Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw, OECD 423, EU Method B.1 tris, EPA OPPTS 870.1100, Matting (2013).

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:
15 January 2013 to 30 January 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: CRL:(WI)
- Age at study initiation: Young healthy adult rats, 9 – 10 weeks old.
- Weight at study initiation: 202 – 211 g
- Fasting period before study: Overnight.
- Housing: Standard housing conditions, in groups of three per cage. Type II polypropylene/polycarbonate cages were used.
- Diet: Complete diet for rats and mice was provided ad libitum.
- Water: Tap water from the municipal supply was provided ad libitum.
- Acclimation period: at least 12 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2 – 21.9 °C
- Humidity (%): 34 – 66 %
- Air changes (per hr): 15 – 20 air exchanges/hour.
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 15 January 2013 To: 30 January 2013.
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test material was freshly formulated at a concentration of 200 mg/mL in the vehicle, on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Two groups of three females were dosed.
Control animals:
no
Details on study design:
- Dosing procedure: Initially, three females (Group 1) were dosed, and then based on the observations a further group of three females (Group 2) were dosed.
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
> Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
> Body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in either Group 1 or 2.
Clinical signs:
Treatment at the dose level of 2000 mg/kg bw caused vocalisation (3/6), hunched back (6/6), irritability (3/6). Group 1 was symptom free from 6 hours after the treatment and Group 2 was symptom free from one day after the treatment. See Table 1 for results.
Body weight:
Body weight gains of treated animals during the study showed no indication of a treatment related effect, see Table 2 for results.
Gross pathology:
There was no evidence of any gross findings at a dose level of 2000 mg/kg bw.

Table 1: Clinical Observations

Group No.

Animal No.

Observation

Observation Time

Frequency

30 min

1 h

2 h

3 h

4 h

6 h

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7-14

1

8897

Symptom Free

-

-

-

-

-

+

+

+

+

+

+

+

+

15/20

Vocalisation

+

+

+

-

-

-

-

-

-

-

-

-

-

3/20

Irritability

1

1

-

-

-

-

-

-

-

-

-

-

-

2/20

Hunched Back

+

+

+

+

+

-

-

-

-

-

-

-

-

5/20

8898

Symptom Free

-

-

-

-

-

+

+

+

+

+

+

+

+

15/20

Vocalisation

+

+

-

-

-

-

-

-

-

-

-

-

-

2/20

Irritability

1

1

-

-

-

-

-

-

-

-

-

-

-

2/20

Hunched Back

+

+

+

+

+

-

-

-

-

-

-

-

-

5/20

8899

Symptom Free

-

-

-

-

-

+

+

+

+

+

+

+

+

15/20

Vocalisation

+

+

-

-

-

-

-

-

-

-

-

-

-

2/20

Irritability

1

1

-

-

-

-

-

-

-

-

-

-

-

2/20

Hunched Back

+

+

+

+

+

-

-

-

-

-

-

-

-

5/20

2

8900

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Hunched Back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

8901

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Hunched Back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

8902

Symptom Free

-

-

-

-

-

-

+

+

+

+

+

+

+

14/20

Hunched Back

+

+

+

+

+

+

-

-

-

-

-

-

-

6/20

+ = present; - = absent

Frequency of observations = number of occurance of observation/ total number of observations

Severities: 1 = Slight/Small/Few; 2 = Moderate/Medium; 3 = Market/Large/Many

 

Table 2: Body Weight

Group No.

Animal No.

Body weight (g)

Day

Body Weight Gain (g)

Days

-1

0

7

14

-1 - 0

0 - 7

7 - 14

-1 - 14

1

8897

223

208

235

265

-15

27

30

42

8898

223

210

229

242

-13

19

13

19

8899

215

202

226

244

-13

24

18

29

2

8900

218

211

237

245

-7

26

8

27

8901

211

202

244

249

-9

42

5

38

8902

205

195

228

234

-10

33

6

29

Mean:

215.8

204.7

233.2

246.5

-11.2

28.5

13.3

30.7

Standard Deviation:

7.1

6.1

6.8

10.3

3.0

8.0

9.5

8.2

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female Wistar rats.
Executive summary:

The acute oral toxicity of the test material was determined in a GLP study conducted in line with OECD 423, EU Method B.1 tris and EPA OPPTS 870.110, according to the acute toxic class method.

A total of six fasted female Wistar rats were exposed to the test material at 2000 mg/kg bw by oral gavage. Individuals were observed for mortality, clinical signs of toxicity, bodyweight gain and then submitted for necropsy 14 days after exposure.

Initially, three female animals were treated with the test material at 2000 mg/kg bw. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines.

Under the conditions of the test no mortality was observed, individual weight gain showed no signs of treatment related effects, and t here was no evidence of any gross findings at necropsy. Clinical signs were observed in some individuals, vocalisation (3/6), hunched back (6/6), irritability (3/6). However, Group 1 was symptom free from 6 hours after the treatment and Group 2 was symptom free from one day after the treatment.

Based on these observations the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female Wistar rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The quality of the dataset is considered to be good and sufficient for classification and labelling purposes.

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

Oral Toxicity

The acute oral toxicity of the test material was determined in a GLP study conducted in line with OECD 423, EU Method B.1 tris and EPA OPPTS 870.110, according to the acute toxic class method.

A total of six fasted female Wistar rats were exposed to the test material at 2000 mg/kg bw by oral gavage. Individuals were observed for mortality, clinical signs of toxicity, bodyweight gain and then submitted for necropsy 14 days after exposure.

Initially, three female animals were treated with the test material at 2000 mg/kg bw. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines.

Under the conditions of the test no mortality was observed, individual weight gain showed no signs of treatment related effects, and t here was no evidence of any gross findings at necropsy. Clinical signs were observed in some individuals, vocalisation (3/6), hunched back (6/6), irritability (3/6). However, Group 1 was symptom free from 6 hours after the treatment and Group 2 was symptom free from one day after the treatment.

Based on these observations the acute oral LD50 of the test material was determined to be > 2000 mg/kg bw in female Wistar rats.


Justification for selection of acute toxicity – oral endpoint
This is the only acute toxicity study available for this substance. The study was conducted in line with GLP and standardised guidelines, according to the acute toxic class method. The study was assigned a reliability score of 1 in line with the principles for assessing data quality as defined in Klimisch (1977). This study was therefore considered suitable to be assigned as the key study for this endpoint.

Justification for classification or non-classification

Oral Toxicity

In accordance with Regulation (EC) No. 1272/2008, the test material does not meet the criteria for classification as an oral toxicant.

Dermal and Inhalation Toxicity

In the absence of dermal and inhalation toxicity data, the substance is not classifed for either of these endpoints.