Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

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 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
A total of five animals were therefore treated at a dose level of300 mg/kg in the study. All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5 female
Control animals:
no
Details on study design:
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14. Due to a technician error the body weight at death was not performed on the animal treated at a dose level of 2000 mg/kg that was humanely killed 4 hours after dosing. At the end ofthe observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
The following computerized system was used in the study:
Delta Controls - ORCA view

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Signs of hunched posture and lethargy were noted during the day of dosing in the initial treated animal. No other clinical observations were noted
Body weight:
All animals showed expected gains in body weight over the observation period except for two females who showed an expected gain in body weight during the first week but a body weight loss during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Body weight

    Dose Level mglkg Animal Number    and Sex        Body Weight (g) at Day     Body Weight Gain (g) During Week
 0 7 14 1

2

2000 

 

 

 

 

 

 

 

 

 1-0 Female

 176

 189

 200

 13

 11

 2-0 Female

 184

 197

 217

 13

 20

 2-1 Female

 195

 214

 213

 19

 -1

 2-2 Female

 181

 198

 205

 17

 7

 2-3 Female

 198

 218

 206

 20

 -12

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System − Unclassified).
Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test item, as a solution in dimethyl sulfoxide, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. There were no deaths.

Clinical Observations. Signs of hunched posture and lethargy were noted during the day of dosing in the initial treated animal. No other clinical observations were noted

Body Weight. All animals showed expected gains in body weight over the observation period except for two females who showed an expected gain in body weight during the first week but a body weight loss during the second week.

Necropsy. No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System - Category 4).