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EC number: 404-740-9 | CAS number: 115895-09-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 Nov-12 Dec 1988
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Guideline study with acceptable restrictions. The study was performed according to the 1981 version of OECD guideline 407; compared to the current version there was no neurobehavioural examination, no detailed clinical observations outside the cage, and few tissues/organs were preserved and examined.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- current version
- Deviations:
- yes
- Remarks:
- no neurobehavioural examination, no detailed clinical observations outside the cage, few tissues/organs were preserved and examined
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted in May 1981
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 404-740-9
- EC Name:
- -
- Cas Number:
- 115895-09-5
- Molecular formula:
- C26H40Cl2O5
- IUPAC Name:
- ethyl 3,5-dichloro-4-{[(hexadecyloxy)carbonyl]oxy}benzoate
- Details on test material:
- - Name of test material (as cited in study report): AF-366
- Physical state: white powder
- Storage condition of test material: at room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Wistar (Bor:WISW)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: F. Winkelmann, Institute for the Breeding of Laboratory Animals GmbH & Co., KG, Borchen, Germany
- Age at study initiation: approximately 4 weeks
- Weight at study initiation: 52.3-61.6 g (range, males), 50.0-62.5 g (range, females)
- Housing: the rats were housed 5 per cage/sex, in in suspended, stainless steel cages, fitted with a wire-screen bottom and front
- Diet: CIVO cereal-based, basal diet for rats and mice, ad libitum. Twice a week the feed remains in the feeders were replaced by new portions of the diets.
- Water: tap water, ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 55-75
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 14 Nov 1988 To: 12 Dec 1988
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): fresh batches were prepared twice, on 11 Nov and 24 Nov 1988. The test diet with the highest concentration was prepared first. To obtain a homogeneous distribution of the test substance in the diet, AF-366 was thoroughly mixed with a small portion of stock diet in an electric coffee grinder, and then further diluted with stock diet to the intended concentration in a mechanical blender (Stephan cutter). The lower concentrations were obtained by diluting the top-dose diet with stock diet.
- Mixing appropriate amounts with (Type of food): CIVO cereal-based, basal diet for rats and mice
- Storage temperature of food: -20 °C - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Immediately after preparation of the first batch of the diets, 5 samples of each test diet were taken at different locations in the blender and analysed by HPLC to determine the content and the homogeneous distribution of the test substance in the diet. The mean concentrations of test substance found in the test diets were close to the nominal concentrations. The analyses yielded coefficients of variation between 1 and 3 %, indicating a satisfactory homogeneity at all dietary levels, with a recorevy rate of 91-98%.
In separate experiments, partly performed prior to the start of the toxicity study, the stability of AF-366 in the basal diet was determined by analysing diet samples after storage at room temperature in open containers (4 days) or in a freezer at -20 °C in closed containers (14 and 21 days). The test substance was shown to be stable in the diet under the tested conditions. - Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
250, 1750 and 12250 ppm
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
31, 205 and 1419 mg/kg bw/day (males); 28, 199 and 1373 mg/kg bw/day (females)
Basis:
other: calculated based on the food intake per cage per week
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: the doses were selected based on the results (body weight and food intake) of a 5-day range-finding study (data not reported)
- Rationale for animal assignment (if not random): the weight of one female was more than 20% lower than the mean body weight on the day of study start. Therefore the rat was replaced by a reserve rat with a suitable body weight.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: yes
- Time schedule: twice daily Monday-Friday and once daily on Saturday and Sunday
BODY WEIGHT: yes
- Time schedule for examinations: the body weight was recorded on Day 0 (prior to dosing) and weekly thereafter
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, food consumption per cage per week was measured and divided by the number of animals in a cage to reach the individual intake.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: no
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: yes
WATER CONSUMPTION: yes
- Time schedule for examinations: water intake was measured daily per cage, during the first week of the study
OPHTHALMOSCOPIC EXAMINATION: no
HAEMATOLOGY: yes
- Time schedule for collection of blood: Day 23
- Anaesthetic used for blood collection: no
- Animals fasted: no
- How many animals: all the rats in all the groups
- Parameters examined: haemoglobin, packed cell volume, red blood cells, white blood cells, differential white blood cell count, reticulocytes, prothrombin time, thrombocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular haemoglobin concentration
CLINICAL CHEMISTRY: yes
- Time schedule for collection of blood: Day 28
- Animals fasted: no
- How many animals: all the rats in all the groups
- Parameters examined: alkaline phosphatase activity, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total protein, albumin, urea, creatinine, total bilirubin, sodium, potassium, calcium, chloride, inorganic phosphate, cholesterol, triglycerides, phospholipids. In addition, on Day 25 a blood sample was drawn from the tail vein of all the rats in all the groups to measure the glucose level. The rats were deprived of water for 24 h and of feed for 16 h prior to this blood collection.
URINALYSIS: yes
- Time schedule for collection of urine: on Day 24-25
- Metabolism cages used for collection of urine: yes, during the last 16 hours of the period
- Animals fasted: yes, all the rats in all the groups were deprived of water for 24 hours and of food during the last 16 hours of this period
- Parameters examined: volume, density
NEUROBEHAVIOURAL EXAMINATION: no - Sacrifice and pathology:
- GROSS PATHOLOGY: yes, the rats were examined for gross pathological changes. The adrenals, kidneys, liver and testes were weighed. Samples of the adrenals, spleen, heart, testes, kidneys, liver and all gross lesions were preserved in a neutral, aqueous, phosphate-buffered 4% solution of formaldehyde.
HISTOPATHOLOGY: yes. The tissue samples for microscopic examination were processed and embedded in paraffin wax. Sections were cut, stained with haematoxylin and eosin and then examined microscopically. Histopathological examination was carried out on the liver, kidneys, heart, adrenals, and spleen of all animals of the control group and of the high-dose group. Due to treatment-related morphological changes in the liver of the high-dose rats, microscopy of this organ was performed on liver samples of all the rats in the low-dose and mid-dose group. - Statistics:
- Body weights were evaluated by one-way analysis of co-variance followed by Dunnett’s multiple comparison test. Red blood cell characteristics, total white blood cells, absolute numbers of lymphocytes and neutrophils, clinical chemistry values, volume and density of the urine, and organ weights were evaluated by one-way analysis of variance (ZiNOVA), followed by Dunnett’s multiple comparison test. Reticulocytes and differential white blood cell counts were analysed by the Mann-Whitney U-test. The histopathological changes were examined by Fisher’s exact probability test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 12250 ppm, males: convulsions
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 12250 ppm, males: convulsions
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 12250 ppm, males: decrease in mean body weight on Day 21 and 28
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 12250 ppm: decrease in hemoglobin and thrombocyte levels, both sexes
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 1750 ppm: decreased alkaline phosphatase levels in both sexes
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- 12250 ppm: increased liver weight
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 12250 ppm, males: increased Kupffer cells, hepatic mitotic activity
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
There was no mortality during the study period.
2/5 males in the high-dose group had convulsions lasting around 1 minute; one on Day 23 and 24 and the other on Day 2, 15, 23 and 24. This may have been due to the relatively high doses the rats were exposed to. One of the rats displaying convulsions also had alopecia on Day 3. In 1/5 males, encrustations on the nose was noted on 10 days during the first 2 weeks. No clinical signs were observed in the females.
BODY WEIGHT AND WEIGHT GAIN
The body weight of males in the high-dose group was statistically significantly reduced (by approximately 10%) on Day 21 and 28, compared to the control group on the same days, respectively. The two rats suffering from convulsions had a lower weight gain, compared with the other rats in the group, thereby affecting the mean value (see Table 1). There was no statistically significant difference in body weight between the female groups.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
The food consumption was comparable between the control and treatment groups. The intake of AF-366 per kg bw in successive weeks showed the normal decrease with increasing study duration for each of the three test groups. This is due to the decrease in feed intake per unit body weight with increasing age of the rats. The mean intake over the whole study period was similar in the males and females in the same dose group.
FOOD EFFICIENCY
The food efficiency was comparable between the control and treatment groups during the study period.
WATER CONSUMPTION
The water consumption was comparable between the control and treatment groups.
HAEMATOLOGY
In both male and female high-dose groups, a statistically significant decrease (approximately 25%) in the level of thrombocytes was observed, compared to the control group (see Table 2). As the reduction was notable and observed in both sexes, it is considered to be treatment-related. A statistically significant decrease was noted in the high dose group for the hemoglobin level in both sexes, and for the mean corpuscular hemoglobin in males. However, the levels are within the historical data range (Technical Bulletin, Spring 1998. Charles River Laboratories, Wilmington, USA). The mean corpuscular volume in males administered the highest dose were statistically significantly decreased. A statistically significant increase in neutrophil level (absolute and percentage) in high dose males is considered to be treatment-related, while a decrease in the percentage of lymphocytes only is a consequence of the increase in neutrophiles. Although the reticulocyte levels in high-dose females were statistically significantly increased, the control level was very low compared to the treated groups, so the toxicological significance of the result is unclear. Also, no effect on the reticulocytes was seen in the males.
Statistically significant increases in several parameters in the female low-dose group are considered to be incidental, as no effect was seen in the high-dose group or in the males.
CLINICAL CHEMISTRY
The levels of alkaline phosphatase was statistically significantly decreased in males and females in the mid- and high-dose groups in a dose-related manner (see Table 3). The effect is considered to be treatment-related, with toxicological significance only in the high-dose groups, as no additional histopathological or clinical chemistry effects were observed at the mid-dose level. Aspartate aminotransferase concentrations were statistically significantly decreased in females administered the highest dose only, and all results were within the historical data range (Technical Bulletin, Spring 1998. Charles River Laboratories, Wilmington, USA), indicating an incidental effect. A statistically significant increase in potassium in the female low-dose group is considered to be incidental, as no effect was seen in the high-dose group or in the males.
URINALYSIS
No effects were observed on the urinalysis parameters.
ORGAN WEIGHTS
The relative liver weight of males and females in the high-dose group was statistically significantly increased (see Table 4). This is considered to be treatment-related and toxicologically relevant for the males, as histopathological effects in the liver were noted in the male high-dose group only.
GROSS PATHOLOGY
No treatment-related effects were observed during necropsy and gross pathology.
HISTOPATHOLOGY: NON-NEOPLASTIC
In the liver of 3/5 males administered the highest dose, increased mitotic activity in the hepatocytes was observed (see Table 5). An increased focal accumulation of Kupffer cells in the sinusoids was noted in 4/5 high-dose male rats. No effects were observed in female rats.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 1 373 other: mg/kg bw/day, calculated based on the food intake per cage per week
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- NOAEL
- Effect level:
- 205 other: mg/kg bw/day, calculated based on the food intake per cage per week
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: Overall effects; clinical signs: convulsions; haematology: thrombocytes, mean corpuscular volume; clinical chemistry: alkaline phosphatase; organ weights: liver; histopathology: liver. Intake in mg/kg bw/day is calculated from 1750 ppm.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Body weights (mean ± SD)
Day |
Sex/N |
Control |
250 ppm |
1750 ppm |
12250 ppm |
0 |
M/5 |
56.8 ± 1.7 |
56.1 ± 1.8 |
57.2 ± 1.6 |
56.8 ± 1.5 |
7 |
M/5 |
91.2 ± 2.4 |
86.6 ± 2.0 |
90.6 ± 3.1 |
86.4 ± 1.8 |
14 |
M/5 |
126.6 ± 3.3 |
122.9 ± 1.8 |
124.6 ± 3.9 |
118.5 ± 3.2 |
21 |
M/5 |
165.4 ± 3.4 |
159.1 ± 3.2 |
163.4 ± 4.5 |
148.4 ± 6.7* |
28 |
M/5 |
196.8 ± 4.0 |
189.5 ± 4.6 |
191.5 ± 4.8 |
175.9 ± 6.9* |
|
|
|
|
|
|
0 |
F/5 |
56.2 ± 1.7 |
58.0 ± 1.6 |
55.8 ± 1.8 |
56.1 ± 1.9 |
7 |
F/5 |
86.6 ± 1.7 |
86.3 ± 2.0 |
82.1 ± 2.7 |
80.9 ± 1.8 |
14 |
F/5 |
114.3 ± 4.0 |
112.8 ± 3.7 |
108.1 ± 2.6 |
104.5 ± 2.5 |
21 |
F/5 |
132.0 ± 4.4 |
133.0 ± 4.5 |
127.8 ± 3.7 |
122.6 ± 3.3 |
28 |
F/5 |
153.0 ± 6.7 |
149.8 ± 5.8 |
147.0 ± 4.4 |
137.6 ± 3.8 |
* p < 0.05, Covar + Dunnett’s tests (two-sided)
Table 2: Hematological parameters (mean ± SD)
Parameter |
Sex/N |
Control |
250 ppm |
1750 ppm |
12250 ppm |
Hemoglobin1(mmol/L) |
M/5 |
8.3 ± 0.1 |
8.1 ± 0.1 |
8.1 ± 0.1 |
7.4 ± 0.3** |
Hemoglobin1(mmol/L) |
F/5 |
8.6 ± 0.1 |
8.6 ± 0.1 |
8.3 ± 0.2 |
8.1 ± 0.1* |
Thrombocytes1(109/L) |
M/5 |
1085 ± 37 |
1176 ± 49 |
1162 ± 29 |
916 ± 58* |
Thrombocytes1(109/L) |
F/5 |
1083 ± 42 |
1089 ± 43 |
1162 ± 27 |
918 ± 54* |
Reticulocytes2(/1000) |
M/5 |
24.8 ± 3.8 |
19.2 ± 2.0 |
25.6 ± 3.7 |
36.0 ± 7.2 |
Reticulocytes2(/1000) |
F/5 |
9.6 ± 2.8 |
17.6 ± 2.1 |
13.2 ± 4.3 |
21.2 ± 3.2* |
Mean corpuscular volume1(fL) |
M/5 |
70.0 ± 1.0 |
70.2 ± 0.7 |
66.8 ± 1.1 |
59.1 ± 3.4** |
Mean corpuscular volume1(fL) |
F/5 |
68.0 ± 1.6 |
71.0 ± 1.3 |
69.9 ± 1.7 |
69.7 ± 1.3 |
Mean corpuscular haemoglobin1(fmol) |
M/5 |
1.39 ± 0.02 |
1.38 ± 0.03 |
1.33 ± 0.01 |
1.10 ± 0.11** |
Mean corpuscular haemoglobin1(fmol) |
F/5 |
1.36 ± 0.03 |
1.42 ± 0.02 |
1.36 ± 0.03 |
1.35 ± 0.02 |
Neutrophils1(109/L) |
M/5 |
0.9 ± 0.1 |
0.9 ± 0.2 |
0.9 ± 0.3 |
2.5 ± 0.5* |
Neutrophils1(109/L) |
F/5 |
0.7 ± 0.2 |
0.7 ± 0.1 |
0.7 ± 0.2 |
0.8 ± 0.2 |
Neutrophils2(%) |
M/5 |
7.2 ± 1.0 |
7.6 ± 2.0 |
8.0 ± 2.5 |
16.6 ± 2.3** |
Neutrophils2(%) |
F/5 |
9.2 ± 2.5 |
7.8 ± 1.7 |
8.8 ± 2.7 |
10.2 ± 2.0 |
Lymphocytes1(109/L) |
M/5 |
11.6 ± 0.4 |
11.8 ± 1.5 |
10.7 ± 1.1 |
11.8 ± 1.2 |
Lymphocytes1(109/L) |
F/5 |
6.6 ± 0.2 |
8.3 ± 0.3** |
6.6 ± 0.2 |
6.6 ± 0.4 |
Lymphocytes2(%) |
M/5 |
91.4 ± 1.2 |
91.6 ± 2.0 |
91.2 ± 2.9 |
82.6 ± 2.2** |
Lymphocytes2(%) |
F/5 |
88.6 ± 2.2 |
91.4 ± 1.5 |
89.0 ± 2.5 |
88.2 ± 1.8 |
1* p < 0.05, ** p < 0.01, Anova + Dunnett’s tests (two-sided)
2* p < 0.05, ** p < 0.02, *** p < 0.002, Mann/Whitney U-test (two-sided)
Table 3: Clinical chemistry parameters (mean ± SD)
Parameter |
Sex/N |
Control |
250 ppm |
1750 ppm |
12250 ppm |
Alkaline phosphatase(U/L) |
M/5 |
429.8 ± 19.2 |
381.0 ± 15.7 |
337.6 ± 14.1** |
302.8 ± 22.4** |
Alkaline phosphatase(U/L) |
F/5 |
273.3 ± 20.1 |
272.3 ± 11.4 |
190.5 ± 4.3** |
135.4 ± 5.9** |
Aspartate aminotransferase (U/L) |
M/5 |
70.7 ± 1.8 |
63.2 ± 1.8 |
64.6 ± 2.3 |
85.9 ± 12.1 |
Aspartate aminotransferase (U/L) |
F/5 |
67.6 ± 1.0 |
65.8 ± 2.0 |
58.6 ± 1.9** |
58.6 ± 1.5** |
* p < 0.05, ** p < 0.01, Anova + Dunnett’s tests (two-sided)
Table 4: Liver weights
Parameter |
Sex/N |
Control |
250 ppm |
1750 ppm |
12250 ppm |
Relative liver weight (g/kg bw) |
M/5 |
44.2 ± 1.0
|
44.36 ± 1.4
|
44.46 ± 1.3 |
51.26 ± 1.3** |
Relative liver weight (g/kg bw) |
F/5 |
42.46 ± 0.5 |
41.46 ± 0.6 |
43.56 ± 0.8 |
49.06 ± 1.3** |
* p < 0.05, ** p < 0.01, Anova + Dunnett’s tests (two-sided)
Table 5: Histopathological results
Parameter |
Sex/N |
Control |
250 ppm |
1750 ppm |
12250 ppm |
Focal increased number of Kupffer cells |
M/5 |
0/5 |
0/5 |
0/5 |
4/5* |
Focal increased number of Kupffer cells |
F/5 |
0/5 |
0/5 |
0/5 |
0/5 |
Hepatocellular mitotic increase - slight - moderate |
M/5 |
0/5 0/5 |
0/5 0/5 |
0/5 0/5 |
1/5 2/5 |
Hepatocellular mitotic increase - slight - moderate |
F/5 |
0/5 0/5 |
0/5 0/5 |
0/5 0/5 |
0/5 0/5 |
* p < 0.05, ** p < 0.01, pairwise (Fisher’s) test
Applicant's summary and conclusion
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