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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
data is from experimental report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Principles of method if other than guideline:
Acute Oral toxicity test was carried out to study the effects of test chemical on rats.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name of test material (IUPAC name): Sodium salicylate
- Common name: Monosodium salicylate
- Molecular formula: C7H6O3.Na
- Molecular weight: 160.1035 g/mol
- Smiles notation: c1(c(cccc1)O)C(=O)[O-].[Na+]
- InChl: 1S/C7H6O3.Na/c8-6-4-2-1-3-5(6)7(9)10;/h1-4,8H,(H,9,10);/q;+1/p-1
- Substance type: Organic

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Age:7 to 9 weeks
Sex: Female, nulliparous and non pregnant. It has been observed that females are generally more sensitive than males to toxic effects
Body weight range:200±20g
Identification:By cage tag and corresponding colour body marking
Acclimation:One week in experimental room after veterinary examination.
Randomization:After acclimation and veterinary examination randomly selected in groups of three females.
Nutritional conditions:Fasted overnight prior to treatment. Food was offered three hours after dosing.
Husbandry
Environmental conditions:Air conditioned rooms with 10-15 air changes per hour, temperature between 22-25 0C, relative humidity 40-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
Accommodation:Groups of three animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
Diet:Pelleted feed
Water: Aqua Guard filter water was kept in PVC bottles, ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
- Concentration in vehicle: 2000 mg/kg b. wt and 300 mg/kg b. wt
- Amount of vehicle (if gavage):10 ml/kg b.wt
Doses:
No. of dose groups:Three + one vehicle control
Group I: Dist. water, 10ml/kg body wt.
Group II : 2000 mg/kg body wt.
Group III : 300 mg/kg body wt.
Group IV : 300 mg/kg body wt.
No. of animals per sex per dose:
No. of animals per dose group:Three (3 females)/step
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: BODY WEIGHT: The body weight of all animals was observed weekly on day 0 (pre treatment),7th and 14th (post treatment).
CLINICAL SIGNS: The treated animals were closely observed for clinical signs of intoxication ,first 4 hours and every 1 hours interval for 24 hrs after dosing and thereafter twice a day for 14 days.All rats were observed at least twice daily to observe any clinical signs or behavioral changes.
- Necropsy of survivors performed: yes,necropsy was carried out on all animals which died during the study or surviving animals were sacrified at the end of the study to observe any gross pathological changes.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology study:The organ which showed gross pathological change during necropsy subjected for histopathological study.
Statistics:
no data available

Results and discussion

Preliminary study:
no data available
Effect levels
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
Dose level 300 mg/kg b.wt
Step-I: The test compound did not produce any mortality throughout observation period.
Step-II: The test compound did not produce any mortality throughout the period of observation.
Dose level 2000 mg/kg b.wt.
All the Wistar albino rats died within the 4 hrs. of administration of test compound.
Clinical signs:
Dose level 300 mg/kg b.wt- Test compound did not produce any clinical signs of intoxication throughout the observation period of 14 days.
Dose level 2000 mg/kg b.wt- Test compound produced high to sever signs of intoxication viz; abdominal respiration, convulsion, tremor and hind leg paralysis and finally death after 4 hrs.
Body weight:
All the animals treated with test chemical at the dose level of 300 mg/kg b.wt showed decrease in normal gain in body weight on day 7th as compared to control group. Whereas, on day 14th all the rats showed normal gain weight as compared to control group
Gross pathology:
Necropsy finding:
A.EXTRENAL:
i:skin: skin and hair coat was observed wet
ii:all external orifices: normal
B.INTERNAL:
i:subcutaneous: no change was observed
ii:superficial and deep lymph node: no change in mesenteric lymph node
ABDOMINAL CAVITY:
i. opening and general examination: in the abdominal cavity all the organs were present in normal position
ii. spleen: normal upto highest tested dose level 2000 mg/kg bw
iii. digestive sysytem: no gross changes were observed in stomach and intestine upto highest tested dose level 2000 mg/kg bw
iv. liver and biliary ducts: no gross pathological changes were observed
v. excretory sysytem: no gross pathological changes were observed upto highest tested dose level 2000 mg/kg bw
vi. adrenal: observed normal
vii. male/female genital organs: showed normal color,consistancy and no inflammartory changes upto highest tested dose level 2000 mg/kg bw
2. THORACIC CAVITY:
i. opening and general examination: thoracic cavity was found to be normal withut any fluid,mucous or blood etc.
ii. lungs: severe congestion was observed at the dose level of 2000 mg/kg bw
iii. heart: no changes were observed in color and consistancy. heart found normal upto highest tested dose level 2000 mg/kg bw
iv. thyroid: normal in shape,size and surface upto highest tested dose level 2000 mg/kg bw
3. CRANIAL CAVITY:
brain: normal in shape and size
Other findings:
no data available

Any other information on results incl. tables

SUMMARY OF BODY WEIGHT (GM)

Group

Day 0

Day 7

% Gain/loss

Day 14

% Gain/loss

Group-I distilled water 10ml/kg

211.10

215.91

3.76

219.5

6.28

Group-II

2000 mg/kg b. wt

205.11

-

-

-

-

Group-III

300 mg/kg b. wt

211.91

215.51

1.69

218.26

5.99

Group-IV

300 mg/kg b. wt

204.98

209.65

2.27

211.1

6.44

CLINICAL SIGNS AND MORTALITY

Group: I (Vehicle Control)                                                           Dose: 10 ml/kg b.wt

                                                                                                                                 

                                                           

FEMALE RATS

 

 

 

Parameters

Incidence of clinical signs observed after dosing

Mortality

Day 0

DAY

Min

Hour

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total*

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 

0/3

 

Clinical Signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

0         =   No clinical sign (Normal)

+         =   Clinical Sign

CLINICAL SIGNS AND MORTALITY

Group: II                                                                                           Dose: 2000 mg/kg b. wt.

 

FEMALE RATS

 

 

Parameters

Incidence of clinical signs observed after dosing

Mortality

Day 0

DAY

Min

Hour

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total*

Mortality (total)

0

0

0

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 

 

3/3

Clinical Signs

3

3

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Convulsion

++

+++

+++

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Tremor

++

+++

++++

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Abdominal respiration

+++

+++

+++

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Paralysis

++

+++

+++

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

 0           =   Normal

+            =    Mild

++           =   Moderate

+++         =    High

++++      =   Severe

CLINICAL SIGNS AND MORTALITY

Group: III                                                                                          Dose: 300 mg/kg b.wt

                                            

 

FEMALE RATS

 

 

Parameters

Incidence of clinical signs observed after dosing

Mortality

Day 0

DAY

Min

Hour

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

0/3

Clinical Signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

0            =   Normal

+            =    Mild

++           =   Moderate

+++         =   High

 ++++=        Severe

CLINICAL SIGNS AND MORTALITY

Group: IV                                                                                         Dose: 300 mg/kg b.wt.

FEMALE RATS

 

 

Parameters

Incidence of clinical signs observed after dosing

Mortality

Day 0

DAY

Min

Hour

30

1

2

4

6

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Total*

Mortality (total)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

0/3

Clinical Signs

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

0            =   Normal

+            =    Mild

++           =   Moderate

+++         =   High

++++      =   Severe

SUMMARY OF NECROPSY FINDINGS

 

S. No.

 

Fate

 

Wistar albino rats

Dose (mg/kg b. wt)

Distilled water (10 ml/kg)

 

2000

 

 

300

 

300

1

Terminal sacrifice

3/3

0/3

3/3

3/3

2

Found Dead

0/3

3/3

0/3

0/3

3

Abnormalities detected

NAD

Severe congestion

In lung

NAD

NAD

 

 

NAD - No abnormality recorded

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: I (Vehicle Control)                                                           Dose: 10ml/kg b.wt

                                                                                                                    

FEMALE RATS

 

Animal ID

Fate

Time

Gross Findings

20161-1

TS

Day 14

NAD

20161-2

TS

Day 14

NAD

20161-3

TS

Day 14

NAD

 

Day 0 is the day of dose administration.

TS- Terminal Sacrifice

NAD- No abnormality Detected

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: II                                                                                            Dose: 2000 mg/kg b.wt.                  

FEMALE RATS

 

Animal ID

Fate

Time

Gross Findings

20161-4

FD

4 hrs.

 

Severe congestion in lungs

20161-5

FD

4 hrs.

20161-6

FD

4 hrs.

 

Day 0 is the day of dose administration.

TS- Terminal Sacrifice

NAD- No abnormality Detected

FD- Found Dead

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The lethal concentration (LD50) cut-off value for acute oral toxicity test was considered to be 1000 mg/kg bw, when female wistar albino rats were treated with test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).
Executive summary:

The acute oral toxicity study of the given test chemical was conducted in wistar albino rats under the OECD Guideline-423 for testing of chemicals. The healthy wistar albino rats of body weight 200±20 gm were selected for study after acclimatization to standard laboratory condition and divided into test group and vehicle control group each having three animals. The study was conducted stepwise as follow: Starting dose 2000 mg/kg body weight: The test chemical was mixed with distilled water and administered orally at the dose level of 2000 mg/kg body weight (dose volume 10ml/kg) to three female rats. However; vehicle control group treated with the distilled water at the dose level of 10 ml/kg b.wt.  The treated animals were closely observed continuously for clinical signs of intoxication during first four hours of test compound administration. Thereafter, all the animals were observed periodically at one hour interval for 24 hrs and once daily for a period of 14 days.  The necropsy was performed on all animals died during the study. The Wistar albino rats treated with the test chemical showed convulsion, tremor, abdominal respiration, hind leg paralysis condition and death within the 4 hrs of administration of test compound. No clinical signs and mortality were observed in vehicle control group. The necropsy finding showed severe congestion in lungs of the test group. Furthermore, no gross pathological change was observed in vehicle control group. Final dose 300 mg/kg body weight: Step -I: The test chemical was mixed with distilled water and administered orally at the dose level of 300 mg/kg body wt. (dose volume 10 ml/kg) to three female rats. All the animals were closely observed individually for clinical sign of toxicity and mortality once in 30 minutes, 1, 2, 4 and 6 hrs intervals during the first 24 hrs and thereafter, once daily for a period of 14 days. Necropsy was conducted on all the animals at the termination of study. The test chemical administered at the dose level of 300 mg/kg b.wt did not produce any mortality throughout the observation period of 14 days. Furthermore, no clinical signs toxicity was recorded in any of the treated rats throughout the period of observation. The necropsy finding did not show any gross pathological changes. Step -II: After 72 hrs, the result of step-I was confirmed by administration of same dose level (300 mg/kg. b.wt) of test chemical in additional three animals of same sex (OECD-423 guidelines). The test chemical administered at the dose level of 300 mg/kg b.wt did not produce any mortality and clinical sign of intoxication throughout the observation period of 14 days. The test chemical did not elicit any gross pathological changes in animals sacrificed at the end of experimentation. The lethal concentration (LD50) cut-off value for acute oral toxicity test was considered to be 1000 mg/kg bw, when female wistar albino rats were treated with test chemical orally via gavage according to OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).