
2.1647 |
0.09222 |
0.15317 |
0.06683 |
0.00245 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
442.12 |
0.0530 |
1.930 |
1.4830 |
1.474 |
3.172 |
12.198 |
0.8484 |
4.0182 |
0.3410 |
0.0244 |
|
SD |
38.069 |
0.00742 |
0.1424 |
0.11812 |
0.0521 |
0.2520 |
2.1146 |
0.10889 |
0.34339 |
0.07041 |
0.00598 |
Females |
|
Body weight |
Adrenals |
Brain |
Heart |
Kidneys |
Liver |
Ovaries |
Spleen |
Thymus |
Thyroid |
Uterus |
|
|
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
(g) |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
256.34 |
0.0584 |
1.735 |
0.979 |
1.651 |
6.607 |
0.1254 |
0.5970 |
0.2410 |
0.0210 |
0.5406 |
|
SD |
24.342 |
0.00971 |
0.1379 |
0.1623 |
0.2396 |
1.4251 |
0.01383 |
0.06660 |
0.04632 |
0.00200 |
0.13906 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
248.80 |
0.0588 |
1.814 |
0.949 |
1.529 |
6.406 |
0.1364 |
0.6016 |
0.2134 |
0.0232 |
0.6300 |
|
SD |
15.680 |
0.01028 |
0.0431 |
0.1295 |
0.1772 |
0.7354 |
0.02962 |
0.11855 |
0.02692 |
0.00396 |
0.13957 |
Relative (to body weight) organ weight - Terminal sacrifice - Group mean data
Males |
|
Body weight |
Adrenals |
Brain |
Epididymides |
Heart |
Kidneys |
Liver |
Spleen |
Testes |
Thymus |
Thyroid |
|
|
(g) |
|
|
|
|
|
|
|
|
|
|
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
427.89 |
0.0138 |
0.4377 |
0.3226 |
0.3382 |
0.6360 |
2.6677 |
0.1796 |
0.9299 |
0.0754 |
0.0059 |
|
SD |
32.077 |
0.00247 |
0.03881 |
0.02272 |
0.02820 |
0.03698 |
0.14363 |
0.02022 |
0.07382 |
0.00754 |
0.00220 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
440.59 |
0.0138 |
0.4322 |
0.3324 |
0.3410 |
0.6327 |
2.7753 |
0.1889 |
0.8978 |
0.0863 |
0.0048 |
|
SD |
40.093 |
0.00215 |
0.04174 |
0.03362 |
0.03073 |
0.05399 |
0.13949 |
0.01817 |
0.06920 |
0.02107 |
0.00126 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
436.84 |
0.0128 |
0.4369 |
0.3120 |
0.3285 |
0.6148 |
2.8736+D |
0.1796 |
0.8480 |
0.0782 |
0.0055 |
|
SD |
40.037 |
0.00196 |
0.02737 |
0.05419 |
0.01543 |
0.03024 |
0.10664 |
0.01801 |
0.21473 |
0.01786 |
0.00152 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
404.34 |
0.0141 |
0.4542 |
0.3320 |
0.3327 |
0.6351 |
3.3421+D |
0.1796 |
0.9929 |
0.0756 |
0.0048 |
|
SD |
21.486 |
0.00215 |
0.02057 |
0.02776 |
0.02388 |
0.09630 |
0.18709 |
0.01741 |
0.04181 |
0.00851 |
0.00139 |
Females |
|
Body weight |
Adrenals |
Brain |
Heart |
Kidneys |
Liver |
Ovaries |
Spleen |
Thymus |
Thyroid |
Uterus |
|
|
(g) |
|
|
|
|
|
|
|
|
|
|
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
Control |
Mean |
253.73 |
0.0231 |
0.6956 |
0.3783 |
0.6137 |
2.7177 |
0.0520 |
0.2461 |
0.0944 |
0.0104 |
0.4311 |
|
SD |
11.839 |
0.00343 |
0.04290 |
0.02443 |
0.04321 |
0.14280 |
0.00810 |
0.03969 |
0.01673 |
0.00100 |
0.20526 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
50 mg/kg |
Mean |
249.08 |
0.0241 |
0.7091 |
0.3752 |
0.6335 |
2.8534 |
0.0529 |
0.2412 |
0.0950 |
0.0098 |
0.2305*C |
|
SD |
13.140 |
0.00362 |
0.04777 |
0.03439 |
0.02515 |
0.26763 |
0.00768 |
0.02514 |
0.01594 |
0.00125 |
0.07765 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
200 mg/kg |
Mean |
242.72 |
0.0232 |
0.7208 |
0.3781 |
0.6185 |
3.0089+D |
0.0541 |
0.2532 |
0.1118 |
0.0108 |
0.3402 |
|
SD |
19.348 |
0.00373 |
0.06257 |
0.02967 |
0.03461 |
0.14404 |
0.00636 |
0.02482 |
0.01210 |
0.00175 |
0.18950 |
|
(n) |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
10 |
800 mg/kg |
Mean |
240.31 |
0.0252 |
0.7306 |
0.3785 |
0.6283 |
3.4195+D |
0.0474 |
0.2444 |
0.0934 |
0.0117 |
0.2515*C |
|
SD |
19.257 |
0.00517 |
0.06155 |
0.02593 |
0.05162 |
0.16480 |
0.00612 |
0.02270 |
0.02063 |
0.00206 |
0.09083 |
Relative (to body weight) organ weight - Recovery sacrifice - Group mean data
Males |
|
Body weight |
Adrenals |
Brain |
Epididymides |
Heart |
Kidneys |
Liver |
Spleen |
Testes |
Thymus |
Thyroid |
|
|
(g) |
|
|
|
|
|
|
|
|
|
|
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
472.18 |
0.0118 |
0.3889 |
0.2916 |
0.3213 |
0.6833 |
2.8227 |
0.1676 |
0.8465 |
0.0662 |
0.0058 |
|
SD |
57.045 |
0.00153 |
0.02800 |
0.02619 |
0.03577 |
0.07627 |
0.24615 |
0.01076 |
0.07623 |
0.00716 |
0.00110 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
442.12 |
0.0121 |
0.4400 |
0.3375 |
0.3358 |
0.7205 |
2.7434 |
0.1919*D |
0.9090 |
0.0774 |
0.0055 |
|
SD |
38.069 |
0.00264 |
0.05862 |
0.03936 |
0.03789 |
0.06950 |
0.30758 |
0.01829 |
0.01457 |
0.01623 |
0.00095 |
Females |
|
Body weight |
Adrenals |
Brain |
Heart |
Kidneys |
Liver |
Ovaries |
Spleen |
Thymus |
Thyroid |
Uterus |
|
|
(g) |
|
|
|
|
|
|
|
|
|
|
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
Control |
Mean |
256.34 |
0.0227 |
0.6783 |
0.3808 |
0.6420 |
2.5582 |
0.0490 |
0.2331 |
0.0935 |
0.0082 |
0.2121 |
|
SD |
24.342 |
0.00274 |
0.03887 |
0.03945 |
0.03783 |
0.33112 |
0.00415 |
0.01823 |
0.01146 |
0.00077 |
0.05635 |
|
(n) |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
800 mg/kg |
Mean |
248.80 |
0.0235 |
0.7309 |
0.3802 |
0.6151 |
2.5726 |
0.0544 |
0.2404 |
0.0863 |
0.0094 |
0.2558 |
|
SD |
15.680 |
0.00318 |
0.03464 |
0.03481 |
0.06943 |
0.23437 |
0.00890 |
0.03293 |
0.01510 |
0.00168 |
0.06799 |
Macroscopic findings - Group incidence
Males |
|
Terminal sacrifice |
|
Recovery sacrifice |
||||
|
Treatment: |
Control |
50 mg/kg |
200 mg/kg |
800 mg/kg |
|
Control |
800 mg/kg |
|
Number of animals: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Finding |
Number examined: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Epididymides |
Abnormal size |
0 |
0 |
1 |
0 |
|
|
|
Eyes |
Staining |
1 |
0 |
0 |
0 |
|
|
|
Kidneys |
Cyst(s) |
1 |
0 |
0 |
0 |
|
|
|
Spleen |
Abnormal shape |
0 |
1 |
1 |
0 |
|
|
|
Stomach |
Abnormal area(s) |
1 |
0 |
1 |
0 |
|
|
|
Tail |
Abnormal shape |
1 |
0 |
0 |
0 |
|
|
|
Testes |
Abnormal size |
0 |
0 |
2 |
0 |
|
|
|
Thymus |
Abnormal area(s) |
0 |
1 |
0 |
1 |
|
|
|
|
Abnormal colour |
0 |
0 |
1 |
0 |
|
|
|
|
|
|
|
|
|
|
|
|
No abnormalities |
|
8 |
8 |
7 |
9 |
|
5 |
5 |
Females |
|
Terminal sacrifice |
|
Recovery sacrifice |
||||
|
Treatment: |
Control |
50 mg/kg |
200 mg/kg |
800 mg/kg |
|
Control |
800 mg/kg |
|
Number of animals: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Finding |
Number examined: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Adrenals |
Abnormal size |
0 |
0 |
0 |
1 |
|
|
|
Cervical nodes |
Abnormal colour |
1 |
0 |
0 |
0 |
|
|
|
Ovaries |
Abnormal size |
4 |
4 |
4 |
0 |
|
0 |
3 |
Stomach |
Abnormal area(s) |
0 |
1 |
0 |
1 |
|
|
|
Thymus |
Abnormal area(s) |
0 |
0 |
1 |
0 |
|
|
|
|
Abnormal size |
3 |
2 |
0 |
1 |
|
1 |
1 |
Uterus |
Abnormal contents |
6 |
1 |
3 |
1 |
|
|
|
|
Abnormal size |
6 |
1 |
3 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
No abnormalities |
|
1 |
3 |
3 |
7 |
|
4 |
2 |
Microscopic findings - Group incidence
Males |
|
Terminal sacrifice |
|
Recovery sacrifice |
||||
|
Treatment: |
Control |
50 mg/kg |
200 mg/kg |
800 mg/kg |
|
Control |
800 mg/kg |
|
Number of animals: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Finding |
Number examined: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Adrenals |
Cortical vacuolation |
0 |
0 |
0 |
2 |
|
|
|
|
Hypertrophy |
1 |
0 |
0 |
0 |
|
|
|
Epididymides |
Hypospermia |
0 |
0 |
1 |
0 |
|
|
|
Heart |
Inflammatory cell foci |
2 |
0 |
0 |
1 |
|
|
|
Kidneys |
Cyst(s) |
1 |
0 |
0 |
0 |
|
|
|
|
Nephropothy |
8 |
0 |
0 |
0 |
|
|
|
Liver |
Hepatocytic hypertophy |
0 |
0 |
0 |
8 |
|
|
|
|
Hepatocytic vacuolation |
7 |
5 |
2 |
0 |
|
1 |
0 |
|
Inflammatory cell foci |
10 |
10 |
10 |
10 |
|
3 |
5 |
Lungs |
Inflammatory cell foci |
0 |
0 |
0 |
1 |
|
|
|
|
Mineralisation |
0 |
0 |
0 |
2 |
|
|
|
Prostate gland |
Inflammatory cell foci |
4 |
0 |
0 |
1 |
|
|
|
Testes |
Germ cell depletion |
1 |
0 |
2 |
0 |
|
|
|
Tail |
Luxation |
1 |
0 |
0 |
0 |
|
|
|
Females |
|
Terminal sacrifice |
|
Recovery sacrifice |
||||
|
Treatment: |
Control |
50 mg/kg |
200 mg/kg |
800 mg/kg |
|
Control |
800 mg/kg |
|
Number of animals: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Finding |
Number examined: |
10 |
10 |
10 |
10 |
|
5 |
5 |
Cervical nodes |
Congestion |
1 |
0 |
0 |
0 |
|
|
|
Heart |
Inflammatory cell foci |
0 |
0 |
0 |
1 |
|
|
|
Kidneys |
Nephropathy |
4 |
0 |
0 |
1 |
|
|
|
Liver |
Hepatocytic hypertrophy |
0 |
0 |
0 |
8 |
|
|
|
|
Inflammatory cell foci |
6 |
6 |
7 |
10 |
|
4 |
5 |
Lungs |
Mineralisation |
1 |
0 |
0 |
0 |
|
|
|
Oesophagus |
Chronic inflammation |
1 |
0 |
0 |
1 |
|
|
|
Stomach |
Mucosal erosion |
0 |
1 |
0 |
0 |
|
|
|
Thyroid gland |
Follicular cyst(s) |
1 |
0 |
0 |
0 |
|
|
|
Uterus |
Luminal dilatation |
5 |
1 |
3 |
1 |
|
|
|
Vagina |
Diestrus |
0 |
0 |
0 |
3 |
|
|
|
|
Estrus |
6 |
0 |
0 |
3 |
|
|
|
|
Metestrus |
2 |
0 |
0 |
2 |
|
|
|
|
Proestrus |
2 |
0 |
0 |
2 |
|
|
|
Key to tables
SD = Standard deviation
*D or * = Dunnett LSD Test Significant at the 0.05 level
+D or + = Dunnett LSD Test Significant at the 0.01 level
*C = Cochran and Cox Test Significant at the 0.05 level
+C = Cochran and Cox Test Significant at the 0.01 level
#C = Cochran and Cox Test Significant at the 0.001 level
($) = Data inhomogeneous by Bartlett’s test
@ = Number examined reduced due to excluded data
e = Excluded
- = Deceased animal or missing data or unsuitable sample
Applicant's summary and conclusion
- Conclusions:
- There were no significant changes in clinical signs, body weight or food consumption. Minor changes in some blood chemistry parameters, together with organ weights suggest an effect in the liver.
Microscopic pathology indicated changes to the liver which could be attributed to administration of the substance.
The NO(A)EL in this study was considered to be 800 mg/kg bw/day in males & females. - Executive summary:
Sub-chronic toxicity has been investigated in a study conducted according to OECD/EU test guidelines.
There were no significant changes in clinical signs, body weight or food consumption. Minor changes in some blood chemistry parameters, together with organ weights suggest an effect in the liver. Microscopic pathology indicated changes, probably adaptive, to the liver which could be attributed to administration of the substance. Examination of sex organs revealed no changes indicative of a potential effect of the substance on reproductive capacity. In partuicular, seminiferous tubules were evaluated with respect to their stage in the spermatogenic cycle and to the integrity of the various cell types within the different stages. Regular layering in the germinal epithelium was noted and the cycle of spermatogenesis in the high dose males was regarded as normal with no treatment-related effect apparent. Normal physiology of the oestrous cycle (oestrus, metestrus, diestrus and proestrus) was noted in control and treated females. The morphological changes seen were normal when compared to each “oestrus phase” in the ovaries, uterus/cervix and vagina.
The NO(A)EL in this study was considered to be 800 mg/kg bw/day in males and females.
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.
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