Registration Dossier
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EC number: 617-769-9 | CAS number: 858956-08-8
Endpoint summary
Administrative data
Description of key information
Subchronic toxicity, oral
NOAEL (rat): 6000 ppm (corresponding to 349 and 448 mg/kg bw/day in males and females, respectively)
NOAEL (mouse): 7000 ppm (corresponding to 1088 and 1623 mg/kg bw/day in males and females, respectively)
NOAEL (dog): 15000 ppm (corresponding to 426 and 388 mg/kg bw/day in males and females, respectively)
Subacute toxicity, dermal:
NOAEL (rat): 1000 mg/kg bw/day
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 02 February 2007 to 01 July 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- adopted 21 September 1998
- Deviations:
- no
- Remarks:
- no hormonal measurements performed
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crl:CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina, USA
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 7 weeks
- Weight at study initiation: 253.0 - 256.4 g (males), 173.7 - 179.4 (females)
- Housing: individually in stainless steel, wire-mesh cages suspended above cage boards
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet 5002®, ad libitum
- Water: tap water, ad libitum
- Acclimation period: approximately 9 days
DETAILS OF FOOD AND WATER QUALITY: water samples were ananalyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 -26
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: test substance was added directly to the diet to achieve the target concentrations specified by the study design; the test diets were thoroughly mixed to ensure homogeneous distribution of the test substance throughout the diet.
DIET PREPARATION
- Rate of preparation of diet: weekly, except in two instances in which diets were prepared for 10 or 11 days, after stability was confirmed.
- Mixing appropriate amounts with: PMI® Nutrition International, LLC Certified Rodent LabDiet 5002®.
- Storage temperature of food: all diets were refrigerated until used.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Duplicate samples (concentration verification and homogeneity (from top, middle bottom of the sample) of all dietary concentrations were collected at the initial diet preparation and analyzed to verify the concentration (average of homogeneity samples) and homogeneity of test substance in the diets. Near the middle and end of the study, samples were taken to verify concentration. Duplicate samples were taken from the lowest (300 ppm) and the highest (18,000 ppm) dietary concentration of the initial diet preparation and were analyzed to verify the stability of the test substance in the diets. The 300 ppm concentration was included in the initial diet preparation to establish the stability to cover the dietary concentrations of the present study (600 to 18,000 ppm) as well as the concurrent mouse study (300 to 7000 ppm).
The certificate of analysis (COA) included in the original finalized report listed a purity of 92.2%, which did not fully account for all the inorganic impurities associated with this sample. Due to follow-up analysis of the test substance the COA was revised for the purity 90.5% that accounts for the full impurity profile. This reduction in determined purity of 1.7% had minimal impact on the reported doses determined by chemical analyses and on the values utilized for risk assessments. Therefore, the reported dose values were not adjusted. - Duration of treatment / exposure:
- approximately 90 days (94 or 95 days in males and 96 or 97 days in females)
- Frequency of treatment:
- daily
- Dose / conc.:
- 600 ppm
- Remarks:
- Males: corresponding to 35 mg/kg bw/day
Females: corresponding to 45 mg/kg bw/day - Dose / conc.:
- 2 000 ppm
- Remarks:
- Males: corresponding to 114 mg/kg bw/day
Females: corresponding to 146 mg/kg bw/day - Dose / conc.:
- 6 000 ppm
- Remarks:
- Males: corresponding to 349 mg/kg bw/day
Females: corresponding to 448 mg/kg bw/day - Dose / conc.:
- 18 000 ppm
- Remarks:
- Males:corresponding to 1045 mg/kg bw/day
Females:corresponding to 1425 mg/kg bw/day - No. of animals per sex per dose:
- 15
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: The test substance is a metabolite of methyl 6-amino-5-chloro-2-(cyclopropyl)-4-pyrimidinecarboxylate. A previous 28-day study in rats was conducted with methyl 6-amino-5-chloro-2-(cyclopropyl)-4-pyrimidinecarboxylate at dietary concentrations of 600, 2000, 6000, and 20,000 ppm. No test substance-related effects occurred on ophthalmogical observations, clinical observations, clinical pathology parameters, food consumption, organ weights, gross morphological observations, or survival. A test substance-related decrease in body weight, weight gain, and food efficiency occurred in 20,000 ppm males and females. Males in the 20,000 ppm group had thyroid follicular cell hypertrophy and pancreatic acinar cell apoptosis. Females in the 20,000 ppm group had induction of hepatic ß-oxidation activity. Based on these findings, the dietary concentrations selected for the current 90-day study were 600, 2000, 6000, and 18,000 ppm.
- Rationale for selecting satellite groups: on test day 56, blood was collected from satellite animals for evaluation of test substance and/or metabolite concentration in plasma (separate report was not available). - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily
- Cage side observations checked: moribund/dead rats, abnormal behavior/appearance and acute clinical signs of systemic toxicity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Day 0 and weekly thereafter
BODY WEIGHT: Yes
- Time schedule for examinations: Day 0 and weekly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
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 AND COMPOUND INTAKE: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pretest and week 13
- Dose groups that were examined: all dose groups
HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 14
- Anaesthetic used for blood collection: not specified
- Animals fasted: not specified
- How many animals: all dose groups
- Parameters checked in table No. 1 in the "Any other information and methods incl. tables" section were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: week 14
- Animals fasted: not specified
- How many animals: all dose groups
- Parameters checked in table No.2 in the "Any other information and methods incl. tables" section were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: week 14
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked in table No.3 in the "Any other information and methods incl. tables" section were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: pretest and weeks 4, 8, and 13
- Dose groups that were examined: all dose groups
- Battery of functions tested: motor activity / grip strength, rectal body temperature other: please refer to table No 4 in the "Any other information and methods incl. tables" section.
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (Please refer to table 5 in the "Any other information and methods incl. tables" section.)
HISTOPATHOLOGY: Yes (Please refer to table 6 in the "Any other information and methods incl. tables" section.)
Organ weights determined for organs/tissues listed in table 7 in the "Any other information and methods incl. tables" section.) - Other examinations:
- Subchronic Neurotoxicity:
On test days 94 and 95, rats were designated for neuropathology (5 rats/sex/group) analysis. Animals were anesthetized and underwent whole-body in situ perfusion.
(For tissues analysed and further details, please refer to table 8 in the "Any other information and methods incl. tables" section.)
Evaluation of test substance and/or metabolite concentration in plasma (satellite animals)
Approximately 0.5 mL of blood was collected from the satellite animals (5 rats/sex/concentration) on test day 56, for determination of plasma concentration of test substance and/or metabolites. - Statistics:
- Significance was judged at p < 0.05. Separate analyses were performed on the data collected for each sex.
For details on statistics please refer to table 9 in the "Any other information and methods incl. tables" section. - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 600 ppm and 2000 ppm: one female of each dose group had abnormal gait. However, abnormal gait was not observed in these animals during any of the neurobehavioral evaluations. Since no dose response was evident and occurrence was limited to 1 animal/group, these observations were considered to be spurious and not treatment-related.
Other clinical signs observed throughout the study were typical for rats of this age and strain, and included hair loss, eye, ear, or nose discharge hyperactivity, high posture, protrusion in abdomen, absent teeth, clipped teeth, maloccluded teeth, ear twitch, corneal opacity and wound. These clinical signs were observed at low incidence and with no dose response.
(Please refer to table 10 in the "Any other information on results incl. tables" section.) - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- control and 6000 ppm: one control male rat and one female rat in the 6000 ppm group were accidentally killed during blood collection just prior to necropsy (non-treatment-related).
(Please refer to table 10 in the "Any other information on results incl. tables" section.) - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 18,000 ppm: significant decrease in mean body weights and body weight gains were observed in males and females. In males, mean body weight was 9% lower than that of controls on the final test day 91. Overall (test days 0-91) body weight gain in males was 15% lower (statistically significant) than that of controls. In females, mean body weight was 8% lower than that of controls on the final test day 91. Overall (test days 0-91) body weight gain in males was 18% lower (statistically significant) than that of controls.The effects were considered treatment-related and adverse.
6000 ppm: statistically significantly lower body weights and body weight gains compared to controls were observed in males and females over test days 21-28 and 14-21, respectively. (non-treatment-related and non-adverse)
600 ppm: statistically significantly lower body weights and body weight gains compared to controls were observed in females over test days 84-91 (non-treatment-related and non-adverse)..
Changes observed at 6000 and 600 ppm were considered spurious because they occurred only in one time interval and there was no dose response.
(Please refer to table 11 and 12 in the "Any other information on results incl. tables" section.) - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- 18,000 ppm: mean daily food consumption was statistically significantly lower in males over test day intervals 0-7, 21-28, and 42-49 and in females over test day interval 70-77. These sporadic changes were considered incidental and not treatment-related, because overall mean food consumption was not significantly different from control.
- Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- 18,000 ppm: significant decrease in food efficiency was observed in males and females. The overall food efficiency (test days 0-91) in males and females of this dose group was 89% and 83% of control, respectively. In addition, statistically significantly lower mean food efficiency was noted in males over test day intervals 21-28, 70-77, and 77-84 and in females over test day interval 62-70. Since the changes in mean food efficiency were consistent with decreased body weight parameters, they were considered treatment-related and adverse.
6000 ppm: statistically significant reductions in food efficiency were noted in males over test days 21-28 (non-treatment-related and non-adverse).
600 ppm: statistically significant reductions in food efficiency were noted in females over test days 84-91 (non-treatment-related and non-adverse).
Since the findings at 6000 and 600 ppm occurred only over one weekly interval, they were considered spurious, non-treatment-related and non-adverse.
(Please refer to table 13 in the "Any other information on results incl. tables" section.) - Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 600 ppm: one male had a posterior lens opacity and one female had a lens opacity and dislocation, retinal degeneration and iritis. Since effects were observed only in single animals and no dose-response relationship was visible, the observations were not considered treatment-related and non-adverse.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- (Please refer to table 14 in the "Any other information on results incl. tables" section.)
- Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 6000 ppm: triglyceride (69% of control), total protein and albumin (94% and 93% of control, respectively) and calcium (95% of control) were decreased in female rats. The observed statistically significant changes in group mean clinical chemistry parameters at test days 96-97 in females were considered to be non-treatment-related and non-adverse, because the change did not occur in a dose-related manner.
(Please refer to table 15 in the "Any other information on results incl. tables" section.) - Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 18,000 ppm: urine volume was decreased (52% of control) in male rats. However, urine volumes ranging from 2.0 to 14.6 mL in male rats were within the urine volume range of the male control group, 0.7 to 21.0 mL. In addition, there were no correlative clinical pathology or histopathology changes and a similar decrease in urine volume was not observed in females. Therefore, this change was considered non-treatment-related and non-adverse. Furthermore, pH was minimally decreased (91% of control) in female rats dosed. This change was considered non-adverse due to the minimal nature of the change and the lack of associated changes in other urinalysis or clinical chemistry parameters.
(Please refer to table 16 in the "Any other information on results incl. tables" section.) - Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 18,000 ppm: in males, a small (9%) decrease in the mean final body weight, as compared to the control value, was associated with a similar decrease in the mean absolute liver, heart, spleen, and thymus weights. Some of these decreases were statistically significant. Since, there were no gross or microscopic pathology correlates observed and most mean relative (% body weight) organ weights were comparable to control values, the small decreases in mean absolute organ weights were interpreted to be a result of the decreased mean final body weight and not an indication of an organ-specific effect. There was a statistically significant decrease (12%) in the mean relative (% brain weight) liver weight in males, as compared to controls. This difference was also attributed to the decrease in final body weight and secondary to decrease in mean absolute liver weights.
(Please refer to table 17 in the "Any other information on results incl. tables" section.) - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All gross observations were consistent with normal background lesions in rats of this age and strain and thus non-treatment-related and non-adverse.
(Please refer to table 18 in the "Any other information on results incl. tables" section.) - Neuropathological findings:
- no effects observed
- Description (incidence and severity):
- (Please refer to table 23 and 24 in the "Any other information on results incl. tables" section.)
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All microscopic findings were consistent with normal background lesions in rats of this age and strain and thus non-treatment-related and non-adverse.
(Please refer to table 19 in the "Any other information on results incl. tables" section.) - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- Neurobehavioral evaluation
Functional Observational Battery: There were no treatment-related or statistically significant effects/differences on forelimb or hindlimb grip strength, in footsplay and in the number of rearing movements in the open field arena in males and females of any dose group. (Please refer to table 20, 21 and 22 in the "Any other information on results incl. tables" section.)
600 and 6000 ppm: occasional occurrence of abnormal gait in either the home cage or open field were noted in one 600 ppm male and one 6000 ppm female. Since a dose-response relationship was not evident for either males or females, these incidents were considered to be spurious, non-treatment-related and non-adverse.
Motor acitivity: There were no treatment-related or statistically significant effects on duration of movement or number of movements for males or females of any dose group. - Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 18 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food efficiency
- Remarks on result:
- other: corresponding to 1045 and 1425 mg/kg bw/day in males and females, respectively.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 6 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect observed
- Remarks on result:
- other: corresponding to 349 and 448 mg/kg bw/day in males and females, respectively.
- Critical effects observed:
- no
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 28 February - 30 May 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)
- Version / remarks:
- not specified
- Deviations:
- yes
- Remarks:
- dosage: the highest dose level did not induce toxicity and no hormonal measurements performed
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- dog
- Strain:
- Beagle
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Covance Research Products Inc., Kalamazoo, Michigan, USA
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 9 months
- Weight at study initiation: 8.26 to 12.03 kg (males), 7.59 to 9.81 kg (females),
- Housing: double-housed (single sex) in double-sized stainless steel suspended cages (arrival), two days after arrival dogs were housed individually in single-sized stainless steel suspended cages in an environmentally controlled room.
- Diet: powdered Lab Diet® (Certified Canine Diet #5007, PMI Nutrition International, Inc.), ad libitum. The animals were offered approximately 400 g of meal daily for approximately 2 h.
- Water: tap water, ad libitum
- Acclimation period: 15 days
DETAILS OF FOOD AND WATER QUALITY: Yes
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 28
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 28 February 2007 To: 30 May 2007 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: All test diets were prepared on a weight by weight basis with the ground Lab Diet® and were blended for approximately 5 min using a Hobart blender, and approximately 10 min using a twin-shell blender.
DIET PREPARATION
- Rate of preparation of diet: weekly
- Mixing appropriate amounts with: ground Lab Diet® (Certified Canine Diet #5007, PMI Nutrition International, Inc.)
- Storage temperature of food: refrigerated
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The diet was analysed for homogeneity, stability and concentration of the test substance. For analysis of homogeneity duplicate samples (25.0 g) were collectedfrom the top, middle, and bottom portions of the prepared diets for Week 1 at 250, 1250, 5000, and 15000 ppm and were placed in plastic bags. Samples were stored frozen at approximately -20°C until analysis. For analysis of stability, 8 numbered samples (25.0 g each) were collected from the middle portion of the prepared diets for Week 1 at 250 and 15000 ppm (two sets of duplicate samples at each concentration) and were placed in plastic bags. Samples were stored refrigerated or at room temperature for 7 and 14 days, and then frozen at approximately -20ºC. The Day 7 samples were stored frozen at approximately -20ºC at MPI Research, Inc., for possible future analysis. The Day 14 samples were shipped frozen for analysis. For analysis of the concentration, duplicate samples (25.0 g) were collected from the middle portion of the prepared diets for Weeks 1, 5, 9, and 13 at 250, 1250, 5000, and 15000 ppm and and the respective control sample and placed in plastic bags. Samples were stored frozen at approximately -20°C until shipped frozen for analysis. All analytical work was conducted by the Sponsor. Concentrations of test substance were determined by high-performance liquid chromatography (HPLC) with UV detection. The analytical results demonstrated that the test substance was at the targeted concentrations, was homogeneously mixed in the diet, and was stable in the diet under the study storage conditions for all dietary levels. Test substance was not detected in the control samples.
- Duration of treatment / exposure:
- 91 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 250 ppm
- Remarks:
- Males: corresponding to 6.46 mg/kg bw/day
Females: corresponding to 7.02 mg/kg bw/day - Dose / conc.:
- 1 250 ppm
- Remarks:
- Males: corresponding to 33.31 mg/kg bw/day
Females: corresponding to 37.94 mg/kg bw/day - Dose / conc.:
- 5 000 ppm
- Remarks:
- Males: corresponding to 126.23 mg/kg bw/day
Females: corresponding to 124.12 mg/kg bw/day - Dose / conc.:
- 15 000 ppm
- Remarks:
- Males: corresponding to 425.71 mg/kg bw/day
Females: corresponding to 387.53 mg/kg bw/day - No. of animals per sex per dose:
- 4
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: The dose levels were selected on the basis of the results of previous studies conducted with a related chemical.
- Fasting period before blood sampling for clinical biochemistry: yes - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked: morbidity, mortality and injury
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: day after arrival, on day -7, day -1 and weekly during the study
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
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
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 AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pretest and prior to the scheduled terminal necropsy
- Dose groups that were examined: all animals
HAEMATOLOGY: Yes
- Time schedule for collection of blood: weeks -2, -1, 4, 8, and 12
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked in table No.1 in the "Any other information and methods incl. tables" section were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: weeks -2, -1, 4, 8, and 12
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked in table No.1 in the "Any other information and methods incl. tables" section were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: weeks -2, -1, 4, 8, and 12
- Metabolism cages used for collection of urine: No
- Animals fasted: Yes
- Parameters checked in table No.1 in the "Any other information and methods incl. tables" section were examined.
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: once weekly (approximately 4 h after food removal)
- Dose groups that were examined: all animals
- Battery of functions tested: changes in the level of activity, gait, posture, altered strength, and response to handling as well as the presence of clonic or tonic movements, stereotypies (e.g., excessive grooming, repetitive circling) or bizarre behavior (e.g., self-mutilation).
IMMUNOLOGY: No
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (Please refer to table 2 in the "Any other information and methods incl. tables" section.)
HISTOPATHOLOGY: Yes (Please refer to table 3 in the "Any other information and methods incl. tables" section.) - Other examinations:
- Liver Biochemical Analysis:
Liver samples were snap frozen in liquid nitrogen for analysis of cytochrome P-450 (total and isozyme profile). The microsomal suspensions were analyzed for total cytochrome P-450 levels and quantification of cytochrome P-450 1A1, 1A2, 2B1/2, 2E1, 3A2, and 4A1/2/3. The total microsomal cytochrome P-450 contents were measured by spectral analysis. The spectra were recorded at room temperature with a spectrophotometer. Quantification of cytochrome P-450 isozymes 1A1, 1A2 , 2B1/2, 2E, 3A2 (Chemicon, Temecula, California,USA) and 4A1/2/3 (ABR, Golden, Colorado, USA) were done by Western Blot analysis using commercially available antibodies.
Plasma analysis for determination of test substance and metabolite:
- Time schedule for collection of blood: once during week 9 (approximately 2 h after food removal)
- Animals fasted: No
- How many animals: all animals - Statistics:
- Data for each sex within a set were analyzed separately. The raw data were tabulated within each time interval, and the mean and standard deviations were calculated for each endpoint by sex and group. For each endpoint, treatment groups were compared to the control group. Data for some endpoints, as indicated, were transformed by either a log or rank transformation prior to conducting the specified analysis. For details on statistics please refer to table 4 in the "Any other information and methods incl. tables" section.
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 250, 1250, 5000 and 15,000 ppm: increased incidence of scaling skin on the feet compared to control animals were noted mainly over the last month of dietary exposure in males and females. Incidences per dose were as followed (number of time observed/number of animals affected): 0/0, 182/1, 32/2, 410/2, 1184/4 (males) and 0/0, 43/1, 464/2, 129/2, 444/2 (females) (no strict dose-related pattern was observed). It can not be exluded that this finding is test substance-related, but it was not considered to be an adverse effect as it was not associated with any other clinical or pathological responses.
control, 250, 1250, 5000 and 15,000 ppm: higher incidence of soft and mucoid feces were observed in males and females, but these observations were noted in all dose groups and thus not considerer treatment-related. Incidences per dose were as followed (number of time observed/number of animals affected): feces mucoid: 6/3, 56/4, 56/4, 33/3 and 15/3 (males), 13/1, 9/3, 69/3, 3/3 and 19/3 (females); feces soft: 122/4, 250/4, 352/4, 144/4 and 92/4 (males), 69/4, 122/4, 163/4, 108/4 and 70/4 (females)
Other clinical observations noted are common in this species and not considered related to treatment.
(Please refer to table 5 in the "Any other information on results incl. tables" section.) - Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- control, 250, 1250, 5000 and 15,000 ppm: statistically significant lower mean body weight gain was observed in all male dose groups over the week 1 through 2 interval. These differences were considered spurious as they did not exhibit a dose-response. In addition, mean body weight gain in these groups exceeded that of control in week -1 to 13 (not statistically significant).
(Please refer to table 6, 7 and 8 in the "Any other information on results incl. tables" section.) - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were sporadic statistically significant differences in the mean weekly food consumption in different dose groups and time intervals, but these were not considered treatment-related as they did not exhibit a dose response and there were no treatment-related differences in the mean total food consumption over the entire study period.
(Please refer to table 9 and 10 in the "Any other information on results incl. tables" section.) - Food efficiency:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were sporadic statistically significant differences in the mean weekly food efficiency in different dose groups and time intervals, but these were not considered treatment-related as they did not exhibit a dose response and there were no treatment-related differences in food efficiency over
the entire study period.
(Please refer to table 11 and 12 in the "Any other information on results incl. tables" section.) - Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 1250 ppm: one female had a detached retina in the right eye noted during the pretest evaluation. This minor abnormality was not noted at the terminal opthalmoscopic examination and was considered to have spontaneously healed without intervention during the study. No test article-related observations were noted in the ophthalmoscopic examinations.
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 15,000 ppm: erythrocytes and mean activated partial thromboplastin time (APTT) values were statistically significantly decreased in males (week -1).
1250 ppm: lymphocytes (week -1 and -2 ) and large unstained cells (LUC) ( week 8 and 12) were statistically significantly decreased in males.
All observations were considered not meaningful due to the interval involved (pretest) or lack of dose-dependency.
(Please refer to table 13 in the "Any other information on results incl. tables" section.) - Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 250 and 15,000 ppm: statistically significant decreases in urine pH were observed in males (week 12).
5000 ppm: statistically significant decreases in urine pH were observed in females (week 8).
250 and 1250: statistically significant increases in urine pH were observed in females (week 8).
All observations were considered to be not treatment-related due to the lack of dose-dependency, unusually low urine pH in the female controls, and high urine pH in the male controls.
(Please refer to table 14 in the "Any other information on results incl. tables" section.) - Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- 1250, 5000, and 15,000 ppm: mean thyroid/parathyroid gland weights were greater in females. Considering the variability among normal dogs, the observation that 2 control female dogs probably had thyroid gland weights at the low end of the range, and no microscopic abnormalities were detected in thyroid glands indicates that the observed differences were not treatment-related.
1250 ppm: absolute brain weight of males and the absolute heart weight of females were statistically significantly different from control animals. Since a dose-response was not visible and these organs were microscopically normal at the highest dose level, it was concluded that these differences were a result of biological variability, rather than treatment-related.
(Please refer to table 15 in the "Any other information on results incl. tables" section.) - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Findings observed were usual and/or incidental in dogs of this type and age. (Please refer to table 16 in the "Any other information on results incl. tables" section.)
- Neuropathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No treatment-related neurobehavioral findings observed. (Please refer to table 18 in the "Any other information on results incl. tables" section.)
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Findings observed were usual and/or incidental in dogs of this type and age. (Please refer to table 17 in the "Any other information on results incl. tables" section.)
- Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Findings observed were usual and/or incidental in dogs of this type and age. (Please refer to table 17 in the "Any other information on results incl. tables" section.)
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Liver Biochemical Analysis: oral exposure of male and female dogs to the test substance induced several individual hepatic cytochrome P-450 enzymes.
15, 000 ppm: in males a statistically significant decrease in cytochrome P-450 4A1/2/3 was observed (89% of control). This decrease was not considered treatment- related due to the low magnitude of change and sample variability.
5000 and 15,000 ppm: in male dogs enzymes 1A1 (501 and 518% of control, respectively) and 2B1/2 (225 and 191% of control, respectively) were treatment-related increased. At 5000 ppm, the increases in both 1A1 and 2B1/2 were statistically significant whereas increases observed at 15,000 ppm were not statistically significant. However at both doses the increases were considered treatment-related.
In female dogs, cytochrome P-450 isozymes 2B1/2 (193 and 134% of control, respectively) were treatment-related increased. At 5000 ppm, the increases in both 1A1 and 2B1/2 were statistically significant whereas increases observed at 15,000 ppm were not statistically significant. However at both doses the increases were considered treatment-related.
1250, 5000 and 15000 ppm: in female dogs, cytochrome P-450 isozymes 4A1/2/3 (113, 109 and 115% of control, respectively) were treatment-related increased. The increases at 1250 and 15,000 ppm were statistically significant. Although the increase observed at 5000 ppm was not statistically significant, it appears to be treatment-related increased due to the low variability between the samples.
1250 ppm: in female dogs, a statistically significant increase in cytochrome P-450 2E1 (187% of control) was observed .
This increase was not considered treatment-related due to high variability between animals and the lack of increase at the higher levels.
In males, no treatment-related alterations were observed in total cytochrome P-450 content or the cytochrome P-450 1A2, 2E1, 3A2, or 4A1/2/3 content. In females, no treatment-related alterations were observed in total cytochrome P-450 content or the cytochrome P-450 1A1, 1A2, 2E1 or 3A2 content.
(Please refer to table 21 in the "Any other information on results incl. tables" section.)
Plasma analyis for test substance and metabolite:
In both male and female dogs, test substance was by far the most abundant analyte, with the highest concentrations reaching 63,000 and 82,575 ng/mL for 15000 ppm males and females, respectively. In contrast, the plasma levels of the metabolite were significantly lower for this dose group with concentrations of approximately 12 ng/mL for males and females. This value was just above the limit of quantitation. The concentration of test substance in plasma was higher in females than in males at all dose levels, which may suggest greater dietary absorption by female dogs. There was no apparent plateau for the test substance plasma concentrations versus the dietary intake levels.
(Please refer to table 20 in the "Any other information on results incl. tables" section.) - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 15 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect observed
- Remarks on result:
- other: corresponding to 426 and 388 mg/kg bw/day in males and females
- Critical effects observed:
- no
Referenceopen allclose all
Table 10: Summary of detailed clinical observations and mortality data
Males | |||||
Group Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
Number | 15 | 15 | 15 | 15 | 15 |
Discharge - black – eye(s)/ear(s) |
|
|
|
|
|
Number of Observations | 2 |
|
| 7 | 4 |
Number of Animals | 1 |
|
| 2 | 1 |
Days from - to | 49 - 56 |
|
| 7 - 62 | 28 – 49 |
Discharge - brown - nose |
|
|
|
|
|
Number of Observations |
|
|
| 3 |
|
Number of Animals |
|
|
| 1 |
|
Days from - to |
|
|
| 7 – 21 |
|
Hair loss |
|
|
|
|
|
Number of Observations | 13 |
| 40 |
| 11 |
Number of Animals | 1 |
| 4 |
| 2 |
Days from - to | 7 - 91 |
| 7 - 91 |
| 21 - 91 |
Hyperreactive |
|
|
|
|
|
Number of Observations |
|
| 7 |
|
|
Number of Animals |
|
| 1 |
|
|
Days from - to |
|
| 49 - 91 |
|
|
Posture - high |
|
|
|
|
|
Number of Observations |
|
| 7 |
|
|
Number of Animals |
|
| 1 |
|
|
Days from - to |
|
| 49 - 91 |
|
|
Protrusion - abdomen |
|
|
| 13 |
|
Number of Observations |
|
|
| 1 |
|
Number of Animals |
|
|
| 7 - 91 |
|
Days from - to |
|
|
|
|
|
Teeth absent |
|
|
|
|
|
Number of Observations | 7 |
|
| 12 |
|
Number of Animals | 1 |
|
| 1 |
|
Days from - to | 49 - 91 |
|
| 14 – 91 |
|
Teeth clipped |
|
|
|
|
|
Number of Observations |
|
|
| 12 | 8 |
Number of Animals |
|
|
| 1 | 1 |
Days from - to |
|
|
| 14 – 91 | 42 – 91 |
Teeth maloccluded |
|
|
|
|
|
Number of Observations |
|
|
| 23 | 10 |
Number of Animals |
|
|
| 2 | 1 |
Days from - to |
|
|
| 7 - 91 | 28 - 91 |
Accidentally Killed |
|
|
|
|
|
Number of Observations | 1 |
|
|
|
|
Number of Animals | 1 |
|
|
|
|
Days from - to | 95 - 95 |
|
|
|
|
Neuropathology sacrifice |
|
|
|
|
|
Number of Observations | 5 | 5 | 5 | 5 | 5 |
Number of Animals | 5 | 5 | 5 | 5 | 5 |
Days from - to | 94 - 95 | 94 - 95 | 94 - 95 | 94 - 95 | 94 - 95 |
Scheduled sacrifice |
|
|
|
|
|
Number of Observations | 9 | 10 | 10 | 10 | 10 |
Number of Animals | 9 | 10 | 10 | 10 | 10 |
Days from - to | 94 - 95 | 94 - 95 | 94 - 95 | 94 - 95 | 94 - 95 |
Females | |||||
Number | 15 | 15 | 15 | 15 | 15 |
Abnormal gait |
|
|
|
|
|
Number of Observations |
| 1 | 4 |
|
|
Number of Animals |
| 1 | 1 |
|
|
Days from - to |
| 91 - 91 | 70 – 91 |
|
|
Ear twitch |
|
|
|
|
|
Number of Observations | 1 |
|
| 1 |
|
Number of Animals | 1 |
|
| 1 |
|
Days from - to | 7 -7 |
|
| 70 -70 |
|
Eye corneal opacity |
|
|
|
|
|
Number of Observations |
| 9 |
|
|
|
Number of Animals |
| 1 |
|
|
|
Days from - to |
| 35 - 91 |
|
|
|
Hair loss |
|
|
|
|
|
Number of Observations |
| 18 | 7 | 6 | 16 |
Number of Animals |
| 2 | 1 | 1 | 2 |
Days from - to |
| 7 - 91 | 49 - 91 | 56 - 91 | 14 – 91 |
Wound - superficial - neck |
|
|
|
|
|
Number of Observations |
|
|
|
| 3 |
Number of Animals |
|
|
|
| 1 |
Days from - to |
|
|
|
| 14 -28 |
Accidentally Killed |
|
|
| 1 |
|
Number of Observations |
|
|
| 1 |
|
Number of Animals |
|
|
| 96 – 96 |
|
Days from - to |
|
|
|
|
|
Neuropathology sacrifice |
|
|
|
|
|
Number of Observations | 5 | 5 | 5 | 5 | 5 |
Number of Animals | 5 | 5 | 5 | 5 | 5 |
Days from - to | 94 - 95 | 94 - 95 | 94 - 95 | 94 - 95 | 94 - 95 |
Scheduled sacrifice |
|
|
|
|
|
Number of Observations | 10 | 10 | 10 | 10 | 10 |
Number of Animals | 10 | 10 | 10 | 10 | 10 |
Days from - to | 96 - 97 | 96 - 97 | 96 - 97 | 96 - 97 | 96 - 97 |
Table 11: Mean body weights (g)
Males | |||||
Group Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
BW:DAY0 | 256.4 | 254.7 | 253.7 | 255.3 | 253.0 |
| 11.3(15) | 13.3(15) | 13.7(15) | 13.0(15) | 10.7(15) |
BW:DAY7 | 311.7 | 310.4 | 308.9 | 309.4 | 300.6 |
| 15.8(15) | 15.3(15) | 17.6(15) | 19.8(15) | 11.8(15) |
BW:DAY14 | 358.2 | 357.1 | 356.9 | 354.6 | 345.7 |
| 21.1(15) | 17.6(15) | 22.9(15) | 36.2(15) | 15.3(15) |
BW:DAY21 | 390.4 | 390.3 | 390.2 | 384.3 | 371.9 |
| 27.3(15) | 20.4(15) | 27.8(15) | 35.5(15) | 17.7(15) |
BW:DAY28 | 429.4 | 424.7 | 424.0 | 416.1 | 401.7* |
| 31.9(15) | 24.9(15) | 30.6(15) | 36.2(15) | 17.2(15) |
BW:DAY35 | 459.7 | 451.9 | 455.3 | 450.3 | 427.2* |
| 36.0(15) | 26.2(15) | 35.6(15) | 39.6(15) | 19.7(15) |
BW:DAY42 | 486.3 | 480.3 | 482.3 | 479.9 | 452.1* |
| 38.7(15) | 29.6(15) | 39.0(15) | 41.6(15) | 23.8(15) |
BW:DAY49 | 506.3 | 497.7 | 504.1 | 498.9 | 470.1* |
| 41.9(15) | 31.8(15) | 42.8(15) | 46.1(15) | 25.3(15) |
BW:DAY56 | 520.8 | 512.8 | 517.5 | 513.1 | 483.3 |
| 47.5(15) | 36.5(15) | 41.9(15) | 49.7(15) | 26.0(15) |
BW:DAY62 | 538.7 | 531.2 | 534.6 | 533.7 | 500.2* |
| 46.0(15) | 36.2(15) | 44.0(15) | 50.2(15) | 27.1(15) |
BW:DAY70 | 551.6 | 543.6 | 551.7 | 549.5 | 514.2 |
| 46.4(15) | 38.9(15) | 46.7(15) | 45.1(15) | 26.4(15) |
BW:DAY77 | 571.0 | 560.6 | 566.7 | 566.4 | 524.5* |
| 48.1(15) | 39.7(15) | 50.2(15) | 47.9(15) | 30.4(15) |
BW:DAY84 | 578.7 | 568.5 | 575.1 | 575.3 | 526.5* |
| 48.1(15) | 42.6(15) | 51.2(15) | 50.9(15) | 31.9(15) |
BW:DAY91 | 580.7 | 572.9 | 580.3 | 578.9 | 529.4* |
| 50.4(15) | 43.6(15) | 51.4(15) | 53.0(15) | 34.9(15) |
Females | |||||
Group Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
BW:DAY0 | 179.4 | 176.7 | 180.2 | 173.7 | 174.6 |
| 10.2(15) | 8.8(15) | 9.8(15) | 10.1(14) | 9.8(15) |
BW:DAY7 | 196.5 | 193.9 | 200.3 | 189.1 | 188.7 |
| 13.0(15) | 9.6(15) | 16.3(15) | 11.1(15) | 11.7(15) |
BW:DAY14 | 214.9 | 216.5 | 221.7 | 209.9 | 206.2 |
| 15.5(15) | 14.8(15) | 20.2(15) | 12.6(15) | 16.5(15) |
BW:DAY21 | 226.9 | 228.0 | 236.3 | 214.5 | 213.9 |
| 17.2(15) | 14.9(15) | 21.8(15) | 11.6(15) | 16.5(15) |
BW:DAY28 | 244.6 | 242.9 | 247.5 | 234.3 | 229.7 |
| 22.1(15) | 18.2(15) | 23.8(15) | 14.6(15) | 18.2(15) |
BW:DAY35 | 254.0 | 251.7 | 261.1 | 243.5 | 239.3 |
| 22.9(15) | 18.8(15) | 28.5(15) | 13.8(15) | 22.4(14) |
BW:DAY42 | 261.5 | 262.6 | 268.9 | 251.5 | 248.3 |
| 22.6(15) | 20.2(15) | 31.3(15) | 13.7(15) | 23.1(15) |
BW:DAY49 | 267.1 | 268.3 | 273.5 | 254.6 | 250.0 |
| 22.5(15) | 25.0(15) | 29.5(15) | 16.2(15) | 19.3(15) |
BW:DAY56 | 276.8 | 273.8 | 279.4 | 262.7 | 254.0* |
| 24.1(15) | 22.4(15) | 27.9(15) | 18.3(15) | 22.4(15) |
BW:DAY62 | 280.9 | 280.1 | 288.2 | 269.3 | 262.0 |
| 23.3(15) | 20.0(15) | 29.7(15) | 20.9(15) | 21.5(15) |
BW:DAY70 | 287.4 | 289.6 | 293.6 | 276.1 | 261.7* |
| 24.9(15) | 24.1(15) | 30.3(15) | 23.2(15) | 23.1(15) |
BW:DAY77 | 293.7 | 292.2 | 302.9 | 279.9 | 264.7* |
| 24.3(15) | 26.1(15) | 31.7(15) | 25.9(15) | 24.1(15) |
BW:DAY84 | 293.4 | 294.9 | 301.9 | 282.9 | 269.6 |
| 29.8(15) | 24.2(15) | 32.9(15) | 23.0(15) | 21.2(15) |
BW:DAY91 | 294.6 | 288.6 | 304.9 | 284.1 | 270.6 |
| 30.5(15) | 24.6(15) | 34.5(15) | 23.4(15) | 22.6(15) |
Data arranged as: Mean Standard deviation (Number of values included in calculation)
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric comparison to control (Dunn’s) significant
Table 12: Mean body weight gains (g)
Males | |||||
Group Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
BWG:DAY0-DAY7 | 55.3 | 55.7 | 55.2 | 54.1 | 47.6* |
| 8.1(15) | 4.6(15) | 6.0(15) | 10.3(15) | 5.4(15) |
BWG:DAY7-DAY14 | 46.5 | 46.7 | 48.1 | 45.2 | 45.1 |
| 6.6(15) | 5.9(15) | 7.3(15) | 21.0(15) | 7.2(15) |
BWG:DAY14-DAY21 | 32.2 | 33.2 | 33.3 | 29.7 | 26.2 |
| 9.1(15) | 6.5(15) | 9.1(15) | 8.7(15) | 6.0(15) |
BWG:DAY21-DAY28 | 39.0 | 34.4 | 33.8 | 31.7* | 29.7* |
| 7.1(15) | 6.6(15) | 8.5(15) | 5.5(15) | 6.3(15) |
BWG:DAY28-DAY35 | 30.3 | 27.3 | 31.3 | 34.2 | 25.5 |
| 6.0(15) | 4.4(15) | 6.4(15) | 7.2(15) | 6.5(15) |
BWG:DAY35-DAY42 | 26.6 | 28.3 | 27.0 | 29.7 | 24.9 |
| 5.6(15) | 5.8(15) | 6.8(15) | 4.9(15) | 7.3(15) |
BWG:DAY42-DAY49 | 19.9 | 17.5 | 21.8 | 18.9 | 17.9 |
| 6.8(15) | 5.7(15) | 6.5(15) | 6.7(15) | 8.2(15) |
BWG:DAY49-DAY56 | 14.6 | 15.0 | 13.4 | 14.2 | 13.2 |
| 8.2(15) | 8.9(15) | 7.3(15) | 7.9(15) | 7.1(15) |
BWG:DAY56-DAY62 | 17.9 | 18.5 | 17.0 | 20.6 | 16.9 |
| 4.2(15) | 7.0(15) | 4.5(15) | 5.6(15) | 6.8(15) |
BWG:DAY62-DAY70 | 12.9 | 12.4 | 17.1 | 15.9 | 14.0 |
| 5.4(15) | 6.8(15) | 6.0(15) | 9.0(15) | 3.4(15) |
BWG:DAY70-DAY77 | 19.4 | 17.0 | 15.1 | 16.9 | 10.3* |
| 6.2(15) | 5.8(15) | 6.5(15) | 4.5(15) | 8.0(15) |
BWG:DAY77-DAY84 | 7.6 | 7.9 | 8.4 | 8.9 | 1.9* |
| 4.6(15) | 5.5(15) | 5.2(15) | 7.6(15) | 4.8(15) |
BWG:DAY84-DAY91 | 2.0 | 4.3 | 5.2 | 3.7 | 2.9 |
| 6.4(15) | 6.5(15) | 6.3(15) | 6.8(15) | 7.2(15) |
BWG:DAY0-DAY91 | 324.3 | 318.1 | 326.7 | 323.6 | 276.4* |
| 45.0(15) | 36.5(15) | 41.5(15) | 42.7(15) | 30.0(15) |
Females | |||||
Goup Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
BWG:DAY0-DAY7 | 17.1 | 17.3 | 20.1 | 16.0 | 14.1 |
| 8.6(15) | 6.7(15) | 7.6(15) | 4.4(14) | 7.0(15) |
BWG:DAY7-DAY14 | 18.3 | 22.6 | 21.4 | 20.9 | 17.5 |
| 9.1(15) | 9.2(15) | 9.4(15) | 5.2(15) | 7.3(15) |
BWG:DAY14-DAY21 | 12.0 | 11.5 | 14.6 | 4.6* | 7.7 |
| 10.8(15) | 6.4(15) | 6.5(15) | 5.8(15) | 8.0(15) |
BWG:DAY21-DAY28 | 17.7 | 14.9 | 11.2 | 19.8 | 15.7 |
| 9.6(15) | 9.9(15) | 8.1(15) | 8.8(15) | 6.5(15) |
BWG:DAY28-DAY35 | 9.4 | 8.8 | 13.5 | 9.2 | 10.0 |
| 7.6(15) | 7.2(15) | 6.9(15) | 5.9(15) | 7.3(14) |
BWG:DAY35-DAY42 | 7.5 | 10.9 | 7.9 | 8.0 | 8.9 |
| 9.6(15) | 9.5(15) | 6.1(15) | 4.9(15) | 4.8(14) |
BWG:DAY42-DAY49 | 5.6 | 5.7 | 4.5 | 3.1 | 1.7 |
| 5.2(15) | 7.9(15) | 5.5(15) | 6.5(15) | 6.6(15) |
BWG:DAY49-DAY56 | 9.7 | 5.5 | 6.0 | 8.1 | 4.0 |
| 8.7(15) | 7.5(15) | 8.7(15) | 6.6(15) | 9.8(15) |
BWG:DAY56-DAY62 | 4.1 | 6.3 | 8.8 | 6.6 | 8.0 |
| 9.6(15) | 6.5(15) | 9.0(15) | 10.1(15) | 8.8(15) |
BWG:DAY62-DAY70 | 6.5 | 9.5 | 5.4 | 6.8 | -0.2@ |
| 4.5(15) | 8.5(15) | 5.4(15) | 4.0(15) | 5.6(15) |
BWG:DAY70-DAY77 | 6.3 | 2.6 | 9.2 | 3.8 | 2.9 |
| 5.6(15) | 8.3(15) | 5.2(15) | 9.0(15) | 6.9(15) |
BWG:DAY77-DAY84 | -0.3 | 2.7 | -1.0 | 3.0 | 4.9 |
| 8.0(15) | 9.1(15) | 6.4(15) | 6.7(15) | 7.9(15) |
BWG:DAY84-DAY91 | 1.2 | -6.3* | 3.1 | 1.3 | 1.0 |
| 8.8(15) | 7.1(15) | 9.4(15) | 6.5(15) | 6.3(15) |
BWG:DAY0-DAY91 | 115.2 | 111.9 | 124.7 | 112.5 | 94.9* |
| 26.9(15) | 19.3(15) | 26.1(15) | 17.5(14) | 16.9(14) |
Data arranged as: Mean Standard deviation (Number of values included in calculation)
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric comparison to control (Dunn’s) significant
Table 13: Food efficiency (body weight (g)/ food consumed (g))
Males | |||||
Group Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
FE:DAY0-DAY7 | 0.305 | 0.310 | 0.307 | 0.295 | 0.286 |
| 0.037(15) | 0.021(15) | 0.016(15) | 0.045(15) | 0.032(15) |
FE:DAY7-DAY14 | 0.256 | 0.252 | 0.262 | 0.228 | 0.247 |
| 0.030(15) | 0.029(15) | 0.025(15) | 0.151(15) | 0.030(15) |
FE:DAY14-DAY21 | 0.179 | 0.181 | 0.186 | 0.170 | 0.151 |
| 0.046(15) | 0.032(15) | 0.039(15) | 0.052(15) | 0.031(15) |
FE:DAY21-DAY28 | 0.204 | 0.180 | 0.182 | 0.173* | 0.168* |
| 0.032(15) | 0.026(15) | 0.039(15) | 0.029(15) | 0.037(15) |
FE:DAY28-DAY35 | 0.158 | 0.143 | 0.165 | 0.175 | 0.142 |
| 0.026(15) | 0.023(15) | 0.022(15) | 0.028(15) | 0.031(15) |
FE:DAY35-DAY42 | 0.134 | 0.147 | 0.140 | 0.152 | 0.135 |
| 0.026(15) | 0.026(15) | 0.029(15) | 0.020(15) | 0.037(15) |
FE:DAY42-DAY49 | 0.102 | 0.091 | 0.114 | 0.096 | 0.097 |
| 0.033(15) | 0.028(15) | 0.029(15) | 0.028(15) | 0.040(15) |
FE:DAY49-DAY56 | 0.077 | 0.081 | 0.074 | 0.076 | 0.073 |
| 0.040(15) | 0.043(15) | 0.039(15) | 0.036(15) | 0.039(15) |
FE:DAY56-DAY62 | 0.109 | 0.111 | 0.103 | 0.124 | 0.106 |
| 0.027(15) | 0.041(15) | 0.022(15) | 0.033(15) | 0.041(15) |
FE:DAY62-DAY70 | 0.060 | 0.056 | 0.078 | 0.072 | 0.068 |
| 0.024(15) | 0.030(15) | 0.025(15) | 0.039(15) | 0.018(15) |
FE:DAY70-DAY77 | 0.101 | 0.090 | 0.076 | 0.086 | 0.056* |
| 0.027(15) | 0.031(15) | 0.028(15) | 0.018(15) | 0.042(15) |
FE:DAY77-DAY84 | 0.041 | 0.042 | 0.046 | 0.045 | 0.011* |
| 0.024(15) | 0.026(15) | 0.027(15) | 0.035(15) | 0.027(15) |
FE:DAY84-DAY91 | 0.010 | 0.023 | 0.027 | 0.018 | 0.014 |
| 0.036(15) | 0.036(15) | 0.034(15) | 0.033(15) | 0.043(15) |
FE:DAY0-DAY91 | 0.133 | 0.131 | 0.135 | 0.132 | 0.119* |
| 0.015(15) | 0.012(15) | 0.007(15) | 0.008(15) | 0.009(15) |
Females | |||||
Goup Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
FE:DAY0-DAY7 | 0.131 | 0.142 | 0.150 | 0.138 | 0.107 |
| 0.063(15) | 0.052(15) | 0.049(15) | 0.040(14) | 0.048(15) |
FE:DAY7-DAY14 | 0.139 | 0.164 | 0.160 | 0.161 | 0.127 |
| 0.073(15) | 0.059(15) | 0.066(15) | 0.043(15) | 0.051(15) |
FE:DAY14-DAY21 | 0.088 | 0.087 | 0.109 | 0.038 | 0.055 |
| 0.073(15) | 0.052(15) | 0.044(15) | 0.048(15) | 0.057(15) |
FE:DAY21-DAY28 | 0.128 | 0.105 | 0.079 | 0.147 | 0.118 |
| 0.068(15) | 0.068(15) | 0.053(15) | 0.065(15) | 0.054(15) |
FE:DAY28-DAY35 | 0.070 | 0.065 | 0.095 | 0.068 | 0.070 |
| 0.055(15) | 0.058(15) | 0.046(15) | 0.041(15) | 0.055(14) |
FE:DAY35-DAY42 | 0.052 | 0.080 | 0.055 | 0.062 | 0.068 |
| 0.068(15) | 0.069(15) | 0.043(15) | 0.038(15) | 0.035(14) |
FE:DAY42-DAY49 | 0.040 | 0.034 | 0.034 | 0.024 | 0.014 |
| 0.039(15) | 0.049(15) | 0.040(15) | 0.049(15) | 0.054(15) |
FE:DAY49-DAY56 | 0.077 | 0.046 | 0.045 | 0.064 | 0.027 |
| 0.066(15) | 0.063(15) | 0.068(15) | 0.052(15) | 0.075(15) |
FE:DAY56-DAY62 | 0.030 | 0.057 | 0.072 | 0.055 | 0.073 |
| 0.079(15) | 0.060(15) | 0.069(15) | 0.084(15) | 0.080(15) |
FE:DAY62-DAY70 | 0.042 | 0.058 | 0.034 | 0.042 | -0.005* |
| 0.029(15) | 0.047(15) | 0.036(15) | 0.021(15) | 0.040(15) |
FE:DAY70-DAY77 | 0.047 | 0.016 | 0.066 | 0.028 | 0.023 |
| 0.040(15) | 0.059(15) | 0.037(15) | 0.070(15) | 0.057(15) |
FE:DAY77-DAY84 | -0.008 | 0.020 | -0.009 | 0.023 | 0.038 |
| 0.063(15) | 0.067(15) | 0.052(15) | 0.054(15) | 0.062(15) |
FE:DAY84-DAY91 | 0.000 | -0.050@ | 0.020 | 0.009 | 0.007 |
| 0.080(15) | 0.065(15) | 0.068(15) | 0.050(15) | 0.050(15) |
FE:DAY0-DAY91 | 0.066 | 0.064 | 0.071 | 0.067 | 0.055* |
| 0.010(15) | 0.009(15) | 0.012(15) | 0.012(14) | 0.010(14) |
Data arranged as: Mean Standard deviation (Number of values included in calculation)
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric comparison to control (Dunn’s) significant
Table 14 : Summary of haematology and coagulation values
Male |
|
|
|
|
|
Groups Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
RBC (x106/µL) |
|
|
|
|
|
DAY 94-95 | 8.80 | 8.82 | 8.91 | 8.60 | 8.88 |
| 0.34(10) | 0.25(10) | 0.23(10) | 0.29(9) | 0.51(10) |
HGB (g/dL) |
|
|
|
|
|
DAY 94-95 | 15.7 | 15.4 | 15.6 | 15.5 | 15.6 |
| 0.6(10) | 0.7(10) | 0.4(10) | 0.5(9) | 0.7(10) |
HCT (%) |
|
|
|
|
|
DAY 94-95 | 47.8 | 47.0 | 47.8 | 46.8 | 47.6 |
| 2.0(10) | 2.0(10) | 1.7(10) | 1.6(9) | 2.2(10) |
MCV (fL) |
|
|
|
|
|
DAY 94-95 | 54.3 | 53.4 | 53.7 | 54.5 | 53.7 |
| 1.7(10) | 1.7(10) | 1.6(10) | 2.5(9) | 1.2(10) |
MCH (pg) |
|
|
|
|
|
DAY 94-95 | 17.8 | 17.5 | 17.6 | 18.0 | 17.5 |
| 0.6(10) | 0.5(10) | 0.4(10) | 0.6(9) | 0.5(10) |
MCHC (g/dL) |
|
|
|
|
|
DAY 94-95 | 32.7 | 32.7 | 32.7 | 33.0 | 32.7 |
| 0.6(10) | 0.5(10) | 0.6(10) | 0.5(9) | 0.7(10) |
RDW (%) |
|
|
|
|
|
DAY 94-95 | 12.6 | 12.6 | 12.6 | 12.8 | 12.7 |
| 0.6(10) | 0.6(10) | 0.5(10) | 0.5(9) | 0.6(10) |
ARET (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 153.0 | 142.8 | 159.8 | 169.2 | 148.4 |
| 32.0(10) | 30.4(10) | 23.6(10) | 16.8(9) | 36.0(10) |
PLT (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 965 | 1030 | 1012 | 1074 | 1030 |
| 147(7) | 149(10) | 131(5) | 96(6) | 93(8) |
WBC (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 10.18 | 10.55 | 11.66 | 12.05 | 9.11 |
| 2.00(10) | 3.02(10) | 3.70(10) | 3.96(9) | 2.78(10) |
ANEU (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 1.71 | 1.50 | 1.80 | 1.64 | 1.64 |
| 0.39(10) | 0.50(10) | 0.76(10) | 0.49(9) | 0.87(10) |
ALYM (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 7.96 | 8.54 | 9.26 | 9.81 | 7.03 |
| 1.91(10) | 2.78(10) | 3.36(10) | 3.45(9) | 2.47(10) |
AMON (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 0.23 | 0.24 | 0.27 | 0.24 | 0.20 |
| 0.07(10) | 0.10(10) | 0.11(10) | 0.10(9) | 0.07(10) |
AEOS (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 0.11 | 0.12 | 0.15 | 0.16 | 0.09 |
| 0.03(10) | 0.06(10) | 0.05(10) | 0.08(9) | 0.03(10) |
ABAS (x10³/µL) |
|
|
|
|
|
DAY 94-95 | 0.03 | 0.04 | 0.05 | 0.04 | 0.03 |
| 0.02(10) | 0.01(10) | 0.02(10) | 0.02(9) | 0.02(10) |
ALUC (x10³/µL) |
|
|
|
|
|
| 0.14 | 0.12 | 0.14 | 0.16 | 0.12 |
| 0.02(10) | 0.06(10) | 0.06(10) | 0.07(9) | 0.07(10) |
Summary of coagulation values | |||||
DAY 94-95 PT (sec) | 14.9 | 14.7 | 14.7 | 14.5 | 15.4 |
0.4(9) | 0.8(10) | 0.9(10) | 0.6(10) | 0.9(10) |
|
APTT (sec) |
|
|
|
|
|
DAY 94-95 | 16.3 | 15.6 | 15.5 | 15.0 | 16.0 |
1.8(9) | 1.4(10) | 1.4(10) | 1.0(10) | 1.8(10) |
|
Female |
|
|
|
|
|
Groups Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
RBC (x106/µL) |
|
|
|
|
|
DAY 96-97 | 8.42 | 8.37 | 8.43 | 8.53 | 8.34 |
| 0.30(10) | 0.25(10) | 0.41(10) | 0.29(10) | 0.23(10) |
HGB (g/dL) |
|
|
|
|
|
DAY 96-97 | 15.6 | 15.4 | 15.5 | 15.7 | 15.4 |
| 0.6(10) | 0.6(10) | 0.7(10) | 0.5(10) | 0.5(10) |
HCT (%) |
|
|
|
|
|
DAY 96-97 | 47.9 | 46.8 | 47.0 | 47.6 | 46.6 |
| 1.8(10) | 1.6(10) | 2.2(10) | 1.9(10) | 1.5(10) |
MCV (fL) |
|
|
|
|
|
DAY 96-97 | 56.9 | 55.8 | 55.8 | 55.8 | 55.9 |
| 1.6(10) | 1.5(10) | 1.0(10) | 1.9(10) | 1.2(10) |
MCH (pg) |
|
|
|
|
|
DAY 96-97 | 18.6 | 18.3 | 18.4 | 18.5 | 18.5 |
| 0.6(10) | 0.5(10) | 0.4(10) | 0.6(10) | 0.5(10) |
MCHC (g/dL) |
|
|
|
|
|
DAY 96-97 | 32.7 | 32.8 | 33.0 | 33.1 | 33.1 |
| 0.3(10) | 0.4(10) | 0.5(10) | 0.4(10) | 0.3(10) |
RDW (%) |
|
|
|
|
|
DAY 96-97 | 11.9 | 11.8 | 11.8 | 11.4 | 11.8 |
| 0.5(10) | 0.5(10) | 0.4(10) | 0.5(10) | 0.4(10) |
ARET (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 162.5 | 133.9 | 142.6 | 136.7 | 145.3 |
| 34.1(10) | 37.1(10) | 22.3(10) | 20.1(10) | 31.0(10) |
PLT (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 1012 | 1081 | 940 | 1032 | 1012 |
| 63(9) | 113(9) | 92(9) | 125(10) | 62(8) |
WBC (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 9.09 | 10.03 | 8.63 | 9.86 | 9.30 |
| 2.13(10) | 2.39(10) | 2.22(10) | 1.74(10) | 2.80(10) |
ANEU (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 0.92 | 1.10 | 1.10 | 1.25 | 1.04 |
| 0.56(10) | 0.90(10) | 0.50(10) | 0.78(10) | 0.35(10) |
ALYM (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 7.76 | 8.43 | 7.11 | 8.11 | 7.83 |
| 1.88(10) | 2.33(10) | 2.23(10) | 1.19(10) | 2.48(10) |
AMON (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 0.17 | 0.20 | 0.18 | 0.19 | 0.19 |
| 0.05(10) | 0.12(10) | 0.10(10) | 0.06(10) | 0.07(10) |
AEOS (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 0.10 | 0.10 | 0.10 | 0.12 | 0.09 |
| 0.05(10) | 0.03(10) | 0.03(10) | 0.06(10) | 0.03(10) |
ABAS (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 0.04 | 0.06 | 0.05 | 0.04 | 0.05 |
| 0.03(10) | 0.04(10) | 0.03(10) | 0.02(10) | 0.03(10) |
ALUC (x10³/µL) |
|
|
|
|
|
DAY 96-97 | 0.10 | 0.13 | 0.09 | 0.15 | 0.11 |
| 0.05(10) | 0.08(10) | 0.03(10) | 0.09(10) | 0.05(10) |
Summary of coagulation values | |||||
PT (sec) |
|
|
|
|
|
DAY 96-97 | 13.5 | 13.6 | 13.3 | 13.8 | 13.3 |
0.5(9) | 0.5(10) | 1.0(10) | 0.5(9) | 0.7(10) |
|
APTT (sec) |
|
|
|
|
|
DAY 96-97 | 13.8 | 14.2 | 14.0 | 13.4 | 13.3 |
0.7(9) | 2.1(10) | 1.5(10) | 1.4(9) | 1.6(10) |
|
Data summarized as: Mean Standard Deviation (n)
Statistical Analysis: Statistical significance is indicated by the following (p < 0.05):
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric comparison to control (Dunn's) significant
Table 15: Summary of clinical chemistry values
Male |
|
|
|
|
|
Groups Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
AST (U/L) |
|
|
|
|
|
DAY 94-95 | 72 | 70 | 84 | 78 | 70 |
| 10(10) | 15(10) | 21(10) | 11(10) | 16(10) |
ALT (U/L) |
|
|
|
|
|
DAY 94-95 | 26 | 26 | 27 | 30 | 24 |
| 3(10) | 3(10) | 6(10) | 5(10) | 2(10) |
SDH (U/L) |
|
|
|
|
|
DAY 94-95 | 14.8 | 12.9 | 12.5 | 13.2 | 12.0 |
| 4.2(10) | 3.4(10) | 8.2(10) | 4.1(10) | 3.6(9) |
ALKP (U/L) |
|
|
|
|
|
DAY 94-95 | 84 | 88 | 76 | 82 | 74 |
| 23(10) | 16(10) | 9(10) | 20(10) | 23(10) |
BILI (mg/dL) |
|
|
|
|
|
DAY 94-95 | 0.14 | 0.13 | 0.13 | 0.14 | 0.13 |
| 0.03(10) | 0.02(10) | 0.01(10) | 0.02(10) | 0.01(10) |
BUN (mg/dL) |
|
|
|
|
|
DAY 94-95 | 13 | 14 | 13 | 13 | 13 |
| 2(10) | 2(10) | 2(10) | 2(10) | 2(10) |
CREA (mg/dL) |
|
|
|
|
|
DAY 94-95 | 0.41 | 0.40 | 0.41 | 0.41 | 0.40 |
| 0.05(10) | 0.05(10) | 0.04(10) | 0.06(10) | 0.05(10) |
CHOL (mg/dL) |
|
|
|
|
|
DAY 94-95 | 54 | 51 | 49 | 55 | 60 |
| 9(10) | 6(10) | 10(10) | 13(10) | 17(10) |
TRIG (mg/dL) |
|
|
|
|
|
DAY 94-95 | 63 | 53 | 50 | 53 | 47 |
| 20(10) | 29(10) | 11(10) | 14(10) | 14(10) |
GLUC (mg/dL) |
|
|
|
|
|
DAY 94-95 | 132 | 136 | 145 | 142 | 131 |
| 23(10) | 34(10) | 35(10) | 26(10) | 27(10) |
TP (g/dL) |
|
|
|
|
|
DAY 94-95 | 6.7 | 6.6 | 6.7 | 6.6 | 6.5 |
| 0.3(10) | 0.3(10) | 0.2(10) | 0.2(10) | 0.2(10) |
ALB (g/dL) |
|
|
|
|
|
DAY 94-95 | 3.4 | 3.3 | 3.4 | 3.3 | 3.3 |
| 0.2(10) | 0.1(10) | 0.1(10) | 0.1(10) | 0.2(10) |
GLOB (g/dL) |
|
|
|
|
|
DAY 94-95 | 3.3 | 3.2 | 3.4 | 3.3 | 3.2 |
| 0.2(10) | 0.2(10) | 0.2(10) | 0.2(10) | 0.2(10) |
CALC (mg/dL) |
|
|
|
|
|
DAY 94-95 | 10.5 | 10.6 | 10.5 | 10.5 | 10.4 |
| 0.4(10) | 0.4(10) | 0.3(10) | 0.3(10) | 0.4(10) |
IPHS (mg/dL) |
|
|
|
|
|
DAY 94-95 | 7.8 | 7.8 | 7.8 | 8.3 | 8.3 |
| 1.3(10) | 0.9(10) | 1.3(10) | 1.8(10) | 1.5(10) |
NA (mmol/L) |
|
|
|
|
|
DAY 94-95 | 144.8 | 144.3 | 144.4 | 144.5 | 144.3 |
| 1.7(10) | 1.4(10) | 1.9(10) | 1.6(10) | 1.1(10) |
K (mmol/L) | |||||
DAY 94-95 | 5.85 | 5.85 | 5.69 | 5.57 | 6.20 |
| 0.43(10) | 0.60(10) | 0.53(10) | 0.55(10) | 0.49(10) |
CL (mmol/L) |
|
|
|
|
|
DAY 94-95 | 101.3 | 101.4 | 100.9 | 101.8 | 101.0 |
| 1.3(10) | 1.6(10) | 1.6(10) | 2.6(10) | 1.4(10) |
Female |
|
|
|
|
|
Groups Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
AST (U/L) |
|
|
|
|
|
DAY 96-97 | 91 | 88 | 96 | 94 | 102 |
| 51(10) | 38(10) | 55(10) | 38(10) | 51(10) |
ALT (U/L) |
|
|
|
|
|
DAY 96-97 | 46 | 40 | 47 | 43 | 39 |
| 40(10) | 24(10) | 32(10) | 17(10) | 15(10) |
SDH (U/L) |
|
|
|
|
|
DAY 96-97 | 19.8 | 17.2 | 18.7 | 16.9 | 19.8 |
| 7.6(10) | 5.4(10) | 6.5(10) | 6.1(10) | 7.0(10) |
ALKP (U/L) |
|
|
|
|
|
DAY 96-97 | 51 | 54 | 59 | 59 | 46 |
| 12(10) | 13(10) | 17(10) | 24(10) | 9(10) |
BILI (mg/dL) |
|
|
|
|
|
DAY 96-97 | 0.19 | 0.20 | 0.18 | 0.19 | 0.18 |
| 0.02(10) | 0.03(10) | 0.03(10) | 0.04(10) | 0.03(10) |
BUN (mg/dL) |
|
|
|
|
|
DAY 96-97 | 15 | 15 | 16 | 15 | 15 |
| 2(10) | 2(10) | 2(10) | 2(10) | 2(10) |
CREA (mg/dL) |
|
|
|
|
|
DAY 96-97 | 0.46 | 0.44 | 0.47 | 0.45 | 0.46 |
| 0.05(10) | 0.04(10) | 0.03(10) | 0.05(10) | 0.04(10) |
CHOL (mg/dL) |
|
|
|
|
|
DAY 96-97 | 98 | 92 | 79 | 76 | 91 |
| 25(10) | 15(10) | 16(10) | 25(10) | 25(10) |
TRIG (mg/dL) |
|
|
|
|
|
DAY 96-97 | 62 | 49 | 52 | 43* | 57 |
| 16(10) | 17(10) | 13(10) | 9(10) | 22(10) |
GLUC (mg/dL) |
|
|
|
|
|
DAY 96-97 | 110 | 112 | 113 | 105 | 100 |
| 15(10) | 23(10) | 22(10) | 9(10) | 10(10) |
TP (g/dL) |
|
|
|
|
|
DAY 96-97 | 8.0 | 7.7 | 7.7 | 7.5@ | 7.8 |
| 0.4(10) | 0.4(10) | 0.4(10) | 0.4(10) | 0.6(10) |
ALB (g/dL) |
|
|
|
|
|
DAY 96-97 | 4.2 | 4.1 | 4.0 | 3.9@ | 4.1 |
| 0.3(10) | 0.3(10) | 0.3(10) | 0.2(10) | 0.4(10) |
GLOB (g/dL) |
|
|
|
|
|
DAY 96-97 | 3.7 | 3.6 | 3.7 | 3.6 | 3.7 |
| 0.2(10) | 0.2(10) | 0.2(10) | 0.2(10) | 0.2(10) |
CALC (mg/dL) |
|
|
|
|
|
DAY 96-97 | 11.2 | 11.0 | 10.9 | 10.6* | 11.0 |
| 0.5(10) | 0.4(10) | 0.2(10) | 0.3(10) | 0.5(10) |
IPHS (mg/dL) |
|
|
|
|
|
DAY 96-97 | 5.9 | 5.5 | 5.2 | 5.2 | 5.0 |
| 1.7(10) | 1.0(10) | 0.9(10) | 1.0(10) | 0.6(10) |
NA (mmol/L) |
|
|
|
|
|
DAY 96-97 | 144.9 | 144.6 | 144.0 | 144.4 | 144.8 |
| 1.5(10) | 2.1(10) | 1.6(10) | 1.3(10) | 2.0(10) |
K (mmol/L) | |||||
DAY 96-97 | 5.67 | 5.40 | 5.60 | 5.50 | 5.44 |
| 0.46(10) | 0.29(10) | 0.38(10) | 0.44(10) | 0.41(10) |
CL (mmol/L) |
|
|
|
|
|
DAY 96-97 | 99.8 | 99.4 | 99.2 | 99.4 | 99.5 |
| 2.1(10) | 1.6(10) | 1.6(10) | 2.0(10) | 2.9(10) |
Data summarized as: Mean Standard Deviation (n)
Statistical Analysis: Statistical significance is indicated by the following (p < 0.05):
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric
Table 16 : Summary of urinalysis values
Male |
|
|
|
|
|
Groups Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
UVOL (mL) |
|
|
|
|
|
DAY 94-95 | 12.0 | 9.7 | 10.2 | 8.3 | 6.2@ |
6.1(10) | 6.4(10) | 4.9(10) | 5.6(10) | 3.7(10) |
|
UOSM (mOsm/kg) |
|
|
|
|
|
DAY 94-95 | 1276 | 1552 | 1168 | 1728 | 1693 |
1163(10) | 1079(10) | 479(10) | 997(10) | 791(10) |
|
pH |
|
|
|
|
|
DAY 94-95 | 6.7 | 6.6 | 7.0 | 6.5 | 6.5 |
0.3(10) | 0.3(10) | 0.3(10) | 0.4(10) | 0.3(10) |
|
URO (EU/dL) |
|
|
|
|
|
DAY 94-95 | 0.2 | 0.4 | 0.2 | 0.4 | 0.3 |
0.0(10) | 0.3(10) | 0.0(10) | 0.4(10) | 0.3(10) |
|
UMTP (mg/dL) |
|
|
|
|
|
DAY 94-95 | 107 | 81 | 67 | 89 | 85 |
121(10) | 60(10) | 29(10) | 55(10) | 31(10) |
|
Female |
|
|
|
|
|
Groups Concentration (ppm) | Control | 600 | 2000 | 6000 | 18000 |
UVOL (mL) |
|
|
|
|
|
DAY 96-97 | 5.7 | 6.8 | 6.5 | 7.7 | 4.3 |
| 2.3(10) | 4.2(10) | 4.2(10) | 3.9(10) | 2.4(9) |
UOSM (mOsm/kg) |
|
|
|
|
|
DAY 96-97 | 1211 | 1375 | 1175 | 1140 | 1860 |
| 767(10) | 974(10) | 477(10) | 1177(10) | 1627(9) |
pH |
|
|
|
|
|
DAY 96-97 | 6.8 | 6.6 | 6.5 | 6.9 | 6.2@ |
| 0.4(10) | 0.5(10) | 0.4(10) | 0.6(10) | 0.3(9) |
URO (EU/dL) |
|
|
|
|
|
DAY 96-97 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
| 0.0(10) | 0.0(10) | 0.0(10) | 0.0(10) | 0.0(9) |
UMTP (mg/dL) |
|
|
|
|
|
DAY 96-97 | 19 | 19 | 17 | 47 | 27 |
| 15(10) | 14(10) | 11(10) | 95(10) | 25(9) |
Data summarized as: Mean Standard Deviation (n)
Statistical Analysis: Statistical significance is indicated by the following (p < 0.05):
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric comparison to control (Dunn's) significant
Table 17: Summary of organ weight values
MALES | |||||
Groups Concentration (ppm)
| 0 | 600 | 2000 | 6000 | 18000 |
Mean final body weight and absolute organ weights (g) | |||||
Final body weight |
565 |
556 |
567 |
568 |
509* |
| 55(9) | 42(10) | 35(10) | 62(10) | 35(10) |
Adrenal glands | 0.060 | 0.060 | 0.063 | 0.064 | 0.060 |
| 0.009(9) | 0.012(10) | 0.013(10) | 0.012(10) | 0.010(10) |
Brain | 2.164 | 2.164 | 2.185 | 2.173 | 2.125 |
| 0.067(9) | 0.121(10) | 0.075(10) | 0.085(10) | 0.073(10) |
Epididymides | 1.633 | 1.569 | 1.654 | 1.600 | 1.623 |
| 0.116(9) | 0.187(10) | 0.215(10) | 0.133(10) | 0.150(10) |
Heart | 1.792 | 1.753 | 1.744 | 1.787 | 1.601* |
| 0.148(9) | 0.147(10) | 0.178(10) | 0.201(10) | 0.113(10) |
Kidneys | 4.218 | 4.109 | 4.186 | 4.146 | 4.012 |
| 0.555(9) | 0.415(10) | 0.349(10) | 0.405(10) | 0.193(10) |
Liver | 14.992 | 14.991 | 15.100 | 15.226 | 12.865* |
| 1.433(9) | 1.839(10) | 1.376(10) | 1.802(10) | 0.839(10) |
Spleen | 0.896 | 0.854 | 0.871 | 0.880 | 0.780 |
| 0.163(9) | 0.149(10) | 0.074(10) | 0.099(10) | 0.096(10) |
Testes | 3.735 | 3.484 | 3.552 | 3.553 | 3.512 |
| 0.330(9) | 0.302(10) | 0.240(10) | 0.361(10) | 0.243(10) |
Thymus | 0.299 | 0.359 | 0.346 | 0.370 | 0.270 |
| 0.058(9) | 0.133(10) | 0.081(10) | 0.094(10) | 0.072(10) |
Mean relative organ weight (% of brain weight) | |||||
Adrenal glands/ brain * 100 |
2.780 |
2.765 |
2.891 |
2.950 |
2.802 |
| 0.414(9) | 0.587(10) | 0.623(10) | 0.528(10) | 0.447(10) |
Epididymides/ brain * 100 |
75.601 |
72.377 |
75.794 |
73.708 |
76.498 |
| 6.756(9) | 6.128(10) | 10.315(10) | 6.211(10) | 7.671(10) |
Heart/ brain * 100 |
82.835 |
81.166 |
79.826 |
82.347 |
75.480 |
| 6.639(9) | 7.342(10) | 8.029(10) | 9.590(10) | 6.747(10) |
Kidneys/ brain * 100 |
194.760 |
189.998 |
191.839 |
190.738 |
188.992 |
| 23.783(9) | 16.345(10) | 18.312(10) | 16.191(10) | 10.279(10) |
Liver/ brain * 100 |
691.668 |
693.084 |
691.514 |
701.519 |
606.506* |
| 50.435(9) | 77.623(10) | 63.465(10) | 85.394(10) | 49.654(10) |
Spleen/ brain * 100 |
41.318 |
39.697 |
39.874 |
40.504 |
36.810 |
| 6.825(9) | 7.907(10) | 3.292(10) | 4.386(10) | 5.222(10) |
Testes/ brain * 100 |
172.749 |
161.169 |
162.633 |
163.641 |
165.368 |
| 16.499(9) | 12.615(10) | 11.079(10) | 16.434(10) | 10.550(10) |
Thymus/ brain * 100 |
13.784 |
16.519 |
15.862 |
17.036 |
12.727 |
| 2.566(9) | 5.800(10) | 3.787(10) | 4.467(10) | 3.572(10) |
Mean relative organ weight (% of body weight) | |||||
Adrenal glands/ final body * 100 |
0.011 |
0.011 |
0.011 |
0.011 |
0.012 |
| 0.002(9) | 0.002(10) | 0.002(10) | 0.002(10) | 0.002(10) |
Brain/ Final body * 100 |
0.386 |
0.391 |
0.387 |
0.386 |
0.419 |
| 0.032(9) | 0.033(10) | 0.024(10) | 0.037(10) | 0.035(10) |
Epididymides/ final body * 100 |
0.292 |
0.283 |
0.292 |
0.284 |
0.321 |
| 0.038(9) | 0.034(10) | 0.037(10) | 0.038(10) | 0.042(10) |
Heart/ final body * 100 Final body * 100 |
0.318 |
0.316 |
0.307 |
0.316 |
0.315 |
| 0.020(9) | 0.020(10) | 0.021(10) | 0.035(10) | 0.018(10) |
Kidneys/ final body * 100 Final body * 100 |
0.746 |
0.741 |
0.739 |
0.732 |
0.791 |
| 0.056(9) | 0.065(10) | 0.059(10) | 0.051(10) | 0.054(10) |
Liver/ final body * 100 Final body * 100 |
2.657 |
2.694 |
2.664 |
2.682 |
2.529 |
| 0.152(9) | 0.195(10) | 0.175(10) | 0.177(10) | 0.084(10) |
Spleen/ final body * 100 Final body * 100 |
0.159 |
0.153 |
0.154 |
0.156 |
0.153 |
| 0.024(9) | 0.021(10) | 0.009(10) | 0.019(10) | 0.017(10) |
Testes/ final body * 100 Final body * 100 |
0.664 |
0.629 |
0.628 |
0.631 |
0.693 |
| 0.065(9) | 0.061(10) | 0.045(10) | 0.081(10) | 0.065(10) |
Thymus/ final body * 100 Final body * 100 |
0.053 |
0.065 |
0.061 |
0.066 |
0.053 |
| 0.007(9) | 0.024(10) | 0.013(10) | 0.018(10) | 0.012(10) |
Feales |
|
|
|
|
|
Groups Concentration (ppm)
| 0 | 600 | 2000 | 6000 | 18000 |
Mean final body weight and absolute organ weights (g) |
|
|
|
|
|
Final body weight |
285 |
283 |
291 |
269 |
262 |
| 30(10) | 22(10) | 38(10) | 22(9) | 19(10) |
Adrenal glands | 0.066 | 0.069 | 0.071 | 0.062 | 0.068 |
| 0.010(10) | 0.010(10) | 0.014(10) | 0.015(9) | 0.013(10) |
Brain | 1.971 | 1.956 | 1.961 | 1.957 | 1.907 |
| 0.086(10) | 0.052(10) | 0.099(10) | 0.087(9) | 0.075(10) |
Heart | 1.097 | 1.118 | 1.101 | 0.994 | 1.026 |
| 0.167(10) | 0.154(10) | 0.129(10) | 0.068(9) | 0.080(10) |
Kidneys | 2.104 | 2.053 | 2.053 | 1.980 | 2.056 |
| 0.279(10) | 0.157(10) | 0.232(10) | 0.237(9) | 0.186(10) |
Liver | 8.006 | 7.784 | 7.857 | 7.306 | 7.459 |
| 0.837(10) | 0.672(10) | 0.899(10) | 0.590(9) | 0.779(10) |
Ovaries | 0.124 | 0.127 | 0.137 | 0.118 | 0.142 |
| 0.028(10) | 0.029(10) | 0.022(10) | 0.022(9) | 0.056(10) |
Spleen | 0.520 | 0.571 | 0.566 | 0.548 | 0.531 |
| 0.042(10) | 0.093(10) | 0.081(10) | 0.039(9) | 0.078(10) |
Thymus | 0.268 | 0.298 | 0.257 | 0.271 | 0.261 |
| 0.059(10) | 0.068(10) | 0.067(10) | 0.066(9) | 0.057(10) |
Uterus | 0.720 | 0.697 | 0.666 | 0.709 | 0.698 |
| 0.186(10) | 0.233(10) | 0.219(10) | 0.196(9) | 0.182(10) |
Mean relative organ weight (% of brain weight) | |||||
Adrenal glands/ brain * 100 |
3.366 |
3.542 |
3.633 |
3.197 |
3.551 |
| 0.514(10) | 0.533(10) | 0.746(10) | 0.825(9) | 0.658(10) |
Heart/ brain * 100 |
55.717 |
57.198 |
56.201 |
50.900 |
53.898 |
| 8.439(10) | 8.008(10) | 6.274(10) | 4.226(9) | 4.775(10) |
Kidneys/ brain * 100 |
106.548 |
105.078 |
104.856 |
101.386 |
107.740 |
| 11.471(10) | 9.205(10) | 11.605(10) | 12.737(9) | 7.858(10) |
Liver/ brain * 100 |
405.992 |
398.564 |
402.451 |
373.319 |
391.640 |
| 36.623(10) | 39.299(10) | 55.286(10) | 23.693(9) | 43.691(10) |
Ovaries/ brain * 100 |
6.272 |
6.476 |
6.982 |
6.008 |
7.453 |
| 1.377(10) | 1.520(10) | 1.145(10) | 0.963(9) | 3.074(10) |
Spleen/ brain * 100 |
26.404 |
29.161 |
28.966 |
28.071 |
27.851 |
| 2.479(10) | 4.486(10) | 4.650(10) | 2.381(9) | 4.180(10) |
Thymus/ brain * 100 |
13.618 |
15.240 |
13.138 |
13.822 |
13.673 |
| 2.948(10) | 3.387(10) | 3.327(10) | 3.091(9) | 2.684(10) |
Uterus/ brain * 100 |
36.604 |
35.559 |
34.009 |
36.328 |
36.585 |
| 9.742(10) | 11.690(10) | 11.128(10) | 10.018(9) | 9.381(10) |
Mean relative organ weight (% of body weight) | |||||
Adrenal glands/ final body * 100 |
0.024 |
0.025 |
0.024 |
0.024 |
0.026 |
| 0.005(10) | 0.004(10) | 0.004(10) | 0.007(9) | 0.005(10) |
Brain/ final body * 100 Final body * 100 |
0.698 |
0.694 |
0.686 |
0.732 |
0.731 |
| 0.063(10) | 0.055(10) | 0.120(10) | 0.062(9) | 0.054(10) |
Heart/ final body * 100 Final body * 100 |
0.386 |
0.395 |
0.380 |
0.371 |
0.392 |
| 0.043(10) | 0.045(10) | 0.036(10) | 0.023(9) | 0.020(10) |
Kidneys/ final body * 100 Final body * 100 |
0.741 |
0.726 |
0.709 |
0.740 |
0.786 |
| 0.088(10) | 0.044(10) | 0.062(10) | 0.092(9) | 0.050(10) |
Liver/ final body * 100 Final body * 100 |
2.815 |
2.755 |
2.705 |
2.738 |
2.852 |
| 0.182(10) | 0.234(10) | 0.125(10) | 0.343(9) | 0.261(10) |
Ovaries/ final body * 100 Final body * 100 |
0.043 |
0.045 |
0.048 |
0.044 |
0.054 |
| 0.009(10) | 0.011(10) | 0.010(10) | 0.008(9) | 0.020(10) |
Spleen/ final body * 100 Final body * 100 |
0.184 |
0.202 |
0.196 |
0.205 |
0.202 |
| 0.020(10) | 0.028(10) | 0.025(10) | 0.022(9) | 0.025(10) |
Thymus/ final body * 100 Final body * 100 |
0.094 |
0.105 |
0.088 |
0.102 |
0.099 |
| 0.016(10) | 0.022(10) | 0.016(10) | 0.029(9) | 0.016(10) |
Uterus/ final body * 100 Final body * 100 |
0.255 |
0.245 |
0.232 |
0.266 |
0.270 |
| 0.076(10) | 0.075(10) | 0.083(10) | 0.080(9) | 0.086(10) |
Data summarized as: Mean Standard Deviation (n)
Statistical Analysis: Statistical significance is indicated by the following (p < 0.05):
* Parametric comparison to control (Dunnett/Tamhane-Dunnett) significant
@ Nonparametric comparison to control (Dunn's) significant
Table 18: Selected incidences of gross observations in males and females
Groups Concentration (ppm) | Sex | 0 | 600 | 2000 | 6000 | 18000 |
Pancreas | m |
|
|
|
|
|
no visible lesion |
| 10 | 10 | 10 | 10 | 9 |
discoloration |
| 0 | 0 | 0 | 0 | 1 |
Eye(s) | f |
|
|
|
|
|
no visible lesion |
| 9 | 9 | 10 | 10 | 10 |
discoloration |
| 0 | 1 | 0 | 0 | 0 |
rupture |
| 1 | 0 | 0 | 0 | 0 |
Kidneys | f |
|
|
|
|
|
no visible lesion |
| 10 | 10 | 10 | 9 | 10 |
dilatation |
| 0 | 0 | 0 | 1 | 0 |
No further visible lesions observed in males and females at any concentrations | ||||||
Table 19: Selected incidences of microscopic findings (neoplastic and non-neoplastic lesions)
Groups Concentration (ppm) | Sex | 0 | 600 | 2000 | 6000 | 18000 |
Bone marrow | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 10 |
necrosis, focal |
| 1 | 0 | 0 | 0 | 0 |
Cecum | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 6 | 0 | 0 | 0 | 6 |
inflammation, mucosal |
| 4 | 0 | 0 | 0 | 4 |
Colon | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 10 |
inflammation, mucosal |
| 1 | 0 | 0 | 0 | 0 |
Eye(s) | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 8 |
fold/rosette, retinal |
| 1 | 0 | 0 | 0 | 2 |
Heart | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 5 | 0 | 0 | 0 | 5 |
cardiomyopathy |
| 4 | 0 | 0 | 0 | 5 |
fibrosis, endocardial, focal/multifocal |
| 1 | 0 | 0 | 0 | 0 |
Kidneys | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 6 | 0 | 0 | 0 | 2 |
chronic progressive nephropathy |
| 4 | 0 | 0 | 0 | 7 |
aggregates, lymphoid |
| 0 | 0 | 0 | 0 | 1 |
hydronephrosis, unilateral |
| 1 | 0 | 0 | 0 | 0 |
hyaline droplets |
| 1 | 0 | 0 | 0 | 0 |
Spleen | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 2 | 0 | 0 | 0 | 2 |
inflammation, subacute to chronic |
| 7 | 0 | 0 | 0 | 8 |
fatty change, median cleft |
| 3 | 0 | 0 | 0 | 1 |
fatty change, periportal |
| 1 | 0 | 0 | 0 | 0 |
Lungs |
|
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 0 | 0 | 0 | 0 | 8 |
inflammation, alveolar |
| 0 | 0 | 0 | 0 | 2 |
Mandibular lymph node | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 9 |
hyperplasia, lymphoid |
| 0 | 0 | 0 | 0 | 1 |
hyperplasia, plasma cell |
| 1 | 0 | 0 | 0 | 0 |
Mesenteric lymph node | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 0 | 0 | 0 | 0 | 9 |
erythrocytosis/hemosiderosis, sinus |
| 0 | 0 | 0 | 0 | 1 |
Nose |
|
|
|
|
|
|
examined | m | (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 9 |
odontodysplasia; bilateral |
| 1 | 0 | 0 | 0 | 1 |
inflammation, teeth |
| 1 | 0 | 0 | 0 | 0 |
erosion/ulcer, oral mucosa |
| 1 | 0 | 0 | 0 | 1 |
Optic nerve | m |
|
|
|
|
|
examined |
| (9) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 0 |
not examined, missing |
| 1 | 0 | 0 | 0 | 0 |
Pancreas | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 9 |
atrophy, lobular |
| 1 | 0 | 0 | 0 | 1 |
Parathyroid glands | m |
|
|
|
|
|
examined |
| (9) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 0 |
not examined: missing |
| 1 | 0 | 0 | 0 | 0 |
Pituitary gland | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 0 |
cyst |
| 1 | 0 | 0 | 0 | 0 |
Prostate | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 3 | 0 | 0 | 0 | 3 |
aggregates, lymphoid |
| 7 | 0 | 0 | 0 | 7 |
Skeletal muscle | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 0 | 0 | 0 | 0 | 9 |
Inflammation, subacute to chronic |
| 0 | 0 | 0 | 0 | 1 |
Thymus | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 0 |
hyperplasia, epithelial |
| 1 | 0 | 0 | 0 | 0 |
Thyroid gland | m |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (10) |
within normal limits |
| 9 | 0 | 0 | 0 | 0 |
hypertrophy, follicular cell |
| 1 | 0 | 0 | 0 | 0 |
|
|
|
|
|
|
|
FEMALES |
|
|
|
|
|
|
Cecum | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 8 | 0 | 0 | 1 | 8 |
inflammation, mucosal |
| 8 | 0 | 0 | 0 | 2 |
Eye(s) | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 8 | 0 | 0 | 1 | 10 |
fold/rosette, retinal |
| 1 | 0 | 0 | 0 | 0 |
Ruptured (iatrogenic), unilateral |
| 1 |
|
|
| 0 |
Heart | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1 | (10) |
within normal limits |
| 10 | 0 | 0 | 0 | 9 |
cardiomyopathy |
| 0 | 0 | 0 | 1 | 1 |
Kidneys | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 10 | 0 | 0 | 1 | 8 |
chronic progressive nephropathy |
| 0 | 0 | 0 | 0 | 2 |
dilated tubules, medullary |
| 0 | 0 | 0 | 0 | 1 |
Spleen | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 5 | 0 | 0 | 1 | 4 |
inflammation, subacute to chronic |
| 4 | 0 | 0 | 0 | 5 |
fatty change, median cleft |
| 1 | 0 | 0 | 0 | 2 |
necrosis, focal |
| 0 | 0 | 0 | 0 | 2 |
Mandibular lymph node | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 5 | 0 | 0 | 1 | 6 |
hyperplasia, lymphoid |
| 2 | 0 | 0 | 0 | 1 |
hyperplasia, plasma cell |
| 1 | 0 | 0 | 0 | 0 |
erythrocytosis/hemosiderosis, sinus |
| 3 | 0 | 0 | 0 | 3 |
Mesenteric lymph node | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 8 | 0 | 0 | 1 | 9 |
erythrocytosis/hemosiderosis, sinus |
| 1 | 0 | 0 | 0 | 0 |
hyperplasia, lymphoid |
| 1 | 0 | 0 |
| 1 |
Nose |
|
|
|
|
|
|
examined | f | (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 9 | 0 | 0 | 1 | 10 |
erosion/ulcer, oral mucosa |
| 1 | 0 | 0 | 0 | 0 |
Ovaries | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 9 | 0 | 0 | 1 | 8 |
corpora lutea decreased |
| 1 | 0 | 0 | 0 | 1 |
cyst, unilateral |
| 0 | 0 | 0 | 0 | 0 |
Pancreas | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 10 | 0 | 0 | 1 | 9 |
atrophy, lobular |
| 0 | 0 | 0 | 0 | 1 |
Parathyroid glands | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (0) | (8) |
within normal limits |
| 10 | 0 | 0 | 0 | 8 |
not examined: missing |
| 0 | 0 | 0 | 0 | 2 |
Peyers patch | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (9) |
within normal limits |
| 10 | 0 | 0 | 1 | 8 |
not examined: missing |
| 0 | 0 | 0 | 0 | 1 |
mineralization |
| 0 | 0 | 0 | 0 | 1 |
Sciatic nerve | f |
|
|
|
|
|
examined |
| (9) | (0) | (0) | (1) | (10) |
within normal limits |
| 9 | 0 | 0 | 1 | 10 |
not examined: missing |
| 1 | 0 | 0 | 0 | 0 |
Skeletal muscle | f |
|
|
|
|
|
examined |
| (9) | (0) | (0) | (1) | (10) |
within normal limits |
| 9 | 0 | 0 | 1 | 10 |
not examined: missing |
| 1 | 0 | 0 | 0 | 0 |
Spleen | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 10 | 0 | 0 | 1 | 9 |
aggregates, macrophage |
| 0 | 0 | 0 | 0 | 1 |
Thymus | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 9 | 0 | 0 | 1 | 9 |
hyperplasia, epithelial |
| 1 | 0 | 0 | 0 | 1 |
Thyroid gland | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 9 | 0 | 0 | 1 | 10 |
cyst, ultimobranchial |
| 1 | 0 | 0 | 0 | 0 |
Urinary bladder | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 8 | 0 | 0 | 1 | 10 |
aggregates, lymphoid |
| 2 | 0 | 0 | 0 | 0 |
Vagina | f |
|
|
|
|
|
examined |
| (10) | (0) | (0) | (1) | (10) |
within normal limits |
| 0 | 0 | 0 | 0 | 0 |
Estrus stage: metestrus |
| 3 | 0 | 0 | 0 | 4 |
Estrus stage: estrus |
| 5 | 0 | 0 | 0 | 5 |
Estrus stage: proestrus |
| 2 | 0 | 0 | 1 | 1 |
No further visible lesions observed in males and females at any concentrations | ||||||
Table 20: Mean forelimb and hindlimb grip strength, footsplay, body temperature, and rearing
Males |
|
| |||||
Group | Concentration (ppm) | Number | Forelimb grip strength (kg)
| Hindlimb grip strength (kg) | Footsplay (cm) | Body temperature (ºC) | Rearing (number) |
Baseline |
|
|
|
|
|
|
|
1 | 0 | 10 | 0.81 (0.18) | 0.34 (0.06) | 6.0 (1.4) | 36.4 (0.8) | 5 |
2 | 600 | 10 | 0.81 (0.11) | 0.33 (0.03) | 6.9 (1.6) | 36.2(0.6) | 4 |
3 | 2000 | 10 | 0.86 (0.15) | 0.38 (0.06) | 6.9 (1.7) | 36.2 (0.6) | 5 |
4 | 6000 | 10 | 0.78 (0.13) | 0.37 (0.07) | 6.9 (18) | 36.1(0.5) | 5 |
5 | 18,000 | 10 | 0.85 (0.12) | 0.34 (0.06) | 6.4 (1.8) | 35.9 (0.7) | 3 |
Week 4 |
|
|
|
|
|
|
|
1 | 0 | 10 | 1.26 (0.27) | 0.35 (0.05) | 7.3 (2.6) | 35.5 (1.0) | 4 |
2 | 600 | 10 | 1.17 (0.15) | 0.39(0.09) | 8.4 (2.0) | 35.6 (1.1) | 4 |
3 | 2000 | 10 | 1.17(0.23) | 0.38 (0.07) | 7.1 (2.3) | 35.8 (0.9) | 3 |
4 | 6000 | 10 | 1.18 (0.12) | 0.37 (0.05) | 8.0 (1.8 | 36.0 (1.0) | 3 |
5 | 18,000 | 10 | 1.18 (0.08) | 0.40 (0.09) | 6.9 (1.6) | 35.4 (1.0) | 4 |
Week 8 1 |
0 |
10 |
1.10 (0.21) |
0.45 (0.06) |
7.3 (2.8) |
34.8 (0.6) |
4 |
2 | 600 | 10 | 1.12 (0.14) | 0.41 (0.10) | 8.0 (1.3) | 35.1 (0.8) | 6 |
3 | 2000 | 10 | 1.19 (0.23) | 0.40 (0.10) | 7.1 (2.2) | 35.0 (0.5) | 4 |
4 | 6000 | 10 | 1.20 (0.13) | 0.46 (0.14) | 8.6 (1.5) | 34.8 (0.4) | 4 |
5 | 18,000 | 10 | 1.22 (0.16) | 0.42 (0.07) | 7.0 (2.1) | 34.9 (0.5) | 3 |
WEEK 13 |
|
|
|
|
|
|
|
1 | 0 | 10 | 0.93 (0.23) | 0.40 (0.06) | 7.4 (2.4) | 35.9 (0.9) | 4 |
2 | 600 | 10 | 1.06 (0.19) | 0.45 (0.06) | 7.9 (2.1) | 35.5 (0.6) | 4 |
3 | 2000 | 10 | 1.06 (0.24) | 0.50 (0.07) | 7.7 (1.9) | 36.0 (0.9) | 3 |
4 | 6000 | 10 | 1.15 (0.17) | 0.45 (0.10) | 8.3 (2.4) | 35.7 (0.8) | 3 |
5 | 18,000 | 10 | 1.05 (0.15) | 0.41 (0.06) | 7.9 (2.1) | 35.8 (0.9) | 3 |
Females |
|
|
|
|
|
|
|
Baseline |
|
|
|
|
|
|
|
1 | 0 | 10 | 0.74 (0.18) | 0.36 (0.08) | 5.4 (1.8) | 36.6 (1.0) | 6 |
2 | 600 | 10 | 0.74 (0.17) | 0.34 (0.07) | 5.2 (2.1) | 36.2(1.0) | 5 |
3 | 2000 | 10 | 0.77 (0.14) | 0.34 (0.10) | 6.4 (2.1) | 36.7 (0.5) | 6 |
4 | 6000 | 10 | 0.74 (0.21) | 0.32 (0.06) | 5.5 (1.5) | 36.4(1.0) | 6 |
5 | 18,000 | 10 | 0.72(0.11) | 0.30 (0.04) | 6.3 (1.4) | 36.3 (0.4) | 6 |
Week 4 |
|
|
|
|
|
|
|
1 | 0 | 10 | 1.02 (0.18) | 0.36 (0.08) | 5.6 (1.7) | 36.2 (0.4) | 8 |
2 | 600 | 10 | 0.93 (0.20) | 0.34(0.04) | 6.1 (2.1) | 35.7 (0.5) | 7 |
3 | 2000 | 10 | 0.94 (0.16) | 0.35 (0.08) | 6.4 (2.3) | 35.8 (1.1) | 6 |
4 | 6000 | 10 | 0.99 (0.16) | 0.39 (0.09) | 5.6 (1.4) | 36.2 (0.8) | 7 |
5 | 18,000 | 10 | 0.93 (0.18) | 0.37 (0.08) | 5.8 (2.2) | 36.1(1.0) | 7 |
WEEK 8 |
|
|
|
|
|
|
|
1 | 0 | 10 | 0.96 (0.26) | 0.34 (0.08) | 5.3 (1.8) | 35.7 (0.4) | 10 |
2 | 600 | 10 | 0.92 (0.20) | 0.39 (0.08) | 5.2 (1.5) | 35.8 (0.4) | 8 |
3 | 2000 | 10 | 0.93 (0.18) | 0.38 (0.08) | 6.5 (2.7) | 36.0 (0.6) | 8 |
4 | 6000 | 10 | 0.94 (0.11) | 0.40 (0.07) | 5.6 (1.3) | 35.8 (0.4) | 9 |
5 | 18,000 | 10 | 0.96 (0.19) | 0.37 (0.10) | 6.0 (2.3) | 35.7 (0.4) | 8 |
Week 13
|
|
|
|
|
|
|
|
1 | 0 | 10 | 0.72 (0.21) | 0.37 (0.11) | 5.8 (1.7) | 37.3 (1.0) | 10 |
2 | 600 | 10 | 0.70 (0.16) | 0.36 (0.07) | 6.0 (1.8) | 37.3 (1.0) | 8 |
3 | 2000 | 10 | 0.84 (0.26) | 0.39 (0.08) | 6.4 (2.4) | 36.9 (1.1) | 7 |
4 | 6000 | 10 | 0.80 (0.22) | 0.37 (0.09) | 5.8 (1.2) | 36.5 (1.4) | 9 |
5 | 18,000 | 10 | 0.82 (0.25) | 0.39 (0.08) | 6.9 (1.8) | 36.5 (0.9)# | 8 |
Data arranged as: Mean (Standard Deviation).
# Statistically significant trend compared to the control at p < 0.05 by Jonckheere-Terpstra trend test.
Table 21: Summary of selected functional observational battery findings
Males | Baseline | Week 4 | Week 8 | Week 13 | ||||||||||||||||
Concentration | control | 600 | 2000 | 6000 | 18000 | control | 600 | 2000 | 6000 | 18000 | control | 600 | 2000 | 6000 | 18000 | control | 600 | 2000 | 6000 | 18000 |
Number examined | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Home cage - Posture | ||||||||||||||||||||
Limbs spread out or lying on one side | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Curled up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Sitting, standing or rearing normally, alert | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Jumping | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Removal from cage: | ||||||||||||||||||||
Ease of removal: | ||||||||||||||||||||
Too easy (rat sits quietly, no resistance) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Some resistance (rears, follows observer's hand) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Difficult (runs around cage, may attack) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Ease of handling: | ||||||||||||||||||||
Too easy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Easy (alert, limbs pulled up against body) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Difficult | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Arousal: | ||||||||||||||||||||
Very low (stupor, little or no responsiveness) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Low | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 3 | 2 | 2 | 0 | 0 | 0 | 1 | 2 | 1 | 3 | 1 | 2 | 0 |
Normal (alert, exploratory movements) | 10 | 9 | 8 | 9 | 8 | 9 | 8 | 7 | 7 | 8 | 10 | 10 | 10 | 9 | 8 | 9 | 7 | 9 | 8 | 10 |
High (slight excitement, tense, sudden movements) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Manipulations: | ||||||||||||||||||||
Approach & touch: | ||||||||||||||||||||
No reaction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Normal | 10 | 10 | 8 | 10 | 8 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Increased reaction (jumps away or attacks) | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Tail pinch: | ||||||||||||||||||||
no response | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
normal | 10 | 10 | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
exaggerate response | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Auditory stimulus:
| ||||||||||||||||||||
No reaction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Normal reaction(rat flinches or flicks ear) | 10 | 10 | 10 | 10 | 8 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Exaggerated reaction (rat jumps, flips) | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Posture: | ||||||||||||||||||||
normal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
abnormal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 1 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Gait/coordinations | ||||||||||||||||||||
normal | 10 | 10 | 10 | 10 | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 9 | 10 | 10 | 10 |
unbalance, swaying, uncoordinated | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
ataxic | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
unable to move | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Additional observations: | ||||||||||||||||||||
Waddling | ||||||||||||||||||||
absent | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 9 | 10 | 10 | 10 |
present | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
High posture | ||||||||||||||||||||
absent | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 9 |
present | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Females | ||||||||||||||||||||
Baseline | Week 4 | Week 8 | Week 13 | |||||||||||||||||
Concentration | control | 600 | 2000 | 6000 | 18000 | control | 600 | 2000 | 6000 | 18000 | control | 600 | 2000 | 6000 | 18000 | control | 600 | 2000 | 6000 | 18000 |
Number examined | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Home Cage - Posture | ||||||||||||||||||||
Limbs spread out or lying on one side | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Curled up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Sitting, standing or rearing normally, alert | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Jumping | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Removal from cage: | ||||||||||||||||||||
Ease of removal: | ||||||||||||||||||||
Too easy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Some resistance | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Difficult | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Ease of handling: | ||||||||||||||||||||
Too easy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Easy (alert, limbs pulled up against body) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Difficult | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Posture: | ||||||||||||||||||||
normal | 0 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 8 | 8 | 0 | 0 | 0 | 0 | 0 | 9 | 0 | 8 | 9 | 0 |
abnormal | 10 | 10 | 10 | 10 | 10 | 1 | 10 | 10 | 2 | 2 | 10 | 10 | 10 | 10 | 10 | 1 | 10 | 2 | 1 | 10 |
Arousal: | ||||||||||||||||||||
Very low (stupor, little or no responsiveness) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Low | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Normal | 10 | 10 | 9 | 9 | 10 | 6 | 10 | 8 | 8 | 9 | 8 | 10 | 8 | 8 | 9 | 8 | 9 | 8 | 9 | 10 |
High (slight excitement, tense, sudden movements) | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 1 | 2 | 1 | 1 | 0 | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 0 |
Manipulations: | ||||||||||||||||||||
Approach & touch: | ||||||||||||||||||||
No reaction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Normal | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Increased reaction (jumps away or attacks) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Auditory stimulus:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
No reaction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Normal reaction(rat flinches or flicks ear) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Exaggerated reaction (rat jumps, flips) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Tail pinch: | ||||||||||||||||||||
no response | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
normal | 10 | 9 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
exaggerate response | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Additional observations: | ||||||||||||||||||||
Ear twitch | ||||||||||||||||||||
absent | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 8 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
present | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Extra digit left hindlimb: | ||||||||||||||||||||
absent | 0 | 0 | 0 | 0 | 0 | 10 | 9 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 0 |
present | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
High posture: | ||||||||||||||||||||
absent | 0 | 0 | 0 | 0 | 0 | 9 | 10 | 10 | 8 | 8 | 0 | 0 | 10 | 10 | 10 | 10 | 0 | 8 | 9 | 10 |
present | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 |
Corneal opacity – left eye: | ||||||||||||||||||||
absent | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 0 |
present | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Bent tail | ||||||||||||||||||||
absent | 0 | 0 | 0 | 0 | 0 | 10 | 10 | 10 | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 0 |
present | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Table 22: Motor activity assessment: mean number of movements
Male | ||||||||||||||||
Group | Concentration | Successive 10 minute intervals | ||||||||||||||
| ppm | N | 1 |
| 2 |
| 3 |
| 4 |
| 5 |
| 6 |
| Total | |
Baseline |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 136 | (18) | 137 | (17) | 110 | (28) | 72 | (44) | 45 | (64) | 29 | (40) | 529 | (150) |
2 | 600 | 10 | 122 | (18) | 117 | (43) | 8 8 | (43) | 40 | (51) | 13 | (17) | 17 | (33) | 396 | (108) |
3 | 2000 | 10 | 123 | (20) | 126 | (25) | 120 | (23) | 88 | (51) | 45 | (54) | 23 | (47) | 525 | (148 |
4 | 6000 | 10 | 131 | (19) | 133 | (25) | 104 | (42) | 55 | (37) | 8 | (6) | 10 | (8) | 441 | (86) |
5 | 18,000 | 10 | 143 | (11) | 142 | (17) | 107 | (49) | 71 | (50) | 41 | (60) | 22 | (45) | 526 | (175) |
Week 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 130 | (12) | 133 | (17) | 117 | (23) | 112 | (28) | 102 | (41) | 96 | (47) | 689 | (93) |
2 | 600 | 10 | 118 | (17) | 127 | (8) | 119 | (28) | 113 | (31) | 114 | (42) | 86 | (50) | 676 | (106 |
3 | 2000 | 10 | 124 | (15) | 128 | (14) | 121 | (19) | 126 | (25) | 121 | (46) | 107 | (48) | 725 | (134) |
4 | 6000 | 10 | 43 | (15) | 137 | (17) | 137 | (21) | 130 | (8) | 107 | (45) | 86 | (48) | 740 | (110) |
5 | 18,000 | 10 | 146 | (18) | 133 | (25) | 119 | (34) | 98 | (61) | 63 | (65) | 68 | 63) | 627 | (224) |
Week 8 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 132 | (14) | 131 | (25) | 121 | 35) | 114 | (25) | 106 | (20) | 99 | (36) | 702 | (87) |
2 | 600 | 10 | 131 | (19) | 138 | (18) | 132 | 27) | 126 | (31) | 110 | (41) | 105 | (37) | 742 | (142) |
3 | 2000 | 10 | 135 | (20) | 139 | (22) | 133 | 13) | 128 | (15) | 119 | (37) | 118 | (43) | 771 | (117) |
4 | 6000 | 0 | 3 | (19) | 115 | (28) | 115 | 32) | 101 | (45) | 86 | (51) | 71 | (51) | 622 | (158) |
5 | 18,000 | 10 | 149 | (15) | 146 | (17) | 117 | 37) | 118 | (33) | 87 | (58) | 94 | (55) | 711 | (161) |
Week 13 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 133 | (18) | 127 | (22) | 110 | (32) | 99 | (26) | 91 | (43) | 79 | (44) | 638 | (75) |
2 | 600 | 10 | 132 | (21) | 134 | (18) | 113 | (27) | 107 | (30) | 96( | (42) | 95 | (40) | 676 | (132) |
3 | 2000 | 10 | 131 | (12) | 129 | (16) | 116 | (29) | 96 | (36) | 93 | (34) | 97 | (46) | 662 | (126) |
4 | 6000 | 10 | 137 | (14) | 129 | (20) | 102 | (37) | 102 | (29) | 94 | (38) | 79 | (37) | 642 | (113) |
5 | 18,000 | 10 | 149 | (14) | 138 | (21) | 93 | (37) | 116 | (23) | 79 | (51) | 75 | (42) | 649 | (104) |
Female | ||||||||||||||||
Group | Concentration | Successive 10 minute intervals | ||||||||||||||
| ppm | N | 1 |
| 2 |
| 3 |
| 4 |
| 5 |
| 6 |
| Total | |
Baseline |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 138 | (15) | 117 | (43) | 108 | (42) | 80 | (34) | 50 | (51) | 52 | (49) | 545 | (138) |
2 | 600 | 10 | 134 | (12) | 109 | (42) | 72 | (41) | 74 | (64) | 36 | (46) | 26 | (49) | 452 | (162) |
3 | 2000 | 10 | 134 | (13) | 119 | (29) | 82 | (53) | 80 | (55) | 65 | (52) | 65 | (32) | 505 | (150) |
4 | 6000 | 10 | 132 | (11) | 125 | (25) | 99 | (42) | 89 | (44) | 49 | (47) | 49 | (36) | 528 | (111) |
5 | 18,000 | 10 | 130 | (19) | 134 | (21) | 103 | (38) | 87 | (45) | 47 | (44) | 32 | (36) | 533 | (112) |
Week 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 137 | (22) | 124 | (38) | 124 | (23) | 101 | (39) | 90 | (56) | 89 | (53) | 664 | (133) |
2 | 600 | 10 | 132 | (19) | 120 | (28) | 105 | (44) | 106 | (54) | 92 | (51) | 95 | (60) | 650 | (154) |
3 | 2000 | 10 | 134 | (10) | 133 | (21) | 118 | (41) | 95 | (49) | 82 | (48) | 84 | (62) | 626 | (168) |
4 | 6000 | 10 | 127 | (16) | 122 | (46) | 108 | (34) | 90 | (58) | 95 | (64) | 126 | (35) | 679 | (190) |
5 | 18,000 | 10 | 129 | (20) | 133 | (16) | 105 | (33) | 90 | (47) | 96 | (43) | 76 | (42) | 630 | (107) |
Week 8 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 137 | (16) | 133 | (18) | 110 | (28) | 124 | (22) | 105 | (45) | 89 | (41) | 698 | (120) |
2 | 600 | 10 | 142 | (20) | 137 | (22) | 118 | (43) | 119 | (35) | 120 | (46) | 101 | (62) | 736 | (168) |
3 | 2000 | 10 | 135 | (14) | 148 | (17) | 96 | (49) | 113 | (33) | 103 | (45) | 83 | (55) | 679 | (142) |
4 | 6000 | 0 | 137 | (18) | 123 | (41) | 112 | (50) | 118 | (47) | 86 | (45) | 81 | (63) | 657 | (144) |
5 | 18,000 | 10 | 127 | (24) | 141 | (17) | 106 | (39) | 109 | (29) | 101 | (45) | 107 | (47) | 691 | (92) |
Week 13 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1 | 0 | 10 | 142 | (15) | 129 | (14) | 93 | (38) | 118 | (23) | 104 | (42) | 97 | (50) | 682 | (117) |
2 | 600 | 10 | 143 | (23) | 124 | (11) | 97 | (32) | 98 | (26) | 109 | (47) | 103 | (52) | 674 | (119) |
3 | 2000 | 10 | 131 | (12) | 119 | (27) | 108 | (48) | 95 | (45) | 93 | (45) | 101 | (45) | 647 | (183) |
4 | 6000 | 10 | 131 | (18) | 127 | (12) | 113 | (44) | 110 | (23) | 106 | (35) | 83 | (53) | 670 | (96) |
5 | 18,000 | 10 | 140 | (15) | 132 | (28) | 107 | (29) | 78 | (51) | 101 | (46) | 63 | (43) | 620 | (128) |
Data arranged as: Mean (Standard Deviation).
N = Number examined.
There were no statistically significantdifferencescompared to the control group at p < 0.05.
Table 23: Incidences of gross observations in neuropathology
Males |
|
|
|
|
|
Concentration | Control | 600 | 2000 | 6000 | 18000 |
Number of animals of study | 5 | 5 | 5 | 5 | 5 |
Kidneys |
|
|
|
|
|
no visble lesions | 5 | 5 | 5 | 4 | 5 |
dilatation | 0 | 0 | 0 | 1 | 0 |
Males |
|
|
|
|
|
Concentration | Control | 600 | 2000 | 6000 | 18000 |
Number of animals of study | 5 | 5 | 5 | 5 | 5 |
No gross lesions were observed in any of the female neuropathology rats. | |||||
Table 24: Selected incidences and lesion grades of microscopic findings (neoplastic and non-neoplastic lesions) in neuropathology analysis
Males |
|
|
|
|
|
|
Concentration | Control | 600 | 2000 | 6000 | 18000 |
|
Number of animals of study | 5 | 5 | 5 | 5 | 5 |
|
Gastrocnemius muscle |
|
|
|
|
|
|
examined | 5 | 0 | 0 | 0 | 5 |
|
within normal limits | 5 | 0 | 0 | 0 | 4 |
|
aggregates, macrophage | 0 | 0 | 0 | 0 | 1 |
|
minimal | 0 | 0 | 0 | 0 | 1 |
|
Eye |
|
|
|
|
|
|
examined | 5 | 0 | 0 | 0 | 5 |
|
within normal limits | 5 | 0 | 0 | 0 | 4 |
|
fold/rosette, retinal | 0 | 0 | 0 | 0 | 1 |
|
minimal | 0 | 0 | 0 | 0 | 1 |
|
Females |
|
|
|
|
|
|
Concentration | Control | 600 | 2000 | 6000 | 18000 |
|
Number of animals of study | 5 | 5 | 5 | 5 | 5 |
|
All observations within normal limits | ||||||
Table 5: Summary of clinical findings
Dose group (ppm) | Control | 250 | 1250 | 5000 | 15,000 |
Males |
|
|
|
|
|
Number of Animals Alive at Start of Interval | 4 | 4 | 4 | 4 | 4 |
Observations | Number of times observed/Total number of animals affected | ||||
Behavior/Activity
|
|
|
|
|
|
lnappetence | 0/0 | 1/1 | 0/0 | 0/0 | 0/0 |
Salivation | 1/1 | 1/1 | 0/0 | 1/1 | 1/1 |
Excretion
|
|
|
|
|
|
Emesis | 3/1 | 4/2 | 5/4 | 7/3 | 3/2 |
Feces discolored, Red | 0/0 | 2/1 | 0/0 | 2/1 | 0/0 |
Feces discolored, Yellow | 2/2 | 1/1 | 6/3 | 2/2 | 0/0 |
Feces few/absent | 0/0 | 2/1 | 2/1 | 5/2 | 3/2 |
Feces mucoid | 6/3 | 56/4 | 56/4 | 33/3 | 15/3 |
Feces soft | 122/4 | 250/4 | 352/4 | 144/4 | 92/4 |
Feces watery | 12/4 | 52/4 | 64/4 | 19/3 | 7/3 |
Material in pan/bedding, Red | 0/0 | 2/2 | 0/0 | 0/0 | 0/0 |
Material in pan/bedding, Yellow | 0/0 | 1/1 | 0/0 | 0/0 | 0/0 |
External Appearance |
|
|
|
| 0/0 |
Gums discolored, Pale | 0/0 | 0/0 | 1/1 | 0/0 | 0/0 |
Lacrimation | 100/3 | 0/0 | 354/2 | 138/3 | 103/2 |
Thin | 33/2 | 11/2 | 0/0 | 127/1 | 15/2 |
Tooth/teeth retained | 0/0 | 0/0 | 0/0 | 1/1 | 0/0 |
Eye/Ocular |
|
|
|
|
|
Sciera injected | 10/1 | 0/0 | 2/1 | 0/0 | 1/1 |
Pelage/Skin |
|
|
|
|
|
Abrasion(s) | 8/2 | 0/0 | 16/2 | 0/0 | 20/2 |
Hair sparse | 192/2 | 54/1 | 21/3 | 94/3 | 127/2 |
lnterdigital cyst | 0/0 | 7/1 | 0/0 | 6/2 | 1/1 |
Scabbed area | 44/2 | 3/1 | 0/0 | 38/1 | 2/1 |
Scaling | 0/0 | 182/1 | 32/2 | 410/2 | 1184/4 |
Skin discolored, Gray | 0/0 | 0/0 | 0/0 | 1/1 | 0/0 |
Skin discolored, Red | 95/2 | 2/1 | 68/2 | 146/2 | 33/2 |
Females | |||||
Number of Animals Alive at Start of Interval | 4 | 4 | 4 | 4 | 4 |
Observations | Number of times observed/Total number of animals affected | ||||
Behavior/Activity
| 0/0 | 1/1 | 3/1 | 1/1 |
|
Salivation |
|
|
|
| 1/1 |
Excretion
|
|
|
|
|
|
Emesis | 4/2 | 2/2 | 4/3 | 5/2 | 1/1 |
Feces discolored, Orange | 0/0 | 1/1 | 0/0 | 0/0 | 0/0 |
Feces discolored, Red | 0/0 | 0/0 | 3/1 | 0/0 | 0/0 |
Feces discolored, Yellow | 0/0 | 2/2 | 2/2 | 0/0 | 0/0 |
Feces few/absent | 2/1 | 1/1 | 1/1 | 2/2 | 0/0 |
Feces hard | 0/0 | 0/0 | 1/1 | 0/0 | 0/0 |
Feces mucoid | 13/1 | 9/3 | 69/3 | 3/3 | 19/3 |
Feces soft | 69/4 | 122/4 | 163/4 | 108/4 | 70/4 |
Feces watery | 17/4 | 15/4 | 21/4 | 13/4 | 7/2 |
Material in pan/bedding, Red | 53/3 | 14/1 | 1072 | 29/3 | 54/3 |
External Apperance External Appearance |
|
|
|
|
|
Discharge, brown | 0/0 | 0/0 | 0/0 | 0/0 | 1/1 |
Discharge, red | 104/4 | 19/3 | 41/2 | 40/3 | 52/3 |
Discharge, yellow | 0/0 | 0/0 | 0/0 | 4/1 | 0/0 |
Lacrimation | 23/2 | 38/1 | 454/2 | 222/3 | 0/0 |
Limf function lost | 0/0 | 0/0 | 2/1 | 0/0 | 0/0 |
Swelling | 0/0 | 0/0 | 0/0 | 0/0 | 15/1 |
Thin | 0/0 | 77/2 | 7/1 | 0/0 | 71/1 |
Tooth/teeth retained | 4/1 | 2/1 | 0/0 | 0/0 | 0/0 |
Vulva enlarged | 167/4 | 52/3 | 51/2 | 86/3 | 55/3 |
Eye/Ocular |
|
|
|
|
|
Eye discoloured, Red | 0/0 | 0/0 | 6/1 | 0/0 | 0/0 |
Sclera injected Pelage/Skin | 0/0 | 0/0 | 3/1 | 0/0 | 0/0 |
Pelge/Skin |
|
|
|
|
|
Abrasion(s) | 5/1 | 0/0 | 0/0 | 0/0 | 7/1 |
Hair sparse | 0/0 | 52/2 | 72/2 | 151/1 | 103/1 |
lnterdigital cyst | 9/1 | 0/0 | 6/1 | 0/0 | 81/2 |
Nodule, 1-5mm | 48/2 | 0/0 | 0/0 | 28/1 | 0/0 |
Scabbed area | 0/0 | 8/1 | 0/0 | 0/0 | 0/0 |
Scaling | 0/0 | 43/1 | 464/2 | 129/2 | 444/2 |
Skin discolored, Gray | 0/0 | 0/0 | 41/3 | 18/1 | 21/3 |
Skin discolored, Red | 0/0 | 0/0 | 0/0 | 0/0 | 3/1 |
Table 6: Summary of body weight values (kg)
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
-1 | 9.815 | 1.3224 | 4 | 10.715 | 0.9500 | 4 | 10.260 | 1.3468 | 4 | 10.593 | 1.2318 | 4 | 10.008 | 1.5358 | 4 |
1 | 9.808 | 1.4786 | 4 | 10.770 | 1.2679 | 4 | 10.353 | 1.2467 | 4 | 10.773 | 1.0746 | 4 | 10.190 | 1.4356 | 4 |
2 | 10.668 | 1.5999 | 4 | 11.285 | 1.4130 | 4 | 10.715 | 1.4362 | 4 | 11.250 | 1.0122 | 4 | 10.705 | 1.4499 | 4 |
3 | 10.613 | 1.3594 | 4 | 11.678 | 1.5258 | 4 | 10.900 | 1.3214 | 4 | 11.373 | 1.8386 | 4 | 11.050 | 1.3725 | 4 |
4 | 10.435 | 0.9658 | 4 | 11.703 | 1.4194 | 4 | 10.813 | 1.7586 | 4 | 11.380 | 1.3770 | 4 | 10.940 | 1.5942 | 4 |
5 | 10.745 | 1.2494 | 4 | 12.145 | 1.4213 | 4 | 11.160 | 1.5601 | 4 | 11.758 | 1.4282 | 4 | 11.155 | 1.1732 | 4 |
6 | 11.125 | 1.5058 | 4 | 12.275 | 1.5559 | 4 | 11.313 | 1.5740 | 4 | 11.943 | 1.3190 | 4 | 11.403 | 1.3185 | 4 |
7 | 11.115 | 1.1270 | 4 | 12.488 | 1.5020 | 4 | 11.598 | 1.6438 | 4 | 11.955 | 1.6002 | 4 | 11.415 | 1.2792 | 4 |
8 | 11.198 | 1.3066 | 4 | 12.708 | 1.6284 | 4 | 11.663 | 1.5901 | 4 | 12.230 | 1.5503 | 4 | 11.608 | 1.3765 | 4 |
9 | 11.243 | 1.1639 | 4 | 12.900 | 1.6215 | 4 | 11.805 | 1.6404 | 4 | 12.430 | 1.4146 | 4 | 11.800 | 1.3914 | 4 |
10 | 11.435 | 1.4062 | 4 | 13.010 | 1.6869 | 4 | 11.953 | 1.6507 | 4 | 12.453 | 1.6261 | 4 | 11.838 | 1.4103 | 4 |
11 | 11.528 | 1.2018 | 4 | 13.040 | 1.7140 | 4 | 11.963 | 1.7826 | 4 | 12.483 | 1.5883 | 4 | 11.845 | 1.5190 | 4 |
12 | 11.403 | 1.3002 | 4 | 12.860 | 1.7271 | 4 | 11.765 | 1.5938 | 4 | 12.295 | 1.4401 | 4 | 11.710 | 1.5739 | 4 |
13 | 11.618 | 0.9731 | 4 | 12.915 | 1.5862 | 4 | 12.083 | 1.7105 | 4 | 12.563 | 1.5477 | 4 | 11.908 | 1.4183 | 4 |
Females | |||||||||||||||
-1 | 8.838 | 0.5827 | 4 | 8.533 | 0.7043 | 4 | 8.848 | 0.8998 | 4 | 8.628 | 0.5946 | 4 | 8.790 | 0.9489 | 4 |
1 | 9.258 | 0.5835 | 4 | 8.558 | 0.8214 | 4 | 8.860 | 0.8551 | 4 | 8.765 | 0.7257 | 4 | 9.055 | 0.8910 | 4 |
2 | 9.613 | 0.5741 | 4 | 9.050 | 0.9330 | 4 | 9.425 | 1.0546 | 4 | 9.365 | 0.8474 | 4 | 9.343 | 0.9676 | 4 |
3 | 9.845 | 0.6856 | 4 | 9.230 | 1.1155 | 4 | 9.598 | 0.9971 | 4 | 9.478 | 0.6402 | 4 | 9.573 | 1.0158 | 4 |
4 | 9.495 | 0.6683 | 4 | 9.118 | 0.6863 | 4 | 9.315 | 1.2996 | 4 | 9.270 | 0.9241 | 4 | 9.290 | 0.8632 | 4 |
5 | 9.593 | 0.6150 | 4 | 9.320 | 0.9179 | 4 | 9.633 | 0.9304 | 4 | 9.255 | 0.6262 | 4 | 9.455 | 0.9132 | 4 |
6 | 9.720 | 0.7297 | 4 | 9.570 | 0.8605 | 4 | 9.820 | 0.7632 | 4 | 9.595 | 0.6251 | 4 | 9.598 | 0.8553 | 4 |
7 | 9.670 | 0.8202 | 4 | 9.603 | 1.0293 | 4 | 10.083 | 0.9600 | 4 | 9.548 | 0.7522 | 4 | 9.755 | 0.9414 | 4 |
8 | 9.898 | 0.8591 | 4 | 9.910 | 0.7885 | 4 | 10.115 | 0.9926 | 4 | 9.630 | 0.7342 | 4 | 9.810 | 1.1382 | 4 |
9 | 9.743 | 0.7069 | 4 | 10.128 | 0.6257 | 4 | 10.310 | 0.9484 | 4 | 9.828 | 0.5675 | 4 | 9.838 | 1.0649 | 4 |
10 | 10.005 | 0.8428 | 4 | 10.210 | 0.7671 | 4 | 10.333 | 1.0008 | 4 | 9.770 | 0.3515 | 4 | 9.800 | 1.1088 | 4 |
11 | 10.053 | 0.7496 | 4 | 9.978 | 0.3813 | 4 | 10.450 | 0.8641 | 4 | 9.888 | 0.5038 | 4 | 9.865 | 1.1658 | 4 |
12 | 9.793 | 0.9055 | 4 | 10.013 | 0.4896 | 4 | 10.330 | 0.8671 | 4 | 9.755 | 0.6313 | 4 | 9.895 | 1.2094 | 4 |
13 | 10.103 | 0.7850 | 4 | 10.388 | 0.6084 | 4 | 10.535 | 0.9999 | 4 | 9.963 | 0.5569 | 4 | 9.923 | 1.2421 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
Table 7: Summary of body weight change values (kg)
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
(-1)-1 | -0.008 | 0.2178 | 4 | 0.055 | 0.3420 | 4 | 0.093 | 0.1345 | 4 | 0.180 | 0.1691 | 4 | 0.183 | 0.1759 | 4 |
1-2 | 0.860 | 0.1598 | 4 | 0.515 a | 0.2243 | 4 | 0.363 b | 0.2109 | 4 | 0.478a | 0.1209 | 4 | 0.515 a | 0.1139 | 4 |
2-3 | -0.055 | 0.2462 | 4 | 0.393 | 0.3724 | 4 | 0.185 | 0.3744 | 4 | 0.123 | 0.8762 | 4 | 0.345 | 0.1156 | 4 |
3-4 | -0.178 | 0.5206 | 4 | 0.025 | 0.4861 | 4 | -0.088 | 0.5804 | 4 | 0.008 | 0.4871 | 4 | -0.110 | 0.5268 | 4 |
4-5 | 0.310 | 0.4551 | 4 | 0.443 | 0.5827 | 4 | 0.348 | 0.4052 | 4 | 0.378 | 0.1845 | 4 | 0.215 | 0.5022 | 4 |
5-6 | 0.380 | 0.3608 | 4 | 0.130 | 0.2385 | 4 | 0.153 | 0.1190 | 4 | 0.185 | 0.2301 | 4 | 0.248 | 0.1520 | 4 |
6-7 | -0.010 | 0.4434 | 4 | 0.213 | 0.2011 | 4 | 0.285 | 0.0981 | 4 | 0.013 | 0.4308 | 4 | 0.013 | 0.1632 | 4 |
7-8 | 0.083 | 0.2341 | 4 | 0.220 | 0.1669 | 4 | 0.065 | 0.0681 | 4 | 0.275 | 0.0995 | 4 | 0.193 | 0.1305 | 4 |
8-9 | 0.045 | 0.3101 | 4 | 0.193 | 0.2867 | 4 | 0.143 | 0.1704 | 4 | 0.200 | 0.1978 | 4 | 0.193 | 0.1138 | 4 |
9-10 | 0.193 | 0.2532 | 4 | 0.110 | 0.2291 | 4 | 0.148 | 0.1713 | 4 | 0.023 | 0.2877 | 4 | 0.038 | 0.2108 | 4 |
10-11 | 0.093 | 0.3871 | 4 | 0.030 | 0.2462 | 4 | 0.010 | 0.2118 | 4 | 0.030 | 0.1780 | 4 | 0.008 | 0.2182 | 4 |
11-12 | -0.125 | 0.2876 | 4 | -0.180 | 0.3459 | 4 | -0.198 | 0.3311 | 4 | -0.188 | 0.1531 | 4 | -0.135 | 0.2485 | 4 |
12-13 | 0.215 | 0.3587 | 4 | 0.055 | 0.2198 | 4 | 0.318 | 0.1628 | 4 | 0.268 | 0.1436 | 4 | 0.198 | 0.1864 | 4 |
Females | |||||||||||||||
(-1)-1 | 0.420 | 0.3861 | 4 | 0.025 | 0.2716 | 4 | 0.013 | 0.2311 | 4 | 0.138 | 0.1750 | 4 | 0.265 | 0.1524 | 4 |
1-2 | 0.355 | 0.1028 | 4 | 0.493 | 0.2773 | 4 | 0.565 | 0.2301 | 4 | 0.600 | 0.1840 | 4 | 0.288 | 0.1537 | 4 |
2-3 | 0.233 | 0.2458 | 4 | 0.180 | 0.2003 | 4 | 0.173 | 0.0585 | 4 | 0.113 | 0.2439 | 4 | 0.230 | 0.1857 | 4 |
3-4 | -0.350 | 0.1431 | 4 | -0.113 | 0.4951 | 4 | -0.283 | 0.4586 | 4 | -0.208 | 0.4548 | 4 | -0.283 | 0.2142 | 4 |
4-5 | 0.098 | 0.4141 | 4 | 0.203 | 0.2804 | 4 | 0.318 | 0.4005 | 4 | -0.015 | 0.3301 | 4 | 0.165 | 0.1170 | 4 |
5-6 | 0.128 | 0.2246 | 4 | 0.250 | 0.1753 | 4 | 0.188 | 0.3442 | 4 | 0.340 | 0.2655 | 4 | 0.143 | 0.1528 | 4 |
6-7 | -0.050 | 0.2017 | 4 | 0.033 | 0.3685 | 4 | 0.263 | 0.3041 | 4 | -0.048 | 0.2727 | 4 | 0.158 | 0.1315 | 4 |
7-8 | 0.228 | 0.1742 | 4 | 0.308 | 0.3654 | 4 | 0.033 | 0.2893 | 4 | 0.083 | 0.1287 | 4 | 0.055 | 0.2094 | 4 |
8-9 | -0.155 | 0.2546 | 4 | 0.218 | 0.2291 | 4 | 0.195 | 0.2584 | 4 | 0.198 | 0.2024 | 4 | 0.028 | 0.1646 | 4 |
9-10 | 0.263 | 0.3219 | 4 | 0.083 | 0.2178 | 4 | 0.023 | 0.1889 | 4 | -0.058 | 0.2164 | 4 | -0.038 | 0.0950 | 4 |
10-11 | 0.048 | 0.2076 | 4 | -0.233 | 0.4096 | 4 | 0.118 | 0.1769 | 4 | 0.118 | 0.2025 | 4 | 0.065 | 0.2310 | 4 |
11-12 | -0.260 | 0.1794 | 4 | 0.035 | 0.1567 | 4 | -0.120 | 0.2396 | 4 | -0.133 | 0.1763 | 4 | 0.030 | 0.1252 | 4 |
12-13 | 0.310 | 0.4159 | 4 | 0.375 | 0.2369 | 4 | 0.205 | 0.1658 | 4 | 0.208 | 0.2326 | 4 | 0.028 | 0.2388 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
a Significantly different from control; (p<0.05)
b Significantly different from control; (p<0.01)
Table 8: Summary of total body weight change values (kg)
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
(-1)-13 | 1.803 | 0.3672 | 4 | 2.200 | 0.9944 | 4 | 1.823 | 0.8353 | 4 | 1.970 | 0.4464 | 4 | 1.900 | 0.6221 | 4 |
Females |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(-1)-13 | 1.265 | 0.6538 | 4 | 1.855 | 0.5730 | 4 | 1.688 | 0.7256 | 4 | 1.335 | 0.0666 | 4 | 1.133 | 0.5674 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
Table 9: Summary of weekly food consumption (g/animal/day)
| Control | 250 | 1250 | 5000 | 15000 | ||||||||||
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
-1 | 155.71 | 25.280 | 4 | 183.14 | 58.029 | 4 | 171.07 | 30.827 | 4 | 162.14 | 30.229 | 4 | 221.46 | 30.331 | 4 |
1 | 174.21 | 16.467 | 4 | 179.96 | 51.729 | 4 | 188.43 | 43.973 | 4 | 189.07 | 26.630 | 4 | 208.36 | 15.667 | 4 |
2 | 256.04 | 20.660 | 4 | 270.62 | 44.834 | 4 | 250.11 | 63.111 | 4 | 263.36 | 24.876 | 4 | 299.04 | 38.535 | 4 |
3 | 294.00 | 7.140 | 4 | 345.00 | 52.083 | 4 | 312.57 | 53.937 | 4 | 307.50 | 49.915 | 4 | 356.89 | 32.040 | 4 |
4 | 308.57 | 17.868 | 4 | 363.68 | 35.018 | 4 | 325.75 | 55.156 | 4 | 311.75 | 60.014 | 4 | 356.50 | 28.065 | 4 |
5 | 251.25 | 27.364 | 4 | 337.00 a | 47.353 | 4 | 300.68 | 68.177 | 4 | 305.25 | 8.214 | 4 | 314.50 | 31.015 | 4 |
6 | 293.91 | 22.239 | 4 | 328.32 | 49.310 | 4 | 316.65 | 62.228 | 4 | 324.54 | 11.566 | 4 | 334.96 | 27.417 | 4 |
7 | 288.51 | 12.156 | 4 | 344.68 | 39.752 | 4 | 320.82 | 50.672 | 4 | 315.32 | 32.212 | 4 | 329.79 | 30.663 | 4 |
8 | 306.46 | 35.034 | 4 | 345.79 | 47.568 | 4 | 338.71 | 49.799 | 4 | 323.11 | 23.344 | 4 | 355.75 | 43.421 | 4 |
9 | 312.86 | 23.379 | 4 | 330.29 | 40.047 | 4 | 322.49 | 51.033 | 4 | 329.89 | 13.762 | 4 | 336.61 | 50.293 | 4 |
10 | 314.79 | 29.906 | 4 | 338.46 | 45.099 | 4 | 337.57 | 68.499 | 4 | 329.71 | 13.791 | 4 | 334.11 | 53.428 | 4 |
11 | 300.79 | 11.849 | 4 | 345.68 | 41.193 | 4 | 317.86 | 62.912 | 4 | 308.64 | 29.785 | 4 | 332.11 | 52.473 | 4 |
12 | 291.43 | 23.264 | 4 | 305.50 | 32.777 | 4 | 313.54 | 48.470 | 4 | 278.93 | 30.796 | 4 | 308.71 | 66.285 | 4 |
13 | 289.13 | 33.103 | 4 | 279.86 | 36.989 | 4 | 317.86 | 43.089 | 4 | 293.43 | 15.956 | 4 | 320.00 | 41.988 | 4 |
Females | |||||||||||||||
-1 | 184.96 | 57.014 | 4 | 147.21 | 26.880 | 4 | 217.93 | 16.654 | 4 | 174.18 | 37.804 | 4 | 168.21 | 35.322 | 4 |
1 | 207.50 | 40.146 | 4 | 135.68 b | 15.283 | 4 | 199.04 | 9.180 | 4 | 160.71 a | 22.910 | 4 | 174.18 | 21.016 | 4 |
2 | 256.21 | 39.789 | 4 | 240.21 | 21.087 | 4 | 276.68 | 13.848 | 4 | 233.43 | 27.849 | 4 | 239.68 | 6.657 | 4 |
3 | 266.44 | 24.923 | 4 | 279.32 | 13.594 | 4 | 315.82 b | 15.710 | 4 | 252.96 | 22.243 | 4 | 275.96 | 19.062 | 4 |
4 | 273.36 | 62.674 | 4 | 299.89 | 19.808 | 4 | 315.14 | 16.654 | 4 | 264.14 | 27.947 | 4 | 264.96 | 27.131 | 4 |
5 | 254.11 | 27.114 | 4 | 255.82 | 31.325 | 4 | 278.86 | 18.072 | 4 | 203.54 | 29.648 | 4 | 227.18 | 48.276 | 4 |
6 | 276.71 | 40.698 | 4 | 291.18 | 32.029 | 4 | 318.57 | 20.205 | 4 | 240.74 | 26.397 | 4 | 249.93 | 52.736 | 4 |
7 | 253.29 | 56.588 | 4 | 287.04 | 35.002 | 4 | 315.57 | 10.138 | 4 | 250.29 | 33.405 | 4 | 260.82 | 26.723 | 4 |
8 | 269.21 | 51.018 | 4 | 288.39 | 22.521 | 4 | 309.75 | 16.163 | 4 | 256.64 | 16.795 | 4 | 265.54 | 24.481 | 4 |
9 | 272.33 | 56.259 | 4 | 296.14 | 44.457 | 4 | 322.64 | 25.188 | 4 | 242.68 | 26.298 | 4 | 255.46 | 45.157 | 4 |
10 | 294.68 | 73.017 | 4 | 307.57 | 36.334 | 4 | 321.46 | 13.930 | 4 | 245.46 | 41.702 | 4 | 250.07 | 70.087 | 4 |
11 | 267.25 | 58.305 | 4 | 254.57 | 78.708 | 4 | 316.00 | 22.749 | 4 | 258.43 | 47.171 | 4 | 243.29 | 72.057 | 4 |
12 | 281.64 | 73.237 | 4 | 277.61 | 60.711 | 4 | 301.29 | 43.297 | 4 | 235.57 | 28.881 | 4 | 244.93 | 70.042 | 4 |
13 | 273.43 | 49.746 | 4 | 281.21 | 27.667 | 4 | 296.71 | 37.712 | 4 | 233.04 | 18.870 |
| 246.18 | 39.616 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
a Significantly different from control; (p<0.05)
b Significantly different from control; (p<0.01)
Table 10: Summary of total food consumption values (g/animal/day)
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
1-13 | 283 | 13.043 | 4 | 316.50 | 30.314 | 4 | 304.81 | 50.239 | 4 | 298.5 | 9.050 | 4 | 322.1 | 34.781 | 4 |
Females |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1-13 | 265.01 | 44.106 | 4 | 268.82 | 23.844 | 4 | 299.02 | 10.878 | 4 | 236.68 | 15.280 | 4 | 246.01 | 37.186 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
Table 11: Summary of weekly feed efficiency values
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
-1 | -130.39 | 38.965 | 4 | -106.76 | 86.888 | 4 | -88.21 | 29.205 | 4 | 109.43 | 34.558 | 4 | -50.82 a | 19.431 | 4 |
1 | -1.51 | 17.881 | 4 | -1.43 | 29.482 | 4 | 7.72 | 12.571 | 4 | 12.76 | 10.600 | 4 | 12.28 | 11.406 | 4 |
2 | 48.29 | 10.609 | 4 | 26.73 a | 8.206 | 4 | 19.55 b | 8.127 | 4 | 25.64 | 4.808 | 4 | 25.03 a | 6.668 | 4 |
3 | -2.74 | 11.916 | 4 | 14.98 | 13.775 | 4 | 8.55 | 17.640 | 4 | 0.98 | 46.185 | 4 | 13.96 | 4.873 | 4 |
4 | -8.42 | 24.912 | 4 | 2.27 | 19.761 | 4 | -5.72 | 26.356 | 4 | 3.71 | 25.485 | 4 | -4.68 | 20.893 | 4 |
5 | 19.51 | 27.838 | 4 | 17.22 | 23.874 | 4 | 17.24 | 20.679 | 4 | 17.82 | 9.037 | 4 | 11.43 | 23.973 | 4 |
6 | 18.07 | 16.308 | 4 | 5.18 | 9.850 | 4 | 6.90 | 4.757 | 4 | 8.18 | 10.112 | 4 | 10.30 | 5.966 | 4 |
7 | -0.02 | 22.527 | 4 | 8.41 | 8.344 | 4 | 12.62 | 3.549 | 4 | -0.91 | 21.019 | 4 | 0.38 | 6.890 | 4 |
8 | 2.86 | 11.759 | 4 | 8.76 | 6.007 | 4 | 2.94 | 2.983 | 4 | 12.38 | 5.137 | 4 | 7.37 | 4.674 | 4 |
9 | 2.04 | 13.821 | 4 | 7.93 | 12.832 | 4 | 5.91 | 7.063 | 4 | 8.41 | 8.360 | 4 | 8.12 | 4.326 | 4 |
10 | 7.92 | 11.481 | 4 | 4.84 | 9.994 | 4 | 7.03 | 9.096 | 4 | 0.92 | 12.734 | 4 | 1.22 | 9.458 | 4 |
11 | 4.71 | 18.801 | 4 | 1.06 | 10.160 | 4 | -0.45 | 8.623 | 4 | 1.01 | 8.764 | 4 | -0.55 | 9.689 | 4 |
12 | -6.99 | 14.817 | 4 | -8.63 | 17.240 | 4 | -7.77 | 13.412 | 4 | -10.09 | 8.367 | 4 | -6.77 | 13.818 | 4 |
13 | 11.65 | 18.391 | 4 | 1.88 | 10.992 | 4 | 14.49 | 7.190 | 4 | 12.86 | 6.367 | 4 | 9.24 | 9.136 | 4 |
Females | |||||||||||||||
-1 | -49.95 | 41.398 | 4 | -97.34 | 57.101 | 4 | -41.64 | 31.253 | 4 | -52.86 | 39.049 | 4 | -78.09 | 44.702 | 4 |
1 | 27.59 | 23.421 | 4 | 0.97 | 26.379 | 4 | 0.39 | 17.038 | 4 | 10.75 | 15.426 | 4 | 21.76 | 11.299 | 4 |
2 | 19.98 | 5.739 | 4 | 28.52 | 15.663 | 4 | 28.89 | 10.877 | 4 | 36.70 | 9.770 | 4 | 17.18 | 9.267 | 4 |
3 | 12.46 | 12.705 | 4 | 9.01 | 9.881 | 4 | 7.82 | 2.731 | 4 | 7.30 | 15.188 | 4 | 11.51 | 8.995 | 4 |
4 | -18.23 | 5.243 | 4 | -6.50 | 24.245 | 4 | -13.57 | 20.835 | 4 | -12.92 | 25.694 | 4 | -15.46 | 11.384 | 4 |
5 | 5.29 | 22.163 | 4 | 12.70 | 17.163 | 4 | 15.48 | 20.128 | 4 | -1.53 | 21.787 | 4 | 10.74 | 8.885 | 4 |
6 | 5.39 | 11.703 | 4 | 11.74 | 7.154 | 4 | 8.18 | 14.712 | 4 | 19.78 | 14.663 | 4 | 7.23 | 6.267 | 4 |
7 | 4.10 | 11.615 | 4 | 2.01 | 17.934 | 4 | 11.77 | 13.741 | 4 | -2.63 | 14.307 | 4 | 8.69 | 7.277 | 4 |
8 | 12.27 | 9.047 | 4 | 14.29 | 16.641 | 4 | 1.32 | 13.506 | 4 | 4.84 | 7.089 | 4 | 3.13 | 11.124 | 4 |
9 | -7.58 | 13.774 | 4 | 9.93 | 11.823 | 4 | 8.44 | 10.789 | 4 | 10.88 | 11.871 | 4 | 0.53 | 8.145 | 4 |
10 | 10.29 | 13.794 | 4 | 4.05 | 10.951 | 4 | 1.22 | 8.200 | 4 | -5.07 | 15.400 | 4 | -3.09 | 7.360 | 4 |
11 | 4.28 | 12.278 | 4 | -22.20 | 39.521 | 4 | 5.10 | 8.169 | 4 | 6.12 | 11.762 | 4 | 2.24 | 11.358 | 4 |
12 | -14.30 | 12.634 | 4 | 3.08 | 8.656 | 4 | -6.89 | 11.257 | 4 | -7.72 | 10.791 | 4 | 0.09 | 9.013 | 4 |
13 | 17.66 | 23.439 | 4 | 19.65 | 13.933 | 4 | 10.08 | 8.569 | 4 | 12.07 | 13.108 | 4 | 3.15 | 13.229 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
a Significantly different from control; (p<0.05)
b Significantly different from control; (p<0.01)
Table 12: Summary of total feed efficiency (%)
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Study interval (week) | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males | |||||||||||||||
1-13 | 7.04 | 1.686 | 4 | 7.46 | 2.585 | 4 | 6.64 | 2.992 | 4 | 7.23 | 1.506 | 4 | 6.53 | 2.092 | 4 |
Females |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
1-13 | 5.31 | 2.550 | 4 | 7.62 | 2.488 | 4 | 6.21 | 2.711 | 4 | 6.22 | 0.537 | 4 | 5.03 | 2.565 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
Table 13: Summary of haematology values
| Interval of Study (week) | Control | 250 | 1250 | 5000 | 15000 | ||||||||||
| Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | |
Males |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Leukocytes 103/µL | -2 | 9.88 | 2.119 | 4 | 9.50 | 1 .230 | 4 | 10.28 | 2.660 | 4 | 7.73 | 0.419 | 4 | 8.90 | 0.920 | 4 |
-1 | 8.43 | 1 .810 | 4 | 8.65 | 1 .396 | 4 | 10.58 | 3.059 | 4 | 7.95 | 0.443 | 4 | 8.80 | 1 .881 | 4 | |
4 | 10.75 | 5.026 | 4 | 9.28 | 1 .875 | 4 | 10.48 | 0.988 | 4 | 8.98 | 1 .253 | 4 | 9.85 | 1 .182 | 4 | |
8 | 8.53 | 1 .482 | 4 | 9.03 | 1 .561 | 4 | 9.78 | 0.618 | 4 | 9.28 | 1 .676 | 4 | 8.45 | 0.342 | 4 | |
12 | 8.18 | 2.232 | 4 | 9.00 | 2.143 | 4 | 10.20 | 0.432 | 4 | 8.78 | 1 .372 | 4 | 9.98 | 3.670 | 4 | |
Erythro- cytes 10 6 / µL | -2 | 7.320 | 0.5870 | 4 | 7.575 | 0.5043 | 4 | 7.705 | 0.2822 | 4 | 7.158 | 0.3719 | 4 | 6.723 | 0.4066 | 4 |
-1 | 7.415 | 0.5125 | 4 | 7.475 | 0.3064 | 4 | 7.948 | 0.2330 | 4 | 7.463 | 0.2492 | 4 | 6.703 a | 0.3923 | 4 | |
4 | 6.368 | 0.6939 | 4 | 6.568 | 0.4224 | 4 | 7.013 | 0.5102 | 4 | 6.205 | 0.2588 | 4 | 6 .160 | 0.3623 | 4 | |
8 | 6.483 | 0.7957 | 4 | 6.383 | 0.4029 | 4 | 7.173 | 0.3598 | 4 | 6.385 | 0.2124 | 4 | 6.220 | 0.4295 | 4 | |
12 | 6.380 | 0.8176 | 4 | 6.420 | 0.3362 | 4 | 6.975 | 0.3029 | 4 | 6.333 | 0.2474 | 4 | 6.095 | 0.4799 | 4 | |
Haemoglobin g/dL | -2 | 16.58 | 1 .245 | 4 | 16.80 | 0.990 | 4 | 17.18 | 0.881 | 4 | 16.35 | 1 .455 | 4 | 15.83 | 0.746 | 4 |
-1 | 17.10 | 0.849 | 4 | 16.85 | 0.947 | 4 | 17.70 | 0.698 | 4 | 16.93 | 0.793 | 4 | 15.68 | 0.854 | 4 | |
4 | 14.40 | 1 .499 | 4 | 14.70 | 1 .163 | 4 | 15.50 | 1 .405 | 4 | 13.78 | 0.665 | 4 | 14.28 | 0.741 | 4 | |
8 | 14.80 | 1 .476 | 4 | 14.53 | 0.435 | 4 | 15.90 | 0.658 | 4 | 14.13 | 0.403 | 4 | 14.60 | 0.976 | 4 | |
12 | 14.40 | 1 .435 | 4 | 14.50 | 0.572 | 4 | 15.30 | 0.956 | 4 | 14.03 | 0.789 | 4 | 14.13 | 0.806 | 4 | |
Haematocrit % | -2 | 45.60 | 2.918 | 4 | 46.50 | 2.897 | 4 | 46.33 | 1 .866 | 4 | 43.98 | 3.090 | 4 | 42.60 | 2.404 | 4 |
-1 | 46.30 | 2.965 | 4 | 46.65 | 1 .827 | 4 | 49.08 | 1 .846 | 4 | 46.70 | 2.165 | 4 | 43.13 | 2.034 | 4 | |
4 | 40.68 | 3.838 | 4 | 41 .60 | 2.889 | 4 | 44.03 | 3.173 | 4 | 39.35 | 2.074 | 4 | 40.28 | 1 .957 | 4 | |
8 | 41 .10 | 4.436 | 4 | 40.18 | 1 .801 | 4 | 44.78 | 1 .247 | 4 | 39.58 | 0.634 | 4 | 39.85 | 1 .974 | 4 | |
12 | 40.58 | 4.192 | 4 | 40.85 | 1 .928 | 4 | 43.73 | 2.380 | 4 | 39.93 | 2.630 | 4 | 39.80 | 2.102 | 4 | |
MCV fl | -2 | 62.35 | 1 .491 | 4 | 61 .43 | 1 .455 | 4 | 60.15 | 1 .103 | 4 | 61 .40 | 2.020 | 4 | 63.40 | 2.404 | 4 |
-1 | 62.50 | 1 .402 | 4 | 62.45 | 1 .848 | 4 | 61 .75 | 1 .287 | 4 | 62.50 | 1 .417 | 4 | 64.43 | 2.900 | 4 | |
4 | 64.00 | 1 .334 | 4 | 63.33 | 1 .323 | 4 | 62.83 | 1 .565 | 4 | 63.45 | 2.225 | 4 | 65.43 | 1 .692 | 4 | |
8 | 63.50 | 1 .538 | 4 | 63.03 | 1 .567 | 4 | 62.48 | 1.725 | 4 | 62.03 | 1 .539 | 4 | 64.18 | 1.711 | 4 | |
12 | 63.75 | 2.133 | 4 | 63.65 | 1 .936 | 4 | 62.65 | 1 .279 | 4 | 63.05 | 2.844 | 4 | 65.38 | 1.797 | 4 | |
MCH pg | -2 | 22.63 | 0.443 | 4 | 22.23 | 0.981 | 4 | 22.28 | 0.450 | 4 | 22.78 | 0.936 | 4 | 23.60 | 0.808 | 4 |
-1 | 23.08 | 0.512 | 4 | 22.53 | 1 .109 | 4 | 22.25 | 0.451 | 4 | 22.68 | 0.834 | 4 | 23.35 | 0.661 | 4 | |
4 | 22.63 | 0.222 | 4 | 22.38 | 0.556 | 4 | 22.08 | 0.618 | 4 | 22.20 | 0.739 | 4 | 23.20 | 0.374 | 4 | |
8 | 22.90 | 0.535 | 4 | 22.83 | 1 .124 | 4 | 22.18 | 0.591 | 4 | 22.13 | 0.907 | 4 | 23.50 | 0.622 | 4 | |
12 | 22.65 | 0.904 | 4 | 22.55 | 0.700 | 4 | 21 .93 | 0.538 | 4 | 22.13 | 0.862 | 4 | 23.20 | 0.688 | 4 | |
MCHC g/dl | -2 | 36.30 | 0.698 | 4 | 36.15 | 0.896 | 4 | 37.10 | 0.548 | 4 | 37.13 | 0.655 | 4 | 37.18 | 0.591 | 4 |
-1 | 36.90 | 0.688 | 4 | 36.10 | 0.757 | 4 | 36.03 | 0.206 | 4 | 36.28 | 0.741 | 4 | 36.30 | 0.668 | 4 | |
4 | 35.35 | 0.465 | 4 | 35.35 | 0.420 | 4 | 35.15 | 0.719 | 4 | 34.98 | 0.126 | 4 | 35.45 | 0.412 | 4 | |
8 | 36.03 | 0.655 | 4 | 36.25 | 1 .097 | 4 | 35.55 | 0.545 | 4 | 35.63 | 0.746 | 4 | 36.58 | 0.665 | 4 | |
12 | 35.48 | 0.395 | 4 | 35.45 | 0.451 | 4 | 35.03 | 0.263 | 4 | 35.10 | 0.622 | 4 | 35.45 | 0.289 | 4 | |
Platelets 103/µL | -2 | 303.5 | 93.82 | 4 | 290.0 | 39.09 | 4 | 276.3 | 36.30 | 4 | 327.8 | 55.42 | 4 | 254.3 | 74.55 | 4 |
-1 | 275.8 | 92.49 | 4 | 283.0 | 40.73 | 4 | 271 .8 | 54.33 | 4 | 313.5 | 77.88 | 4 | 255.0 | 92.36 | 4 | |
4 | 282.8 | 75.71 | 4 | 276.5 | 56.13 | 4 | 281 .3 | 50.59 | 4 | 321 .5 | 58.45 | 4 | 265.5 | 39.84 | 4 | |
8 | 306.0 | 68.48 | 4 | 285.3 | 74.73 | 4 | 268.8 | 35.98 | 4 | 302.0 | 10.30 | 4 | 250.8 | 57.85 | 4 | |
12 | 314.8 | 58.14 | 4 | 313.5 | 35.60 | 4 | 288.5 | 25.17 | 4 | 330.5 | 36.32 | 4 | 261 .8 | 52.68 | 4 | |
RDW % | -2 | 13.15 | 0.265 | 4 | 13.28 | 0.377 | 4 | 13.25 | 0.465 | 4 | 13.35 | 0.592 | 4 | 12.95 | 0.289 | 4 |
-1 | 12.53 | 0.403 | 4 | 12.78 | 0.369 | 4 | 13.18 | 0.222 | 4 | 12.88 | 0.519 | 4 | 12.63 | 0.340 | 4 | |
4 | 12.78 | 0.550 | 4 | 13.00 | 0.497 | 4 | 12.98 | 0.377 | 4 | 12.45 | 0.420 | 4 | 12.65 | 0.451 | 4 | |
8 | 12.40 | 0.432 | 4 | 12.65 | 0.645 | 4 | 12.78 | 0.550 | 4 | 12.25 | 0.289 | 4 | 12.08 | 0.340 | 4 | |
12 | 12.30 | 0.408 | 4 | 12.53 | 0.512 | 4 | 12.58 | 0.250 | 4 | 12.63 | 0.340 | 4 | 12.15 | 0.129 | 4 | |
Absolute Reticu- locytes 103/µL | -2 | 26.95 | 10.744 | 4 | 31.90 | 14.080 | 4 | 39.65 | 21.137 | 4 | 28.78 | 18.075 | 4 | 23.38 | 2.940 | 4 |
-1 | 31.68 | 16.792 | 4 | 30.08 | 11.140 | 4 | 57.65 | 28.886 | 4 | 37.95 | 19.503 | 4 | 30.38 | 5.629 | 4 | |
4 | 29.83 | 4.464 | 4 | 35.30 | 15.306 | 4 | 47.63 | 20.938 | 4 | 27.43 | 11.700 | 4 | 35.20 | 4.997 | 4 | |
8 | 44.00 | 32.901 | 4 | 35.13 | 13.322 | 4 | 54.25 | 36.076 | 4 | 28.83 | 14.076 | 4 | 29.23 | 4.323 | 4 | |
12 | 42.63 | 31.070 | 4 | 41.00 | 12.580 | 4 | 47.85 | 29.070 | 4 | 41 .88 | 12.908 | 4 | 40.28 | 9.241 | 4 | |
Percent Reticu- locytes % | -2 | 0.35 | 0.129 | 4 | 0.40 | 0.141 | 4 | 0.50 | 0.258 | 4 | 0.38 | 0.222 | 4 | 0.35 | 0.058 | 4 |
-1 | 0.43 | 0.222 | 4 | 0.38 | 0.150 | 4 | 0.73 | 0.377 | 4 | 0.50 | 0.245 | 4 | 0.45 | 0.100 | 4 | |
4 | 0.45 | 0.129 | 4 | 0.53 | 0.206 | 4 | 0.68 | 0.275 | 4 | 0.45 | 0.173 | 4 | 0.55 | 0.100 | 4 | |
8 | 0.68 | 0.492 | 4 | 0.55 | 0.173 | 4 | 0.78 | 0.492 | 4 | 0.45 | 0.208 | 4 | 0.48 | 0.096 | 4 | |
12 | 0.63 | 0.386 | 4 | 0.65 | 0.238 | 4 | 0.70 | 0.408 | 4 | 0.65 | 0.191 | 4 | 0.68 | 0.126 | 4 | |
Neutrophils 103/µL | -2 | 7.280 | 1.5502 | 4 | 5.880 | 1.2234 | 4 | 6.393 | 2.3232 | 4 | 4.948 | 0.4135 | 4 | 5.523 | 0.3344 | 4 |
-1 | 5.595 | 1.5532 | 4 | 5.123 | 1.0679 | 4 | 6.723 | 2.7198 | 4 | 5.070 | 0.4662 | 4 | 5.495 | 0.9580 | 4 | |
4 | 7.335 | 4.1076 | 4 | 5.510 | 1.6918 | 4 | 6.453 | 0.8771 | 4 | 5.510 | 1.2780 | 4 | 6.200 | 0.8581 | 4 | |
8 | 5.583 | 0.9419 | 4 | 5.593 | 1.5127 | 4 | 6.095 | 0.5606 | 4 | 6.013 | 1.2700 | 4 | 5.133 | 0.5311 | 4 | |
12 | 5.398 | 1.6236 | 4 | 5.770 | 1.7758 | 4 | 6.468 | 0.2103 | 4 | 5.760 | 1.1587 | 4 | 6.635 | 2.9940 | 4 | |
Lymphocytes 103/µL | -2 | 1.618 | 0.8681 | 4 | 2.758 | 0.5415 | 4 | 2.968 a | 0.6496 | 4 | 2.080 | 0.2573 | 4 | 2.528 | 0.4957 | 4 |
-1 | 2.128 | 0.2123 | 4 | 2.718 | 0.3820 | 4 | 2.985 a | 0.3574 | 4 | 2.213 | 0.2542 | 4 | 2.498 | 0.6390 | 4 | |
4 | 2.288 | 0.5117 | 4 | 2.848 | 0.2900 | 4 | 3.003 | 0.3812 | 4 | 2.673 | 0.3716 | 4 | 2.800 | 0.4667 | 4 | |
8 | 2.235 | 0.3582 | 4 | 2.758 | 0.2208 | 4 | 2.795 | 0.3415 | 4 | 2.545 | 0.4584 | 4 | 2.610 | 0.5073 | 4 | |
12 | 2.135 | 0.5082 | 4 | 2.460 | 0.3014 | 4 | 2.890 | 0.3114 | 4 | 2.358 | 0.1228 | 4 | 2.503 | 0.5558 | 4 | |
Monocytes 103/µL | -2 | 0.728 | 0.2606 | 4 | 0.565 | 0.0493 | 4 | 0.618 | 0.1144 | 4 | 0.480 | 0.1575 | 4 | 0.533 | 0.1173 | 4 |
-1 | 0.433 | 0.1320 | 4 | 0.530 | 0.1233 | 4 | 0.570 | 0.0408 | 4 | 0.443 | 0.0655 | 4 | 0.445 | 0.1112 | 4 | |
4 | 0.688 | 0.2529 | 4 | 0.565 | 0.1363 | 4 | 0.633 | 0.1005 | 4 | 0.423 | 0.0950 | 4 | 0.473 | 0.0858 | 4 | |
8 | 0.375 | 0.0695 | 4 | 0.450 | 0.0997 | 4 | 0.538 | 0.1571 | 4 | 0.480 | 0.0535 | 4 | 0.340 | 0.0606 | 4 | |
12 | 0.328 | 0.0499 | 4 | 0.465 | 0.0854 | 4 | 0.585 | 0.1448 | 4 | 0.418 | 0.0842 | 4 | 0.478 | 0.3596 | 4 | |
Eosinophils 103/µL | -2 | 0.183 | 0.1682 | 4 | 0.203 | 0.0645 | 4 | 0.163 | 0.0250 | 4 | 0.155 | 0.0342 | 4 | 0.268 | 0.2100 | 4 |
-1 | 0.205 | 0.1300 | 4 | 0.230 | 0.0942 | 4 | 0.160 | 0.0416 | 4 | 0.153 | 0.0457 | 4 | 0.290 | 0.2417 | 4 | |
4 | 0.370 | 0.2997 | 4 | 0.245 | 0.0507 | 4 | 0.268 | 0.1130 | 4 | 0.335 | 0.1229 | 4 | 0.313 | 0.1569 | 4 | |
8 | 0.273 | 0.1903 | 4 | 0.158 | 0.0299 | 4 | 0.210 | 0.0589 | 4 | 0.165 | 0.0332 | 4 | 0.315 | 0.1455 | 4 | |
12 | 0.260 | 0.2002 | 4 | 0.250 | 0.0271 | 4 | 0.178 | 0.0275 | 4 | 0.185 | 0.0592 | 4 | 0.315 | 0.1628 | 4 | |
Basophils 103/µL | -2 | 0.048 | 0.0457 | 4 | 0.055 | 0.0507 | 4 | 0.098 | 0.0556 | 4 | 0.033 | 0.0126 | 4 | 0.043 | 0.0189 | 4 |
-1 | 0.048 | 0.0126 | 4 | 0.038 | 0.0126 | 4 | 0.060 | 0.0271 | 4 | 0.035 | 0.0208 | 4 | 0.040 | 0.0183 | 4 | |
4 | 0.028 | 0.0050 | 4 | 0.038 | 0.0236 | 4 | 0.040 | 0.0163 | 4 | 0.023 | 0.0206 | 4 | 0.030 | 0.0000 | 4 | |
8 | 0.038 | 0.0171 | 4 | 0.030 | 0.0141 | 4 | 0.053 | 0.0126 | 4 | 0.038 | 0.0050 | 4 | 0.043 | 0.0096 | 4 | |
12 | 0.028 | 0.0096 | 4 | 0.025 | 0.0173 | 4 | 0.043 | 0.0150 | 4 | 0.030 | 0.0082 | 4 | 0.033 | 0.0050 | 4 | |
Large Unstained Cells 103/µL | -2 | 0.015 | 0.0129 | 4 | 0.028 | 0.0287 | 4 | 0.043 | 0.0263 | 4 | 0.020 | 0.0082 | 4 | 0.028 | 0.0126 | 4 |
-1 | 0.028 | 0.0050 | 4 | 0.023 | 0.0096 | 4 | 0.050 | 0.0183 | 4 | 0.025 | 0.0100 | 4 | 0.035 | 0.0129 | 4 | |
4 | 0.025 | 0.0058 | 4 | 0.028 | 0.0171 | 4 | 0.043 | 0.0222 | 4 | 0.028 | 0.0189 | 4 | 0.025 | 0.0100 | 4 | |
8 | 0.018 | 0.0050 | 4 | 0.025 | 0.0129 | 4 | 0.040 a | 0.0115 | 4 | 0.030 | 0.0115 | 4 | 0.030 | 0.0082 | 4 | |
12 | 0.018 | 0.0050 | 4 | 0.025 | 0.0100 | 4 | 0.040 a | 0.0082 | 4 | 0.030 | 0.0082 | 4 | 0.033 | 0.0250 | 4 | |
APTT sec | -2 | 10.55 | 0.493 | 4 | 11.20 | 0.927 | 4 | 10.93 | 0.330 | 4 | 10.63 | 0.330 | 4 | 11 .93 a | 1 .072 | 4 |
-1 | 10.80 | 0.392 | 4 | 11.18 | 0.846 | 4 | 11 .15 | 0.342 | 4 | 10.88 | 0.538 | 4 | 11 .95 | 1 .008 | 4 | |
4 | 11.20 | 0.744 | 4 | 11.60 | 1 .030 | 4 | 11 .13 | 0.704 | 4 | 11 .15 | 0.473 | 4 | 11 .85 | 0.597 | 4 | |
8 | 10.58 | 0.427 | 4 | 11.55 | 1 .429 | 4 | 10.88 | 0.525 | 4 | 10.73 | 0.450 | 4 | 11 .40 | 0.744 | 4 | |
12 | 10.30 | 0.271 | 4 | 11.03 | 0.830 | 4 | 10.95 | 0.370 | 4 | 10.73 | 0.427 | 4 | 11 .15 | 0.759 | 4 | |
Prothrombin Time sec | -2 | 6.98 | 0.222 | 4 | 6.83 | 0.275 | 4 | 7.03 | 0.435 | 4 | 6.80 | 0.283 | 4 | 6.93 | 0.250 | 4 |
-1 | 6.90 | 0.245 | 4 | 6.98 | 0.222 | 4 | 7.10 | 0.374 | 4 | 6.90 | 0.392 | 4 | 6.93 | 0.050 | 4 | |
4 | 6.93 | 0.222 | 4 | 7.00 | 0.258 | 4 | 7.08 | 0.574 | 4 | 6.98 | 0.263 | 4 | 7.15 | 0.173 | 4 | |
8 | 6.90 | 0.216 | 4 | 7.00 | 0.216 | 4 | 7.15 | 0.500 | 4 | 6.93 | 0.126 | 4 | 7.13 | 0.320 | 4 | |
12 | 6.95 | 0.208 | 4 | 7.10 | 0.216 | 4 | 7.13 | 0.450 | 4 | 7.10 | 0.163 | 4 | 7.00 | 0.082 | 4 | |
Females |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Leukocytes 103/µL | -2 | 9.18 | 1 .090 | 4 | 9.60 | 2.578 | 4 | 11 .38 | 1 .658 | 4 | 11 .15 | 2.706 | 4 | 9.75 | 2.266 | 4 |
-1 | 8.55 | 1 .950 | 4 | 9.95 | 2.390 | 4 | 10.70 | 1 .364 | 4 | 10.10 | 2.317 | 4 | 9.18 | 1 .318 | 4 | |
4 | 9.70 | 2.258 | 4 | 8.68 | 2.425 | 4 | 10.15 | 1 .245 | 4 | 9.78 | 1 .445 | 4 | 8.98 | 1 .028 | 4 | |
8 | 8.13 | 2.710 | 4 | 9.23 | 2.767 | 4 | 9.28 | 0.929 | 4 | 9.45 | 1 .008 | 4 | 8.85 | 1 .555 | 4 | |
12 | 8.35 | 1 .308 | 4 | 9.35 | 2.504 | 4 | 10.85 | 1 .372 | 4 | 9.83 | 2.053 | 4 | 8.30 | 1 .438 | 4 | |
Erythro- cytes 10 6 / µL | -2 | 7.300 | 0.3766 | 4 | 7.533 | 0.7338 | 4 | 7.793 | 0.7216 | 4 | 7.353 | 0.4279 | 4 | 6.833 | 0.7894 | 4 |
-1 | 7.328 | 0.2640 | 4 | 7.470 | 0.6619 | 4 | 7.213 | 0.3040 | 4 | 7.338 | 0.5226 | 4 | 6.593 | 0.4583 | 4 | |
4 | 6.560 | 0.2121 | 4 | 6.608 | 0.4056 | 4 | 6.453 | 0.1889 | 4 | 6.548 | 0.4167 | 4 | 6.083 | 0.8693 | 4 | |
8 | 6.435 | 0.1443 | 4 | 6.600 | 0.2371 | 4 | 6.685 | 0.2841 | 4 | 6.518 | 0.3692 | 4 | 5.850 | 0.6270 | 4 | |
12 | 6.188 | 0.3544 | 4 | 6.605 | 0.2704 | 4 | 6.448 | 0.3102 | 4 | 6.233 | 0.5823 | 4 | 5.780 | 0.4588 | 4 | |
Haemoglobin g/dL | -2 | 16.65 | 0.785 | 4 | 17.45 | 1 .382 | 4 | 17.18 | 1 .135 | 4 | 16.53 | 0.785 | 4 | 15.85 | 1 .399 | 4 |
-1 | 16.80 | 0.374 | 4 | 17.28 | 1 .590 | 4 | 16.23 | 0.709 | 4 | 16.63 | 1 .429 | 4 | 15.40 | 0.779 | 4 | |
4 | 14.83 | 0.340 | 4 | 14.95 | 0.443 | 4 | 14.48 | 0.386 | 4 | 14.73 | 1 .187 | 4 | 13.95 | 1 .471 | 4 | |
8 | 14.75 | 0.370 | 4 | 15.03 | 0.967 | 4 | 14.95 | 0.238 | 4 | 14.83 | 0.665 | 4 | 13.70 | 1 .030 | 4 | |
12 | 14.10 | 0.688 | 4 | 15.10 | 0.294 | 4 | 14.28 | 0.519 | 4 | 14.08 | 1 .087 | 4 | 13.25 | 0.465 | 4 | |
Haematocrit % | -2 | 45.30 | 2.709 | 4 | 46.98 | 3.568 | 4 | 47.95 | 3.699 | 4 | 44.83 | 2.055 | 4 | 43.70 | 3.387 | 4 |
-1 | 46.33 | 1 .263 | 4 | 47.35 | 4.044 | 4 | 44.88 | 1.773 | 4 | 45.75 | 3.652 | 4 | 43.33 | 1.706 | 4 | |
4 | 41.78 | 0.991 | 4 | 42.40 | 1 .627 | 4 | 41 .03 | 1 .179 | 4 | 41 .70 | 3.263 | 4 | 39.63 | 4.332 | 4 | |
8 | 40.55 | 1.559 | 4 | 41.68 | 2.895 | 4 | 41 .60 | 0.432 | 4 | 41 .20 | 1 .813 | 4 | 37.83 | 3.393 | 4 | |
12 | 39.75 | 2.585 | 4 | 42.58 | 0.727 | 4 | 40.75 | 1 .567 | 4 | 39.83 | 2.816 | 4 | 38.03 | 1 .660 | 4 | |
MCV fl | -2 | 62.00 | 0.726 | 4 | 62.43 | 1 .580 | 4 | 61 .63 | 2.364 | 4 | 61 .05 | 2.133 | 4 | 64.13 | 2.431 | 4 |
-1 | 63.23 | 0.624 | 4 | 63.43 | 1 .806 | 4 | 62.28 | 2.435 | 4 | 62.30 | 2.146 | 4 | 65.75 | 2.363 | 4 | |
4 | 63.75 | 0.995 | 4 | 64.23 | 1 .812 | 4 | 63.63 | 2.941 | 4 | 63.63 | 2.540 | 4 | 65.35 | 2.217 | 4 | |
8 | 63.00 | 1 .227 | 4 | 63.08 | 2.076 | 4 | 62.30 | 2.471 | 4 | 63.28 | 2.500 | 4 | 64.78 | 2.105 | 4 | |
12 | 64.25 | 0.755 | 4 | 64.53 | 2.193 | 4 | 63.25 | 2.082 | 4 | 64.08 | 3.038 | 4 | 65.93 | 2.687 | 4 | |
MCH pg | -2 | 22.83 | 0.096 | 4 | 23.20 | 0.744 | 4 | 22.10 | 1 .257 | 4 | 22.50 | 0.963 | 4 | 23.28 | 0.780 | 4 |
-1 | 22.95 | 0.370 | 4 | 23.10 | 0.632 | 4 | 22.50 | 0.913 | 4 | 22.68 | 0.793 | 4 | 23.40 | 0.983 | 4 | |
4 | 22.60 | 0.337 | 4 | 22.68 | 0.718 | 4 | 22.45 | 1 .002 | 4 | 22.45 | 0.777 | 4 | 23.03 | 1 .005 | 4 | |
8 | 22.90 | 0.294 | 4 | 22.78 | 0.602 | 4 | 22.40 | 0.942 | 4 | 22.78 | 0.950 | 4 | 23.48 | 0.981 | 4 | |
12 | 22.80 | 0.497 | 4 | 22.90 | 1 .023 | 4 | 22.20 | 0.821 | 4 | 22.60 | 0.906 | 4 | 23.00 | 1 .061 | 4 | |
MCHC g/dl | -2 | 36.83 | 0.556 | 4 | 37.18 | 0.519 | 4 | 35.93 | 0.866 | 4 | 36.88 | 0.580 | 4 | 36.28 | 0.624 | 4 |
-1 | 36.25 | 0.311 | 4 | 36.48 | 0.330 | 4 | 36.13 | 0.435 | 4 | 36.38 | 0.320 | 4 | 35.63 | 0.826 | 4 | |
4 | 35.48 | 0.096 | 4 | 35.28 | 0.287 | 4 | 35.28 | 0.096 | 4 | 35.25 | 0.265 | 4 | 35.25 | 0.557 | 4 | |
8 | 36.38 | 0.854 | 4 | 36.15 | 0.436 | 4 | 35.95 | 0.238 | 4 | 36.00 | 0.316 | 4 | 36.28 | 0.556 | 4 | |
12 | 35.48 | 0.699 | 4 | 35.48 | 0.602 | 4 | 35.10 | 0.258 | 4 | 35.25 | 0.370 | 4 | 34.90 | 0.469 | 4 | |
Platelets 103/µL | -2 | 283.3 | 23.89 | 4 | 398.0 | 42.85 | 4 | 350.0 | 43.89 | 4 | 378.3 | 110.68 | 4 | 292.5 | 43.15 | 4 |
-1 | 267.0 | 45.06 | 4 | 351.8 | 41 .45 | 4 | 325.5 | 41 .73 | 4 | 351 .3 | 74.51 | 4 | 286.5 | 92.27 | 4 | |
4 | 313.8 | 35.70 | 4 | 287.0 | 61 .64 | 4 | 301 .8 | 23.16 | 4 | 319.0 | 67.59 | 4 | 243.5 | 47.49 | 4 | |
8 | 326.3 | 21 .23 | 4 | 324.0 | 46.22 | 4 | 322.3 | 54.38 | 4 | 346.5 | 65.54 | 4 | 283.5 | 49.92 | 4 | |
12 | 310.0 | 28.67 | 4 | 352.0 | 48.67 | 4 | 363.8 | 47.35 | 4 | 353.5 | 63.66 | 4 | 290.8 | 60.19 | 4 | |
RDW % | -2 | 13.35 | 0.208 | 4 | 13.35 | 0.465 | 4 | 13.15 | 0.451 | 4 | 13.15 | 0.592 | 4 | 12.90 | 0.245 | 4 |
-1 | 12.95 | 0.507 | 4 | 12.80 | 0.516 | 4 | 12.65 | 0.058 | 4 | 12.68 | 0.591 | 4 | 12.55 | 0.252 | 4 | |
4 | 13.00 | 0.392 | 4 | 12.90 | 0.374 | 4 | 12.48 | 0.299 | 4 | 13.13 | 0.427 | 4 | 12.60 | 0.408 | 4 | |
8 | 12.40 | 0.337 | 4 | 12.88 | 0.556 | 4 | 12.10 | 0.115 | 4 | 12.93 | 0.330 | 4 | 12.80 | 0.283 | 4 | |
12 | 12.78 | 0.403 | 4 | 12.93 | 0.096 | 4 | 12.33 | 0.263 | 4 | 12.80 | 0.408 | 4 | 12.73 | 0.330 | 4 | |
Absolute Reticu- locytes 103/µL | -2 | 25.28 | 11.598 | 4 | 31.58 | 12.309 | 4 | 42.23 | 21.783 | 4 | 37.45 | 25.376 | 4 | 23.10 | 7.008 | 4 |
-1 | 26.58 | 10.465 | 4 | 27.13 | 6.761 | 4 | 30.05 | 13.179 | 4 | 31 .65 | 15.608 | 4 | 19.93 | 5.954 | 4 | |
4 | 31.23 | 6.028 | 4 | 31.43 | 8.472 | 4 | 32.25 | 7.341 | 4 | 33.48 | 16.742 | 4 | 30.90 | 18.189 | 4 | |
8 | 23.73 | 10.950 | 4 | 37.75 | 14.627 | 4 | 37.13 | 10.067 | 4 | 38.95 | 18.545 | 4 | 36.95 | 8.051 | 4 | |
12 | 31.28 | 13.732 | 4 | 43.30 | 10.430 | 4 | 36.83 | 6.874 | 4 | 37.05 | 4.619 | 4 | 45.75 | 6.560 | 4 | |
Percent Reticu- locytes % | -2 | 0.33 | 0.150 | 4 | 0.43 | 0.171 | 4 | 0.55 | 0.238 | 4 | 0.50 | 0.356 | 4 | 0.33 | 0.096 | 4 |
-1 | 0.35 | 0.129 | 4 | 0.38 | 0.096 | 4 | 0.43 | 0.189 | 4 | 0.45 | 0.265 | 4 | 0.30 | 0.082 | 4 | |
4 | 0.50 | 0.082 | 4 | 0.48 | 0.096 | 4 | 0.48 | 0.150 | 4 | 0.53 | 0.222 | 4 | 0.53 | 0.250 | 4 | |
8 | 0.35 | 0.173 | 4 | 0.58 | 0.206 | 4 | 0.55 | 0.129 | 4 | 0.63 | 0.287 | 4 | 0.65 | 0.100 | 4 | |
12 | 0.50 | 0.216 | 4 | 0.65 | 0.173 | 4 | 0.58 | 0.096 | 4 | 0.63 | 0.126 | 4 | 0.78 | 0.126 | 4 | |
Neutrophils 103/µL | -2 | 6.170 | 0.8753 | 4 | 6.310 | 1.7116 | 4 | 7.863 | 1.6274 | 4 | 7.575 | 2.3189 | 4 | 6.863 | 2.0024 | 4 |
-1 | 5.553 | 1.4500 | 4 | 6.598 | 1 5137 | 4 | 7.305 | 1.5155 | 4 | 6.448 | 1.9301 | 4 | 6.188 | 0.7390 | 4 | |
4 | 6.293 | 2.0674 | 4 | 5.368 | 1.5886 | 4 | 6.713 | 1.5148 | 4 | 5.793 | 1.2565 | 4 | 5.593 | 1.2291 | 4 | |
8 | 5.070 | 1.9533 | 4 | 5.905 | 1.7607 | 4 | 5.968 | 1.1280 | 4 | 5.878 | 0.7881 | 4 | 5.398 | 0.8883 | 4 | |
12 | 5.185 | 0.9173 | 4 | 6.088 | 1.9774 | 4 | 7.673 | 1.2746 | 4 | 6.235 | 1.5821 | 4 | 5.180 | 0.7880 | 4 | |
Lymphocytes 103/µL | -2 | 2.333 | 0.3524 | 4 | 2.510 | 0.7276 | 4 | 2.608 | 0.6002 | 4 | 2.655 | 0.3940 | 4 | 2.200 | 0.4347 | 4 |
-1 | 2.343 | 0.3313 | 4 | 2.508 | 0.6356 | 4 | 2.553 | 0.4084 | 4 | 2.818 | 0.6053 | 4 | 2.138 | 1.0582 | 4 | |
4 | 2.728 | 0.3562 | 4 | 2.620 | 0.6750 | 4 | 2.640 | 0.3945 | 4 | 3.105 | 0.3135 | 4 | 2.608 | 0.7066 | 4 | |
8 | 2.545 | 0.6424 | 4 | 2.573 | 0.7406 | 4 | 2.555 | 0.3899 | 4 | 2.905 | 0.3190 | 4 | 2.723 | 0.9172 | 4 | |
12 | 2.660 | 0.4856 | 4 | 2.485 | 0.4241 | 4 | 2.413 | 0.1159 | 4 | 2.850 | 0.2241 | 4 | 2.418 | 0.7083 | 4 | |
Monocytes 103/µL | -2 | 0.470 | 0.0542 | 4 | 0.483 | 0.2053 | 4 | 0.550 | 0.1904 | 4 | 0.605 | 0.0843 | 4 | 0.503 | 0.0714 | 4 |
-1 | 0.443 | 0.2084 | 4 | 0.533 | 0.2825 | 4 | 0.535 | 0.1586 | 4 | 0.538 | 0.1931 | 4 | 0.665 | 0.3003 | 4 | |
4 | 0.430 | 0.0938 | 4 | 0.405 | 0.1493 | 4 | 0.463 | 0.0960 | 4 | 0.460 | 0.1512 | 4 | 0.438 | 0.0922 | 4 | |
8 | 0.313 | 0.1115 | 4 | 0.420 | 0.2503 | 4 | 0.353 | 0.0978 | 4 | 0.378 | 0.0718 | 4 | 0.305 | 0.2042 | 4 | |
12 | 0.288 | 0.0850 | 4 | 0.430 | 0.1208 | 4 | 0.428 | 0.0714 | 4 | 0.353 | 0.0911 | 4 | 0.345 | 0.0443 | 4 | |
Eosinophils 103/µL | -2 | 0.158 | 0.0250 | 4 | 0.210 | 0.1219 | 4 | 0.243 | 0.1603 | 4 | 0.215 | 0.0988 | 4 | 0.150 | 0.0365 | 4 |
-1 | 0.113 | 0.0386 | 4 | 0.230 | 0.1122 | 4 | 0.213 | 0.0427 | 4 | 0.203 | 0.0911 | 4 | 0.110 | 0.0845 | 4 | |
4 | 0.210 | 0.0726 | 4 | 0.220 | 0.0931 | 4 | 0.268 | 0.0695 | 4 | 0.308 | 0.2265 | 4 | 0.300 | 0.2753 | 4 | |
8 | 0.128 | 0.0359 | 4 | 0.238 | 0.1429 | 4 | 0.300 | 0.1481 | 4 | 0.180 | 0.0876 | 4 | 0.408 | 0.5168 | 4 | |
12 | 0.170 | 0.0294 | 4 | 0.263 | 0.1662 | 4 | 0.263 | 0.0789 | 4 | 0.305 | 0.2575 | 4 | 0.305 | 0.2509 | 4 | |
Basophils 103/µL | -2 | 0.040 | 0.0163 | 4 | 0.043 | 0.0096 | 4 | 0.065 | 0.0370 | 4 | 0.068 | 0.0299 | 4 | 0.043 | 0.0287 | 4 |
-1 | 0.053 | 0.0150 | 4 | 0.050 | 0.0082 | 4 | 0.058 | 0.0171 | 4 | 0.065 | 0.0238 | 4 | 0.030 | 0.0294 | 4 | |
4 | 0.035 | 0.0058 | 4 | 0.030 | 0.0183 | 4 | 0.040 | 0.0216 | 4 | 0.055 | 0.0238 | 4 | 0.013 | 0.0150 | 4 | |
8 | 0.033 | 0.0150 | 4 | 0.050 | 0.0141 | 4 | 0.043 | 0.0171 | 4 | 0.050 | 0.0115 | 4 | 0.018 | 0.0171 | 4 | |
12 | 0.030 | 0.0141 | 4 | 0.045 | 0.0058 | 4 | 0.043 | 0.0189 | 4 | 0.040 | 0.0141 | 4 | 0.018 | 0.0171 | 4 | |
Large Unstained Cells 103/µL | -2 | 0.015 | 0.0058 | 4 | 0.020 | 0.0141 | 4 | 0.023 | 0.0126 | 4 | 0.038 | 0.0250 | 4 | 0.023 | 0.0189 | 4 |
-1 | 0.043 | 0.0263 | 4 | 0.033 | 0.0126 | 4 | 0.035 | 0.0129 | 4 | 0.043 | 0.0171 | 4 | 0.028 | 0.0359 | 4 | |
4 | 0.023 | 0.0050 | 4 | 0.033 | 0.0250 | 4 | 0.050 | 0.0283 | 4 | 0.0453 | 0.0100 | 4 | 0.013 | 0.0150 | 4 | |
8 | 0.025 | 0.0129 | 4 | 0.030 | 0.0216 | 4 | 0.030 | 0.0082 | 4 | 0.045 | 0.0129 | 4 | 0.013 | 0.0126 | 4 | |
12 | 0.033 | 0.0189 | 4 | 0.028 | 0.0050 | 4 | 0.033 | 0.0096 | 4 | 0.035 | 0.0129 | 4 | 0.015 | 0.0129 | 4 | |
APTT sec | -2 | 10.58 | 0.377 | 4 | 10.90 | 0.735 | 4 | 10.93 | 0.660 | 4 | 11 .33 | 0.900 | 4 | 10.73 | 0.532 | 4 |
-1 | 10.80 | 0.416 | 4 | 10.90 | 0.424 | 4 | 11.18 | 0.785 | 4 | 11 .45 | 0.957 | 4 | 10.95 | 0.719 | 4 | |
4 | 11.28 | 0.585 | 4 | 11.20 | 0.245 | 4 | 11.38 | 0.499 | 4 | 11 .53 | 0.513 | 3 | 11 .10 | 0.920 | 4 | |
8 | 11.13 | 0.340 | 4 | 11.13 | 0.250 | 4 | 11 .10 | 0.825 | 4 | 11 .18 | 0.727 | 4 | 11 .00 | 0.800 | 4 | |
12 | 10.65 | 0.465 | 4 | 11.10 | 0.583 | 4 | 10.80 | 0.837 | 4 | 10.93 | 0.780 | 4 | 10.98 | 0.723 | 4 | |
Prothrombin Time sec | -2 | 6.65 | 0.058 | 4 | 6.68 | 0.350 | 4 | 6.90 | 0.316 | 4 | 6.70 | 0.183 | 4 | 6.68 | 0.263 | 4 |
-1 | 6.53 | 0.171 | 4 | 6.70 | 0.271 | 4 | 7.00 | 0.365 | 4 | 6.78 | 0.126 | 4 | 6.63 | 0.299 | 4 | |
4 | 6.88 | 0.171 | 4 | 6.73 | 0.287 | 4 | 7.15 | 0.238 | 4 | 7.00 | 0.100 | 3 | 6.80 | 0.365 | 4 | |
8 | 6.88 | 0.171 | 4 | 6.85 | 0.129 | 4 | 6.63 | 0.419 | 4 | 6.78 | 0.171 | 4 | 6.78 | 0.287 | 4 | |
12 | 6.85 | 0.129 | 4 | 6.88 | 0.250 | 4 | 7.18 | 0.377 | 4 | 7.13 | 0.206 | 4 | 6.90 | 0.346 | 4 | |
N - Number of measures used to calculate mean
SD - Standard Deviation
a Significantly different from control; (p<0.05)
MCV - Mean Corpuscular Volume
MCH - Mean Corpuscular Hemoglobin
MCHC - Mean Corpuscular Hemoglobin Concentration
RDW - Red Blood Cell Distribution Width
APTT - Activated Partial Thromboplastin Time
Table 14: Summary of Urinalyses values
|
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
| Week | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Males |
| |||||||||||||||
Volume ml | -2 | 231 .3 | 222.24 | 4 | 606.3 | 461 .42 | 4 | 188.8 | 113.02 | 4 | 455.0 | 430.12 | 4 | 348.8 | 431 .34 | 4 |
-1 | 195.0 | 106.38 | 4 | 421 .3 | 501 .19 | 4 | 321 .3 | 139.01 | 4 | 228.8 | 99.61 | 4 | 402.5 | 192.03 | 4 | |
4 | 790.0 | 527.92 | 4 | 925.0 | 425.13 | 4 | 506.3 | 129.64 | 4 | 451 .3 | 241 .98 | 4 | 388.8 | 132.00 | 4 | |
8 | 493.8 | 129.64 | 4 | 470.0 | 162.63 | 4 | 296.3 | 104.27 | 4 | 242.5 | 132.82 | 4 | 340.0 | 252.09 | 4 | |
12 | 421 .3 | 125.39 | 4 | 278.8 | 140.56 | 4 | 257.5 | 244.83 | 4 | 91 .3 | 72.04 | 4 | 293.8 | 283.27 | 4 | |
pH | -2 | 8.13 | 0.479 | 4 | 7.63 | 0.629 | 4 | 7.63 | 0.854 | 4 | 7.63 | 0.629 | 4 | 7.63 | 1 .181 | 4 |
-1 | 7.88 | 0.479 | 4 | 7.25 | 0.500 | 4 | 7.50 | 0.408 | 4 | 7.75 | 0.645 | 4 | 7.63 | 0.250 | 4 | |
4 | 7.13 | 0.250 | 4 | 7.00 | 1 .080 | 4 | 7.88 | 0.750 | 4 | 7.50 | 0.707 | 4 | 6.50 | 0.408 | 4 | |
8 | 6.88 | 0.250 | 4 | 7.13 | 0.629 | 4 | 7.38 | 0.854 | 4 | 6.63 | 0.479 | 4 | 6.50 | 0.408 | 4 | |
12 | 8.00 | 0.707 | 4 | 6.88 a | 0.250 | 4 | 6.975 | 0.3029 | 4 | 6.333 | 0.2474 | 4 | 6.75 a | 0.289 | 4 | |
Osmolality mosm/kg | -2 | 1227.0 | 577.70 | 4 | 544.5 | 217.19 | 4 | 859.8 | 604.39 | 4 | 836.8 | 565.24 | 4 | 1164.0 | 618.35 | 4 |
-1 | 1050.8 | 410.59 | 4 | 1052.0 | 660.07 | 4 | 601 .3 | 363.55 | 4 | 776.8 | 99.88 | 4 | 723.0 | 195.44 | 4 | |
4 | 579.0 | 293.25 | 4 | 458.3 | 114.80 | 4 | 660.0 | 171 .62 | 4 | 930.3 | 427.93 | 4 | 985.8 | 278.25 | 4 | |
8 | 562.3 | 53.51 | 4 | 737.5 | 351 .68 | 4 | 953.3 | 129.83 | 4 | 947.3 | 441 .81 | 4 | 1124.0 | 631 .41 | 4 | |
12 | 755.8 | 179.63 | 4 | 1080.8 | 529.14 | 4 | 659.3 | 96.58 | 4 | 1273.3 | 289.93 | 4 | 897.8 | 235.66 | 4 | |
Females | ||||||||||||||||
Volume ml | -1 | 332.5 | 315.98 | 4 | 113.8 | 26.26 | 4 | 318.8 | 150.63 | 4 | 230.0 | 92.56 | 4 | 255.0 | 275.83 | 4 |
4 | 423.8 | 405.37 | 4 | 176.3 | 75.76 | 4 | 258.8 | 49.05 | 4 | 351 .3 | 274.09 | 4 | 278.8 | 209.26 | 4 | |
8 | 605.0 | 616.29 | 4 | 397.5 | 162.71 | 4 | 475.0 | 270.40 | 4 | 662.5 | 22.17 | 4 | 570.0 | 707.59 | 4 | |
12 | 292.5 | 130.93 | 4 | 452.5 | 187.19 | 4 | 326.3 | 150.58 | 4 | 471 .3 | 146.88 | 4 | 395.0 | 168.28 | 4 | |
-2 | 425.0 | 185.79 | 4 | 335.0 | 234.52 | 4 | 377.5 | 167.01 | 4 | 381 .3 | 232.00 | 4 | 401 .3 | 370.17 | 4 | |
pH | -1 | 7.25 | 0.289 | 4 | 7.38 | 0.250 | 4 | 7.38 | 0.250 | 4 | 7.38 | 0.250 | 4 | 7.13 | 0.479 | 4 |
4 | 7.00 | 0.000 | 4 | 7.13 | 0.250 | 4 | 7.38 | 0.250 | 4 | 7.38 | 0.250 | 4 | 7.25 | 0.289 | 4 | |
8 | 7.00 | 0.408 | 4 | 6.63 | 0.479 | 4 | 7.75 | 0.866 | 4 | 7.00 | 1 .080 | 4 | 6.88 | 0.479 | 4 | |
12 | 6.50 | 0.000 | 4 | 7.38 b | 0.750 | 4 | 7.38 b | 0.750 | 4 | 7.00 a | 0.000 | 4 | 6.38 | 0.250 | 4 | |
-2 | 7.13 | 0.946 | 4 | 6.75 | 0.645 | 4 | 6.88 | 0.479 | 4 | 6.88 | 0.250 | 4 | 6.63 | 0.479 | 4 | |
Osmolality mosm/kg | -1 | 1072.5 | 675.56 | 4 | 1452.8 | 341 .03 | 4 | 895.5 | 261 .98 | 4 | 1093.8 | 369.13 | 4 | 1188.5 | 650.27 | 4 |
4 | 1017.8 | 795.95 | 4 | 1129.8 | 269.89 | 4 | 1013.0 | 146.58 | 4 | 972.3 | 831 .47 | 4 | 881 .5 | 327.83 | 4 | |
8 | 713.0 | 460.66 | 4 | 932.0 | 255.89 | 4 | 1207.5 | 273.09 | 4 | 504.8 | 130.77 | 4 | 953.0 | 612.98 | 4 | |
12 | 867.5 | 297.03 | 4 | 439.8 | 341 .76 | 4 | 1054.5 | 451 .28 | 4 | 573.3 | 174.46 | 4 | 779.3 | 347.03 | 4 | |
| 677.8 | 156.19 | 4 | 1009.3 | 417.54 | 4 | 882.8 | 256.38 | 4 | 806.8 | 417.82 | 4 | 838.8 | 519.69 | 4 | |
N - Number of measures used to calculate mean
SD - Standard Deviation
a Significantly different from control; (p<0.05)
GGT - Gamma Glutamyl Transpeptidase
AST - Aspartate Aminotransferase
ALT - Alanine Aminotransferase
Table 15: Summary of Organ weight values
| Control |
|
| 250 |
|
| 1250 |
|
| 5000 |
|
| 15000 |
|
|
Males | |||||||||||||||
| Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N | Mean | SD | N |
Body weight kg | 10.52 | 1.09 | 4 | 12.00 | 1.86 | 4 | 11.03 | 1.68 | 4 | 11.57 | 1.67 | 4 | 10.98 | 1.61 | 4 |
Brain g | 83.418 | 7.705 | 4 | 75.466 | 5.039 | 4 | 70.337a | 7.750 | 4 | 83.973 | 5.636 | 4 | 75.626 | 4.722 | 4 |
Brain/Bwt % | 0.7953 | 0.0511 | 4 | 0.6424 | 0.1220 | 4 | 0.6458 | 0.0954 | 4 | 0.7364 | 0.1083 | 4 | 0.6955 | 0.0606 | 4 |
Adrenal gl g | 1.074 | 0.215 | 4 | 0.918 | 0.120 | 4 | 0.902 | 0.330 | 4 | 0.991 | 0.165 | 4 | 1.037 | 0.139 | 4 |
Adrenal gl/BWt % | 0.0104 | 0.0030 | 4 | 0.0078 | 0.0015 | 4 | 0.0081 | 0.0030 | 4 | 0.0087 | 0.0021 | 4 | 0.0096 | 0.0020 | 4 |
Adrenal gl/Brwtratio | 0.0130 | 0.0030 | 4 | 0.0122 | 0.0011 | 4 | 0.0128 | 0.0045 | 4 | 0.0119 | 0.0023 | 4 | 0.00138 | 0.0021 | 4 |
Epididymides g | 3.480 | 1.074 | 4 | 3.573 | 0.147 | 4 | 3.440 | 0.567 | 4 | 3.819 | 0.774 | 4 | 3.496 | 0.752 | 4 |
Epididymides/Bwt % | 0.0335 | 0.0112 | 4 | 0.0302 | 0.0042 | 4 | 0.0320 | 0.0089 | 4 | 0.0328 | 0.0036 | 4 | 0.0322 | 0.0074 | 4 |
Epididymides/BrWt ratio | 0.0420 | 0.0130 | 4 | 0.0475 | 0.0042 | 4 | 0.0494 | 0.0104 | 4 | 0.0456 | 0.0101 | 4 | 0.0462 | 0.0091 | 4 |
Heart g | 87.651 | 10.708 | 4 | 94.786 | 3.369 | 4 | 90.907 | 14.216 | 4 | 100.054 | 8.715 | 4 | 0.8166 | 0.0337 | 4 |
Heart/Bwt % | 0.8324 | 0.0280 | 4 | 0.8013 | 0.1029 | 4 | 0.8244 | 0.0343 | 4 | 0.8712 | 0.0637 | 4 | 1.1812 | 0.1173 | 4 |
Heart/Brwt ratio | 1.0505 | 0.0860 | 4 | 1.2624 | 0.1274 | 4 | 1.2993 | 0.2104 | 4 | 1.1930 | 0.0987 | 4 | 0.4262 | 0.1273 | 4 |
Kidneys g | 51.004 | 3.583 | 4 | 54.271 | 8.206 | 4 | 51.923 | 3.014 | 4 | 53.214 | 8.317 | 4 | 275.750 | 53.830 | 4 |
Kidneys/Bwt % | 0.4876 | 0.0450 | 4 | 0.4543 | 0.0537 | 4 | 0.4758 | 0.0448 | 4 | 0.4628 | 0.0662 | 4 | 2.4989 | 0.1909 | 4 |
Kidneys/BrWt ratio | 0.6133 | 0.0416 | 4 | 0.7269 | 0.1563 | 4 | 0.7441 | 0.0861 | 4 | 0.6349 | 0.1017 | 4 | 65.38 | 1.797 | 4 |
Liver g | 322.320 | 40.650 | 4 | 310.338 | 18.643 | 4 | 354.775 | 67.353 | 4 | 320.822 | 60.674 | 4 | 23.35 | 0.661 | 4 |
Liver/Bwt % | 3.0984 | 0.5437 | 4 | 2.6130 | 0.2452 | 4 | 3.2179 | 0.3770 | 4 | 2.7649 | 0.2127 | 4 | 23.20 | 0.374 | 4 |
Liver/BrWt ratio | 3.9003 | 0.6675 | 4 | 4.1352 | 0.4934 | 4 | 5.1146 | 1.3403 | 4 | 3.8084 | 0.5588 | 4 | 23.20 | 0.688 | 4 |
Spleen g | 54.229 | 19.675 | 4 | 48.738 | 20.943 | 4 | 51.175 | 16.531 | 3 | 53.110 | 6.299 | 4 | 59.479 | 28.919 | 4 |
Spleen/BWt % | 0.5261 | 0.2221 | 4 | 0.4210 | 0.2001 | 4 | 0.5103 | 0.2155 | 3 | 0.4686 | 0.1007 | 4 | 0.5299 | 0.2214 | 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Spleen/Brwt ratio | 0.6500 | 0.2443 | 4 | 0.6495 | 0.2991 | 4 | 0.7601 | 0.2388 | 3 | 0.6317 | 0.0542 | 4 | 0.7741 | 0.3438 | 4 |
Testes g | 15.568 | 3.225 | 4 | 15.258 | 2.175 | 4 | 14.139 | 3.562 | 4 | 14.739 | 3.209 | 4 | 13.441 | 1.998 | 4 |
Testes/BWt % | 0.1474 | 0.0214 | 4 | 0.1306 | 0.0315 | 4 | 0.1272 | 0.0166 | 4 | 0.1268 | 0.0137 | 4 | 0.1241 | 0.0221 | 4 |
Testes/Brwt ratio | 0.1853 | 0.0232 | 4 | 0.2022 | 0.0265 | 4 | 0.2013 | 0.0444 | 4 | 0.1753 | 0.0351 | 4 | 0.1777 | 0.0234 | 4 |
Thymus gl g | 8.415 | 1.892 | 4 | 7.800 | 1.462 | 4 | 6.979 | 3.143 | 4 | 5.782 | 3.294 | 4 | 5.831 | 2.219 | 4 |
Thymus gl/BWt % | 0.0806 | 0.0187 | 4 | 0.0665 | 0.0172 | 4 | 0.0620 | 0.0227 | 4 | 0.0518 | 0.0307 | 4 | 0.0527 | 0.0167 | 4 |
Thymus gl/Brwt ratio | 0.1021 | 0.0273 | 4 | 0.1039 | 0.0225 | 4 | 0.0992 | 0.0404 | 4 | 0.0685 | 0.0396 | 4 | 0.0766 | 0.0268 | 4 |
Thyroid/parathyroid gl g | 0.972 | 0.247 |
| 1.187 | 0.198 |
| 0.887 | 0.135 |
| 0.893 | 0.100 | 4 | 0.969 | 0.281 | 4 |
Thyroid/parathyroid gl/BWt % | 0.0093 | 0.0027 | 4 | 0.0101 | 0.0026 | 4 | 0.0082 | 0.0015 | 4 | 0.0078 | 0.0007 | 4 | 0.0088 | 0.0018 | 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Thyroid/parathyroid gl/BrWt ratio | 0.0117 | 0.0032 | 4 | 0.0158 | 0.0032 | 4 | 0.0126 | 0.0013 | 4 | 0.0107 | 0.0012 | 4 | 0.0128 | 0.0033 | 4 |
Females | |||||||||||||||
Bodyweight kg | 9.40 | 0.62 | 4 | 9.44 | 0.64 | 4 | 9.59 | 0.97 | 4 | 9.11 | 0.55 | 4 | 9.14 | 1.39 | 4 |
Brain g | 73.817 | 4.562 | 4 | 73.858 | 4.778 | 4 | 76.258 | 5.054 | 4 | 73.678 | 3.635 | 4 | 71.931 | 8.505 |
|
Brain/Bwt % | 0.7899 | 0.0915 | 4 | 0.7833 | 0.0311 | 4 | 0.7996 | 0.0722 | 4 | 0.8101 | 0.0347 | 4 | 0.8048 | 0.1933 | 4 |
Adrenal gl g | 0.948 | 0.121 | 4 | 1.005 | 0.074 | 4 | 1.035 | 0.209 | 4 | 0.917 | 0.072 | 4 | 1.010 | 0.126 | 4 |
Adrenal gl/BWt % | 0.0101 | 0.0014 | 4 | 0.0107 | 0.0013 | 4 | 0.0110 | 0.0030 | 4 | 0.0101 | 0.0011 | 4 | 0.0112 | 0.0016 | 4 |
Adrenal gl/Brwt ratio | 0.0128 | 0.0012 | 4 | 0.0137 | 0.0019 | 4 | 0.0137 | 0.0032 | 4 | 0.0125 | 0.0009 | 4 | 0.0143 | 0.0032 | 4 |
Heart g | 78.407 | 4.081 | 4 | 76.959 | 1.427 | 4 | 89.816a | 4.103 | 4 | 78.970 | 2.844 | 4 |
|
|
|
Heart/Bwt % | 0.8382 | 0.0821 | 4 | 0.8181 | 0.0492 | 4 | 0.9440 | 0.1036 | 4 | 0.8691 | 0.0486 | 4 | 0.7948 | 0.1118 | 4 |
Heart/Brwt ratio | 1.0630 | 0.0282 | 4 | 1.0455 | 0.0765 | 4 | 1.1816 | 0.0961 | 4 | 1.0731 | 0.0464 | 4 | 1.0202 | 0.2304 | 4 |
Kidneys g | 42.677 | 4.304 | 4 | 40.401 | 4.316 | 4 | 42.717 | 5.288 | 4 | 41.053 | 2.974 | 4 | 42.160 | 2.027 | 4 |
Kidneys/Bwt % | 0.4548 | 0.0418 | 4 | 0.4284 | 0.0383 | 4 | 0.4473 | 0.0556 | 4 | 0.4534 | 0.0574 | 4 | 0.4667 | 0.0505 | 4 |
Kidneys/BrWt ratio | 0.5786 | 0.0522 | 4 | 0.5486 | 0.0667 | 4 | 0.5639 | 0.0989 | 4 | 0.5596 | 0.0662 | 4 | 0.5928 | 0.0784 | 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Liver g | 273.870 | 22.676 | 4 | 284.900 | 16.962 | 4 | 265.465 | 28.756 | 4 | 262.987 | 14.137 | 4 | 256.213 | 30.843 | 4 |
Liver/Bwt % | 2.9154 | 0.1567 | 4 | 3.0257 | 0.2068 | 4 | 2.7699 | 0.1089 | 4 | 2.9003 | 0.2876 | 4 | 2.8187 | 0.2515 | 4 |
Liver/BrWt ratio | 3.7212 | 0.3820 | 4 | 3.8701 | 0.3556 | 4 | 3.4786 | 0.2375 | 4 | 3.5767 | 0.2672 | 4 | 3.6169 | 0.7007 | 4 |
Ovaries g | 1.253 | 0.341 | 4 | 1.150 | 0.526 | 4 | 1.984 | 1.423 | 4 | 1.706 | 0.902 | 4 | 0.733 | 0.197 | 4 |
Ovaries/Bwt % | 0.0132 | 0.0029 | 4 | 0.0124 | 0.0062 | 4 | 0.0214 | 0.0159 | 4 | 0.0188 | 0.0101 | 4 | 0.0081 | 0.0023 | 4 |
Ovaries/BrWt ratio | 0.0172 | 0.0059 | 4 | 0.0159 | 0.0085 | 4 | 0.0262 | 0.0191 | 4 | 0.0232 | 0.0124 | 4 | 0.0103 | 0.0030 | 4 |
Spleen g | 67.737 | 13.458 | 4 | 49.548 | 10.365 | 4 | 62.949 | 5.337 | 4 | 68.543 | 19.443 | 4 | 63.614 | 17.719 | 4 |
Spleen/BWt % | 0.7165 | 0.1085 | 4 | 0.5223 | 0.0774 | 4 | 0.6656 | 0.1178 | 4 | 0.7636 | 0.2589 | 4 | 0.6956 | 0.1758 | 4 |
Spleen/Brwt ratio | 0.9230 | 0.2054 | 4 | 0.6699 | 0.1213 | 4 | 0.8294 | 0.0995 | 4 | 0.9368 | 0.2880 | 4 | 0.9120 | 0.3298 | 4 |
Thymus gl g | 8.010 | 1.809 | 4 | 7.685 | 0.439 | 4 | 5.817 | 0.399 | 4 | 6.003 | 1.467 | 3 | 6.878 | 2.899 | 4 |
Thymus gl/BWt % | 0.0854 | 0.0188 | 4 | 0.0816 | 0.0046 | 4 | 0.0610 | 0.0058 | 4 | 0.0679 | 0.0171 | 3 | 0.0731 | 0.0192 | 4 |
Thymus gl/Brwt ratio | 0.1088 | 0.0250 | 4 | 0.1043 | 0.0077 | 4 | 0.0767 | 0.0092 | 4 | 0.0826 | 0.0176 | 3 | 0.0971 | 0.0407 | 4 |
Thyroid/parathyroid gl g | 0.652 | 0.150 | 4 | 0.634 | 0.157 | 4 | 0.766 | 0.121 | 4 | 0.804 | 0.198 | 4 | 0.880 | 0.109 | 4 |
Thyroid/parathyroid gl/BWt % | 0.0069 | 0.0015 | 4 | 0.0067 | 0.0016 | 4 | 0.0081 | 0.0016 | 4 | 0.0088 | 0.0017 | 4 | 0.0097 | 0.0013 | 4 |
Thyroid/parathyroid gl/BrWt ratio | 0.0088 | 0.0018 | 4 | 0.0086 | 0.0023 | 4 | 0.0101 | 0.0022 | 4 | 0.0108 | 0.0021 | 4 | 0.0125 | 0.0028 | 4 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Uterus w/ cervix g | 11.034 | 5.107 | 4 | 9.091 | 9.169 | 4 | 11.233 | 10.351 | 4 | 13.566 | 9.844 | 4 | 4.310 | 0.906 | 4 |
Uterus w/ cervix/BWt % | 0.1167 | 0.0494 | 4 | 0.0992 | 0.1038 | 4 | 0.1241 | 0.1181 | 4 | 0.1500 | 0.1097 | 4 | 0.0471 | 0.0073 | 4 |
Uterus w/ cervix/Brwt ratio | 0.1532 | 0.0827 | 4 | 0.1292 | 0.1396 | 4 | 0.1475 | 0.1357 | 4 | 0.1867 | 0.1392 | 4 | 0.0610 | 0.0165 | 4 |
N - Number of measures used to calculate mean
SD - Standard Deviation
a Significantly different from control; (p<0.05)
Table 16: Summary of macroscopic observations
| Dose group (ppm) | |||||
Tissue/Observation | Severity | Control | 250 | 1250 | 5000 | 15000 |
Males |
|
|
|
|
|
|
Number of animals |
| 4 | 4 | 4 | 4 | 4 |
all tissues
|
|
|
|
|
|
|
within normal limits |
| 4 | 4 | 3 | 4 | 3 |
heart |
|
|
|
|
|
|
cyst | mild | 0 | 0 | 0 | 0 | 1 |
stomach, pylorus |
|
|
|
|
|
|
focus, foci, red | mild | 0 | 0 | 1 | 0 | 0 |
Females |
|
|
|
|
|
|
Number of animals |
| 4 | 4 | 4 | 4 | 4 |
all tissues
|
|
|
|
|
|
|
within normal limits |
| 4 | 4 | 4 | 4 | 3 |
animal/whole body |
|
|
|
|
|
|
body fat depleted | mild | 0 | 0 | 0 | 0 | 0 |
ovaries |
|
|
|
|
|
|
cyst | mild | 0 | 0 | 0 | 0 | 1 |
vulva |
|
|
|
|
|
|
enlarged | mild | 0 | 0 | 0 | 0 | 1 |
Table 17: Selected microscopic observations
|
| Dose group | ||
Tissue/Observation | Severity | Control | 1250 | 15000 |
Males |
|
|
|
|
epididymides |
| (4) | (0) | (4) |
infiltration, mononuclear cell | minimal | 1 | 0 | 0 |
within normal limits |
| 3 | 0 | 4 |
heart |
| (4) | (0) | (4) |
haematocyst, valvular | moderate | 0 | 0 | 1 |
within normal limits |
| 4 | 0 | 3 |
kidneys |
| (4) | (0) | (4) |
mineralization | minimal | 4 | 0 | 4 |
regeneration, tubular | minimal | 3 | 0 |
|
liver |
| (4) | (0) | (4) |
fibrosis | mild | 1 | 0 | 0 |
hyperplasia, bile duct | mild |
| 0 | 0 |
inflammation, subacute |
| 4 | 0 | 3 |
| minimal | 3 | 0 | 3 |
| mild | 1 | 0 | 0 |
within normal limits |
| 0 | 0 |
|
lung |
| (4) | (0) | (4) |
inflammation, chronic | minimal | 0 | 0 | 1 |
inflammation, subacute | minimal | 1 | 0 | 0 |
within normal limits |
| 3 | 0 | 3 |
pancreas |
| (4) | (0) | (4) |
atrophy, acinar | minimal | 0 | 0 | 1 |
within normal limits |
| 4 | 0 | 3 |
Females | ||||
adrenal glands |
| (4) | (0) | (4) |
ectopic tissue | mild | 1 | 0 | 0 |
within normal limits |
| 3 | 0 | 4 |
eyes |
| (4) | (0) | (4) |
fold/rosette, retinal | minimal | 0 | 0 | 1 |
within normal limits |
| 4 | 0 | 3 |
kidneys |
| (4) | (0) | (4) |
mineralization | minimal | 4 | 0 | 4 |
regeneration, tubular | minimal |
| 0 | 0 |
liver |
| (4) | (0) | (4) |
inflammation, subacute | minimal | 4 | 0 | 3 |
within normal limits |
| 0 | 0 |
|
lung |
| (4) | (0) | (4) |
inflammation, chronic | minimal | 1 | 0 | 0 |
inflammation, subacute | minimal | 0 | 0 |
|
within normal limits |
| 3 | 0 | 3 |
mammary gland |
| (4) | 0 | (4) |
area normal, no mammary tissue present |
| 0 | 0 | 1 |
within normal limits |
| 4 | 0 | 3 |
ovaries |
| (4) | (1) | (4) |
cyst, follicular | mild | 0 | 1 | 0 |
within normal limits |
| 4 | 0 | 4 |
skin |
| (4) | (0) | (4) |
inflammation, hair follicle, demodectic | minimal | 0 | 0 | 1 |
within normal limits |
| 4 | 0 | 3 |
spinal cord, cervical |
| (4) | (0) | (4) |
infiltration, lymphoid, perivascular | minimal | 0 | 0 | 1 |
within normal limits |
| 4 | 0 | 3 |
thymus gland |
| (4) | (0) | (4) |
depletion, lymphoid | mild | 1 | 0 | 1 |
within normal limits |
| 3 | 0 | 3 |
( ) - Number observed
Table 18: Selected neurobehavioral findings
|
| Study Interval (week) | ||||||||||||
Group Observation | Score | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 |
Males | ||||||||||||||
Control group | ||||||||||||||
Lacrimation | 0 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 3/4 | 3/4 | 4/4 | 3/4 | 3/4 | 4/4 | 4/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 1/4 | 1/4 | 0/4 | 1/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 1/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Limb tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
250 ppm | ||||||||||||||
Lacrimation | 0 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Limb tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
1250 ppm | ||||||||||||||
Lacrimation | 0 | 4/4 | 4/4 | 3/4 | 3/4 | 3/4 | 2/4 | 2/4 | 3/4 | 2/4 | 3/4 | 2/4 | 4/4 | 4/4 |
| 1 | 0/4 | 0/4 | 1/4 | 1/4 | 1/4 | 2/4 | 2/4 | 1/4 | 2/4 | 1/4 | 2/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Limb tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
5000 ppm | ||||||||||||||
Lacrimation | 0 | 3/4 | 3/4 | 3/4 | 4/4 | 3/4 | 2/4 | 3/4 | 3/4 | 2/4 | 4/4 | 2/4 | 3/4 | 4/4 |
| 1 | 1/4 | 1/4 | 1/4 | 0/4 | 1/4 | 2/4 | 1/4 | 1/4 | 2/4 | 0/4 | 2/4 | 1/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Limb tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
15000 ppm | ||||||||||||||
Lacrimation | 0 | 4/4 | 3/4 | 4/4 | 3/4 | 4/4 | 3/4 | 4/4 | 3/4 | 3/4 | 3/4 | 4/4 | 4/4 | 3/4 |
| 1 | 0/4 | 1/4 | 0/4 | 1/4 | 0/4 | 1/4 | 0/4 | 1/4 | 1/4 | 1/4 | 0/4 | 0/4 | 1/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Limb tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Females |
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Lacrimation | 0 | 3/4 | 3/4 | 4/4 | 4/4 | 3/4 | 4/4 | 4/4 | 3/4 | 4/4 | 4/4 | 4/4 | 3/4 | 4/4 |
| 1 | 1/4 | 1/4 | 0/4 | 0/4 | 1/4 | 0/4 | 0/4 | 1/4 | 0/4 | 0/4 | 0/4 | 1/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Limb tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
250 ppm |
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Lacrimation | 0 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 3/4 | 3/4 | 3/4 | 3/4 | 4/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 1/4 | 1/4 | 1/4 | 1/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Arousal | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 2 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 3 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 | 4/4 |
| 4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 5 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
Body tone | 0 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 | 0/4 |
| 1 | 4/4 | 4/4 | 4/4 | 4/4 | |||||||||