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Administrative data

Description of key information

The substance was found to not cause mortality in a recent acute oral toxicity test in accordance with OECD and GLP guidelines.

Additional inhalation and dermal acute toxicity testing is not deemed to be needed.

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:
31.05.- 21.06.2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17th December 2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Frambinon methyl ether
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females
- Age at study initiation: 7 weeks old
- Weight at study initiation: 170.9−181.5 g
- Fasting period before study: animals were fasted overnight, approximately 16 hours
- Housing: Stainless wire mesh cage (260W×350D×210H mm)
- Diet: ad libitum, pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C)
- Water: ad libitum, public tap water
- Acclimation period: 4 days after 3 days of quarantine (including health examiniation)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4−23.3
- Humidity (%): 43.1−59.7
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark, 150-300 Lux
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 400 mg/mL
- Lot/batch no. (if required): MKBV2080V

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: due to the low expected toxicity of the test substance a starting dose of 2000 mg/kg was selected.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Step 1: 3
Step 2: 3
Control animals:
no
Details on study design:
- Duration of observation period following administration:14 days
- Frequency of observations: all animals were observed for mortality, general condition and clinical signs 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Day 1−Day 14)
- Necropsy of survivors performed: yes
- Other examinations performed: since no gross findings were observed at necropsy, histopathological examinations were not performed.
Statistics:
Statistical analysis was not performed. Mean scores and values are determined.
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
Abnormal gait was observed in three to four animals from 0.5 to 6 hours after dosing at 2000 mg/kg. A decrease of fecal volume was observed in five animals on Day 1, and it disappeared on Day 2. Therefore, the clinical signs were considered to be test substance-related effects.
Body weight:
A tendency for suppression of body weight gain was observed in three animals at 2000 mg/kg on Day 1. Then, normal body weight gain was observed in these animals from Day 3. Therefore, these changes were considered to be test substance-related effects.
Gross pathology:
No abnormal morphological findings were observed in any animal at 2000 mg/kg.

Individual Body Weights

Step/
Dose (mg/kg)

Animal ID

 

Days after dosing

 

Gain (g)

 

0

1

3

7

14

0 ~ 14

Step 1
2000

2101

186.3

195.7

206.2

224.6

248.6

62.3

2102

182.3

193.9

206.1

222.9

247.6

65.3

2103

183.7

201.3

215.3

231.2

247.4

63.7

Mean

184.1

197.0

209.2

226.2

247.9

63.8

S.D.

2.0

3.9

5.3

4.4

0.6

1.5

N

3

3

3

3

3

3

Step 2

2000

2201

193.3

211.1

229.2

235.7

250.5

57.2

2202

185.9

195.4

214.6

220.7

227.8

41.9

2203

190.5

197.5

218.7

233.3

252.1

61.6

Mean

189.9

201.3

220.8

229.9

243.5

53.6

S.D.

3.7

8.5

7.5

8.1

13.6

10.3

n

3

3

3

3

3

3

 

 

 

 

 

 

 

 

Conclusions:
Based on the result, the acute oral LD50 (rat) for the test item was determined to be >= 5000 mg/kg (cut-off).
Executive summary:

The purpose of this study was to assess the potential toxicity of the test item following a single oral dose administration to female Sprague-Dawley rats and to classify the test substance under the category of GHS classification. The study was performed according to OECD guideline 423 and under GLP.

Two dose groups of three females each were utilized as follows:

Groups 1 and 2 (Steps 1 and 2): 2000 mg/kg of the test substance

Steps 1−2: A dose of 2000 mg/kg was administered and then, there was no mortality (Step 1). A second dose of 2000 mg/kg was administered (Step 2).

All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration.
They were subjected to a gross necropsy at the end of the observation period.

There were no deaths of animals at 2000 mg/kg. Abnormal gait was observed in animals on the day of dosing at 2000 mg/kg. A decrease of fecal volume was observed in animals on Day 1, and it disappeared on Day 2. A tendency for suppression of body weight gain was observed in three animals at 2000 mg/kg on Day 1. Then, normal body weight gain was observed in these animals from Day 3. No test substance-related effects were observed in necropsy findings in any animal at 2000 mg/kg.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance was classified as Category 5 or Unclassified according to the GHS classification and the median lethal dose derived was: LD50 cut off ≥ 5,000 mg/kg b.w.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In accordance with Regulation 1272/2008 on Classification, labelling and packaging of substances and mixtures (CLP) classification for acute toxicity is not needed as the substance has an LD50 value of 5000 mg/kg bw/d.