Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: Key study: Method according to OECD 401, GLP study. The acute oral toxicity LD50 of the test item in rats was 1110 mg/kg bw (both sexes). Supporting studies: Peer reviewed handbook data reported a LD50 of 400 mg/kg in rats and > 800 mg/kg in mice.

Acute inhalation toxicity: Based on peer-reviewed handbook data, the test item has an acute inhalation LC50 of 159 mg/m3 in rats. Data waiving (study scientifically not necessary / other information available): The substance is not classified for acute inhalatory toxicity, according to Annex VI of CLP Regulation (EC) no. 1272/2008.

Acute dermal toxicity: Based on peer-reviewed handbook data, the test item has an acute dermal LD50 of 10 ml/kg in guinea pigs. Data waiving (study scientifically not necessary / other information available): The substance classified as Acute Toxicity, Category 3, according to Annex VI of CLP Regulation (EC) no. 1272/2008.

Acute toxicity: other routes. Peer reviewed handbook data reports an intraperitoneal acute toxicity LC50 value of 10 mg/kg in rats and an intraperitoneal acute toxicity value > 800 mg/kg in mice.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- purity: 99.7%
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Co., Ltd. Japan
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 154-171 (male) - 112-132 (female)
- Fasting period before study: from the day before administration to 3 hours after administration.
- Housing: five animals per cage (same sex)
- Diet: Lab Animals Chow E1 (MF Oriental Yeast Co., Ltd.) ad libitum.
- Water: Tap water filtered through a 5 µm filter, ad libitum. (water quality inspections performed regularly)
- Acclimation period: 6-7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25ºC
- Humidity (%): 40-70%
- Air changes (per hr): 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE: The vehicle and dose selection was based on the results of a preliminary test.
MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg
Doses:
500 (only females), 700, 1000, 1400 and 2000 mg/kg.
No. of animals per sex per dose:
5 male/ 5 female per group
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations of clinical signs and mortality were performed 15, 30 minutes, 1, 2, 4, 6, 7, and 8 hours after administration on the day of administration, and once a day thereafter (up to 14 days). Body weights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 110 other: mg/kg
Based on:
act. ingr.
95% CL:
>= 832 - <= 1 480
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 110 other: mg/kg
Based on:
act. ingr.
95% CL:
>= 877 - <= 1 404
Mortality:
60% of males and females died at concentrations of 1000 and 1400 mg/kg. At 2000 mg/kg, 60% of males and 100% of females died.
Clinical signs:
The following clinical signs were observed in both sexes. These signs were increasing in the first eight hours but the survivors recovered completely: decrease of locomotor activity was seen at 1000 mg/kg and above; hypopnoea was detected at 1400 mg/kg and above, as well as loose stool.
Body weight:
The body weight gain was lower in the 2000 mg/kg male group (females died) and in 1400 mg/kg group in both sexes.
Gross pathology:
Stomach lesions such as focal thickening of the stomach mucosa, adhesion of the stomach and other abdmoninal organs or ulcer were observed from 700 mg/kg in males and from 500 mg/kg in females at necropsy of the animals after the observation period.
In the dead animal's autopsy, the following observations were made: in the heart, there was atrial stretching; at pulmonary level, congestion, edema and/or bleeding, and endotracheal mucus retention were observed; at stomach level, hemorrhage, stomach erosion, ulcer, distension; bleeding, congestion and/or dilatation of the small intestine were observed and finally, yellowing whitening of the liver.

Cumulative mortality/No. of test animals

Sex

Dose

 

Time after administration

Days after administration

Mortality rate

 

mg/kg

15m

30m

1h

2h

4h

6h

7h

8h

1

2

3

4…

14

(%)

male

700

0/5

 

 

 

 

 

 

 

 

 

 

 

0/5

0

1000

0/5

1/5

 

 

 

 

 

 

2/5

3/5

 

 

3/5

60

1400

0/5

 

 

 

 

 

 

 

2/5

3/5

 

 

3/5

60

2000

0/5

 

 

 

 

 

1/5

 

3/5

 

 

 

3/5

60

female

500

0/5

 

 

 

 

 

 

 

 

 

 

 

0/5

0

700

0/5

 

 

 

 

 

 

 

 

 

 

 

0/5

0

1000

0/5

 

 

 

 

 

 

 

2/5

3/5

 

 

3/5

60

1400

0/5

 

 

 

 

 

 

 

3/5

 

 

 

3/5

60

2000

0/5

 

 

3/5

 

 

 

 

5/5

 

 

 

5/5

100

*m: minutes, h: hour(s), d: days.

Mean body weight

Sex

Dose

mg/kg

 

Days after administration

0

7

14

male

700

Mean
SD

Number

162

3.6

5

213

4.2

5

280

10.4

5

1000

Mean
SD

Number

163

6.5

5

210

31.8

2

282

26.2

2

1400

Mean
SD

Number

163

1.3

5

204

0.7

2

265

9.2

2

2000

Mean
SD

Number

163

5.8

5

189

14.8

2

266

15.6

2

female

500

Mean
SD

Number

120

4.7

5

160

8.6

5

187

14.7

5

700

Mean
SD

Number

120

6.6

5

157

10.2

5

181

13.0

5

1000

Mean
SD

Number

119

4.3

5

150

5.7

2

170

6.4

2

1400

Mean
SD

Number

122

6.9

5

156

19.1

2

188

17.7

2

2000

Mean
SD

Number

126

4.7

5

AD

 

*units: g; AD: all animals were dead.

Clinical signs (male): No. of animals with findings / No. of surviving animals

Dose

(mg/kg)

Clinical signs

Time after administration

15 m

30 m

1h

2h

4h

6h

7h

8h

700

Loose stool

 

 

 

 

2/5

 

 

 

 

Normal

 

5/5

5/5

5/5

3/5

5/5

5/5

5/5

5/5

1000

Decrease of locomotor activity

+

1/5

1/4

2/4

 

4/4

4/4

4/4

4/4

Hypopnoea

 

1/5

1/4

2/4

 

 

 

 

 

Salivation

+

4/5

3/4

 

 

 

 

 

 

Loose stool

 

 

 

1/4

1/4

1/4

 

1/4

1/4

Normal

 

1/5

1/4

0/4

3/4

0/4

0/4

0/4

0/4

1400

Decrease of locomotor activity

+

 

4/5

3/5

1/5

4/5

4/5

3/5

3/5

++

 

1/5

 

 

1/5

1/5

 

 

+++

 

 

 

 

 

 

1/5

1/5

Hypopnoea

 

 

3/5

1/5

 

1/5

2/5

2/5

1/5

Salivation

+

2/5

 

 

 

 

 

 

 

Loose stool

 

 

 

2/5

3/5

2/5

 

1/5

2/5

Tiptoe gait

 

 

 

 

 

 

1/5

 

 

Crouching

 

 

 

 

 

 

 

1/5

 

Prone position

 

 

 

 

 

 

 

 

1/5

Normal

 

3/5

0/5

1/5

2/5

0/5

0/5

1/5

1/5

2000

Decrease of locomotor activity

+

 

3/5

5/5

2/5

3/5

3/5

2/4

¾

++

 

 

 

1/5

2/5

2/5

1/4

 

+++

 

 

 

 

 

 

1/4

1/4

Hypopnoea

 

 

2/5

2/5

2/5

2/5

2/5

2/4

1/4

Salivation

+

1/5

1/5

 

 

 

 

 

 

Loose stool

 

 

 

1/5

3/5

3/5

 

3/4

3/4

Crouching

 

 

 

 

 

 

 

1/4

1/4

Normal

 

4/5

1/5

0/5

0/5

0/5

0/5

0/4

0/4

*m: minutes, h: hour(s), d: days; +: slight, ++: moderate; +++: severe.

 

Clinical signs (male):No. of animals with findings / No. of surviving animals

Dose

(mg/kg)

Clinical signs

Days after administration

1

2

3

4

5

6

7

8

9

10

-14d

Normal

 

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

- 5/5

1000

Decrease of locomotor activity

+

2/3

1/2

1/2

1/2

 

 

1/2

1/2

 

 

 

--

1/3

 

 

 

 

 

 

 

 

 

 

Hypopnoea

 

2/3

 

 

 

 

 

1/2

1/2

 

 

 

Soiled perineal region

 

1/3

 

 

 

 

 

 

 

 

 

 

Normal

 

0/3

1/2

1/2

1/2

2/2

2/2

1/2

1/2

2/2

2/2

- 2/2

1400

Decrease of locomotor activity

+

2/3

 

 

 

 

 

 

 

 

 

 

++

1/3

 

 

 

 

 

 

 

 

 

 

Hypopnoea

 

1/3

 

½

 

 

 

 

 

 

 

 

Normal

 

0/3

2/2

½

2/2

2/2

2/2

2/2

2/2

2/2

2/2

- 2/2

2000

Decrease of locomotor activity

+

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hypopnoea

 

 

1/2

2/2

2/2

 

 

 

 

 

 

 

Soiled perineal region

 

2/2

2/2

1/2

1/2

 

 

 

 

 

 

 

Abdominal distention

 

 

2/2

 

 

 

 

 

 

 

 

 

Normal

 

0/2

0/2

0/2

0/2

0/2

0/2

0/2

0/2

2/2

2/2

- 2/2

*m: minutes, h: hour(s), d: days; +: slight, ++: moderate; +++: severe.

 

Clinical signs (female): No. of animals with findings / No. of surviving animals

Dose

(mg/kg)

Clinical signs

Time after administration

15 m

30 m

1h

2h

4h

6h

7h

8h

500

Normal

 

5/5

5/5

5/5

3/5

5/5

5/5

5/5

5/5

700

Loose stool

 

 

 

 

2/5

3/5

 

 

 

Normal

 

5/5

5/5

5/5

3/5

2/5

5/5

5/5

5/5

1000

Decrease of locomotor activity

+

2/5

4/5

 

1/5

3/5

4/5

4/5

3/5

++

1/5

1/5

 

 

 

 

 

1/5

Hypopnoea

 

 

 

 

1/5

1/5

1/5

1/5

1/5

Irrgular respiration

 

1/5

 

 

 

 

 

 

 

Salivation

+

2/5

1/5

 

1/5

 

 

 

 

++

 

1/5

1/5

 

 

 

 

 

Crouching

 

1/5

 

 

 

 

 

 

 

Normal

 

2/5

0/5

4/5

4/5

2/5

1/5

1/5

1/5

1400

Decrease of locomotor activity

+

 

 

1/5

2/5

2/5

2/5

2/5

2/5

++

2/5

3/5

 

 

1/5

2/5

2/5

2/5

Hypopnoea

 

 

2/5

 

 

2/5

2/5

2/5

2/5

Salivation

+

1/5

3/5

 

 

 

 

 

 

Crouching

 

2/5

2/5

 

 

 

1/5

1/5

1/5

Normal

 

3/5

1/5

4/5

3/5

2/5

1/5

1/5

1/5

2000

Decrease of locomotor activity

+

2/5

2/5

2/5

1/2

2/2

2/2

1/2

1/2

++

1/5

2/5

 

1/2

 

 

1/2

1/2

+++

 

1/5

2/5

 

 

 

 

 

Hypopnoea

 

4/5

4/5

3/5

1/2

2/2

2/2

2/2

1/2

Gasping

 

 

 

1/5

 

 

 

 

 

Salivation

+

4/5

4/5

1/5

 

 

 

 

 

Tiptoe gait

 

 

 

 

 

 

 

 

1/2

Crouching

 

 

 

 

 

 

 

 

1/2

Prone position

 

 

1/5

 

 

 

 

 

 

Loose stool

 

 

 

 

1/2

1/2

 

 

1/2

Normal

 

1/5

0/5

0/5

0/2

0/2

0/2

0/2

0/2

*m: minutes, h: hour(s), d: days; +: slight, ++: moderate; +++: severe.

  

Clinical signs (female): No. of animals with findings / No. of surviving animals

Dose

(mg/kg)

Clinical signs

Days after administration

1

2

3

4

5

6

7

8

9

10

-14d

500

Normal

 

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

- 5/5

700

Normal

 

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

5/5

- 5/5

1000

Decrease of locomotor activity

+

2/3

1/2

 

 

 

 

 

 

 

 

 

++

1/3

 

 

 

 

 

 

 

 

 

 

Hypopnoea

 

2/3

 

 

 

 

 

 

 

 

 

 

Normal

 

0/3

1/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

2/2

- 2/2

1400

Decrease of locomotor activity

+

2/2

1/2

1/2

1/2

1/2

1/2

1/2

1/2

 

 

 

Hypopnoea

 

2/2

1/2

2/2

 

 

 

 

 

 

 

 

Tiptoe gait

 

1/2

 

 

 

 

 

 

 

 

 

 

Normal

 

0/2

1/2

0/2

1/2

1/2

1/2

1/2

1/2

2/2

2/2

1/2

2000

-

 

AD

 

 

 

 

 

 

 

 

 

 

*m: minutes, h: hour(s), d: days; +: slight, ++: moderate; +++: severe; AD: all animals were dead.

Autopsy findings (male):No. of animals with findings / No. of animals examined

 

Organ

findings

Dose (mg/kg)

700

1000

1400

2000

Dead animals

Heart

Dilatation of atrium

-

1/3

0/3

3/3

Lung

Congestion/edema

-

1/3

0/3

2/3

Trachea

Mucus stagnation

-

1/3

0/3

0/3

Stomach

Focal hemorrhage (glandular area)

-

1/3

1/3

2/3

Erosion/ulcer (glandular area)

-

2/3

2/3

1/3

dilatation

-

1/3

2/3

1/3

Small intestine

Focal hemorrhage

-

1/3

0/3

0/3

Congestion

-

1/3

0/3

0/3

Dilatation

-

1/3

0/3

0/3

Liver

Yellowish change / whitish dot

-

1/3

1/3

0/3

Urinary bladder

Dark-red urine

-

1/3

0/3

0/3

Normal

 

-

0/3

0/3

0/3

Surviving animals

Stomach

Focal thickening of mucosa (non-glandular area)

5/5

2/2

2/2

2/2

Adhesion (stomach and other abdominal organs)

4/5

2/2

2/2

2/2

Kidney

Dilatation of the renal pelvis

0/5

1/2

0/2

0/2

Normal

 

0/5

0/2

0/2

0/2

 *m: minutes, h: hour(s), d: days; +: slight, ++: moderate; +++: severe; AD: all animals were dead.

Autopsy findings (female):No. of animals with findings / No. of animals examined

 

Organ

findings

 

Dose (mg/kg)

500

700

1000

1400

2000

Dead animals

Heart

Dilatation of atrium

-

-

0/3

1/3

3/5

Lung

Focal hemorrhage

-

-

0/3

0/3

1/5

Trachea

Mucus stagnation

-

-

0/3

0/3

1/5

Stomach

Focal hemorrhage (glandular area)

-

-

2/3

1/3

3/5

Focal hemorrhage (non- glandular area)

-

-

1/3

0/3

0/5

Erosion/ulcer (glandular area)

-

-

0/3

3/3

1/5

dilatation

-

-

1/3

1/3

1/5

Small intestine

Congestion

-

-

1/3

2/3

0/5

Dilatation

-

-

0/3

0/3

1/5

Liver

Yellowish change / whitish dot

-

-

1/3

1/3

1/5

Normal

 

-

-

0/3

0/3

0/5

Surviving animals

Stomach

Focal thickening of mucosa

(non-glandular area)

5/5

5/5

2/2

2/2

-

Adhesion (stomach and other abdominal organs)

4/5

4/5

2/2

2/2

-

Kidney

Dilatation of the renal pelvis

0/5

1/5

0/2

0/2

-

Normal

 

0/5

0/5

0/2

0/2

-

 *m: minutes, h: hour(s), d: days; +: slight, ++: moderate; +++: severe; AD: all animals were dead.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
EU criteria.
Conclusions:
The LD50 for the test substance in the Acute Oral Toxicity test was found to be 1110 mg/kg bw for both sexes.
Executive summary:

The Acute Oral Toxicity Test was performed according to OECD Guideline 401 (GLP Study). Four concentrations of the test substance were assayed in five males (700, 1000, 1400 and 2000 mg/kg) and five in females (500, 700, 1000, 1400 and 2000 mg/kg) in a single dose toxicity test in Crj:CD (SD) rats; 5 male and 5 female per group. All animals were subject to daily observations and weekly determinations of body weight. Necropsy was performed on the day of their death or after sacrifice, at the end of the observation period. 60% of males and females died at concentrations of 1000 and 1400 mg/kg. At 2000 mg/kg, 60% of males and 100% of females died. Decreased locomotor activity was seen at 1000 mg/kg and above; hypopnoea and loose stool were detected at 1400 mg/kg and above. These signs increased in the first eight hours but survivors recovered completely. The body weight gain was lower in the 2000 mg/kg male group (females died) and in 1400 mg/kg group in both sexes. Autopsies showed stomach lesions at all doses tested. The LD50 for the test item in rats was found to be 1110 mg/kg bw for both sexes.

Endpoint:
acute toxicity: oral
Type of information:
other: data from peer-reviewed handbook
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
Data from peer reviewed handbook. No information provided on methods.
GLP compliance:
no
Remarks:
reference dated 6-14-63.
Test type:
other: not specified.
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Doses:
Range 200 - 3200 mg/kg.
No. of animals per sex per dose:
10 rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: up to 5 days
- Other examinations performed: clinical signs, body weight.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
400 mg/kg bw
Based on:
not specified
Mortality:
Deaths reported at 5h - 5 days.
Clinical signs:
Slight to quite weak, rough coat, sides caved in, diarrhea.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
EU criteria.
Conclusions:
The test item has an acute oral LD50 = 400 mg/kg bw in rats.
Executive summary:

According to 'Sax’s Dangerous Properties of Industrial Materials. 11th ed. (2004)' (peer reviewed handbook data), the test item has an acute oral LD50 = 400 mg/kg bw in rats.

Endpoint:
acute toxicity: oral
Type of information:
other: data from peer-reviewed handbook
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
Data from peer reviewed handbook. No information provided on methods.
GLP compliance:
no
Remarks:
reference dated 6-14-63.
Test type:
other: not specified.
Limit test:
no
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10%
Doses:
Dose range 200 - 800 mg/kg bw.
No. of animals per sex per dose:
6 mice.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: up to 5 days.
- Other examinations performed: clinical signs, body weight.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 800 mg/kg bw
Based on:
not specified
Clinical signs:
Normal to moderate weakness, rough coat.
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
EU criteria.
Conclusions:
The test item has an acute oral LD50 > 800 mg/kg bw in mice.
Executive summary:

According to 'Sax’s Dangerous Properties of Industrial Materials. 11th ed. (2004)' (peer reviewed handbook data), the test item has an acute oral LD50 > 800 mg/kg bw in mice.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 110 mg/kg bw
Quality of whole database:
The study is a GLP study and has Klimisch score 2.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
other: data from peer-reviewed handbook
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
Data from peer reviewed handbook. No information provided on methods.
GLP compliance:
no
Remarks:
reference dated 6-14-63.
Test type:
other: not specified
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: gas washing bottle heated in a water bath at 50ºC.
- Temperature, humidity, pressure in air chamber: Chamber temperature 25ºC.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
0.159 mg/L (18.9 ppm), 0.417 mg/L (49.5 ppm), and 1.32 mg/L (156.7 ppm).
No. of animals per sex per dose:
3 rats per dose (sex not specified).
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: up to 14d.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight.
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
159 mg/m³ air
Based on:
not specified
Exp. duration:
6 h
Mortality:
- Dose 0.159 mg/L (18.9 ppm): 0/3 after 6h, 1/3 in 48h.
- Dose 0.417 mg/L (49.5 ppm): 0/3 after 6h, 3/3 in 48h.
- Dose 1.32 mg/L (156.7 ppm): 0/3 after 6h, 1/3 in 24h.
Clinical signs:
- Dose 0.159 mg/L (18.9 ppm): after 5 minutes, pilo-erection and vasodilation were observed.
- Dose 0.417 mg/L (49.5 ppm): after 5 minutes, pilo-erection; after 10 minutes, lacrimation; after 15 minutes, vasodilation.
- Dose 1.32 mg/L (156.7 ppm): after 5 minutes, pilo-erection; after 10 minutes, blinking, lacrimation; after 15 minutes, vasodilation; after 6h, dyspnea.
Body weight:
- Dose 0.159 mg/L (18.9 ppm): after 14 days, 1 rat + 34 g; 1 rat - 13 g.
- Dose 1.32 mg/L (156.7 ppm): after 14 days, 1 rat - 79 g.

Under test conditions, the acute inhalation LC50 value was found to be 159 mg/m3 (0.159 mg/L; 18.9 ppm) in rats.

Interpretation of results:
study cannot be used for classification
Remarks:
EU criteria.
Conclusions:
The acute inhalation LC50 value was found to be 159 mg/m3 in rats.
Executive summary:

According to 'Sax’s Dangerous Properties of Industrial Materials. 11th ed. (2004)' (peer reviewed handbook data), the test item has an acute inhalation LC50 of 159 mg/m3 in rats.

Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
No further testing on the substance is deemed necessary since there is valid data available to allow classification of the substance according to the rules laid down in Regulation (EC) no. 1272/2008 (CLP).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
159 mg/m³
Quality of whole database:
The study is a supporting study and has Klimisch score 3.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
other: data from peer-reviewed handbook
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
Data from peer reviewed handbook. No information provided on methods.
GLP compliance:
no
Remarks:
reference dated 6-14-63.
Test type:
other: not specified.
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
Not specified. Observations up to 14 d.
Doses:
1.0 - 10.0 ml/kg
No. of animals per sex per dose:
2 animals.
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, body weight.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
10 mL/kg bw
Based on:
not specified
Mortality:
No.
Clinical signs:
Moderate to gross edema, #3 erythema or hemorrhagic. Eschar over entire patch at 1 week. #2 eschar, heavy scarring, no hair or heavy black eschar at 2 weeks.
Interpretation of results:
study cannot be used for classification
Remarks:
EU criteria.
Conclusions:
The test item has an acute dermal LC50 of 10 ml/kg in guinea pigs.
Executive summary:

According to 'Sax’s Dangerous Properties of Industrial Materials. 11th ed. (2004)' (peer reviewed handbook data), the test item has an acute dermal LC50 of 10 ml/kg in guinea pigs.

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
No further testing on the substance is deemed necessary since there is valid data available to allow classification of the substance according to the rules laid down in Regulation (EC) no. 1272/2008 (CLP).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
10 mg/kg bw
Quality of whole database:
The study is a supporting study and has Klimisch score 3.

Additional information

Acute oral toxicity: Key study. Method according OECD 401 (GLP study). Five male and five female Crj:CD (SD) rats per group were orally administered a single dose of the test item at concentrations of 500 - 2000 mg/kg bw. All animals were subject to daily observations and weekly determinations of body weight; necropsy was performed after animal's death. Based on the results, the acute oral LD50 in male and female rats was determined to be 1110 mg/kg bw. Supporting studies: Peer reviewed handbook data reports a LD50 of 400 mg/kg in rats and > 800 mg/kg in mice.

Acute inhalation toxicity: According to 'Sax’s Dangerous Properties of Industrial Materials. 11th ed. (2004)' (peer reviewed handbook data), the test item has an acute inhalation LC50 of 159 mg/m3 in rats.

Data waiving (study scientifically not necessary / other information available): No further testing on the substance is deemed necessary since there is valid data available to allow classification of the substance according to the rules laid down in Regulation (EC) no. 1272/2008 (CLP). The substance is not classified for acute inhalatory toxicity, according to Annex VI of CLP Regulation (EC) no. 1272/2008.

Acute dermal toxicity: According to 'Sax’s Dangerous Properties of Industrial Materials. 11th ed. (2004)' (peer reviewed handbook data), the test item has an acute dermal LD50 of 10 ml/kg in guinea pigs.

Data waiving (study scientifically not necessary / other information available): No further testing on the substance is deemed necessary since there is valid data available to allow classification of the substance according to the rules laid down in Regulation (EC) no. 1272/2008 (CLP). The substance classified as Acute Toxicity, Category 3, according to Annex VI of CLP Regulation (EC) no. 1272/2008.

Acute toxicity: other routes. Peer reviewed handbook data reports an intraperitoneal acute toxicity LC50 value of 10 mg/kg in rats and an intraperitoneal acute toxicity value > 800 mg/kg in mice.

Justification for classification or non-classification

Acute oral toxicity: Based on the available data, the substance is classified as Acute Tox. Category 4, H302, according to CLP Regulation (EC) No. 1272/2008.

Acute dermal toxicity: Based on the available data, the substance is classified as Acute Tox. Category 3, H311, according to CLP Regulation (EC) No. 1272/2008.