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Description of key information

In accordance with Regulation (EC) No. 1907/2008, Annex VII, one key study for the endpoint acute oral toxicity has been performed. The study was performed in accordance with OECD 420 and under the conditions of GLP.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 14 August 2018 and 31 August 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of Inspection: 18 July 2017 - 20 July 2017 Date of Issue: 28 November 2017
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 20171106
- Expiration date of the lot/batch: 10 April 2020

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark


FORM AS APPLIED IN THE TEST (if different from that of starting material) : suspension

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: No data available. The body weight variation did not exceed ±20% of the mean body weight of any previously treated animals.
- Fasting period before study: Overnight immediately before dosing
- Housing: housed in groups of up to four in suspended solid-floor polypropylene cages furnished with softwood flake bedding.
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK provided ad libitum
- Water: mains drinking water provided ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): At least fifteen
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): The volume administered to each animal was calculated according to the fasted body weight at the time of dosing
- Justification for choice of vehicle: Arachis oil was used because the test item did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose
Doses:
2000 mg/kg
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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, early and late during normal working days, and once daily at weekends and public holidays.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
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:
No signs of systemic toxicity were noted during the observation period
Body weight:
All animals showed expected gains in body weight over the observation period
Gross pathology:
No abnormalities were noted at necropsy.

Appendix 1 Individual Clinical Observations and Mortality Data

Dose Level (mg/kg)

Animals Number and Sex

Effects Noted After Dosing (Hours)

Effects Noted During Period After Dosing (Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

 

 

 

2000

1-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 = No signs of systemic toxicity

Appendix 2 Individual Body Weights and Body Weight Changes

Dose Level (mg/kg)

Animal Number and Sex

Body Weight (g) at Day

Body Weight Gain (g) During Week

0

7

14

1

2

 

 

2000

1-0 Female

159

174

182

15

8

2-0 Female

163

174

189

11

15

2-1 Female

177

192

204

15

12

2-2 Female

174

179

195

5

16

2-3 Female

173

193

209

20

16

 

Appendix 3 Individual Necropsy Findings

Dose Level (mg/kg)

Animal Number and Sex

Time of Death

Macroscopic Observations

 

 

2000

1-0 Female

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

2-3 Female

Killed Day 14

No abnormalities detected

 

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).
The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures
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 suspension in arachis oil BP, 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. There were no signs of systemic toxicity.

Body Weight. All animals showed expected gains in body weight.

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 greater than 2000 mg/kg body weight (Globally Harmonized Classification System 􀀐 Unclassified).

The test item did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Key study is performed in accordance with an appropriate OECD guideline and under the conditions of GLP.

Additional information

Justification for classification or non-classification

The substance is not anticipated to be classified based on the information available and in accordance with Regulation (EC) No. 1272/2008.