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SUMMARY OF THE STUDY

The purpose of this study was to evaluate the acute oral toxicity study of LAS02 in female Sprague Dawley rat model. The study was performed as per OECD guideline 420 for acute oral toxic city. Animals were acclimatized in standard animal house environmental conditions at least for 5 days before the start of experiment. On last day acclimatization, the animals were randomized on the basis of their body weight. The study was initiated by limit test procedure. Total 25 animals were selected with female sex ( age 8 to 12 weeks; with mean body weight range 180±5 g) and divided into five groups . Each group of animals has 5 female rat. In limit test procedure, initially one animal was dosed at 5000 mg/kg .Since at this dose level, animal was survived then further four additional animals were dosed approximately after 24 to 48 hours. A total 5 animals were dosed at every dose levels. Same procedure was followed for other respective groups. After each dose levels, each group of animals were observed mortality, clinical sign of toxicity and any behavioral changes after post dosing for 5, 15 30minutes and once daily for 14 days. Body weight and feed consumption were recorded daily up to 14 days. Our findings showed that No effects of toxicity or moralities were observed post dosing and during the 14-day observation period in any of the animals. All five rats gained body weight by Day 7 and at the end of the study. At the end of the 14-day observation period, each animal was sacrificed and submitted for gross necropsy. No gross pathological findings were observed in organs of any rat during necropsy. Based on the foregoing results, the acute oral LD50 in rats of the test article, LAS 02 was found to be in excess of 5000 mg/kg. Therefore, the test article is considered not to present a significant acute toxic risk if swallowed. The Globally Harmonized System of Classification and Labelling of Chemicals classifies compounds in which the estimated LD50 is greater than 2000 mg/kg with no deaths or evidence of toxicity as being Category 5 chemicals. The Office of Prevention, Pesticides and Toxic Substances classifies compounds in which the estimated LD50 is greater than 5000 mg/kg with no deaths or evidence of toxicity as being Category IV chemicals. On the basis of above findings and classification of label as GSH &OPPTS, Las02 is safe and test substance under category 5 &IV.

OBJECTIVE

The objective of this study was to provide information on health hazards likely to a rise from a short term exposure of test substance LAS02 by oral route in female Sprague dawley rats.

SAFETY PRECAUTIONS

Personal protection equipments like gloves, masks, aprons, footwear were employed as requirederm while handling the test item and test system.

MATERIALS AND METHODS

Description of the Test Procedure

Sprague dawley rats (25 female) weighting 180±5g was used for the study. All animals to be acclimatized in Standard animal house environment for at least 5 days before initiation of experiment. After the acclimatization, animals to be randomized into five groups of 5 animals each. The study was initiated by limit test procedure. In limit test procedure, initially one animal was dosed at 5000 mg/kg .Since at this dose level, animal was survived then further four additional animals were dosed approximately after 24 to 48 hours. A total 5 animals were dosed at every dose levels. Group I was treated with 5000 mg/kg at dose 10 ml/kg body weight , whereas group II treated with 5500mg/kg and group III treated 6000mg/kg. Group IV animals were treated with test item LAS02 at the dose level 7000mg/kg and last group V was treated with test item LAS01 at the dose level 10000mg/kg body weight. All animals were located into groups as given below.

 

 

Groups No of animal/Sex Dose regimen Doses (mg/kg body weight) Test Item
I 5 F Single 5000 mg/kg LAS02
II 5 F Single 5500 mg/kg LAS02
III 5 F Single 6000 mg/Kg LAS02
IV 5 F Single 7000mg/kg LAS02
V 5 F Single 10000 mg/kg LAS02

 

 

Each group of animals were administrated dose (Ascending orders order after 24 hour observation) and observed clinical sign of toxicity and mortality and body weight and food consumption record measurement for 14 days.

OBSERVATIONS

Body weight

All group of each animals were recorded body weight per day for 14 days.

Feed intake

Each cage of animals were offered 150 gm per day pelleted feed and consumption was recorded next day for 14 days. Feed intake by animals were calculated by deducting the amount of feed consumed from the feed offered. The feed consumption was recorded throughout the experiment for 14 days

Clinical signs of toxicity

Clinical signs of toxicity were observed in individual animal of treated groups per day twice daily for 14 days. All clinical signs of toxicity were recorded per day in raw data sheet for 14days .

Mortality

All animals were observed twice daily for morbidity/mortality during the entire experimental period for 14 days.

Necropsy pathology

Necropsy was performed for each group of animals in severe distress/ morbid condition and end of the study for observation of lesions in organs related to any test item related toxicity

RESULTS

 

Days 1st 7th day 14th day p values
G1(5000mg/Kg) 180.2 ± 1.92 231.2 ± 6.72 265.6±8.0 P<0.0001
G2 (5500 mg/Kg) 180.2 ± 1.48 233.2 ± 8.58 268.4±1.82 P<0.0001
G3 (6000mg/Kg) 180.6 ± 0.89 231.4 ± 12.0 271.6±5.27 P<0.0001
G4 (7000mg/kg) 180.4 ±3.43 241.2 ± 5.93 266.6±4.21 P<0.0001
G5 (10000mg/Kg) 180.4 ± 1.51 238.0 ± 11.0 274.4±4.93 P<0.0001
All data are mean ± SD of each groups for 14 days at 1st, 7th and 14th day. Newman Kurl post t test was performed between 1st, 7th and 14th days for statistical significance . Where P<0.0001 is highly significant.

 

CONCLUSION

On the basis of above parameters, it is concluded that the test item LAS02 was found to be safe in excess of 5000 mg/kg. Therefore, the test article is considered not to present a significant acute toxic risk if swallowed. The Globally Harmonized System of Classification and Labelling of Chemicals classifies compounds in which the estimated LD50 is greater than 2000 mg/kg with no deaths or evidence of toxicity as being Category 5 chemicals. The Office of Prevention, Pesticides and Toxic Substances classifies compounds in which the estimated LD50 is greater than 5000 mg/kg with no deaths or evidence of toxicity as being Category IV chemicals. On the basis of above findings and classification of label as GSH &OPPTS, Las02 is safe and test substance under category 5 &IV and LD50 is more than 5000 mg/kg through oral route in female SD rat.

Histological analysis of organs

 

Liver

Figure A
Spleen

Figure B
Heart

Figure C
Kidney

Figure D
Lung

Figure E
Brain

Figure F
Intestine

Figure G
Colon and elementary canal

Figure H