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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Sept 2017 - May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Version / remarks:
1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Constituent 1
Reference substance name:
Phosphoric acid, butyl ester (mono and di ester)
IUPAC Name:
Phosphoric acid, butyl ester (mono and di ester)
Test material form:
other: liquid
Details on test material:
no data

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Breeding, RCC Laboratories India Private Limited, Genome Valley, Turkapally, Shameerpet (Mandal), Ranga Reddy District, Hyderabad -500 078 India.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7-8 weeks
- Weight at study initiation: Male: 164.5 to 198.9 g, Female: 132.6 to 158.2 g
- Housing: In groups of two animals of same sex in Polycarbonate cages (Approximate internal dimensions of 365 mm x 202 mm x 180 mm height) with corncob bedding.
- Diet (e.g. ad libitum): Teklad Certified Global 14% Protein Rodent Maintenance Diet (Lot No. 2014C-082417MA) from ENVIGO was provided ad libitum.
- Water (e.g. ad libitum): Aquaguard filtered tap water was provided ad libitum.
- Acclimation period: 9 days

DETAILS OF FOOD AND WATER QUALITY:
Results of analyses for contaminants are archived at RCC Laboratories India Private

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9 to 22.8°C
- Humidity (%): 57 to 65%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 4.25. Sept. 2017 To: 1. Feb. 2018

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
The test item was administered to the test system, for the period of 90 consecutive days by oral route using oral gavage needle.
Vehicle:
corn oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Justification for use and choice of vehicle (if other than water): based on preliminary solubility testing which was performed in the test facility before the study initiation date
- Concentration in vehicle: 5 mg/mL, 20 mg/mL, 40 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Gas chromotography
Samples of the dose formulations were taken immediately after dilution of the test item with the diluent (vehicle) on treatment start date and last week of treatment for homogeneity (mean of homogeneity was given as dose concentration) analyses. On week 7, samples of all dose formulations were assayed for the applied dose in triplicates. The method was developed and validated prior to analysis. The method was either matrix assisted validation or external standard method of validation. The validation and analysis was carried out as per SANCO/3029/99 rev.4.
The test item in corn oil was assayed on three occasions
01 Stability of test item at 0th, 2nd and 4th hour in corn oil matrix for the fortified concentrations of 5 mg/mL and 40 mg/mL.
02 Initial homogeneity test on Top, mid and bottom layers of corn oil fortified with of test item Viz., 5 mg/mL (Low dose), 20 mg/mL (Intermediate dose), and 40 mg/mL (High dose)
03 Dose concentration of test item in corn oil fortified with 5 mg/mL (Low dose), 20 mg/mL (Intermediate dose), and 40 mg/mL (High dose).
04 Final homogeneity test on Top, mid and bottom layers of corn oil fortified with of test item Viz., 5 mg/mL (Low dose), 20 mg/mL (Intermediate dose), and 40 mg/mL (High dose). Calibration solution, CS5 was used as bracketing standard.
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Dose / conc.:
200 mg/kg bw/day (actual dose received)
Dose / conc.:
400 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The doses to be employed for this study were selected, based on the 28 days repeated dose toxicity dose range finding study
- Post-exposure recovery period in satellite groups: 28 days
Positive control:
n.a.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
twice daily for mortality and on the first 3 days of treatment for clinical observations
once daily for clinical observations

DETAILED CLINICAL OBSERVATIONS: Yes
Once prior to the first exposure and weekly thereafter

BODY WEIGHT: Yes
once weekly

FOOD CONSUMPTION AND COMPOUND INTAKE:
once weekly

OPHTHALMOSCOPIC EXAMINATION: Yes
Prior to the administration of the test item (in 20% of total population) and during week 13 in all animals of group 1 and 4. animals during week 17. Tropicamide was used as a mydriatic agent.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 13 (main groups), week 17 (recovery groups)
- Anaesthetic used for blood collection: Yes, isoflurane inhalation anaesthesia
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked:
erythrocyte count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular concentration, platelet count, total leukocyte count, differential leukocyte count, reticulocytes, prothrombin time, activated partial thromboplastin time

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: week 13 (main groups), week 17 (recovery groups)
- Animals fasted: Yes
- How many animals: all animals
- Parameters checked:
glucose, urea, blood urea nirtogen, creatinine, cholesterol, triglycerides. aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, bilirubin, sodium, potassium, chloride, protein total, albumin, globulin, A G ratio

URINALYSIS: Yes
- Time schedule for collection of urine: week 13 (main groups), week 17 (recovery groups)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked:
volume, specific gravitiy, colour, clarity, pH, erythrocytes, leukocytes, bilirubin, urobiliongen, ketone bodies, proteins and glucose

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations:during week 12 and 17
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Necropsy: all animals
organ weight (all animals): brain ,heart, liver, thymus, kidneys, adrenals, spleen, testes, epididymides, oavaries, uterus, prostate and seminal vescles with coagulating glands

HISTOPATHOLOGY: Yes
in control and high dose animals (main groups)
addtionally organs that revealed changes in low, mid dose (main groups) and all recovery groups
Adrenal glands, Aorta, Bone marrow (Sternum), Brain (cerebrum, cerebellum, medulla/ pons), Cecum, Cervix, Colon, Duodenum, Epididymides, Eye, Heart, Ileum with Peyer's patches, Jejunum, Kidneys, Liver, Lungs (inflated with NBF at necropsy), Lymph nodes (mesenteric, axillary), Oesophagus, Ovaries, Pancreas, Peripheral nerve (sciatic or tibial), Pituitary, Prostate, Rectum, Salivary gland, Seminal vesical with coagulating glands, Skeletal muscle, Skin with Mammary gland, Spinal cord (cervical, midthoracic, lumbar), Spleen,stomach, Testes, Thymus, Thyroid with parathyroid, Trachea, Urinary bladder (inflated with NBF at necropsy), Uterus, Vagina, All Gross lesions



Statistics:
The following statistical methods were used to analyze the body weight, feed consumption, functional observation battery parameters,organ weights as well as clinical pathology data.
• Data was summarized in tabular form. Statistical analysis was performed using statplus program.
• All the data was checked for normality with Shapiro-Wilk W test
• Statistical significances of differences was calculated with one-way analysis of variance(ANOVA). Values were given as mean ± standard deviation (SD).
• t-test/ all ANOVA with group variables were used to compare the difference between treated and control groups.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No test item related clinical signs of illness were observed in any of the animals during treatment in groups of control (G1), Low dose (G2), Intermediate dose (G3) and recovery period (G1R). However, Dullness was obesrved in high dose (G4) in one male and one female, similarly one male and two females exhibited dullness in high dose recovery (G4R).
Mortality:
no mortality observed
Description (incidence):
Animals treated with test item at dose levels of 50, 200 and 400 mg/kg bw/d did not show any mortality in both males and females during the experimental period of 90 days and the recovery period.
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
The body weight of male animals of all treatment groups were comparable with the control group animals during the dosing period and recovery period.
In females, significant decreases in body weight gain were observed for (G4) on day 85 when compared to the vehicle treated animals. The body weight gain of female animals of recovery high dose group was comparable with the recovery control group animals during the dosing period and recovery period.
The changes observed were considered to be as biological variation commonly recorded for this species, strain and age.
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
During the 90 consecutive days of dosing period, the quantity of feed consumed by animals across different dose groups was found to be no significantly different as compared with the control animals.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Males: Significant increase of NEU and decrease of lymph in intermediate dose (G3) and high dose (G4) as compared with control dose (G1). Significant increase of mono in high (G4), intermediate dose (G3) low dose (G2) as compared with control group (G1). Significant decrease of EOS in low dose (G2) as compared with control group (G1).
Females: There was significant increase in Neut and decrease in Lymph in (G4) as compared with (G1).

In recovery males, there was significant increase of PCV in G4R as compared with control recovery (G1R). In recovery females, there was significant decrease of white blood cell count (WBC) in female as compared with control recovery (G1R). The changes observed in the hematological parameters are marginal and could not be attributed to the test item administration as these values were within biological variation.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
Males: Significant increase of ALP and AST in intermediate (G3) and high (G4) dose as compared with control (G1) group. Significant increase of ALT in high (G4) dose as compared with control (G1).
Females: there was significant increase of AST in intermediate (G3) as compared with control (G1). Significant increase of CREA in intermediate (G3) dose as compared with (G1) dose.
In recovery males, there was significant decrease in ALP (G4R) when compared with control recovery (G1R). In recovery females, there was significant increase in UREA, BUN, CREA and ALB in (G4R) when compared with control recovery (G1R). The changes observed in the clinical biochemistry parameters are marginal and could not be attributed to the test item administration as these values were within biological variation.
Urinalysis findings:
effects observed, non-treatment-related
Description (incidence and severity):
In males, there was significant decrease of volume in high (G4) dose as compared with control (G1). In females there was significant increase of SG in intermediate (G3) ) and low (G2) as compared with control (G1). The changes observed in the urine analysis parameters are marginal and could not be attributed to the test item administration as these values were within biological variation.
Behaviour (functional findings):
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
There was no significance changes observed in absolute and relative organ weights of treatment and recovery groups. In relative organ weights of males, there was significant increase of liver in high (G4) dose as compared with control (G1).
Despite this macroscopical difference, no test item related change was observed in these organs from treatment groups. Hence, the changes observed in organ weight were considered to be as biological variation.
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Treatment related histopathological findings included chronic inflammation in the non glandular region of stomach observed in treated males and females. Additionally hyperplasia and hyperkeratosis of squamous epithelium of non glandular stomach was also observed in a few animals in these groups. There was single incidence of erosion in glandular stomach in one male treated at 400 mg/kg bw. Chronic inflammation in non glandular stomach consisted of infiltration in lamina propria and/or submucosa with mostly mononuclear cells and occasional polymorphonuclear cells. Edema or/and necrosis of the squamous epithelium was observed in a few cases. The distribution of the lesion was focal or multifocal. The lesion in non glandular stomach was observed in all the treated groups. The severity of the lesion was minimal to mild in all the treated groups. . The incidence and severity of the lesion in females treated at 400mg/kg was higher when compared to males treated with the same dose. The lesions observed in the forestomach may be attributed to direct local effects of the test item administered orally. In the recovery high dose groups, all the stomach tissues were within normal histological limits indicating complete recovery. The lesion was considered non adverse as the incidence and severity of the lesion was low and complete recovery was at the end of 28 day recovery period.

Incidence of stomach effects
- Males:
Inflammation: 0/10 (0 mg/kg bw/d), 4/10 (50 mg/kg bw/d), 4/10 (200 mg/kg bw/d), 2/10 (400 mg/kg bw/d), 0/10 (0 mg/kg bw/d recovery group), 0/10 (400 mg/kg bw/d recovery group)
Hyperpalsia/Hyperkeratosis: 0/10 (0 mg/kg bw/d), 1/10 (50 mg/kg bw/d), 1/10 (200 mg/kg bw/d), 2/10 (400 mg/kg bw/d), 0/10 (0 mg/kg bw/d recovery group), 0/10 (400 mg/kg bw/d recovery group)
Erosion (glandular, focal): 0/10 (0 mg/kg bw/d), 0/10 (50 mg/kg bw/d), 0/10 (200 mg/kg bw/d), 1/10 (400 mg/kg bw/d), 0/10 (0 mg/kg bw/d recovery group), 0/10 (400 mg/kg bw/d recovery group)

- Females:
Inflammation: 0/10 (0 mg/kg bw/d), 3/10 (50 mg/kg bw/d), 4/10 (200 mg/kg bw/d), 6/10 (400 mg/kg bw/d), 0/10 (0 mg/kg bw/d recovery group), 0/10 (400 mg/kg bw/d recovery group)
Hyperpalsia/Hyperkeratosis: 0/10 (0 mg/kg bw/d), 0/10 (50 mg/kg bw/d), 2/10 (200 mg/kg bw/d), 6/10 (400 mg/kg bw/d), 0/10 (0 mg/kg bw/d recovery group), 0/10 (400 mg/kg bw/d recovery group)

Single incidence of microscopic findings observed in other organs in various groups were considered incidental.

Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
400 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: local irritation in stomach related to irrtant properties of test item

Target system / organ toxicity

Key result
Critical effects observed:
no
Lowest effective dose / conc.:
400 mg/kg bw/day (actual dose received)
System:
gastrointestinal tract
Organ:
stomach

Any other information on results incl. tables

FEED CONSUMPTION (G/ANIMAL/DAY)

MALES

TREATMENT

Group 1

Group 2

Group 3

Group 4

Week 1

Mean

19.15

19.48

19.84

17.55

SD

1.018

0.346

0.816

3.400

Week 2

Mean

20.26

18.31

17.31

20.25

SD

3.435

1.397

2.147

1.541

Week 3

Mean

22.58

20.68

20.17

19.93

SD

1.740

2.347

2.173

2.585

Week 4

Mean

20.18

19.87

16.46

17.54

SD

1.448

3.768

1.238

2.397

Week 5

Mean

18.83

17.17

17.07

19.22

SD

2.033

1.440

0.901

2.938

Week 6

Mean

17.42

15.25

15.42

17.36

SD

1.546

0.801

1.323

4.212

Week 7

Mean

16.71

15.67

14.68

15.76

SD

1.635

0.918

0.730

1.610

Week 8

Mean

16.79

16.20

16.49

15.79

SD

1.423

1.852

1.205

1.844

Week 9

Mean

17.75

16.70

16.96

16.26

SD

1.346

1.471

1.374

1.693

Week 10

Mean

16.11

15.99

15.24

14.87

SD

1.202

1.483

0.617

1.380

Week 11

Mean

17.50

17.62

17.56

16.87

SD

0.395

1.680

1.425

1.681

Week 12

Mean

18.18

18.72

18.55

17.41

SD

1.619

1.219

1.073

2.447

Week 13

Mean

15.37

15.98

15.93

15.87

SD

1.046

1.991

1.351

0.729

FEED CONSUMPTION (G/ANIMAL/DAY) (CONTD.)

MALES

Recovery (R)

Group 1R

Group 4R

 

Recovery (R)

Group 1R

Group 4R

Week 1

Mean

17.77

17.18

 

Week 10

Mean

17.99

17.06

SD

2.256

2.757

 

SD

1.000

0.700

Week 2

Mean

21.57

20.22

 

Week 11

Mean

17.78

17.36

SD

1.711

1.194

 

SD

1.175

0.916

Week 3

Mean

21.55

21.25

 

Week 12

Mean

18.98

18.70

SD

2.132

2.176

 

SD

0.373

0.563

Week 4

Mean

17.68

17.65

 

Week 13

Mean

19.28

17.99

SD

1.097

1.107

 

SD

1.405

1.265

Week 5

Mean

18.40

18.41

 

Week 14

Mean

19.41

19.22

SD

1.468

1.364

 

SD

0.238

0.959

Week 6

Mean

16.98

16.76

 

Week 15

Mean

19.43

19.13

SD

0.822

0.691

 

SD

0.227

0.455

Week 7

Mean

16.39

16.49

 

Week 16

Mean

19.52

19.24

SD

3.537

1.029

 

SD

0.245

0.293

Week 8

Mean

16.56

15.88

 

Week 17

Mean

21.44

21.79

SD

0.927

0.834

 

SD

0.174

1.147

Week 9

Mean

18.80

18.57

 

 

 

 

 

SD

0.377

0.691

 

 

 

 

 

FEED CONSUMPTION (G/ANIMAL/DAY) (CONTD.)

FEMALES

TREATMENT

Group 1

Group 2

Group 3

Group 4

Week 1

Mean

13.28

12.57

11.93

10.70

SD

0.631

1.286

2.569

2.459

Week 2

Mean

13.37

11.46

12.84

13.13

SD

2.122

1.356

1.356

1.491

Week 3

Mean

16.69

13.41*

14.24

12.42*

SD

1.260

2.296

1.679

1.635

Week 4

Mean

11.87

11.54

11.33

     9.79*#&

SD

0.774

1.041

0.819

0.496

Week 5

Mean

12.06

11.56

12.35

12.10

SD

0.694

1.102

1.081

1.580

Week 6

Mean

12.12

10.97

12.07

10.37

SD

0.801

2.383

0.558

1.316

Week 7

Mean

11.88

10.67

11.90

11.76

SD

0.650

1.193

0.658

2.780

Week 8

Mean

12.99

11.82

12.22

11.05

SD

1.143

2.046

1.538

2.076

Week 9

Mean

13.07

12.14

12.81

11.58

SD

1.206

1.391

1.240

1.147

Week 10

Mean

12.44

10.53

11.05

9.53

SD

1.870

1.939

1.893

1.193

Week 11

Mean

13.93

11.39

13.50

10.21*

SD

1.127

1.645

3.353

1.295

Week 12

Mean

15.57

11.99*

13.24

11.98*

SD

1.686

0.726

0.916

1.597

Week 13

Mean

13.61

10.94

11.94

11.15

SD

1.490

1.727

1.428

1.643

*-Significant at p ≤ 0.05 with Group 1, # - Significant at p ≤ 0.05 with Groups 2, & - Significant at p ≤ 0.05 with Group 3

FEED CONSUMPTION (G/ANIMAL/DAY) (CONTD.)

FEMALES 

Recovery (R)

Group 1R

Group 4R

 

Recovery (R)

Group 1R

Group 4R

Week 1

Mean

11.36

10.65

 

Week 10

Mean

11.58

10.13

SD

2.607

2.559

 

SD

1.067

1.306

Week 2

Mean

15.15

13.57

 

Week 11

Mean

12.32

10.74

SD

2.458

0.936

 

SD

1.051

1.233

Week 3

Mean

15.43

14.77

 

Week 12

Mean

13.25

12.14

SD

1.916

1.502

 

SD

0.739

1.384

Week 4

Mean

12.65

12.36

 

Week 13

Mean

15.35

13.21

SD

0.408

1.016

 

SD

1.074

2.537

Week 5

Mean

12.69

12.99

 

Week 14

Mean

14.40

14.57

SD

0.944

1.038

 

SD

0.662

0.573

Week 6

Mean

11.39

10.82

 

Week 15

Mean

13.98

13.78

SD

0.841

0.608

 

SD

0.532

1.285

Week 7

Mean

11.95

11.65

 

Week 16

Mean

13.78

14.04

SD

1.156

1.172

 

SD

0.812

1.410

Week 8

Mean

11.15

12.25

 

Week 17

Mean

15.23

14.77

SD

1.357

0.862

 

SD

0.619

0.722

Week 9

Mean

13.56

12.39

 

 

 

 

 

SD

2.170

1.407

 

 

 

 

 

 

 

1.1       BODY WEIGHTS (G)

MALES

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 1

Mean

178.0

181.4

182.4

179.0

SD

5.28

3.16

7.30

4.88

Min

170.5

178.4

172.9

171.4

Max

187.3

189.0

198.9

188.8

N

10

10

10

10

Day 8

Mean

211.2

209.4

217.0

214.5

SD

10.91

10.20

8.69

11.50

Min

197.2

190.7

206.6

196.1

Max

229.3

223.4

234.3

229.7

N

10

10

10

10

Day 15

Mean

240.2

237.5

239.9

236.6

SD

15.56

8.32

8.93

18.79

Min

219.8

224.9

227.5

215.1

Max

270.1

254.2

252.5

267.0

N

10

10

10

10

Day 22

Mean

264.4

257.6

259.4

253.6

SD

18.55

8.62

11.09

22.02

Min

246.5

243.3

237.6

224.5

Max

302.2

273.2

273.4

292.3

N

10

10

10

10

Day 29

Mean

288.6

276.5

277.1

273.8

SD

19.44

11.87

13.94

25.40

Min

265.0

254.6

249.3

238.7

Max

325.9

301.2

296.4

320.7

N

10

10

10

10

 

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 36

Mean

307.0

290.0

291.1

293.3

SD

26.28

18.65

16.38

28.65

Min

272.5

260.8

263.9

257.7

Max

362.0

334.3

317.0

345.4

N

10

10

10

10

Day 43

Mean

322.8

308.3

305.5

303.3

SD

26.48

19.24

18.31

32.64

Min

287.5

280.4

274.4

258.1

Max

367.7

354.1

332.6

361.5

N

10

10

10

10

Day 50

Mean

332.2

320.1

317.5

316.6

SD

29.26

20.37

20.93

37.44

Min

292.7

289.3

281.8

260.4

Max

379.1

367.8

349.9

382.3

N

10

10

10

10

Day 57

Mean

343.2

331.4

328.3

325.4

SD

33.77

23.73

23.29

36.23

Min

293.8

300.6

292.5

273.9

Max

391.1

389.8

365.7

385.2

N

10

10

10

10

Day 64

Mean

353.1

343.3

340.6

336.8

SD

34.42

26.55

24.15

38.57

Min

303.2

306.3

307.0

284.9

Max

399.1

404.6

381.7

399.6

N

10

10

10

10

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 71

Mean

363.1

352.8

352.9

347.9

SD

37.12

29.17

26.84

39.29

Min

308.8

314.6

311.6

297.5

Max

417.2

422.2

397.2

416.3

N

10

10

10

10

Day 78

Mean

370.8

362.6

364.1

358.9

SD

37.21

30.89

26.86

41.69

Min

316.6

320.9

327.4

296.8

Max

429.1

430.2

412.9

431.7

N

10

10

10

10

Day 85

Mean

376.7

371.2

371.8

359.3

SD

39.46

31.04

29.82

43.68

Min

320.9

328.9

331.8

294.8

Max

434.9

438.9

420.3

429.7

N

10

10

10

10

Day 90

Mean

384.1

378.0

379.0

370.1

SD

39.17

32.20

27.96

44.67

Min

331.9

337.4

340.5

305.5

Max

443.9

451.6

426.4

446.9

N

10

10

10

10

MALES (Recovery)

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 1

Mean

180.6

177.8

 

Day 36

Mean

297.2

294.6

SD

5.01

7.87

 

SD

17.46

18.29

Min

172.1

164.5

 

Min

254.7

256.7

Max

189.1

189.0

 

Max

316.8

318.1

N

10

10

 

N

10

10

Day 8

Mean

212.6

209.3

 

Day 43

Mean

313.7

313.3

SD

7.89

11.72

 

SD

19.34

20.33

Min

198.7

196.1

 

Min

273.9

272.7

Max

224.0

226.5

 

Max

336.9

343.9

N

10

10

 

N

10

10

Day 15

Mean

236.5

236.3

 

Day 50

Mean

327.8

322.5

SD

9.46

11.46

 

SD

21.69

23.41

Min

214.6

220.6

 

Min

284.8

275.9

Max

249.9

257.4

 

Max

352.8

359.4

N

10

10

 

N

10

10

Day 22

Mean

261.0

259.0

 

Day 57

Mean

338.3

332.5

SD

12.75

14.34

 

SD

23.93

27.96

Min

232.2

237.8

 

Min

294.1

285.4

Max

280.8

280.1

 

Max

368.6

372.9

N

10

10

 

N

10

10

Day 29

Mean

281.5

278.0

 

Day 64

Mean

349.8

344.5

SD

14.56

15.18

 

SD

24.35

26.92

Min

246.3

252.9

 

Min

304.4

296.7

Max

301.1

296.5

 

Max

382.6

380.5

N

10

10

 

N

10

10

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 71

Mean

360.1

356.9

 

Day 98

Mean

386.7

385.5

SD

24.83

26.86

 

SD

26.17

28.46

Min

313.7

311.0

 

Min

338.1

329.4

Max

396.6

391.7

 

Max

426.7

412.6

N

10

10

 

N

10

10

Day 78

Mean

367.6

362.6

 

Day 105

Mean

394.6

394.5

SD

24.78

28.60

 

SD

27.87

29.04

Min

321.3

311.0

 

Min

342.9

337.2

Max

402.9

401.7

 

Max

437.5

421.3

N

10

10

 

N

10

10

Day 85

Mean

373.8

363.1

 

Day 112

Mean

405.0

404.9

SD

26.40

30.75

 

SD

28.67

29.22

Min

325.0

310.2

 

Min

352.1

349.6

Max

413.8

409.3

 

Max

451.8

436.8

N

10

10

 

N

10

10

Day 91

Mean

381.7

379.5

 

Day 118

Mean

410.9

411.2

SD

26.10

28.33

 

SD

31.05

29.69

Min

337.7

328.7

 

Min

355.9

356.7

Max

425.7

410.4

 

Max

464.1

443.5

N

10

10

 

N

10

10

BODY WEIGHTS (G)

FEMALES

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 1

Mean

142.7

143.1

142.5

141.0

SD

5.75

4.32

6.97

4.73

Min

132.6

136.9

133.7

135.2

Max

153.2

149.1

158.2

150.6

N

10

10

10

10

Day 8

Mean

160.8

160.7

158.7

155.1

SD

8.33

6.72

6.46

6.78

Min

147.5

148.8

146.3

146.1

Max

172.5

170.5

170.2

168.8

N

10

10

10

10

Day 15

Mean

171.4

172.5

170.5

168.2

SD

7.85

6.56

6.55

6.88

Min

159.7

165.3

159.2

154.7

Max

184.0

185.7

181.1

181.8

N

10

10

10

10

Day 22

Mean

182.1

183.6

182.9

178.5

SD

7.63

9.12

7.35

6.63

Min

168.4

173.2

171.0

166.7

Max

193.3

201.6

194.0

189.2

N

10

10

10

10

Day 29

Mean

191.8

191.6

191.2

184.2

SD

9.63

11.77

8.25

6.00

Min

177.8

178.5

180.4

176.5

Max

202.6

219.8

203.7

195.3

N

10

10

10

10

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 36

Mean

195.5

197.9

197.4

187.4

SD

10.33

13.76

14.21

7.91

Min

180.3

178.8

175.3

177.7

Max

206.1

224.1

217.9

203.5

N

10

10

10

10

Day 43

Mean

203.6

205.0

206.2

191.6*

SD

8.63

15.85

13.37

8.80

Min

185.7

184.7

183.6

181.6

Max

212.1

236.7

225.3

208.2

N

10

10

10

10

Day 50

Mean

211.2

211.2

212.3

199.0

SD

9.88

16.82

15.44

9.84

Min

193.3

189.3

192.9

187.1

Max

221.0

240.9

238.9

217.2

N

10

10

10

10

Day 57

Mean

213.9

215.4

214.6

200.5

SD

9.51

16.66

16.37

11.49

Min

195.5

191.8

193.1

186.8

Max

225.8

246.3

244.5

218.1

N

10

10

10

10

Day 64

Mean

216.3

217.6

216.4

203.0

SD

8.83

16.20

17.62

11.03

Min

202.9

197.3

196.4

188.3

Max

230.7

246.9

252.9

221.1

N

10

10

10

10

* Significant at p ≤ 0.05 with Group 3,

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 71

Mean

219.8

222.8

219.6

208.7

SD

7.42

20.63

18.07

12.81

Min

210.2

197.5

197.8

190.3

Max

233.4

270.8

257.2

229.4

N

10

10

10

10

Day 78

Mean

222.0

224.9

220.7

208.6

SD

7.33

21.17

19.66

11.54

Min

212.6

197.8

198.2

192.1

Max

235.4

274.3

262.9

226.4

N

10

10

10

10

Day 85

Mean

226.1

226.5

223.8

206.2*

SD

8.76

21.09

19.26

13.37

Min

214.5

199.3

202.9

194.3

Max

242.0

275.4

266.1

229.3

N

10

10

10

10

Day 90

Mean

228.3

228.3

226.2

212.8

SD

8.70

21.19

19.34

11.67

Min

215.3

200.2

203.8

199.1

Max

242.3

276.6

267.4

231.0

N

10

10

10

10

Significant at p ≤ 0.05 with Groups 1, 2 and 3

BODY WEIGHTS (G) (Recovery)

FEMALES

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 1

Mean

141.1

141.8

 

Day 36

Mean

194.5

193.2

SD

4.46

5.58

 

SD

10.05

10.45

Min

133.2

133.3

 

Min

182.3

174.7

Max

146.2

150.8

 

Max

210.2

212.0

N

10

10

 

N

10

10

Day 8

Mean

159.4

156.9

 

Day 43

Mean

202.7

199.9

SD

8.07

6.82

 

SD

11.53

8.43

Min

146.4

144.3

 

Min

184.1

188.8

Max

168.7

167.7

 

Max

221.3

215.7

N

10

10

 

N

10

10

Day 15

Mean

172.4

167.5

 

Day 50

Mean

211.6

206.0

SD

8.21

5.53

 

SD

7.90

10.94

Min

164.1

156.0

 

Min

197.6

189.4

Max

191.2

175.2

 

Max

223.1

224.8

N

10

10

 

N

10

10

Day 22

Mean

182.7

181.4

 

Day 57

Mean

214.1

209.2

SD

8.71

6.65

 

SD

9.64

14.64

Min

174.6

169.3

 

Min

198.3

188.4

Max

199.5

190.5

 

Max

228.4

238.2

N

10

10

 

N

10

10

Day 29

Mean

190.6

187.0

 

Day 64

Mean

215.6

210.2

SD

10.05

7.01

 

SD

8.47

15.02

Min

175.1

174.7

 

Min

201.6

189.2

Max

207.3

197.1

 

Max

229.0

238.4

N

10

10

 

N

10

10

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 71

Mean

218.0

214.6

 

Day 98

Mean

228.5

219.5

SD

8.04

17.24

 

SD

11.30

16.21

Min

202.5

196.2

 

Min

207.6

200.7

Max

230.0

249.9

 

Max

250.1

252.1

N

10

10

 

N

10

10

Day 78

Mean

220.8

213.2

 

Day 105

Mean

231.3

221.2

SD

9.31

15.77

 

SD

11.36

17.27

Min

202.9

192.6

 

Min

209.6

201.3

Max

234.8

246.1

 

Max

251.2

257.2

N

10

10

 

N

10

10

Day 85

Mean

221.4

210.6

 

Day 112

Mean

234.2

223.0

SD

10.34

18.01

 

SD

12.05

17.97

Min

204.3

188.6

 

Min

210.2

202.9

Max

235.1

248.1

 

Max

252.6

260.2

N

10

10

 

N

10

10

Day 91

Mean

224.6

217.3

 

Day 118

Mean

236.4

225.5

SD

13.15

16.76

 

SD

12.30

17.82

Min

206.4

198.7

 

Min

211.7

205.2

Max

249.4

251.9

 

Max

255.2

261.9

N

10

10

 

N

10

10

BODY WEIGHT GAIN (%)

MALES

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 1

Mean

0.0

0.0

0.0

0.0

SD

0.00

0.00

0.00

0.00

Min

0.0

0.0

0.0

0.0

Max

0.0

0.0

0.0

0.0

N

10

10

10

10

Day 8

Mean

18.6

15.4

19.0

19.8

SD

3.08

5.29

2.76

4.70

Min

12.4

6.5

16.5

14.4

Max

22.4

22.8

25.7

27.1

N

10

10

10

10

Day 15

Mean

34.8

30.9

31.6

32.1

SD

5.64

4.27

5.90

9.10

Min

26.4

24.7

22.9

22.5

Max

44.2

39.7

43.4

47.7

N

10

10

10

10

Day 22

Mean

48.4

42.0

42.3

41.6

SD

6.68

4.78

7.20

10.88

Min

40.4

35.8

28.4

29.9

Max

61.3

50.2

55.3

61.7

N

10

10

10

10

Day 29

Mean

62.0

52.4

52.0

52.8

SD

7.28

6.26

7.76

12.62

Min

53.5

42.2

34.7

39.3

Max

74.0

65.6

61.3

77.4

N

10

10

10

10

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 36

Mean

72.3

59.9

59.7

63.7

SD

11.78

10.06

9.13

14.24

Min

56.3

45.6

42.6

47.3

Max

93.3

83.8

71.7

91.0

N

10

10

10

10

Day 43

Mean

81.3

69.9

67.7

69.3

SD

13.13

10.62

11.13

16.52

Min

58.5

56.6

48.2

48.3

Max

96.3

94.7

83.6

99.9

N

10

10

10

10

Day 50

Mean

86.6

76.4

74.2

76.7

SD

14.82

11.27

12.26

19.31

Min

61.4

61.5

52.2

51.9

Max

103.3

102.2

93.1

111.4

N

10

10

10

10

Day 57

Mean

92.7

82.7

80.2

81.7

SD

17.52

13.33

14.11

18.73

Min

62.0

67.8

58.0

58.2

Max

112.9

114.3

101.8

113.1

N

10

10

10

10

Day 64

Mean

98.3

89.3

86.9

88.0

SD

17.87

14.99

14.32

19.85

Min

67.1

71.0

65.9

61.8

Max

118.2

122.4

110.7

121.0

N

10

10

10

10

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 71

Mean

103.9

94.5

93.7

94.2

SD

19.06

16.31

16.01

20.06

Min

70.2

75.7

68.3

66.4

Max

123.6

132.1

119.2

130.3

N

10

10

10

10

Day 78

Mean

108.2

99.9

99.9

100.4

SD

19.20

17.35

16.61

21.33

Min

74.5

79.2

76.9

64.4

Max

129.4

136.5

127.9

138.8

N

10

10

10

10

Day 85

Mean

111.6

104.7

104.1

100.5

SD

20.41

17.46

17.95

21.84

Min

76.9

83.6

79.3

70.0

Max

132.8

141.3

132.0

137.7

N

10

10

10

10

Day 90

Mean

115.7

108.4

108.1

106.6

SD

19.96

17.97

17.61

22.45

Min

83.0

88.4

84.0

74.2

Max

137.0

148.3

135.3

147.2

N

10

10

10

10

MALES

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 1

Mean

0.0

0.0

 

Day 36

Mean

64.5

65.8

SD

0.00

0.00

 

SD

8.55

9.37

Min

0.0

0.0

 

Min

48.0

55.4

Max

0.0

0.0

 

Max

76.3

80.2

N

10

10

 

N

10

10

Day 8

Mean

17.7

17.8

 

Day 43

Mean

73.7

76.5

SD

3.82

5.54

 

SD

10.36

12.11

Min

12.5

6.9

 

Min

59.2

64.2

Max

23.5

27.4

 

Max

91.3

94.8

N

10

10

 

N

10

10

Day 15

Mean

30.9

33.1

 

Day 50

Mean

81.5

81.6

SD

3.83

6.58

 

SD

11.37

13.43

Min

23.9

20.3

 

Min

64.9

67.0

Max

36.4

44.8

 

Max

100.3

99.8

N

10

10

 

N

10

10

Day 22

Mean

44.4

45.7

 

Day 57

Mean

87.3

87.3

SD

4.83

6.59

 

SD

12.86

16.23

Min

34.9

31.5

 

Min

67.8

64.0

Max

49.8

57.5

 

Max

109.3

107.7

N

10

10

 

N

10

10

Day 29

Mean

55.8

56.5

 

Day 64

Mean

93.7

94.0

SD

6.49

8.27

 

SD

13.22

15.06

Min

43.1

37.9

 

Min

73.6

69.6

Max

65.0

68.0

 

Max

117.3

113.6

N

10

10

 

N

10

10

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 71

Mean

99.4

100.9

 

Day 98

Mean

114.2

117.0

SD

13.77

14.49

 

SD

14.66

14.59

Min

79.5

76.6

 

Min

94.0

92.7

Max

125.2

117.7

 

Max

142.3

133.8

N

10

10

 

N

10

10

Day 78

Mean

103.5

104.0

 

Day 105

Mean

118.5

122.0

SD

13.55

14.14

 

SD

15.76

14.94

Min

84.4

79.8

 

Min

97.5

95.8

Max

128.8

123.3

 

Max

148.4

138.5

N

10

10

 

N

10

10

Day 85

Mean

107.0

104.3

 

Day 112

Mean

124.3

127.9

SD

14.42

14.84

 

SD

16.39

15.54

Min

86.7

77.5

 

Min

103.5

99.6

Max

135.0

127.5

 

Max

156.6

148.1

N

10

10

 

N

10

10

Day 91

Mean

111.4

113.6

 

Day 118

Mean

127.6

131.5

SD

14.93

14.69

 

SD

18.05

16.06

Min

90.5

86.1

 

Min

106.0

102.8

Max

141.7

129.6

 

Max

163.5

152.3

N

10

10

 

N

10

10

BODY WEIGHTS GAIN (%)

FEMALES

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 1

Mean

0.0

0.0

0.0

0.0

SD

0.00

0.00

0.00

0.00

Min

0.0

0.0

0.0

0.0

Max

0.0

0.0

0.0

0.0

N

10

10

10

10

Day 8

Mean

12.7

12.3

11.5

10.0

SD

4.58

4.60

5.14

5.05

Min

6.0

3.8

4.4

1.1

Max

20.9

16.9

18.7

15.8

N

10

10

10

10

Day 15

Mean

20.2

20.6

19.8

19.3

SD

4.76

5.52

5.55

4.84

Min

11.3

10.9

10.9

9.3

Max

28.1

31.1

29.1

25.1

N

10

10

10

10

Day 22

Mean

27.7

28.4

28.5

26.7

SD

4.60

7.27

5.96

5.27

Min

17.3

16.2

15.9

17.8

Max

34.6

42.4

34.7

32.6

N

10

10

10

10

Day 29

Mean

34.5

34.0

34.3

30.7

SD

5.11

9.01

5.72

4.10

Min

23.8

21.8

22.2

24.7

Max

40.8

55.2

40.4

36.3

N

10

10

10

10

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 36

Mean

37.1

38.4

38.7

32.9

SD

6.27

10.38

9.64

3.32

Min

28.6

22.0

18.8

25.6

Max

46.7

58.3

52.1

37.6

N

10

10

10

10

Day 43

Mean

42.9

43.4

44.9

35.9

SD

7.20

12.64

9.53

4.95

Min

32.8

26.0

29.5

28.3

Max

52.9

67.2

58.1

44.1

N

10

10

10

10

Day 50

Mean

48.2

47.7

49.1

41.1

SD

7.05

12.69

10.02

4.21

Min

34.6

29.1

32.4

35.5

Max

57.0

70.1

67.6

46.9

N

10

10

10

10

Day 57

Mean

50.0

50.7

50.8

42.2

SD

7.07

12.84

10.98

5.36

Min

36.1

30.8

32.9

33.4

Max

60.7

73.9

71.6

49.1

N

10

10

10

10

Day 64

Mean

51.7

52.1

52.0

43.9

SD

7.01

11.95

11.85

5.66

Min

41.7

34.6

33.8

35.8

Max

64.2

74.4

77.5

51.2

N

10

10

10

10

TREATMENT

Group 1

Group 2

Group 3

Group 4

Day 71

Mean

54.2

55.8

54.3

48.0

SD

6.86

15.72

12.36

6.46

Min

43.4

34.7

36.9

37.2

Max

66.1

91.2

80.5

58.5

N

10

10

10

10

Day 78

Mean

55.8

57.3

55.0

47.9

SD

7.07

15.83

13.40

5.50

Min

44.3

34.9

37.9

38.5

Max

67.5

93.7

84.5

55.8

N

10

10

10

10

Day 85

Mean

58.6

58.4

57.3

46.1*

SD

7.56

15.95

13.59

6.22

Min

48.0

35.9

37.7

39.9

Max

72.2

94.5

86.7

58.5

N

10

10

10

10

Day 90

Mean

60.2

59.7

59.0

50.9

SD

7.56

16.06

14.14

5.52

Min

49.8

36.6

38.1

43.5

Max

72.5

95.3

87.6

61.0

N

10

10

10

10

* Significant at p ≤ 0.05 with Groups 1, 2 and 3

FEMALES (Recovery)

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 1

Mean

0.0

0.0

 

Day 36

Mean

37.9

36.3

SD

0.00

0.00

 

SD

8.00

6.49

Min

0.0

0.0

 

Min

25.2

29.2

Max

0.0

0.0

 

Max

49.8

47.6

N

10

10

 

N

10

10

Day 8

Mean

13.0

10.6

 

Day 43

Mean

43.8

41.1

SD

4.65

1.66

 

SD

9.95

6.82

Min

4.8

8.3

 

Min

25.9

31.1

Max

18.7

13.5

 

Max

57.7

50.2

N

10

10

 

N

10

10

Day 15

Mean

22.2

18.2

 

Day 50

Mean

50.1

45.4

SD

6.41

2.16

 

SD

7.03

6.97

Min

15.8

13.9

 

Min

37.7

37.5

Max

37.2

21.4

 

Max

59.0

56.5

N

10

10

 

N

10

10

Day 22

Mean

29.5

28.0

 

Day 57

Mean

51.8

47.5

SD

7.46

2.83

 

SD

7.59

8.60

Min

20.2

23.5

 

Min

41.2

39.9

Max

43.1

31.3

 

Max

62.8

65.9

N

10

10

 

N

10

10

Day 29

Mean

35.2

31.9

 

Day 64

Mean

52.9

48.2

SD

8.03

4.04

 

SD

7.00

8.28

Min

27.5

25.5

 

Min

41.7

37.4

Max

47.8

37.3

 

Max

63.2

66.0

N

10

10

 

N

10

10

RECOVERY (R)

Group 1R

Group 4R

 

RECOVERY (R)

Group 1R

Group 4R

Day 71

Mean

54.6

51.3

 

Day 98

Mean

62.1

54.8

SD

7.19

10.08

 

SD

10.74

9.16

Min

43.1

38.3

 

Min

42.0

43.9

Max

65.2

74.0

 

Max

78.3

75.6

N

10

10

 

N

10

10

Day 78

Mean

56.6

50.3

 

Day 105

Mean

64.1

56.0

SD

8.08

9.37

 

SD

11.09

9.85

Min

43.8

40.4

 

Min

43.4

44.1

Max

68.7

71.4

 

Max

79.6

79.1

N

10

10

 

N

10

10

Day 85

Mean

57.1

48.5

 

Day 112

Mean

66.2

57.2

SD

9.38

10.47

 

SD

11.67

10.20

Min

40.8

38.5

 

Min

43.8

44.5

Max

71.3

72.8

 

Max

84.8

81.2

N

10

10

 

N

10

10

Day 91

Mean

59.3

53.2

 

Day 118

Mean

67.7

59.0

SD

11.19

9.64

 

SD

11.87

10.04

Min

41.2

41.4

 

Min

44.8

47.2

Max

77.8

75.4

 

Max

86.5

82.4

N

10

10

 

N

10

10

FUNCTIONAL OBSERVATION BATTERY

MALES

TREATMENT(WEEK -13)

Grip Strength

Rotarod

IR Activity

Fore limb

In seconds

S - Movement

F - Movement

S - Steriotypic

F - Steriotypic

Group 1

Mean

469.1

63

54.0

133.0

22.9

111.9

SD

31.60

4.0

9.83

38.59

10.77

29.45

Group 2

Mean

462.3

63

53.4

71.0

21.7

89.7

SD

96.44

4.5

13.36

45.30

1.67

30.15

Group 3

Mean

442.0

62

65.1

105.8

20.3

102.2

SD

57.44

5.7

9.98

56.93

2.52

29.89

Group 4

Mean

478.1

65

56.9

119.7

20.7

103.2

SD

80.85

4.0

11.39

71.62

2.04

29.75

Group 1R

Mean

585.9

58

54.9

161.3

38.7

106.8

SD

42.19

9.72

11.20

55.05

23.26

33.45

Group 4R

Mean

602.1

64

80.6

180.4

39.2

124.8

SD

62.81

2.96

35.20

63.33

29.06

26.77

FEMALES

TREATMENT(WEEK -13)

Grip Strength

Rotarod

IR Activity

Fore limb

In seconds

S - Movement

F - Movement

S - Steriotypic

F - Steriotypic

Group 1

Mean

506.3

65

53.2

145.3

20.8

122.3

SD

99.43

4.8

10.53

42.91

2.62

23.81

Group 2

Mean

509.6

63

61.5

186.2

21.1

133.1

SD

89.24

7.3

9.79

42.69

3.16

16.45

Group 3

Mean

460.8

63

58.4

177.4

20.3

119.9

SD

40.00

3.0

10.70

108.63

3.82

40.53

Group 4

Mean

460.3

65

63.1

193.5

21.7

136.2

SD

90.85

5.0

8.54

30.51

2.91

19.65

Group 1R

Mean

612.8

62

49.1

180.7

41.9

114.2

SD

50.12

8.44

10.99

40.03

25.88

30.67

Group 4R

Mean

593.9

63

54.5

171.4

42.4

118.0

SD

28.09

6.64

14.53

76.45

33.41

35.66

 

MALES (Recovery)

 

TREATMENT(WEEK -17)

Grip Strength

Rotarod

IR Activity

Fore limb

In seconds

S - Movement

F - Movement

S - Steriotypic

F - Steriotypic

Group 1R

Mean

604.1

59

47.4

99.3

50.4

88.7

SD

55.03

6.5

14.73

36.07

27.06

27.13

Group 4R

Mean

630.6

64

85.7

109.1

64.5

94.4

SD

43.63

4.6

18.80

12.96

26.75

17.87

 

FEMALES (Recovery)

TREATMENT(WEEK -17)

Grip Strength

Rotarod

IR Activity

Fore limb

In seconds

S - Movement

F - Movement

S - Steriotypic

F - Steriotypic

Group 1R

Mean

597.6

63

58.5

134.4

21.2

120.5

SD

50.64

7.0

8.96

48.79

3.12

27.58

Group 4R

Mean

602.8

64

56.2

134.5

23.4

105.9

SD

64.14

5.8

9.03

66.72

4.77

23.82

 

HEMATOLOGY

MALES

TREATMENT(WEEK -13)

RBC

Hb

PCV

MCV

MCH

MCHC

x106Cells/µL

g/dL

%

fL

pg

g/dL

Group 1

Mean

8.67

15.93

48.12

55.62

18.44

33.14

SD

0.596

0.638

2.312

1.936

0.847

0.806

Group 2

Mean

8.60

15.48

47.56

55.28

18.02

32.59

SD

0.292

0.516

1.506

0.675

0.551

0.764

Group 3

Mean

8.73

15.90

48.23

55.26

18.21

32.95

SD

0.493

0.899

2.733

1.034

0.614

0.789

Group 4

Mean

8.56

15.62

47.10

55.04

18.26

33.15

SD

0.397

0.509

2.085

1.004

0.576

0.737

 

TREATMENT(WEEK -13)

PLT

WBC

RET

DC (%)

PT

APTT

x103cells/µL

x103cells/ µL

%

NEUT

LYMPH

MONO

EOS

BASO

Sec

Sec

Group 1

Mean

718.20

5.66

2.07

17.29

77.93$

1.86

1.42

0.36

15.76

12.16

SD

74.730

1.622

0.285

4.176

4.898

0.643

0.447

0.107

1.009

1.709

Group 2

Mean

706.50

6.01

1.91

21.30

73.65

2.77*

0.83*

0.30

15.67

12.81

SD

86.314

1.839

0.259

6.391

6.094

0.538

0.320

0.067

0.990

1.717

Group 3

Mean

624.10

6.94

1.84

29.37*#

65.03*#

2.95*

1.13

0.32

14.71

11.89

SD

181.323

1.527

0.273

6.484

6.872

0.610

0.633

0.092

0.940

1.225

Group 4

Mean

770.80&

5.77

2.17

26.31*

68.22*

2.78*

1.29

0.26

15.26

12.78

SD

87.519

1.322

0.321

6.552

6.697

0.786

0.522

0.084

0.650

1.495

*Significant at p ≤ 0.05 with Group 1, #- Significant at p ≤ 0.05 with Group 2, &-Significant at p ≤ 0.05 with Group 3

MALES

RECOVERY

(WEEK 17)

RBC

Hb

PCV

MCV

MCH

MCHC

x106Cells/µL

g/dL

%

fL

pg

g/dL

Group 1R

Mean

8.31

14.77

44.85

54.45

17.81

32.95

SD

0.568

0.556

2.227

1.258

0.759

0.664

Group 4R

Mean

8.63

15.19

47.38*

54.25

17.63

32.48

SD

0.289

0.341

1.056

0.755

0.414

0.339

 

RECOVERY

(WEEK 17)

PLT

WBC

RET

 

DC (%)

PT

APTT

x103cells/µL

x103cells/ µL

%

NEUT

LYMPH

MONO

EOS

BASO

Sec

Sec

Group

1R

Mean

808.40

4.55

2.13

26.58

68.11

2.69

1.08

0.23

15.72

12.08

SD

96.212

1.138

0.299

7.319

7.226

0.805

0.457

0.309

1.165

1.067

Group

4R

Mean

811.80

4.39

2.04

23.96

70.26

2.93

1.63

0.19

15.93

12.72

SD

77.334

1.193

0.205

6.263

6.861

0.558

0.862

0.099

1.012

1.173

*Significant at p ≤ 0.05 with Group 1R

FEMALES

TREATMENT(WEEK -13)

RBC

Hb

PCV

MCV

MCH

MCHC

x106Cells/µL

g/dL

%

fL

pg

g/dL

Group 1

Mean

8.08

14.92

45.80

56.76

18.47

32.58

SD

0.468

0.464

2.076

1.213

0.633

0.705

Group 2

Mean

7.90

14.69

44.62

56.49

18.57

32.88

SD

0.234

0.493

1.352

0.656

0.467

0.620

Group 3

Mean

8.00

15.09

45.67

57.10

18.88

33.05

SD

0.295

0.314

1.432

1.140

0.663

0.776

Group 4

Mean

7.90

15.02

45.34

57.43

19.02

33.12

SD

0.279

0.421

1.490

1.059

0.555

0.668

 

TREATMENT(WEEK -13)

PLT

WBC

RET

 

DC (%)

PT

APTT

x103cells/µL

x103cells/ µL

%

NEUT

LYMPH

MONO

EOS

BASO

Sec

Sec

Group 1

Mean

823.80

3.39

1.97

15.77

79.65

2.05

1.16

0.27

15.70

12.74

SD

177.020

0.615

0.398

4.606

4.918

0.357

0.237

0.125

0.738

1.695

Group 2

Mean

874.80

3.80

2.25

16.73

78.68

2.15

0.98

0.28

15.17

12.42

SD

123.591

0.973

0.368

3.823

4.102

0.562

0.249

0.140

0.962

1.040

Group 3

Mean

834.90

3.39

2.13

19.29

76.10

2.28

0.96

0.25

15.43

12.83

SD

66.542

0.684

0.350

6.391

6.784

0.625

0.227

0.085

0.538

1.491

Group 4

Mean

804.20

3.46

2.30

23.41*#

71.28*#

2.61

1.25

0.26

15.15

13.03

SD

78.816

1.787

0.530

5.895

5.780

0.465

0.631

0.324

0.682

1.411

*Significant at p ≤ 0.05 with Group 1, #-Significant at p ≤ 0.05 with Group 2

FEMALES 

RECOVERY

(WEEK 17)

RBC

Hb

PCV

MCV

MCH

MCHC

x106Cells/µL

g/dL

%

fL

pg

g/dL

Group 1R

Mean

7.96

14.81

45.02

56.55

18.57

32.88

SD

0.290

0.463

1.521

0.848

0.490

0.598

Group 4R

Mean

8.15

14.99

46.65

56.63

18.20

32.52

SD

0.476

0.456

1.434

1.821

0.876

0.611

 

RECOVERY

(WEEK 17)

PLT

WBC

RET

DC (%)

PT

APTT

x103cells/µL

x103cells/ µL

%

NEUT

LYMPH

MONO

EOS

BASO

Sec

Sec

Group

1R

Mean

833.10

2.78

1.78

13.63

81.82

1.99

1.37

0.14

16.32

13.11

SD

147.485

0.693

0.220

1.310

7.344

0.191

0.744

0.097

0.665

0.971

Group

4R

Mean

758.30

1.68*

1.64

18.22

76.59

2.33

1.73

0.14

15.92

12.93

SD

96.524

0.441

0.179

4.682

5.053

0.576

0.538

0.117

0.866

1.108

 *Significant at p ≤ 0.05 with Group 1R

CLINICAL BIOCHEMISTRY (CONTD.)

MALES

TREATMENT(WEEK 13)

GLU

UREA

BUN

CREA

CHOL

TRIGL

AST

ALT

ALP

mmol/L

mmol/L

mmol/L

µmol/L

mmol/L

mmol/L

U/L

U/L

U/L

Group 1

Mean

9.51

5.48

2.56

43.06

1.81

0.53

62.00

34.13

77.42

SD

1.754

1.219

0.570

8.132

0.350

0.190

5.219

4.551

26.735

Group 2

Mean

10.21

5.53

2.59

37.86

1.97

0.69

61.70

34.80

88.55

SD

2.161

1.512

0.706

5.190

0.284

0.245

5.582

4.177

21.158

Group 3

Mean

9.76

6.01

2.81

47.12#

2.02

1.03

75.40*#

41.87

133.35*

SD

1.813

1.199

0.560

6.666

0.460

1.096

13.237

9.319

66.920

Group 4

Mean

9.11

5.76

2.67

46.12

2.00

0.70

81.76*#

45.30*

122.34*

SD

1.129

0.899

0.401

9.777

0.407

0.263

14.515

13.528

59.983

 

TREATMENT(WEEK 13)

BIL

GGT

Na

K

Cl

TPO

ALB

GLB

A/G

µmol/L

U/L

mmol/L

mmol/L

mmol/L

g/L

g/L

g/L

_

Group 1

Mean

1.48

0.00

142.26

3.64

108.03

67.57

44.74

22.84

2.04

SD

0.710

0.00

1.095

0.141

0.762

3.973

2.785

3.824

0.554

Group 2

Mean

0.85

0.00

141.21

3.70

107.94

66.82

43.73

23.09

1.90

SD

0.620

0.00

1.526

0.259

0.991

3.612

3.176

1.287

0.158

Group 3

Mean

1.03

0.00

142.07

3.79

107.87

67.63

43.83

24.32

1.86

SD

0.773

0.00

1.470

0.348

0.913

3.246

1.984

3.275

0.276

Group 4

Mean

1.18

0.00

141.89

3.84

108.28

66.10

44.20

21.90

2.03

SD

0.719

0.00

1.265

0.429

0.399

2.692

1.213

1.733

0.125

*-Significant at p ≤ 0.05 with Group 1, # - Significant at p ≤ 0.05 with Group 2.

MALES

RECOVERY

(WEEK 17)

GLU

UREA

BUN

CREA

CHOL

TRIGL

AST

ALT

ALP

mmol/L

mmol/L

mmol/L

µmol/L

mmol/L

mmol/L

U/L

U/L

U/L

Group 1R

Mean

10.54

6.33

2.96

41.13

2.10

0.62

60.67

34.29

65.86

SD

1.389

0.800

0.374

4.603

0.318

0.125

14.096

15.181

9.311

Group 4R

Mean

9.76

6.28

2.94

38.20

2.27

0.72

61.80

32.32

53.69*

SD

1.132

1.147

0.536

4.274

0.171

0.174

9.370

5.683

11.373

 

RECOVERY

(WEEK 17)

BIL

GGT

Na

K

Cl

TPO

ALB

GLB

A/G

µmol/L

U/L

mmol/L

mmol/L

mmol/L

g/L

g/L

g/L

_

Group 1R

Mean

1.03

0.00

145.12

3.85

106.84

63.74

41.47

22.27

2.22

SD

0.589

0.00

1.137

0.408

1.206

1.817

5.333

5.806

1.613

Group 4R

Mean

0.76

0.00

145.47

3.89

106.92

64.70

43.52

21.18

2.06

SD

0.540

0.00

0.943

0.300

0.884

1.791

2.282

1.128

0.198

*-Significant at p ≤ 0.05 with Group 1R

FEMALES

TREATMENT(WEEK 13)

GLU

UREA

BUN

CREA

CHOL

TRIGL

AST

ALT

ALP

mmol/L

mmol/L

mmol/L

µmol/L

mmol/L

mmol/L

U/L

U/L

U/L

Group 1

Mean

7.66

6.28

2.94

43.85

1.62

0.48

60.84

26.78

40.67

SD

1.816

2.645

1.236

11.498

0.387

0.176

9.058

6.606

29.926

Group 2

Mean

9.18

6.51

3.04

45.10

1.77

0.51

61.47

29.19

39.15

SD

1.686

1.475

0.689

5.859

0.358

0.089

7.767

5.150

14.333

Group 3

Mean

8.73

6.89

3.22

50.84*

1.86

0.59

79.24*#

29.03

57.04

SD

1.079

1.168

0.546

7.642

0.433

0.193

16.562

8.981

40.442

Group 4

Mean

9.39

7.37

3.51

47.81

1.70

0.62

69.84

30.18

44.01

SD

1.404

1.354

0.637

6.199

0.317

0.365

10.845

10.816

22.765

 

TREATMENT(WEEK 13)

BIL

GGT

Na

K

Cl

TPO

ALB

GLB

A/G

µmol/L

U/L

mmol/L

mmol/L

mmol/L

g/L

g/L

g/L

_

Group 1

Mean

1.64

0.00

140.46

3.44

107.85

69.48

50.21

19.27

2.64

SD

0.990

0.00

1.153

0.163

1.801

4.462

4.020

2.315

0.390

Group 2

Mean

0.96

0.00

140.20

3.48

107.42

71.99

51.58

20.42

2.62

SD

0.398

0.00

1.391

0.246

1.900

3.685

4.016

3.709

0.573

Group 3

Mean

1.39

0.00

140.97

3.49

107.76

71.60

50.55

21.05

2.45

SD

0.930

0.00

1.018

0.529

0.706

3.045

3.468

2.581

0.431

Group 4

Mean

1.38

0.00

140.05

3.58

108.20

70.38

51.71

18.68

2.79

SD

0.972

0.00

1.400

0.520

1.194

4.139

4.585

1.509

0.408

*- Significant at p ≤ 0.05 with Group 1,#-Significant at p ≤ 0.05 with Group 2.

FEMALES

RECOVERY

(WEEK 17)

GLU

UREA

BUN

CREA

CHOL

TRIGL

AST

ALT

ALP

mmol/L

mmol/L

mmol/L

µmol/L

mmol/L

mmol/L

U/L

U/L

U/L

Group 1R

Mean

9.58

8.12

3.80

40.86

1.53

0.56

65.66

31.59

25.98

SD

1.565

0.903

0.368

2.538

0.378

0.074

23.576

10.057

10.694

Group 4R

Mean

9.09

9.33*

4.36*

45.81*

2.18

0.47

61.93

26.50

23.38

SD

1.623

0.926

0.433

4.525

0.355

0.115

11.343

5.049

5.666

 

RECOVERY

(WEEK 17)

BIL

GGT

Na

K

Cl

TPO

ALB

GLB

A/G

µmol/L

U/L

mmol/L

mmol/L

mmol/L

g/L

g/L

g/L

_

Group 1R

Mean

1.31

0.00

144.31

3.49

106.33

68.42

49.61

18.81

2.68

SD

0.854

0.00

1.318

0.199

1.193

3.014

3.541

1.981

0.462

Group 4R

Mean

1.00

0.00

144.34

3.50

106.42

72.16

53.58*

18.58

3.26

SD

0.566

0.00

1.582

0.299

2.126

7.046

3.022

4.991

1.698

*Significant at p ≤ 0.05 with Group 1R.

URINE ANALYSIS

MALES

TREATMENT (Week 13)

Volume

SG

pH

Pro

GLU

KET

UBG

BIL

Color

Clarity

mL

-

-

mg/dl

-

mg/dl

mg/dl

mg/dl

-

-

Group 1

Mean

5.97

1.02

8.50

37.50

0.00

5.00

0.00

0.00

NA

NA

SD

0.691

0.002

0.527

39.528

0.000

4.082

0.000

0.000

NA

NA

Group 2

Mean

5.54

1.01*

8.20

17.50

0.00

3.00

0.00

0.00

NA

NA

SD

0.629

0.003

1.033

12.076

0.000

2.582

0.000

0.000

NA

NA

Group 3

Mean

5.43

1.02*

8.15

17.50

0.00

3.50

0.00

0.10

NA

NA

SD

0.519

0.005

1.375

12.076

0.000

4.743

0.000

0.316

NA

NA

Group 4

Mean

5.10*

1.02

8.35

50.00

0.00

4.00

0.00

0.00

NA

NA

SD

0.556

0.003

0.944

44.096

0.000

4.595

0.000

0.000

NA

NA

 

TREATMENT (WEEK 13)

ERY

LEU

EPI

RBC

PUS

CAST

CRY

SPER

/µL

/µL

/field

/field

/field

/field

/field

/field

Group 1

Mean

0.00

117.50

0.90

0.00

0.00

0.00

2.30

0.00

SD

0.000

138.969

0.316

0.000

0.000

0.000

0.823

0.000

Group 2

Mean

0.00

125.00

0.90

0.00

0.00

0.00

2.50

0.00

SD

0.000

135.401

0.316

0.000

0.000

0.000

0.850

0.000

Group 3

Mean

1.00

67.50

1.00

0.00

0.00

0.00

2.20

0.00

SD

3.162

42.573

0.000

0.000

0.000

0.000

1.033

0.000

Group 4

Mean

1.00

150.00

1.00

0.00

0.00

0.00

2.10

0.00

SD

3.162

187.824

0.000

0.000

0.000

0.000

0.738

0.000

Key: NA = Not Applicable,*Significant at p ≤ 0.05 with Group 1.

MALES

RECOVERY (Week 17)

Volume

SG

pH

Pro

GLU

KET

UBG

BIL

Color

Clarity

mL

-

-

mg/dl

-

mg/dl

mg/dl

mg/dl

-

-

Group 1R

Mean

5.82

1.02

8.20

70.00

0.00

4.50

0.10

0.00

NA

NA

SD

0.469

0.003

0.789

151.291

0.000

4.378

0.316

0.000

NA

NA

Group 4R

Mean

5.41

1.01

8.40

42.50

0.00

4.50

0.00

0.00

NA

NA

SD

0.769

0.002

0.699

28.988

0.000

4.378

0.000

0.000

NA

NA

 

RECOVERY (Week 17)

ERY

LEU

EPI

RBC

PUS

CAST

CRY

SPER

/µL

/µL

/field

/field

/field

/field

/field

/field

Group

1R

Mean

12.50

80.00

0.90

0.00

0.00

0.00

2.60

0.00

SD

17.678

149.443

0.316

0.000

0.000

0.000

0.843

0.000

Group

4R

Mean

1.00

117.50

1.00

0.00

0.00

0.00

2.70

0.20

SD

3.162

138.969

0.000

0.000

0.000

0.000

0.823

0.422

Key: NA = Not Applicable

FEMALES

TREATMENT (Week 13)

Volume

SG

pH

Pro

GLU

KET

UBG

BIL

Color

Clarity

mL

-

-

mg/dl

-

mg/dl

mg/dl

mg/dl

-

-

Group 1

Mean

5.36

1.02

8.60

85.00

0.00

2.50

0.10

0.00

NA

NA

SD

0.602

0.000

0.516

153.749

0.000

4.859

0.316

0.000

NA

NA

Group 2

Mean

5.82

1.02

8.80

37.50

0.00

2.00

0.00

0.00

NA

NA

SD

0.643

0.003

0.422

44.49

0.000

4.830

0.000

0.000

NA

NA

Group 3

Mean

5.41

1.02

8.90

20.00

0.00

3.50

0.00

0.00

NA

NA

SD

0.540

0.003

0.316

22.973

0.000

4.743

0.000

0.000

NA

NA

Group 4

Mean

5.37

1.02

8.90

82.50

0.00

3.50

0.40

0.00

NA

NA

SD

0.699

0.003

0.316

149.560

0.000

4.743

1.265

0.000

NA

NA

 

TREATMENT (WEEK 13)

ERY

LEU

EPI

RBC

PUS

CAST

CRY

/µL

/µL

/field

/field

/field

/field

/field

Group 1

Mean

0.00

92.50

1.00

0.00

0.00

0.00

2.70

SD

0.000

148.160

0.000

0.000

0.000

0.000

0.823

Group 2

Mean

0.00

132.50

1.00

0.00

0.00

0.00

2.50

SD

0.000

196.515

0.000

0.000

0.000

0.000

0.850

Group 3

Mean

0.00

50.00

0.90

0.00

0.00

0.00

2.60

SD

0.000

44.096

0.316

0.000

0.000

0.000

1.075

Group 4

Mean

2.50

92.50

1.00

0.00

0.00

0.00

2.40

SD

7.906

148.160

0.000

0.000

0.000

0.000

1.075

Key: NA = Not Applicable

FEMALES 

RECOVERY (Week 17)

Volume

SG

pH

Pro

GLU

KET

UBG

BIL

Color

Clarity

mL

-

-

mg/dl

-

mg/dl

mg/dl

mg/dl

-

-

Group 1R

Mean

5.13

1.02

8.40

72.50

0.00

2.50

0.00

0.00

NA

NA

SD

0.457

0.002

0.699

151.589

0.000

2.635

0.000

0.000

NA

NA

Group 4R

Mean

5.25

1.02

8.40

162.50

0.00

5.00

0.10

0.00

NA

NA

SD

0.703

0.003

0.699

186.059

0.000

5.774

0.316

0.000

NA

NA

 

RECOVERY (Week 17)

ERY

LEU

EPI

RBC

PUS

CAST

CRY

/µL

/µL

/field

/field

/field

/field

/field

Group

1R

Mean

5.00

47.50

0.80

0.00

0.00

0.00

2.60

SD

10.541

36.228

0.422

0.000

0.000

0.000

1.506

Group

4R

Mean

0.00

110.00

0.90

0.00

0.00

0.00

1.80

SD

0.000

142.009

0.568

0.000

0.000

0.000

0.632

Key: NA = Not Applicable

ORGAN WEIGHTS (G)

MALES  

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

Body Weight (G)

Mean

369.47

360.84

364.16

355.55

394.22

396.05

SD

37.01

32.47

28.26

42.83

29.22

29.14

N

10

10

10

10

10

10

Adrenals

Mean

0.0882

0.1584

0.0904

0.0916

0.0879

0.0886

SD

0.0262

0.2056

0.0220

0.0413

0.0181

0.0177

N

10

10

10

10

10

10

Kidneys

Mean

2.0028

1.9861

2.0283

2.0210

2.0407

2.0053

SD

0.2367

0.1940

0.1235

0.2424

0.1787

0.1864

N

10

10

10

10

10

10

Liver

Mean

10.0878

10.0878

10.3265

10.4688

10.8801

11.3502

SD

1.2526

1.2525

0.9455

1.4035

1.2492

0.8907

N

10

10

10

10

10

10

Heart

Mean

1.1699

1.1751

1.1510

1.2151

1.2401

1.1954

SD

0.1596

0.1235

0.1039

0.1373

0.1623

0.1102

N

10

10

10

10

10

10

Thymus

Mean

0.4725

0.4662

0.4653

0.4646

0.4347

0.4638

SD

0.0962

0.0700

0.0652

0.1016

0.0933

0.0683

N

10

10

10

10

10

10

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

Spleen

Mean

0.7067

0.6786

0.6670

0.6829

0.6731

0.7299

SD

0.1865

0.1228

0.0676

0.1051

0.0978

0.0997

N

10

10

10

10

10

10

Testes

Mean

3.9717

3.9355

3.9715

3.9018

3.7815

4.0577

SD

0.2906

0.2662

0.2892

0.3083

0.3458

0.2464

N

10

10

10

10

10

10

Epididymides

Mean

1.6972

1.6259

1.6547

1.6242

1.6922

1.7497

SD

0.1265

0.1590

0.1632

0.1931

0.1807

0.1652

N

10

10

10

10

10

10

Prostate + Seminal vesicles with coagulating gland

Mean

2.8477

2.7193

2.8320

2.5825

3.0185

3.1790

SD

0.2176

0.3672

0.4523

0.2898

0.4887

0.4975

N

10

10

10

10

10

10

Brain

Mean

2.1798

2.1177

2.1717

2.1813

2.1824

2.1123

SD

0.0894

0.0818

0.1193

0.0941

0.0653

0.1032

N

10

10

10

10

10

10

FEMALES

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

Body Weight (G)

Mean

214.8

216.2

215.0

202.0

223.2

214.8

SD

11.33

19.30

16.90

11.44

11.59

15.96

N

10

10

10

10

10

10

Adrenals

Mean

0.1049

0.1012

0.1006

0.1022

0.1106

0.1084

SD

0.0306

0.0397

0.0297

0.0278

0.0147

0.0213

N

10

10

10

10

10

10

Kidneys

Mean

1.5102

1.4336

1.4582

1.3354

1.4855

1.3923

SD

0.1102

0.1435

0.1783

0.1618

0.1164

0.1493

N

10

10

10

10

10

10

Liver

Mean

7.0277

7.0319

7.2701

6.6108

6.9474

6.8568

SD

0.5982

0.8065

0.9244

0.6169

0.8519

0.8777

N

10

10

10

10

10

10

Heart

Mean

0.8961

0.8668

0.8401

0.8359

0.8643

0.9149

SD

0.0950

0.0887

0.1118

0.0798

0.0933

0.2533

N

10

10

10

10

10

10

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

 

Thymus

Mean

0.3618

0.3923

0.3553

0.3340

0.3215

0.2984

SD

0.0683

0.0499

0.0726

0.0443

0.0645

0.0789

N

10

10

10

10

10

10

Spleen

Mean

0.4599

0.4720

0.4976

0.4787

0.5188

0.4749

SD

0.1710

0.0721

0.0668

0.0735

0.0700

0.0737

N

10

10

10

10

10

10

Ovaries

Mean

0.1880

0.2528

0.1864

0.1662

0.1867

0.1719

SD

0.0441

0.1440

0.0315

0.0378

0.0399

0.0465

N

10

10

10

10

10

10

Uterus

Mean

0.7340

0.9319

0.7671

0.8519

0.7735

0.7830

SD

0.0471

0.3839

0.2269

0.3005

0.1508

0.1130

N

10

10

10

10

10

10

Brain

Mean

2.0723

2.0588

2.0869

1.9738

2.0267

2.0657

SD

0.1224

0.1395

0.1025

0.1207

0.0893

0.1561

N

10

10

10

10

10

10

1.1       ORGAN WEIGHT RATIO (%)

MALES

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

Body Weight (G)

Mean

369.47

360.84

364.16

355.55

394.22

396.05

SD

37.01

32.47

28.26

42.83

29.22

29.14

N

10

10

10

10

10

10

Adrenals

Mean

0.0246

0.0253

0.0249

0.0269

0.0225

0.0225

SD

0.0097

0.0050

0.0059

0.0144

0.0053

0.0050

N

10

10

10

10

10

10

Kidneys

Mean

0.5423

0.5507

0.5582

0.5694

0.5185

0.5066

SD

0.0385

0.0284

0.0302

0.0354

0.0415

0.0359

N

10

10

10

10

10

10

Liver

Mean

2.7925

2.7926

2.8364

2.9438*

2.7641

2.8677

SD

0.1806

0.1806

0.1589

0.1594

0.2920

0.1270

N

10

10

10

10

10

10

Heart

Mean

0.3164

0.3262

0.3161

0.3408

0.3147

0.3019

SD

0.0243

0.0281

0.0149

0.0264

0.0341

0.0181

N

10

10

10

10

10

10

Thymus

Mean

0.1276

0.1292

0.1285

0.1308

0.1103

0.1174

SD

0.0213

0.0151

0.0200

0.0243

0.0237

0.0175

N

10

10

10

10

10

10

*Significant at p ≤ 0.05 with Group 1

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

Spleen

Mean

0.1913

0.1871

0.1833

0.1922

0.1713

0.1848

SD

0.0465

0.0192

0.0129

0.0211

0.0250

0.0244

N

10

10

10

10

10

10

Testes

Mean

1.0800

1.0951

1.0939

1.1063

0.9610

1.0271

SD

0.0786

0.0854

0.0894

0.1096

0.0788

0.0620

N

10

10

10

10

10

10

Epididymides

Mean

0.4620

0.4531

0.4555

0.4597

0.4301

0.4438

SD

0.0421

0.0555

0.0441

0.0536

0.0428

0.0512

N

10

10

10

10

10

10

Prostate + Seminal vesicles with coagulating gland

Mean

0.7749

0.7536

0.7794

0.7332

0.7727

0.8093

SD

0.0672

0.0714

0.1166

0.0972

0.1584

0.1557

N

10

10

10

10

10

10

Brain

Mean

0.5955

0.5905

0.5986

0.6207

0.5565

0.5359

SD

0.0657

0.0494

0.0444

0.0699

0.0469

0.0450

N

10

10

10

10

10

10

FEMALES

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

Body Weight (G)

Mean

214.8

216.2

215.0

202.0

223.2

214.8

SD

11.33

19.30

16.90

11.44

11.59

15.96

N

10

10

10

10

10

10

Adrenals

Mean

0.0492

0.0473

0.0472

0.0511

0.0498

0.0505

SD

0.0156

0.0204

0.0144

0.0154

0.0081

0.0098

N

10

10

10

10

10

10

Kidneys

Mean

0.7046

0.6634

0.6778

0.6598

0.6667

0.6487

SD

0.0585

0.0378

0.0618

0.0535

0.0560

0.0561

N

10

10

10

10

10

10

Liver

Mean

3.2733

3.2555

3.3861

3.2715

3.1076

3.1889

SD

0.2270

0.2767

0.4064

0.2250

0.2989

0.2723

N

10

10

10

10

10

10

Heart

Mean

0.4182

0.4018

0.3904

0.4139

0.3873

0.4273

SD

0.0483

0.0358

0.0380

0.0340

0.0366

0.1243

N

10

10

10

10

10

10

Organs

TREATMENT

RECOVERY

Group 1

Group 2

Group 3

Group 4

Group 1R

Group 4R

 

Thymus

Mean

0.1681

0.1832

0.1648

0.1649

0.1447

0.1396

SD

0.0275

0.0314

0.0291

0.0155

0.0320

0.0389

N

10

10

10

10

10

10

Spleen

Mean

0.2147

0.2186

0.2315

0.2366

0.2321

0.2209

SD

0.0797

0.0293

0.0268

0.0296

0.0247

0.0283

N

10

10

10

10

10

10

Ovaries

Mean

0.0881

0.1176

0.0876

0.0829

0.0831

0.0802

SD

0.0228

0.0680

0.0184

0.0215

0.0170

0.0226

N

10

10

10

10

10

10

Uterus

Mean

0.3433

0.4333

0.3587

0.4170

0.3486

0.3646

SD

0.0371

0.1807

0.1134

0.1243

0.0769

0.0463

N

10

10

10

10

10

10

Brain

Mean

0.9689

0.9570

0.9736

0.9801

0.9104

0.9659

SD

0.0975

0.0852

0.0526

0.0857

0.0642

0.0943

N

10

10

10

10

10

10

Applicant's summary and conclusion

Conclusions:
In conclusion, under the conditions of this experiment the No Observed Adverse Effect Level (NOAEL) was 400 mg/kg body weight.
Executive summary:

The test item Hordaphos MDB was administered daily by oral route to Wistar rats for a period of 90 consecutive days. A recovery period of 28 days without test item treatment was included in this study.

Three groups consisting of 10 male and 10 female rats each were treated at dose levels of 50, 200 and 400 mg/kg, respectively.Concurrently, vehicle control, vehicle control recovery and test item high dose recovery groups (400 mg/kg) were used in the present study.

All the animals survived up to the scheduled sacrifice.

No test item related changes in clinical signs, detailed clinical observation, functional observation battery, ophthalmic examination findings, organ weight and body weight changes were noted. The dullness observed in the in high dose (G4 & G4R) were considered to be without toxicological relevance.

Minor changes in hematological, clinical biochemistry, body weight, feed consumption and urine analysis were recorded at the end of treatment and recovery periods, but the variations were considered incidental as there was no dose dependent trend in the observed variations and the respective tissues revealed no abnormalities in macroscopic and histopathological examination.

Post-mortem examinations revealed no test item-related macroscopic findings in treated animals.

Microscopic examination revealed abnormalities in non glandular stomach attributable to the test item HORDAPHOS MDB at 50, 200 and 400 mg/kg bw in both sexes. The lesion was considered non adverse as complete recovery was observed at the end of 28 day recovery period.