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Description of key information

Acute oral toxicity: OECD TG 420: LD50 >2000 mg/kg bw.

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 17 January 2018 and 13 February 2018.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliability 1 is assigned because the study conducted according to OECD TG 420 in compliance with GLP, without deviations that influence the quality of the results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Specific details on test material used for the study:
Identification: FRET 11-0539
Physical state / Appearance: clear colourless liquid
Storage Conditions: room temperature in the dark
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Animal Information
Female Wistar (RccHan™:WIST) strain rats were supplied by Envigo RMS (UK) Limited, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the mean body weight of any previously treated animals.

Animal Care and Husbandry
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Route of administration:
oral: gavage
Vehicle:
other: 2000 mg/kg dose level: unchanged (no vehicle) 300 mg/kg dose level: arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL
- Justification for choice of vehicle: Arachis oil was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: at 300 mg/kg = 10 mL/Kg at 2000 mg/kg = 2.24 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.

TEST ITEM PREPARATION AND ANALYSIS:
- The test item was formulated within 2 hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
300 mg/kg: 1 animal/female
2000 mg/kg: 5 animals/female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed 30 minutes, 1, 2 and 4 hours after application and thereafter daily for up to 14 days.
- Necropsy of survivors performed: yes, at the end of the observation period the 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.
- Body weights: Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths at 300 mg/kg and 2000 mg/kg dose levels.
Clinical signs:
No signs of systemic toxicity were noted during the observation period at 300 mg/kg and 2000 mg/kg dose levels.
Body weight:
All animals showed expected gains in bodyweight over the observation period at 300 mg/kg and 2000 mg/kg dose levels.
Gross pathology:
No abnormalities were noted at necropsy at 300 mg/kg and 2000 mg/kg dose levels.

Individual Clinical Observations and Mortality Data - 300mg/kg

Dose Level (mg/kg)

Animal 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

300

1-0
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Individual Bodyweights and Bodyweight Changes -300mg/kg

Dose Level

(mg/kg)

Animal Number
and Sex

Body Weight (g) at Day

Body Weight Gain (g)
During Week

0

7

14

1

2

300

1-0 Female

162

190

211

28

21

Individual Necropsy Findings -300 mg/kg

Dose Level
(mg/kg)

Animal Number
and Sex

Time of Death

Macroscopic Observations

300

1-0 Female

Killed Day 14

No abnormalities detected

Individual Clinical Observations and Mortality Data - 2000mg/kg

Dose Level (mg/kg)

Animal 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

2-0
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3
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

Individual Bodyweights and Bodyweight Changes - 2000mg/kg

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

2-0 Female

157

178

191

21

13

3-0 Female

190

212

226

22

14

3-1 Female

191

202

227

11

25

3-2 Female

173

190

214

17

24

3-3 Female

174

188

204

14

16

 

Individual Necropsy Findings - 2000mg/kg

Dose Level
(mg/kg)

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

3-0 Female

Killed Day 14

No abnormalities detected

3-1 Female

Killed Day 14

No abnormalities detected

3-2 Female

Killed Day 14

No abnormalities detected

3-3 Female

Killed Day 14

No abnormalities detected

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: CLP
Conclusions:
The acute oral toxicity test showed an LD50 of >2000 mg/kg bw
Executive summary:

Acute oral toxicity: In this study, 1 female Wistar strain rat was administered the substance at dose levels of 300 mg/kg bw followed by 5 female Wistar strain rats that were administered the substance at dose levels of 2000 mg/kg bw.

The rats showed 0 mortality, clinical signs, body weight, necropsy.The acute oral LD50 for the substance in female rats was determined to be >2000 mg/kg bw. The substance is considered as unclassified based on CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity: In this study, 1 female Wistar strain rat was administered the substance at dose levels of 300 mg/kg bw followed by 5 female Wistar strain rats that were administered the substance at dose levels of 2000 mg/kgbw.

The rats showed 0 mortality, clinical signs, body weight, necropsy.The acute oral LD50 for the substance in female rats was determined to be >2000 mg/kg bw. The substance is considered as unclassified based on CLP.

Justification for classification or non-classification

According to the criteria outlined in Annex I of 67/548/EEC (DSD) and Annex VI of 1272/2008/EC (CLP), the substance does not have to be classified as acute toxic by the oral route.