Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Experimental test result performed using standard test guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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:
The aim of this study was to assess the toxicity potential of test chemical after single oral administration in rats and an observation period of 14 days.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Name: Zinc distearate
Molecular Formula: C36H70O4.Zn
Molecular Weight: 632.335 g/mole
Appearance: Free flowing white powder
AI Content (purity): 99.86%

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:In-House Bred at Sa-Ford, Animal Facility(CPCSEA Registration No. 1256/bc/09/CPCSEA)
- Age at study initiation:8- 10 weeks at the time of dosing
- Weight at study initiation:Minimum: 137 g Maximum: 168 g (Individual body weights were within ± 8% prior to treatment after overnight fasting)
-Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant
- Housing:The animals were housed individually in polycarbonate cages.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No 400004
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles
- Acclimation period:Animal nos. 1-3 were acclimatized for 6 days and 4-6 for 9 days prior to administration of the test item.
-Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
-Cages and water bottle:All the cages and water bottles were changed at least twice every week
ENVIRONMENTAL CONDITIONS
Temperature : Minimum: 19.80°C Maximum: 23.20°C
Relative humidity:Minimum: 48.60 % Maximum: 63.20 %
Light-dark-rhythm:12:12
Air Changes: More than 12 changes per hour
IN-LIFE DATES: From: May 07, 2014 To: May 27 and 30, 2014

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle :10 ml
- Justification for choice of vehicle:Corn oil was selected as a vehicle because test item was not soluble in distilled water.
- Lot/batch no. (if required):MKBD4650
- Purity:N/A
MAXIMUM DOSE VOLUME APPLIED:10 ml/kg body weight.
Doses:
G1/ 2000mg/kgbw
No. of animals per sex per dose:
6 Females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:daily
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical Observation:- After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all surviving animals were observed once a day during the 14 day observation period.
Mortality - All animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
Body weight - All rats were weighed on days 0 (prior to dosing), 7 and 14.
Pathology - At the end of 14 day observation period, all rats were euthanised by overdose of CO2 for external and internal observations.
Statistics:
not specified

Results and discussion

Preliminary study:
not specified
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No effect on mortality, clinical sign, body weight and gross pathology
Mortality:
No mortality was observed througout the experimentation period in treated female rats.
Clinical signs:
At 2000mg/kg, all the six animals were observed with normal clinical sign till day 14
Body weight:
Mean body weight of animals treated with 2000mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0
Gross pathology:
No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice
Other findings:
not specified

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) andBody Weight Change

Sex:Female

Animal No.

Group/ Dose (mg/kg)

Body Weight (gram)

Body Weight Change (%)

Day 0

Day 7

Day 14

Day

0-7

Day

0-14

1

G1/ 2000

137

169

177

23.36

29.20

2

154

174

188

12.99

22.08

3

139

165

183

18.71

31.65

4

147

175

191

19.05

29.93

5

147

182

194

23.81

31.97

6

168

194

207

15.48

23.21

Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

Sex:Female

Group/ Dose (mg/kg)

Rats Body Weight (g)

Body Weight Changes (%)

Day 0

Day 7

Day 14

0-7

0-14

 

G1/ 2000

Mean

148.67

176.50

190.00

18.90

28.01

SD

11.29

10.33

10.28

4.26

4.30

n

6

6

6

6

6

Keys:SD = Standard Deviation, n = Number of Animals

Table 3: Individual Animal Clinical Signs and Symptoms

 Sex:Female

Animal No.

Group/ Dose (mg/kg)

Hours (Day 0)

1/2

1

2

3

4

1

G1/ 2000

1

1

1

1

1

2

1

1

1

1

1

3

1

1

1

1

1

4

1

1

1

1

1

5

1

1

1

1

1

6

1

1

1

1

1

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Conclusions:
The acute oral LD50 was considered to be >2000 mg/kg body weight, when Wistar female rats were treated with test chemical orally by gavage.


Executive summary:

Acute oral toxicity study of test chemical performed on Rats as per OECD No. 423. Six female Wistar rats were selected for acute oral toxcity. Rats were fasted for 16 to 18 hours, prior to dosing (water was given ad libitum). After test item administration, feed was withheld for a further 4 hours. The time interval between dosing was determined by the onset, duration and severity of toxic signs Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. At 2000mg/kg, all the six animals were observed with normal clinical sign till day 14 . No mortality was observed througout the experimentation period. Mean body weight of animals treated with 2000mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0 .No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice Under the conditions of this; acute oral toxicity study of test chemical in female rats is as given below: The acute oral LD50 value of test chemical was >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not exhibit acute oral toxicity i.e it is acutely non toxic to animals