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EC number: 305-962-8 | CAS number: 95370-96-0
- 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:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 3 February 2022 to 27 May 2022
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 022
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese Ministry of Agriculture, Forestry, and Fisheries (JMAFF) Test Data for Registration of Agricultural Chemicals, 30 Shouan No. 6278, 2019
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- An exception is test item characterization as these tests were performed in accordance with the ISO 9001 quality standard.
- Limit test:
- no
Test material
- Reference substance name:
- Fatty acids, C14-22, 2-ethylhexyl esters, epoxidized
- EC Number:
- 305-962-8
- EC Name:
- Fatty acids, C14-22, 2-ethylhexyl esters, epoxidized
- Cas Number:
- 95370-96-0
- Molecular formula:
- Not necessary, substance is a UVCB
- IUPAC Name:
- Fatty acids, C14-22, 2ethylhexylesters, epoxidized
1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier): Sponsor
- Lot/batch number of test material: WO61290
- Purity: 100% (UVCB)
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored in a tightly closed container, room temperature, 15 to 25ºC.
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions and during storage: Stability was evaluated between 10 and 750 mg/mL (Labcorp Study 8484276). Stable for up to 24 hours at room temperature; up to 8 days at 2 to 8°C; and up to 8 days at -60 to -80°C. All formulations were considered homogeneous (within 70 -120% of the target concentration).
- Solubility and stability of the test material in the solvent/vehicle: Soluble in corn oil and stable (for up to 24 hours at room temperature; up to 8 days at 2 to 8°C; and up to 8 days at -60 to -80°C).
- Reactivity of the test material with the incubation material used (e.g. plastic ware): None
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): None
OTHER SPECIFICS
- Other relevant information needed for characterising the tested material, e.g. if radiolabelled, adjustment of pH, osmolality and precipitate in the culture medium to which the test chemical is added: None
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl:CD[SD]
- Details on species / strain selection:
- Rats have been historically used in safety evaluation studies as recommended and accepted by appropriate regulatory agencies. Sprague Dawley (Crl:CD[SD]) strain.
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Sprague Dawley (Crl:CD[SD]) strain from Charles River Laboratories, Raleigh, North Carolina, USA.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 8 weeks old,
- Weight at study initiation: 216 to 323 g (males) and 163 to 243 g (females).
- Fasting period before study: Overnight for scheduled blood and urine collections and prior to terminal procedures (on day 92).
- Housing: Group-housed (up to three animals of the same sex/cage) in polycarbonate
cages with hardwood chip bedding. Housed individually in stainless steel cages for study-related procedures.
- Diet (ad libitum): Certified Rodent Diet #2014C (Envigo RMS, Inc.)
- Water (ad libitum)
- Acclimation period: At least 16 days.
DETAILS OF FOOD AND WATER QUALITY: Diet routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Water samples routinely analyzed for specified microorganisms and environmental contaminants. Results are retained at Labcorp.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 26°C,
- Humidity (%): 30 to 70%,
- Air changes (per hr): Minimum of 10.
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle (interrupted where required for study-related activities).
IN-LIFE DATES: From: To: 3 February 2022 to (XXX - to be added)
Administration / exposure
- Route of administration:
- oral: gavage
- Details on route of administration:
- The oral route was chosen as it is the most likely route of human exposure. A previous 7-day repeat dose study (Labcorp Study 8484277; Labcorp, 2021) was well tolerated, therefore dose levels of 0, 100, 300, and 1000 mg/kg/day were selected for the present 90-day study.
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Formulations were prepared once daily on Days 1 to 14 (females) or 16 (males) of dosing, then prior to day of dosing for Days 15 to 21(females) or 17 to 23 (males), and then once weekly and apportioned for daily use. Dose concentrations (10, 20 & 100 mg/ml) were based on the test item as supplied. Formulations were stored at 2 to 8°C, protected from light until removed for dosing.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Corn oil is an appropriate vehicle as specified within OECD 408.
- Amount of vehicle (if gavage): Dosed at 10 mL/kg.
- Lot/batch no. (if required): MKCP9878 & MKCQ0649
- Purity: Not specified. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Dose formulations were analyzed by Labcorp using a validated HPLC method (Method 12795).
Duplicate samples (1 mL each) were taken from the middle of the vehicle control item. Two sets of triplicate samples (1 mL each) were taken from the middle of each test item formulation. Samples were collected from vehicle control item and test item formulations prepared for administration on Days 1, 42, and 91 of the dosing phase. For samples collected at the same interval as homogeneity, the mean result from the homogeneity analysis was also used for concentration verification.
All formulations were within 70 -120% of the target concentrations (means ranging from 83.5% to 97.3% of theoretical). No test item detected in any vehicle control item formulation. All formulations met the acceptance criteria and animals were administered the intended dose. - Duration of treatment / exposure:
- 13 weeks (90-days)
- Frequency of treatment:
- Once daily via oral gavage.
Doses / concentrationsopen allclose all
- Remarks:
- Control
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Remarks:
- Low
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- Mid
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- Remarks:
- High
- No. of animals per sex per dose:
- 40 males & 40 females
Control: 10 males & 10 females
Low dose (100 mg/kg day): 10 males & 10 females
Mid dose (300 mg/kg/day): 10 males & 10 females
High dose (1000 mg/kg day): 10 males & 10 females - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels of 0, 100, 300 & 1000 mg/kg/day were selected based on tolerability of dose levels in a previous 7-day repeat dose study (Labcorp Study 8484277; Labcorp, 2021).
- Rationale for animal assignment: Assigned using a computerized procedure.
- Fasting period before blood sampling for clinical biochemistry: Fasted overnight
- Other:
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: During the dosing phase for each animal, once daily.
- Post dose cage side observations: Conducted for each animal once daily (week 1), twice weekly (weeks 2 to 4), or once weekly (weeks 5 to 13) at ca. 2 hours postdose.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Checked twice daily (a.m. and p.m.) and once on days of arrival/sacrifice for mortality, abnormalities, and signs of pain or distress.
BODY WEIGHT: Yes
- Time schedule for examinations: Once during the predose phase, once weekly prior to dosing (based on Day 1) to Week 13, and on Day 91 of the dosing phase.
FOOD CONSUMPTION: yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Food consumed by each cage of animals was recorded once for a 1-week interval during the predose phase, weekly to Week 13, and from Days 85 to 91 of the dosing phase.
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: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Conducted once for each animal during the predose phase
and once during week 12 of the dosing phase.
- Dose groups that were examined: Control and all test item groups.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Dosing phase, on day 92.
- Anaesthetic used for blood collection: Yes, anesthetized with isoflurane
- Animals fasted: Yes, fasted overnight.
- How many animals: All control and test item group animals.
- Parameters checked in table [5.1 (summary) and 6.1 individual)] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Dosing phase, on Day 92.
- Animals fasted: Yes, fasted overnight.
- How many animals: All control and test item group animals.
- Parameters checked in table [5.2 (summary) & 6.2 (individual) No.?] were examined.
THYROID HORMONE & SERUM BILE ACIDS: Yes
- Time of blood sample collection: Collected from fasted animals on Day 92 of the dosing phase.
- Animals fasted: Yes
- How many animals: All control and test item group animals.
URINALYSIS: Yes
- Time schedule for collection of urine: Collected overnight before blood collection from animals fasted overnight. Urine samples were collected on Day 92 of the dosing phase.
- Metabolism cages used for collection of urine: No
- Animals fasted: Yes
- Parameters checked in table [5.3 (summary), 6.3 (individual)] were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Once during the predose phase and once during Week 12 of
the dosing phase. All examinations were completed at the same time of day.
- Dose groups that were examined: All control and test item group animals.
- Battery of functions tested: sensory activity / grip strength / motor activity / other:
Elicited behaviour, Open field observations, Neurobehavioral observations - predose & dosing phase.
IMMUNOLOGY: No
Immunoglobulin A, G & M evaluated under clinical chemistry parameters. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
On day 92 of the dosing phase, all animals (fasted overnight) were anesthetized with isoflurane inhalation, exsanguinated, and necropsied. An examination of the external features of the carcass; external body orifices; abdominal, thoracic, cranial, pelvic, and oral cavities; organs and tissues
HISTOPATHOLOGY: Yes
From all scheduled sacrifices.
Specified tissues (in the Necropsy, Organ Weights, and Macroscopic Observations section of the report) (unless noted as missing) from each animal were embedded in paraffin and sectioned at a nominal 5 μm, and slides prepared and stained with hematoxylin and eosin.
Microscopic Observations
Specified tissues (in the Necropsy, Organ Weights, and Macroscopic Observations section of the report) from the following animals were examined microscopically by the Principal Investigator for Anatomic Pathology.
- Animals in control and high-dose groups.
- Macroscopic lesions from animals in low- and mid-dose groups. - Statistics:
- Means and SD were calculated for: absolute bw, bw change, quantitative food consumption, continuous clinical pathology values, terminal bw, absolute organ weight, organ:bw percentage, and organ:brain weight percentage & FOB evaluations.
Pairwise comparisons were Gp 1 vs Gps 2, 3 & 4.
Prior to the ANOVA, Levene’s test was performed:
- Where Levene’s test was significant (P ≤0.05), a rank transformation was applied before ANOVA.
- Where Levene’s test was not significant (P >0.05), ANOVA was conducted.
For comparisons to a single control or combined identical controls:
- If the group effect of the ANOVA was significant (P ≤0.05), Dunnett’s test was used.
- If the ANOVA was not significant (P >0.05), the Dunnett’s test results were not applicable.
For other comparisons (i.e., not against a single control or combined identical controls):
- If the group effect of the ANOVA is significant (P ≤0.05), t-tests were used.
- If not significant (P >0.05), the t-test results were not applicable.
Where only two groups were available, a two-sample t-test was performed.
Values above/below the LOQ were not analyzed.
All statistical tests were evaluated at the 5% probability level.
Locomotor Activity Assessment Data:
Results reported as significant at 5%.
Basic movements, xy ambulation, fine movement, rearing activity were analyzed using a repeated measures analysis of variance (Winer, 1971). The variance-covariance structure used were the Autoregressive Moving Average (1,1). T-tests were used for group comparisons of treatment groups with control.
Male Reproductive Assessment:
Male reproductive parameters were analyzed using a Kruskal-Wallis nonparametric ANOVA. If significant (P ≤0.05), pairwise comparisons of each test item-treated group with the control group were made using the Wilcoxon Rank Sum Test. If not significant (P > 0.05), no further analyses were conducted.
Where only two groups are available for analysis, a Wilcoxon Rank Sum Test was
performed.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No test-item related clinical observations were noted.
- Mortality:
- no mortality observed
- Description (incidence):
- No test-item-related mortality occurred. All animals survived to scheduled sacrifice.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No test-item alterations in body weight or body weight gain were noted up to 1000 mg/kg/day.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- Effects in a single male (aqueous fibrin clot, anterior chamber, left eye, day 84) at 100 mg/kg/day was not test-item related.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No test-item related effects in haematology or coagulation test results.
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Test-item related effects consisted of minimally higher alkaline phosphatase activity in two males at 100 mg/kg/day, two males at 300 mg/kg/day, and males at 1000 mg/kg/day. Minimally higher serum bile acids were noted in one male at 300 mg/kg/day and males and two females at 1000 mg/kg/day and was likely associated with higher liver weights. Minimally higher T4 was noted in one female at 100 mg/kg/day, one female and three males at 300 mg/kg/day, and three males and four females at 1000 mg/kg/day. All other differences in clinical chemistry test results, statistically significant or not, between control and test-item treated animals were consistent with normal variation and considered incidental. Most or all of the following characterized these differences: of small magnitude, lack of dose relationship, inconsistency between sexes, and/or the absence of correlative findings.
- Endocrine findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Minimally higher T4 was noted in one female at 100 mg/kg/day, one female and three males at 300 mg/kg/day, and three males and four females at 1000 mg/kg/day. This increase was not considered treatment related as it was of a small magnitude with an absence of any clear dose relationship, as well as inconsistent between sexes with an absence of correlative findings.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No test-item related effects in urinalysis were identified.
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Mildly decreased activity were observed for 2/10 females at 1000 mg/kg/day. Decreased activity did not correlate to changes in LMA (no alterations observed). The low incidence (2/10 animals), confined to females only, with no corroborating additional observations, and mild severity, the
decreased activity was considered neither biologically impactful nor test-item related.
Other neurobehavioral findings included increased auditory startle response, decreased
extensor thrust, walking on toes, abnormal grasping loss, increased pain response, absent pinna response, increased reactivity to handling, elevated tail, and mild vocalization. These were considered not test-item related as incidences were comparable with controls, present during the predose collection, or lacked a dose response. - Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean absolute and relative liver weights increased in animals at 1000 mg/kg/day, with mean liver-to-body weight ratios achieving statistical significance. Liver weight increases in animals at 1000 mg/kg/day were considered test item related. No macroscopic or microscopic correlates to the increased liver weights were observed, however, serum chemistry correlates were noted.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No test item-related microscopic findings were noted.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- effects observed, non-treatment-related
- Details on results:
- Male Reproductive Assessment: Decreased sperm concentration was noted for all test item treated males but was only statistically significant for males at 300 mg/kg/day, compared with controls. This decrease was not considered to be treatment related due to the lack of a dose response, as well as the absence of any organ weight effects, or histopathological correlates.
An increase in abnormal sperm morphology in males at 1000 mg/kg/day was observed, compared with controls. This increase was primarily due to a high number of abnormal sperm in two males and was not considered to be related to the test material, due to the lack of a dose response, as well as the absence of organ weight effects, or histopathological correlates.
Effect levels
- 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:
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Results of Homogeneity and Concentration Verification Analyses
Interval | Location | Replicate | Lankroflex ED6 in Corn Oil | |||||||
0 mg/mL | 10 mg/mL | 30 mg/mL | 100 mg/mL | |||||||
Actual | % of Target | Actual | % of Target | Actual | % of Target | Actual | % of Target | |||
Day 1 | Top | 1 | - | - | 9.3 | 93.3 | - | - | 93.2 | 93.2 |
TA 1 |
| 2 | - | - | 9.5 | 95.3 | - | - | 94.6 | 94.6 |
| Middle | 1 | DNS | - | 9.4 | 94.4 | 27.3 | 90.9 | 92.1 | 92.1 |
|
| 2 | - | - | 9.6 | 96.2 | 27.4 | 91.3 | 95.1 | 95.1 |
|
| 3 | - | - | - | - | 27.7 | 92.2 | - | - |
| Bottom | 1 | - | - | 9.6 | 96.1 | - | - | 95.2 | 95.2 |
|
| 2 | - | - | 9.6 | 96.4 | - | - | 94.5 | 94.5 |
| Overall | Mean (n=6) | - | - | - | 95.3 | - | 91.5 | - | 94.5 |
|
| RSD (%) | - | - | - | 1.3 | - | 0.8 | - | 1.3 |
Day | Top | 1 | - | - | 8.26 | 82.6 | - | - | 87.7 | 87.7 |
TA 3 |
| 2 | - | - | 8.22 | 82.3 | - | - | 88.0 | 88.0 |
| Middle | 1 | DNS | - | 8.39 | 83.9 | 26.0 | 86.6 | 89.2 | 89.2 |
|
| 2 | - | - | 8.29 | 82.9 | 26.3 | 87.8 | 88.6 | 88.6 |
|
| 3 |
| - | - | - | 26.1 | 87.0 | - | - |
| Bottom | 1 | - | - | 8.51 | 85.1 | - | - | 87.0 | 87.0 |
|
| 2 | - | - | 8.45 | 84.5 | - | - | 88.9 | 88.9 |
| Overall | Mean (n=6) | - | - | - | 83.5 | - | 87.1 | - | 88.2 |
|
| RSD (%) | - | - | - | 1.4 | - | 0.7 | - | 0.9 |
Day | Top | 1 | - | - | 9.02 | 90.2 | - | - | 91.6 | 91.6 |
TA 24 |
| 2 | - | - | 9.19 | 91.9 | - | - | 87.6 | 87.6 |
| Middle | 1 | DNS | - | 9.23 | 92.3 | - | - | 91.8 | 91.8 |
|
| 2 | - | - | 9.27 | 92.7 | - | - | 92.3 | 92.3 |
| Bottom | 1 | - | - | 9.32 | 93.2 | - | - | 92.4 | 92.4 |
|
| 2 | - | - | 9.79 | 97.9 | - | - | 90.5 | 90.5 |
| Overall | Mean (n=6) | - | - | - | 93.1 | - | - | - | 91.0 |
|
| RSD (%) | - | - | - | 2.8 | - | - | - | 2.0 |
Day | Top | 1 | - | - | 9.33 | 93.3 | - | - | 90.1 | 90.1 |
TA 26 |
| 2 | - | - | 9.53 | 95.3 | - | - | 95.4 | 95.4 |
| Middle | 1 | DNS | - | 10.0 | 100.1 | 26.8 | 89.3 | 96.0 | 96.0 |
|
| 2 | - | - | 9.75 | 97.5 | 28.2 | 94.1 | 96.0 | 96.0 |
|
| 3 |
| - | - | - | 28.5 | 95.0 | - | - |
| Bottom | 1 | - | - | 9.84 | 98.4 | - | - | 98.2 | 98.2 |
|
| 2 | - | - | 9.92 | 99.2 | - | - | 93.9 | 93.9 |
| Overall | Mean (n=6) | - | - | - | 97.3 | - | 92.8 | - | 95.0 |
|
| RSD (%) | - | - | - | 2.6 | - | 3.3 | - | 2.9 |
- = Not applicable |
Results of Homogeneity and Concentration Verification Analyses - Continued
Interval | Location | Replicate | Lankroflex ED6 in Corn Oil | ||||||||
0 mg/mL | 10 mg/mL | 30 mg/mL | 100 mg/mL |
| |||||||
Actual | % of Target | Actual | % of Target | Actual | % of Target | Actual | % of Target |
| |||
TA 33 | Middle | 1 | DNS | - | 9.52 | 95.2 | 27.7 | 92.3 | 89.7 | 89.7 |
|
|
| 2 | - | - | 9.63 | 96.3 | 28.0 | 93.2 | 88.6 | 88.6 |
|
|
| 3 | - | - | 9.72 | 97.2 | 28.4 | 94.6 | 92.4 | 92.4 |
|
|
| Mean | - | - | - | 96.2 | - | 93.4 | - | 90.2 |
|
|
| RSD (%) | - | - | - | 1.0% | - | 1.2% | - | 2.1% |
|
- = Not applicable |
Summary of Clinical Observations - Dosing Phase
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
Observation | No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Normal |
|
| |||||||
No remarkable observations | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Behaviour - other |
| ||||||||
aggression to handler | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
sensitivity to touch, increased | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | |
struggled excessively during sample collection | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | |
Discharge |
| ||||||||
source known, nose, red | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Involuntary movements |
| ||||||||
convulsion, whole body, <1 minute | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
Observation | No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Pelage |
|
| |||||||
abnormal color, ventral, brown | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | |
hair loss, feet, front both | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | |
hair loss, head | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
hair loss, head, right | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
thinning, dorsal | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
thinning, dorsal cervical | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | |
thinning, feet, front both | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | |
thinning, head | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | |
thinning, head, left | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | |
thinning, head, right | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | |
thinning, lateral, left | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
thinning, shoulders, both | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | |
Skin |
| ||||||||
scab, digit(s) | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | |
scab, dorsal thoracic | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
scab, foot, front right | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | |
scab, head, left | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | |
scab, head, right | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | |
scab, ventral | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
Tail |
| ||||||||
bent, tail, distal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | |
Teeth |
| ||||||||
abnormal color, teeth, lower, white | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Summary of Ophthalmic Observations - Dosing Phase - Indirect Ophthalmoscope
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
Observation | No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Anterior chamber aqueous |
|
| |||||||
fibrin clot, left eye | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
No visible lesions |
| ||||||||
no visible lesions, eyes | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | |
no visible lesions, right eye | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Summary of Body Weight Dosing Phase
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g" | |||||||
Gp/sex |
| Day 1 | 8 | 15 | 22 | 29 | 36 |
1/M | Mean | 261 | 312 | 358 | 395 | 436 | 465 |
| SD | 23.8 | 26.9 | 29.6 | 35.0 | 38.5 | 40.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 257 | 310 | 358 | 398 | 439 | 468 |
| SD | 23.1 | 23.8 | 23.7 | 25.8 | 26.0 | 31.1 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 262 | 313 | 357 | 396 | 433 | 462 |
| SD | 23.8 | 27.8 | 34.9 | 42.9 | 46.8 | 50.2 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 261 | 317 | 367 | 407 | 448 | 475 |
| SD | 31.1 | 37.5 | 39.9 | 46.4 | 51.2 | 56.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A |
| A | A |
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g" | |||||||
Gp/sex |
| Day 43 | 50 | 57 | 64 | 71 | 78 |
1/M | Mean | 488 | 510 | 534 | 561 | 580 | 600 |
| SD | 44.0 | 46.6 | 48.8 | 57.0 | 64.6 | 67.3 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 492 | 512 | 536 | 560 | 581 | 600 |
| SD | 39.5 | 43.3 | 45.4 | 49.0 | 56.7 | 62.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 487 | 509 | 533 | 559 | 579 | 593 |
| SD | 54.8 | 58.2 | 59.5 | 62.2 | 64.3 | 66.2 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 502 | 526 | 549 | 573 | 598 | 616 |
| SD | 62.9 | 70.2 | 76.3 | 77.8 | 81.3 | 85.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A | A | A | A |
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
Data Presented in "g" | |||||
Gp/sex |
| Day 85 | 91 |
|
|
1/M | Mean | 610 | 628 |
|
|
| SD | 71.2 | 70.2 |
|
|
| No. | 10 | 10 |
|
|
| |||||
2/M | Mean | 608 | 627 |
|
|
| SD | 60.2 | 65.3 |
|
|
| No. | 10 | 10 |
|
|
| |||||
3/M | Mean | 603 | 619 |
|
|
| SD | 70.6 | 73.0 |
|
|
| No. | 10 | 10 |
|
|
| |||||
4/M | Mean | 631 | 650 |
|
|
| SD | 90.0 | 95.4 |
|
|
| No. | 10 | 10 |
|
|
| Statistics | A | A |
|
|
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g" | |||||||
Gp/sex |
| Day 1 | 8 | 15 | 22 | 29 | 36 |
1/F | Mean | 197 | 228 | 248 | 264 | 274 | 285 |
| SD | 9.1 | 9.5 | 13.1 | 15.5 | 19.2 | 18.5 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 202 | 223 | 246 | 262 | 277 | 286 |
| SD | 21.8 | 26.4 | 28.4 | 29.8 | 32.3 | 35.2 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 204 | 226 | 243 | 265 | 279 | 289 |
| SD | 14.6 | 14.7 | 18.6 | 20.3 | 22.9 | 23.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 199 | 222 | 239 | 254 | 267 | 277 |
| SD | 15.2 | 17.7 | 20.0 | 18.3 | 20.0 | 21.1 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A | A | A | A |
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g" | |||||||
Gp/sex |
| Day 43 | 50 | 57 | 64 | 71 | 78 |
1/F | Mean | 296 | 302 | 307 | 316 | 320 | 321 |
| SD | 19.6 | 20.0 | 24.8 | 24.4 | 28.0 | 29.0 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 296 | 305 | 314 | 320 | 327 | 332 |
| SD | 36.9 | 41.2 | 40.8 | 44.0 | 45.3 | 47.7 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 294 | 306 | 316 | 322 | 319 | 332 |
| SD | 25.5 | 27.8 | 28.2 | 30.9 | 33.5 | 34.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 285 | 291 | 299 | 301 | 303 | 315 |
| SD | 22.2 | 20.5 | 23.6 | 25.9 | 31.8 | 27.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | AT | A | A | A | A |
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
Data Presented in "g" | |||||
Gp/sex |
| Day 85 | 91 |
|
|
1/F | Mean | 323 | 325 |
|
|
| SD | 27.8 | 26.9 |
|
|
| No. | 10 | 10 |
|
|
| |||||
2/F | Mean | 334 | 335 |
|
|
| SD | 49.4 | 49.2 |
|
|
| No. | 10 | 10 |
|
|
| |||||
3/F | Mean | 336 | 338 |
|
|
| SD | 35.9 | 40.1 |
|
|
| No. | 10 | 10 |
|
|
| |||||
4/F | Mean | 320 | 318 |
|
|
| SD | 29.3 | 27.3 |
|
|
| No. | 10 | 10 |
|
|
| Statistics | A | A |
|
|
A = ANOVA and Dunnett's
Summary of Food Consumption - Dosing Phase
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g/animal/day" | |||||||
Gp/sex |
| Day 1-8 | 8-15 | 15-22 | 22-29 | 29-36 | 36-43 |
1/M | Mean | 27 | 25 | 23 | 24 | 23 | 21 |
| SD | 1.1 | 1.5 | 1.1 | 0.7 | 1.5 | 1.4 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
2/M | Mean | 27 | 26 | 24 | 24 | 24 | 22 |
| SD | 1.8 | 2.4 | 2.5 | 2.2 | 2.9 | 4.4 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
3/M | Mean | 27 | 24 | 23 | 23 | 23 | 22 |
| SD | 1.6 | 2.8 | 3.3 | 3.1 | 1.9 | 2.2 |
| No. | 4 | 4 | 4 | 3 | 4 | 4 |
| |||||||
4/M | Mean | 28 | 27 | 25 | 25 | 24 | 22 |
| SD | 2.2 | 2.1 | 2.4 | 1.5 | 2.2 | 1.8 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| Statistics | A | A | A | A | A | A |
ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g/animal/day" | |||||||
Gp/sex |
| Day 43-50 | 50-57 | 57-64 | 64-71 | 71-78 | 78-85 |
1/M | Mean | 20 | 20 | 20 | 22 | 19 | 17 |
| SD | 1.1 | 0.8 | 1.3 | 7.0 | 2.0 | 1.1 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
2/M | Mean | 21 | 23 | 20 | 17 | 19 | 22 |
| SD | 3.9 | 6.1 | 2.6 | 6.4 | 4.4 | 10.2 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
3/M | Mean | 20 | 20 | 20 | 19 | 18 | 16 |
| SD | 1.6 | 0.9 | 1.8 | 1.0 | 1.0 | 1.1 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
4/M | Mean | 22 | 21 | 21 | 20 | 20 | 19 |
| SD | 1.4 | 1.6 | 1.8 | 0.9 | 1.3 | 0.8 |
| No. | 4 | 4 | 3 | 4 | 4 | 4 |
| Statistics | A | AT | A | A | A | AT |
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
Data Presented in "g/animal/day" | |||||
Gp/sex |
| Day 85-91 |
|
|
|
1/M | Mean | 24 |
|
|
|
| SD | 12.5 |
|
|
|
| No. | 4 |
|
|
|
| |||||
2/M | Mean | 18 |
|
|
|
| SD | 4.2 |
|
|
|
| No. | 3 |
|
|
|
| |||||
3/M | Mean | 18 |
|
|
|
| SD | 1.1 |
|
|
|
| No. | 4 |
|
|
|
| |||||
4/M | Mean | 19 |
|
|
|
| SD | 0.9 |
|
|
|
| No. | 3 |
|
|
|
| Statistics | AT |
|
|
|
A = ANOVA and Dunnett's
T = Rank‑transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g/animal/day" | |||||||
Gp/sex |
| Day 1-8 | 8-15 | 15-22 | 22-29 | 29-36 | 36-43 |
1/F | Mean | 17 | 16 | 16 | 15 | 21 | 13 |
| SD | 1.4 | 2.1 | 1.9 | 2.3 | 13.6 | 1.5 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
2/F | Mean | 17 | 17 | 18 | 15 | 15 | 14 |
| SD | 1.7 | 1.0 | 4.0 | 1.0 | 1.4 | 0.9 |
| No. | 4 | 4 | 4 | 3 | 4 | 4 |
| |||||||
3/F | Mean | 16 | 16 | 17 | 16 | 18 | 15 |
| SD | 1.4 | 1.6 | 1.2 | 0.9 | 5.7 | 0.2 |
| No. | 4 | 4 | 4 | 4 | 4 | 3 |
| |||||||
4/F | Mean | 16 | 16 | 16 | 16 | 16 | 15 |
| SD | 2.0 | 1.3 | 1.0 | 1.6 | 1.5 | 0.9 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| Statistics | A | A | A | A | AT | A |
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
Data Presented in "g/animal/day" | |||||||
Gp/sex |
| Day 43-50 | 50-57 | 57-64 | 64-71 | 71-78 | 78-85 |
1/F | Mean | 13 | 13 | 13 | 11 | 11 | 11 |
| SD | 1.6 | 1.4 | 2.1 | 1.4 | 1.4 | 1.8 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
2/F | Mean | 15 | 14 | 18 | 15 | 13 | 11 |
| SD | 1.4 | 1.1 | 7.1 | 5.1 | 1.8 | 0.8 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
3/F | Mean | 16 | 17 | 13 | 13 | 13 | 11 |
| SD | 2.4 | 6.2 | 0.9 | 1.2 | 1.1 | 0.6 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| |||||||
4/F | Mean | 15 | 15 | 13 | 18 | 14 | 13 |
| SD | 1.1 | 1.8 | 2.3 | 6.9 | 2.2 | 1.8 |
| No. | 4 | 4 | 4 | 4 | 4 | 4 |
| Statistics | A | AT | AT | A | A | A |
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
Data Presented in "g/animal/day" | |||||
Gp/sex |
| Day 85-91 |
|
|
|
1/F | Mean | 11 |
|
|
|
| SD | 1.3 |
|
|
|
| No. | 4 |
|
|
|
| |||||
2/F | Mean | 12 |
|
|
|
| SD | 0.7 |
|
|
|
| No. | 4 |
|
|
|
| |||||
3/F | Mean | 11 |
|
|
|
| SD | 0.7 |
|
|
|
| No. | 4 |
|
|
|
| |||||
4/F | Mean | 13* |
|
|
|
| SD | 0.9 |
|
|
|
| No. | 4 |
|
|
|
| Statistics | A |
|
|
|
* P<=0.05
A = ANOVA and Dunnett's
Summary of Elicited Behaviour
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| FORE1 g | FORE2 g | FGSA2 g | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 10 | 79 | 10 | 79 | 10 | 79 |
| |||||||
1/M | Mean | 758 | 2044 | 783 | 1953 | 770 | 1998 |
| SD | 64.2 | 639.0 | 161.5 | 566.4 | 100.5 | 588.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 796 | 2199 | 819 | 2024 | 807 | 2112 |
| SD | 176.9 | 273.4 | 174.1 | 239.2 | 158.5 | 223.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 908 | 2136 | 852 | 2064 | 880 | 2100 |
| SD | 123.7 | 581.6 | 134.4 | 527.4 | 114.5 | 542.9 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 794 | 2338 | 780 | 2218 | 787 | 2278 |
| SD | 132.8 | 236.4 | 135.6 | 372.2 | 113.9 | 283.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | X1 | AT | X1 | AT | X1 | AT |
X1 = No analysis required
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| HIND1 g | HIND2 g | HGSA2 g | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 10 | 79 | 10 | 79 | 10 | 79 |
| |||||||
1/M | Mean | 528 | 814 | 549 | 765 | 538 | 789 |
| SD | 109.4 | 220.0 | 158.6 | 225.3 | 107.1 | 211.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 491 | 818 | 535 | 870 | 513 | 844 |
| SD | 63.3 | 239.1 | 110.2 | 225.1 | 41.4 | 209.7 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 530 | 767 | 513 | 822 | 521 | 795 |
| SD | 133.9 | 236.8 | 95.4 | 246.9 | 94.9 | 235.9 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 478 | 755 | 457 | 718 | 468 | 737 |
| SD | 112.2 | 141.4 | 124.9 | 119.4 | 104.4 | 121.1 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| FOOT1 cm | FOOT2 cm | FSA2 cm | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 10 | 79 | 10 | 79 | 10 | 79 |
| |||||||
1/M | Mean | 8.6 | 12.3 | 7.7 | 12.1 | 8.1 | 12.2 |
| SD | 2.09 | 1.87 | 1.56 | 2.08 | 1.68 | 1.91 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 9.4 | 12.9 | 8.5 | 12.5 | 8.9 | 12.7 |
| SD | 1.45 | 2.70 | 1.40 | 2.42 | 1.28 | 2.39 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 9.0 | 13.5 | 7.6 | 13.2 | 8.3 | 13.3 |
| SD | 1.96 | 1.30 | 1.54 | 1.84 | 1.44 | 1.50 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 8.4 | 13.1 | 8.5 | 12.8 | 8.4 | 12.9 |
| SD | 1.78 | 1.85 | 1.99 | 1.62 | 1.65 | 1.64 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| BODYTEMP °C | RBW g | |||
| Phase | predose | dosing | predose | dosing |
Gp/sex |
| Day 10 | 79 | 10 | 79 |
| |||||
1/M | Mean | 37.6 | 38.9 | 202 | 602 |
| SD | 0.62 | 0.33 | 22.5 | 67.6 |
| No. | 10 | 10 | 10 | 10 |
| |||||
2/M | Mean | 37.7 | 38.5 | 200 | 600 |
| SD | 0.42 | 0.47 | 21.4 | 59.6 |
| No. | 10 | 10 | 10 | 10 |
| |||||
3/M | Mean | 37.4 | 38.5 | 204 | 593 |
| SD | 0.34 | 0.43 | 23.1 | 65.9 |
| No. | 10 | 10 | 10 | 10 |
| |||||
4/M | Mean | 37.5 | 38.7 | 203 | 617 |
| SD | 0.41 | 0.37 | 26.2 | 84.5 |
| No. | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| FORE1 g | FORE2 g | FGSA2 g | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 11 | 78 | 11 | 78 | 11 | 78 |
| |||||||
1/F | Mean | 804 | 1689 | 803 | 1580 | 803 | 1634 |
| SD | 98.8 | 258.1 | 103.9 | 263.1 | 93.3 | 214.0 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 775 | 1562 | 814 | 1595 | 795 | 1579 |
| SD | 149.0 | 305.1 | 192.7 | 330.5 | 156.9 | 290.1 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 828 | 1653 | 834 | 1636 | 831 | 1644 |
| SD | 81.2 | 290.7 | 118.5 | 281.0 | 94.4 | 263.7 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 830 | 1593 | 866 | 1606 | 848 | 1600 |
| SD | 119.7 | 263.0 | 94.6 | 314.7 | 103.5 | 276.2 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| HIND1 G | HIND2 g | HGSA2 g | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 11 | 78 | 11 | 78 | 11 | 78 |
| |||||||
1/F | Mean | 527 | 702 | 498 | 698 | 513 | 700 |
| SD | 122.0 | 134.5 | 126.2 | 154.3 | 109.3 | 133.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 479 | 631 | 484 | 609 | 481 | 620 |
| SD | 100.9 | 188.8 | 109.0 | 185.3 | 92.5 | 181.1 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 528 | 591 | 486 | 582 | 507 | 586 |
| SD | 173.3 | 97.4 | 80.1 | 144.6 | 118.5 | 97.3 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 513 | 593 | 554 | 622 | 533 | 608 |
| SD | 103.1 | 214.0 | 76.9 | 207.6 | 78.9 | 204.7 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| FORE1 g | FORE2 g | FGSA2 g | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 11 | 78 | 11 | 78 | 11 | 78 |
| |||||||
1/F | Mean | 7.9 | 10.2 | 7.2 | 10.2 | 7.5 | 10.2 |
| SD | 2.61 | 1.71 | 1.36 | 1.84 | 1.72 | 1.73 |
| No. | 2.61 | 1.71 | 1.36 | 1.84 | 1.72 | 1.73 |
| |||||||
2/F | Mean | 8.2 | 11.4 | 7.2 | 11.4 | 7.7 | 11.4 |
| SD | 1.34 | 1.67 | 1.14 | 1.68 | 0.97 | 1.65 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 8.3 | 11.4 | 8.1 | 11.5 | 8.2 | 11.4 |
| SD | 1.53 | 1.62 | 1.51 | 1.67 | 1.38 | 1.56 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 9.7 | 11.0 | 8.5 | 10.7 | 9.1 | 10.9 |
| SD | 1.69 | 1.11 | 1.49 | 0.68 | 1.49 | 0.86 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| BODYTEMP °C | RBW g | |||
| Phase | predose | dosing | predose | dosing |
Gp/sex |
| Day 11 | 78 | 11 | 78 |
| |||||
1/F | Mean | 37.8 | 38.5 | 169 | 324 |
| SD | 0.45 | 0.58 | 8.5 | 28.4 |
| No. | 10 | 10 | 10 | 10 |
| |||||
2/F | Mean | 37.7 | 38.7 | 167 | 333 |
| SD | 0.39 | 0.47 | 9.2 | 35.9 |
| No. | 10 | 10 | 10 | 10 |
| |||||
3/F | Mean | 37.9 | 38.9 | 171 | 334 |
| SD | 0.39 | 0.47 | 9.2 | 35.9 |
| No. | 10 | 10 | 10 | 10 |
| |||||
4/F | Mean | 37.9 | 38.8 | 168 | 316 |
| SD | 0.51 | 0.67 | 10.4 | 27.4 |
| No. | 10 | 10 | 10 | 10 |
| Statistics | X1 | A | X1 | A |
X1 = No analysis required
A = ANOVA and Dunnett's
Summary of Open Field Observations
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| LAT sec | REAR | URIPOL | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 10 | 79 | 10 | 79 | 10 | 79 |
| |||||||
1/M | Mean | 0 | 1 | 11 | 11 | 1 | 0 |
| SD | 0.0 | 1.2 | 6.1 | 7.6 | 1.3 | 0.7 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 0 | 1 | 13 | 8 | 0 | 0 |
| SD | 0.0 | 0.5 | 5.1 | 4.4 | 0.9 | 0.7 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 0 | 1 | 12 | 9 | 0 | 0 |
| SD | 0.0 | 0.7 | 4.3 | 5.8 | 0.0 | 0.3 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 0 | 1 | 10 | 8 | 1 | 0 |
| SD | 0.0 | 1.0 | 4.5 | 3.9 | 1.6 | 0.5 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
| |||||
| FECBOL |
| |||
| Phase | predose | dosing |
| |
Gp/sex |
| Day 10 | 79 |
| |
| |||||
1/M | Mean | 1 | 1 |
| |
| SD | 1.3 | 1.3 |
| |
| No. | 10 | 10 |
| |
| |||||
2/M | Mean | 1 | 1 |
| |
| SD | 1.3 | 1.6 |
| |
| No. | 1.3 | 1.6 |
| |
| |||||
3/M | Mean | 0 | 2 |
| |
| SD | 1.3 | 2.0 |
| |
| No. | 10 | 10 |
| |
| |||||
4/M | Mean | 1 | 2 |
| |
| SD | 1.6 | 1.9 |
| |
| No. | 10 | 10 |
|
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| LAT sec | REAR | URIPOL | ||||
| Phase | predose | dosing | predose | dosing | predose | dosing |
Gp/sex |
| Day 11 | 78 | 11 | 78 | 11 | 78 |
| |||||||
1/F | Mean | 1 | 1 | 12 | 15 | 0 | 0 |
| SD | 1.9 | 0.7 | 5.9 | 5.9 | 0.6 | 0.5 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 0 | 0 | 8 | 14 | 0 | 0 |
| SD | 0.0 | 0.5 | 6.1 | 2.7 | 0.9 | 0.0 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 1 | 1 | 8 | 11 | 0 | 0 |
| SD | 2.2 | 0.6 | 3.1 | 5.5 | 0.0 | 0.6 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 0 | 1 | 8 | 12 | 0 | 0 |
| SD | 0.9 | 1.1 | 4.8 | 6.4 | 0.3 | 0.3 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
| |||||
| FECBOL |
| |||
| Phase | predose | dosing |
| |
Gp/sex |
| Day 11 | 78 |
| |
| |||||
1/F | Mean | 0 | 0 |
| |
| SD | 0.0 | 0.0 |
| |
| No. | 10 | 10 |
| |
| |||||
2/F | Mean | 1 | 0 |
| |
| SD | 1.6 | 0.0 |
| |
| No. | 10 | 10 |
| |
| |||||
3/F | Mean | 0 | 0 |
| |
| SD | 0.3 | 0.6 |
| |
| No. | 10 | 10 |
| |
| |||||
4/F | Mean | 0 | 0 |
| |
| SD | 0.0 | 0.7 |
| |
| No. | 10 | 10 |
|
Summary of Neurobehavioral Observations - Dosing Phase
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category Observation | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Activity |
|
| |||||||
decreased, mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | |
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 8 | |
Aggression to cage mate |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Alertness |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Approach response |
| ||||||||
increased | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
normal | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Auditory startle response |
| ||||||||
increased | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 2 | |
normal | 10 | 9 | 9 | 10 | 9 | 10 | 9 | 8 | |
Bar test |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Behaviour - other |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Behaviour - stereotype |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Body tone |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category Observation | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Discharge |
|
| |||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Excretion |
| ||||||||
normal, group house observation | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Extensor thrust |
| ||||||||
decreased | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | |
normal | 9 | 10 | 10 | 9 | 10 | 10 | 10 | 10 | |
Eye closure |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Eyes |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Gait |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 9 | 10 | 10 | |
walking on toes | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | |
Gasping loss |
| ||||||||
abnormal, mild | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | |
normal | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | |
Grip strength |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Involuntary movements |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category Observation | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Lacrimation |
|
| |||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Pain response |
| ||||||||
decreased | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | |
increased | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | |
normal | 10 | 10 | 10 | 9 | 9 | 10 | 10 | 10 | |
Palpebral reflex |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Pelage |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Pinna response |
| ||||||||
absent | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | |
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 9 | |
Posture |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Propreoception (right & hind) |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Pupil status |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Pupillary response |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Test Item | (dosage) | 1 | 2 | 3 | 4 | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 | 0 | 100 | 300 | 1000 |
Category Observation | Gp/Sex: | 1/M | 2/M | 3/M | 4/M | 1/F | 2/F | 3/F | 4/F |
No. in gp. | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Reactivity to handling |
|
| |||||||
abnormal, increased | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | |
normal | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | |
Respiration |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Restlessness |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Righting reflex |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Salivation |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Skin colour |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Tail |
| ||||||||
elevated, mild | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | |
normal | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | |
Visual response |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Vocalization |
| ||||||||
normal | 10 | 9 | 10 | 10 | 9 | 10 | 10 | 9 | |
present, mild | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | |
Waxy rigidity |
| ||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Summary of Hematology
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | RBC E6/uL | HGB g/dL | Hct % | MCV fL | MCH pg | MCHC g/dL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 8.05 | 13.9 | 43.2 | 53.6 | 17.2 | 32.1 |
| SD | 0.342 | 0.56 | 1.99 | 1.29 | 0.60 | 0.55 |
| No. | 9 | 9 | 9 | 9 | 9 | 9 |
| |||||||
2/M | Mean | 8.33 | 14.4 | 44.3 | 53.3 | 17.2 | 32.4 |
| SD | 0.401 | 0.55 | 1.88 | 2.15 | 0.73 | 0.37 |
| No. | 7 | 7 | 7 | 7 | 7 | 7 |
| |||||||
3/M | Mean | 8.35 | 14.1 | 43.8 | 52.4 | 16.8 | 32.1 |
| SD | 0.252 | 0.33 | 1.06 | 0.55 | 0.39 | 0.63 |
| No. | 7 | 7 | 7 | 7 | 7 | 7 |
| |||||||
4/M | Mean | 8.20 | 14.1 | 43.8 | 53.4 | 17.3 | 32.3 |
| SD | 0.192 | 0.62 | 0.94 | 1.35 | 0.78 | 1.07 |
| No. | 7 | 7 | 7 | 7 | 7 | 7 |
| Statistics | A | A | A | AT | A | A |
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | RBC E6/uL | HGB g/dL | Hct % | MCV fL | MCH pg | MCHC g/dL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 7.20 | 13.0 | 39.7 | 55.2 | 18.1 | 32.8 |
| SD | 0.294 | 0.36 | 1.16 | 2.16 | 0.77 | 0.44 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 7.31 | 12.9 | 39.5 | 54.0 | 17.7 | 32.7 |
| SD | 0.282 | 0.67 | 1.99 | 1.66 | 0.62 | 0.44 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 7.15 | 12.9 | 39.3 | 55.0 | 18.0 | 32.8 |
| SD | 0.122 | 0.39 | 1.03 | 1.13 | 0.48 | 0.60 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 7.38 | 13.1 | 40.1 | 54.4 | 17.8 | 32.7 |
| SD | 0.244 | 0.38 | 1.03 | 1.59 | 0.62 | 0.45 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A | A | A | A |
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | RDW % | RETIC E3/uL | PLT E3/uL | WBC E3/uL | NEUT E3/uL | LYM E3/uL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 12.4 | 183.5 | 997 | 7.96 | 1.21 | 6.42 |
| SD | 0.34 | 27.32 | 102.0 | 2.182 | 0.327 | 1.855 |
| No. | 9 | 9 | 9 | 9 | 9 | 9 |
| |||||||
2/M | Mean | 12.6 | 178.0 | 1028 | 9.37 | 1.44 | 7.50 |
| SD | 0.25 | 21.70 | 95.5 | 1.407 | 0.318 | 1.188 |
| No. | 7 | 7 | 7 | 7 | 7 | 7 |
| |||||||
3/M | Mean | 12.3 | 169.2 | 1064 | 8.58 | 1.39 | 6.78 |
| SD | 0.42 | 15.52 | 108.7 | 2.024 | 0.550 | 1.684 |
| No. | 7 | 7 | 7 | 7 | 7 | 7 |
| |||||||
4/M | Mean | 12.9 | 205.8 | 1032 | 8.78 | 1.36 | 6.94 |
| SD | 0.71 | 30.82 | 83.0 | 1.880 | 0.434 | 1.366 |
| No. | 7 | 7 | 7 | 7 | 7 | 7 |
| Statistics | AT | A | A | A | A | A |
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | RDW % | RETIC E3/uL | PLT E3/uL | WBC E3/uL | NEUT E3/uL | LYM E3/uL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 11.0 | 181.6 | 996 | 4.44 | 0.57 | 3.66 |
| SD | 0.21 | 40.20 | 70.6 | 1.432 | 0.170 | 1.334 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 11.2 | 183.2 | 953 | 5.34 | 0.93 | 4.15 |
| SD | 0.33 | 33.43 | 116.2 | 1.873 | 0.326 | 1.757 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 11.2 | 168.3 | 1059 | 4.96 | 0.77 | 3.95 |
| SD | 0.25 | 33.94 | 125.7 | 1.533 | 0.219 | 1.322 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 11.2 | 177.8 | 995 | 4.75 | 0.78 | 3.73 |
| SD | 0.29 | 31.74 | 116.8 | 1.132 | 0.371 | 0.886 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | AT | A | A | A | A | A |
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | MONO E3/uL | EOS E3/uL | BASO E3/uL | LUC E3/uL | PT sec | APTT sec |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 0.21 | 0.09 | 0.02 | 0.01 | 11.4 | 18.2 |
| SD | 0.083 | 0.051 | 0.008 | 0.009 | 0.39 | 2.37 |
| No. | 9 | 9 | 9 | 9 | 10 | 10 |
| |||||||
2/M | Mean | 0.29 | 0.07 | 0.03 | 0.05* | 11.6 | 18.3 |
| SD | 0.063 | 0.019 | 0.005 | 0.030 | 0.80 | 2.21 |
| No. | 7 | 7 | 7 | 7 | 10 | 10 |
| |||||||
3/M | Mean | 0.27 | 0.07 | 0.02 | 0.04 | 11.7 | 17.4 |
| SD | 0.106 | 0.023 | 0.008 | 0.034 | 0.20 | 1.34 |
| No. | 7 | 7 | 7 | 7 | 9 | 9 |
| |||||||
4/M | Mean | 0.34 | 0.07 | 0.03 | 0.04 | 11.1 | 18.5 |
| SD | 0.193 | 0.025 | 0.013 | 0.037 | 0.73 | 2.86 |
| No. | 7 | 7 | 7 | 7 | 10 | 10 |
| Statistics | AT | A | X2 | AT | AT | A |
* P<=0.05
A = ANOVA and Dunnett's
T = Rank transformed data
X2 = Not analyzed (too few distinct values)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | MONO E3/uL | EOS E3/uL | BASO E3/uL | LUC E3/uL | PT sec | APTT sec |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 0.13 | 0.06 | 0.01 | 0.02 | 10.1 | 16.1 |
| SD | 0.050 | 0.022 | 0.005 | 0.007 | 0.41 | 0.99 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 0.17 | 0.07 | 0.01 | 0.01 | 9.9 | 16.7 |
| SD | 0.061 | 0.016 | 0.008 | 0.011 | 0.51 | 1.04 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 0.15 | 0.07 | 0.01 | 0.02 | 10.0 | 16.6 |
| SD | 0.092 | 0.031 | 0.007 | 0.010 | 0.33 | 1.17 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 0.15 | 0.07 | 0.01 | 0.01 | 9.9 | 15.9 |
| SD | 0.040 | 0.023 | 0.005 | 0.008 | 0.51 | 1.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | X2 | X2 | A | A |
A = ANOVA and Dunnett's
X2 = Not analyzed (too few distinct values)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| Phase- Dosing | FIB mg/dL |
|
|
|
Gp/sex |
| Day 92 |
|
|
|
| |||||
1/M | Mean | 155 |
|
|
|
| SD | 8.4 |
|
|
|
| No. | 10 |
|
|
|
| |||||
2/M | Mean | 163 |
|
|
|
| SD | 7.8 |
|
|
|
| No. | 10 |
|
|
|
| |||||
3/M | Mean | 157 |
|
|
|
| SD | 15.9 |
|
|
|
| No. | 10 |
|
|
|
| |||||
4/M | Mean | 161 |
|
|
|
| SD | 5.0 |
|
|
|
| No. | 10 |
|
|
|
| Statistics | A |
|
|
|
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| Phase- Dosing | FIB mg/dL |
|
|
|
Gp/sex |
| Day 92 |
|
|
|
| |||||
1/F | Mean | 132 |
|
|
|
| SD | 9.1 |
|
|
|
| No. | 10 |
|
|
|
| |||||
2/F | Mean | 128 |
|
|
|
| SD | 11.1 |
|
|
|
| No. | 10 |
|
|
|
| |||||
3/F | Mean | 127 |
|
|
|
| SD | 6.3 |
|
|
|
| No. | 10 |
|
|
|
| |||||
4/F | Mean | 132 |
|
|
|
| SD | 9.3 |
|
|
|
| No. | 10 |
|
|
|
| Statistics | A |
|
|
|
A = ANOVA and Dunnett's
Summary of Clinical Chemistry
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | GLU mg/dL | UN mg/dL | CREAT mg/dL | TP g/dL | ALB g/dL | GLOB g/dL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 166 | 8 | 0.3 | 5.4 | 4.0 | 1.4 |
| SD | 24.9 | 1.1 | 0.04 | 0.21 | 0.18 | 0.19 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 168 | 8 | 0.3 | 5.6 | 4.2 | 1.4 |
| SD | 19.8 | 1.0 | 0.05 | 0.26 | 0.22 | 0.17 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 174 | 8 | 0.3 | 5.4 | 4.0 | 1.4 |
| SD | 10.0 | 1.7 | 0.05 | 0.28 | 0.17 | 0.18 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 173 | 9 | 0.3 | 5.5 | 4.1 | 1.4 |
| SD | 22.6 | 1.1 | 0.04 | 0.28 | 0.20 | 0.18 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | AT | A | X2 | A | A | A |
A = ANOVA and Dunnett's
T = Rank transformed data
X2 = Not analyzed (too few distinct values)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | GLU mg/dL | UN mg/dL | CREAT mg/dL | TP g/dL | ALB g/dL | GLOB g/dL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 148 | 10 | 0.3 | 6.2 | 5.0 | 1.2 |
| SD | 16.7 | 2.2 | 0.05 | 0.41 | 0.44 | 0.16 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 152 | 10 | 0.3 | 6.5 | 5.3 | 1.2 |
| SD | 30.1 | 2.3 | 0.05 | 0.44 | 0.33 | 0.26 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 146 | 10 | 0.3 | 6.3 | 5.2 | 1.1 |
| SD | 19.3 | 1.4 | 0.04 | 0.44 | 0.35 | 0.17 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 153 | 12 | 0.3 | 6.2 | 5.0 | 1.2 |
| SD | 25.3 | 2.5 | 0.05 | 0.30 | 0.39 | 0.16 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | X2 | A | A | A |
A = ANOVA and Dunnett's
X2 = Not analyzed (too few distinct values)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | A:G Ratio | CHOL mg/dL | HDL mg/dL | LDL mg/dL | TRIG mg/dL | TBIL mg/dL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 2.9 | 48 | 35 | <7 | 87 | <0.1 |
| SD | 0.46 | 5.7 | 5.9 | 0.9 | 14.3 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 3.0 | 48 | 35 | <8 | 82 | <0.1 |
| SD | 0.35 | 8.4 | 6.4 | 2.3 | 26.9 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 2.9 | 50 | 35 | <8 | 76 | <0.1 |
| SD | 0.33 | 4.5 | 4.4 | 2.1 | 22.1 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 3.0 | 62* | 43* | <10 | 89 | <0.1 |
| SD | 0.41 | 11.9 | 8.1 | 4.2 | 28.8 | 0.01 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | AT | A | X5 | A | X5 |
* P<=0.05
A = ANOVA and Dunnett's
T = Rank‑transformed data
X5 = Not analyzed (values above/below the limit of quantitation)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | A:G Ratio | CHOL mg/dL | HDL mg/dL | LDL mg/dL | TRIG mg/dL | TBIL mg/dL |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 4.4 | 61 | 51 | <6 | 47 | <0.1 |
| SD | 0.83 | 12.1 | 11.5 | 0.7 | 8.2 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 4.9 | 65 | 57 | <6 | 58 | <0.1 |
| SD | 1.39 | 22.5 | 19.0 | 0.6 | 27.4 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 4.7 | 59 | 52 | <6 | 55 | <0.1 |
| SD | 0.72 | 10.5 | 10.6 | 0.2 | 20.5 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 4.3 | 72 | 60 | <6 | 51 | <0.1 |
| SD | 0.92 | 12.9 | 13.1 | 0.4 | 13.3 | 0.00 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A | X5 | A | X5 |
A = ANOVA and Dunnett's
X5 = Not analyzed (values above/below the limit of quantitation)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | AST U/L | ALT U/L | ALP U/L | GGT U/L | SBA umol/L | CK U/L |
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 69 | 30 | 96 | <3 | 34 | 255 |
| SD | 12.2 | 5.9 | 10.6 | 0.0 | 20.4 | 136.0 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 68 | 28 | 100 | <3 | 35 | 283 |
| SD | 15.2 | 5.6 | 26.2 | 0.0 | 28.3 | 213.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 61 | 29 | 109 | <3 | 50 | 137 |
| SD | 8.2 | 8.4 | 33.8 | 0.0 | 22.0 | 79.2 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 62 | 26 | 129 | <3 | 65 | 185 |
| SD | 10.0 | 5.5 | 48.9 | 0.0 | 43.6 | 162.9 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | AT | X5 | AT | AT |
A = ANOVA and Dunnett's
T = Rank transformed data
X5 = Not analyzed (values above/below the limit of quantitation)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | AST U/L | ALT U/L | ALP U/L | GGT U/L | SBA umol/L | CK U/L |
|
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 71 | 18 | 42 | <3 | 26 | 332 |
| SD | 18.9 | 3.6 | 19.3 | 0.0 | 22.4 | 227.5 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 79 | 21 | 43 | <3 | 15 | 384 |
| SD | 16.9 | 7.5 | 29.5 | 0.0 | 13.6 | 280.1 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 65 | 19 | 39 | <3 | 32 | 233 |
| SD | 12.5 | 2.3 | 12.8 | 0.0 | 23.9 | 142.8 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 77 | 23 | 46 | <3 | 47 | 298 |
| SD | 22.0 | 7.0 | 15.4 | 0.0 | 68.4 | 224.4 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A | X5 | AT | A |
A = ANOVA and Dunnett's
X5 = Not analyzed (values above/below the limit of quantitation)
T = Rank‑transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | Ca mg/dL | PHOS mg/dL | Na mmol/L | K mmol/L | Cl mmol/L | TSH uIU/mL |
|
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/M | Mean | 10.1 | 7.0 | 141 | 4.5 | 102 | 1.61 |
| SD | 0.29 | 0.47 | 1.3 | 0.19 | 1.0 | 1.291 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/M | Mean | 10.2 | 7.0 | 140 | 4.6 | 101 | 1.77 |
| SD | 0.26 | 0.39 | 1.0 | 0.23 | 1.1 | 1.295 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/M | Mean | 10.3 | 7.2 | 140 | 4.5 | 101 | 3.59 |
| SD | 0.18 | 0.58 | 1.1 | 0.29 | 0.7 | 3.063 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/M | Mean | 10.5 | 7.2 | 140 | 4.5 | 100* | 2.10 |
| SD | 0.61 | 0.59 | 0.8 | 0.24 | 1.5 | 0.983 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | AT | A | A | A | A | AT |
* P<=0.05
A = ANOVA and Dunnett's
T = Rank transformed data
Test Item | (dosage) | 1 | 2 | 3 | 4 |
|
|
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
|
|
|
|
| Phase- Dosing | Ca mg/dL | PHOS mg/dL | Na mmol/L | K mmol/L | Cl mmol/L | TSH uIU/mL |
|
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 | 92 | 92 | 92 | 92 |
| |||||||
1/F | Mean | 10.3 | 5.8 | 139 | 4.2 | 102 | 0.84 |
| SD | 0.42 | 0.43 | 0.7 | 0.24 | 1.9 | 0.471 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
2/F | Mean | 10.5 | 6.2 | 139 | 4.1 | 101 | 0.94 |
| SD | 0.43 | 0.48 | 1.4 | 0.33 | 1.7 | 0.437 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
3/F | Mean | 10.5 | 6.0 | 139 | 4.1 | 102 | 1.64 |
| SD | 0.45 | 0.56 | 1.4 | 0.19 | 1.1 | 0.965 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| |||||||
4/F | Mean | 10.5 | 6.4 | 139 | 4.2 | 101 | 1.75 |
| SD | 0.61 | 0.65 | 1.1 | 0.22 | 1.6 | 1.455 |
| No. | 10 | 10 | 10 | 10 | 10 | 10 |
| Statistics | A | A | A | A | A | A |
A = ANOVA and Dunnett's
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| Phase- Dosing | T3 ng/dL | T4 ug/dL |
|
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 |
|
|
| |||||
1/M | Mean | 101 | 4.8 |
|
|
| SD | 19.0 | 0.68 |
|
|
| No. | 10 | 10 |
|
|
| |||||
2/M | Mean | 101 | 5.2 |
|
|
| SD | 15.5 | 0.84 |
|
|
| No. | 10 | 10 |
|
|
| |||||
3/M | Mean | 112 | 6.5* |
|
|
| SD | 21.6 | 1.01 |
|
|
| No. | 10 | 10 |
|
|
| |||||
4/M | Mean | 100 | 6.9* |
|
|
| SD | 20.5 | 1.62 |
|
|
| No. | 10 | 10 |
|
|
| Statistics | A | A |
|
|
* P<=0.05
A = ANOVA and Dunnett's
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| Phase- Dosing | T3 ng/dL | T4 ug/dL |
|
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 |
|
|
| |||||
1/F | Mean | 139 | 4.5 |
|
|
| SD | 24.0 | 1.16 |
|
|
| No. | 10 | 10 |
|
|
| |||||
2/F | Mean | 138 | 5.2 |
|
|
| SD | 17.0 | 1.19 |
|
|
| No. | 10 | 10 |
|
|
| |||||
3/F | Mean | 136 | 5.5 |
|
|
| SD | 31.3 | 1.00 |
|
|
| No. | 10 | 10 |
|
|
| |||||
4/F | Mean | 120 | 6.5* |
|
|
| SD | 20.9 | 1.48 |
|
|
| No. | 10 | 10 |
|
|
| Statistics | A | A |
|
|
* P<=0.05
A = ANOVA and Dunnett's
Summary of Urinalysis
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| Phase- Dosing | UVOL mL | SPGR | UpH |
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 | 92 |
|
| |||||
1/M | Mean | 6.1 | 1.047 | 5.6 |
|
| SD | 8.63 | 0.0216 | 0.50 |
|
| No. | 10 | 10 | 10 |
|
| |||||
2/M | Mean | 4.8 | 1.043 | 5.7 |
|
| SD | 2.72 | 0.0137 | 0.35 |
|
| No. | 10 | 10 | 10 |
|
| |||||
3/M | Mean | 5.7 | 1.046 | 5.6 |
|
| SD | 4.83 | 0.0157 | 0.39 |
|
| No. | 10 | 10 | 10 |
|
| |||||
4/M | Mean | 6.2 | 1.055 | 5.5 |
|
| SD | 1.62 | 0.0101 | 0.00 |
|
| No. | 10 | 10 | 10 |
|
| Statistics | A | A | X2 |
|
A = ANOVA and Dunnett's
X2 = Not analyzed (too few distinct values)
Test Item | (dosage) | 1 | 2 | 3 | 4 |
Lankroflex ED6 | mg/kg/day | 0 | 100 | 300 | 1000 |
|
|
|
|
|
|
| Phase- Dosing | UVOL mL | SPGR | UpH |
|
|
|
|
|
|
|
Gp/sex |
| Day 92 | 92 | 92 |
|
| |||||
1/F | Mean | 1.8 | 1.042 | 5.9 |
|
| SD | 0.71 | 0.0097 | 0.34 |
|
| No. | 10 | 10 | 10 |
|
| |||||
2/F | Mean | 1.7 | 1.057* | 5.6 |
|
| SD | 0.96 | 0.0138 | 0.39 |
|
| No. | 10 | 10 | 10 |
|
| |||||
3/F | Mean | 4.1 | 1.041 | 5.9 |
|
| SD | 3.12 | 0.0154 | 0.34 |
|
| No. | 10 | 10 | 10 |
|
| |||||
4/F | Mean | 3.3* | 1.055 | 5.3 |
|
| SD | 1.25 | 0.0123 | 0.26 |
|
| No. | 10 | 10 | 10 |
|
| Statistics | AT | A | X2 |
|
* P<=0.05
A = ANOVA and Dunnett's
T = Rank transformed data
X2 = Not analyzed (too few distinct values)
Applicant's summary and conclusion
- Conclusions:
- Male and female rats were administered corn oil (control) or 100, 300 or 1000 mg/kg/day Lankroflex ED6 once daily via oral gavage for 13 weeks. Clinical pathology changes were minimal in magnitude and included higher alkaline phosphatase activity in two males at 100 mg/kg/day, two males at 300 mg/kg/day, and males at 1000 mg/kg/day. Higher serum bile acid was noted in one male at 300 mg/kg/day and males and two females at 1000 mg/kg/day and was likely associated with higher liver weights. Higher T4 was noted in one female at 100 mg/kg/day, three males and one female at 300 mg/kg/day, and three males and four females at 1000 mg/kg/day. All effects were considered non-adverse due to the mild severity of observed findings. The no observed adverse effect level (NOAEL) is 1000 mg/kg/day.
- Executive summary:
The toxicity of Lankroflex ED6 (Fatty acids, C14-22, 2-ethylhexyl esters, epoxidised) was evaluated when administered once daily via oral gavage to rats for at least 13 weeks. Forty male and 40 female (Sprague Dawley) rats were assigned to four groups, 0(vehicle control, corn oil), 100 mg/kg/day, 300 mg/kg/day and 1000 mg/kg/day. Animals were dosed via oral gavage once daily at 10 mL/kg. Assessment of toxicity was based on mortality, clinical observations, body weights, food consumption, ophthalmic observations, functional observational battery (FOB),
locomotor activity (LMA), estrous phase determination, and clinical and anatomic pathology. Blood samples were collected for thyroid hormone and serum bile acids evaluation.
There were no test item-related mortality, clinical observations, differences in body weights, food consumption, FOB or LMA findings. Clinical chemistry results were minimal in magnitude and consisted of higher alkaline phosphatase activity in in two males at 100 mg/kg/day, two males at 300 mg/kg/day and most males at 1000 mg/kg/day. Higher serum bile acids were noted in one male at 300 mg/kg/day and males and two females at 1000 mg/kg/day and we considered likely associated with higher liver weights. Higher T4 was noted one female at 100 mg/kg/day, three males and one female at 300 mg/kg/day and three males and four females at 1000 mg/kg/day. No test item related effects in hematology, coagulation, or urinalysis were identified.Test item-related mean absolute and relative liver weights were increased in animals at 1000 mg/kg/day, without macroscopic or microscopic correlates. No test item-related macroscopic or microscopic findings were noted.
Decreased sperm concentration was noted for all test item treated males and was statistically significant for males at 300 mg/kg/day compared with controls.
An increase in abnormal sperm morphology was noted in males at 1000 mg/kg/day, compared with controls. These changes were considered not related to the test material, due to a lack of organ weight effects or histopathological correlates. No test item related effect on motility was noted at any dose level.All effects were considered non-adverse due to the mild severity of observed findings. The no observed adverse effect level (NOAEL) is 1000 mg/kg/day.
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