Registration Dossier
Registration Dossier
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EC number: 208-704-1 | CAS number: 538-75-0
Endpoint summary
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
- 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
- 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 or test system 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:
- other: 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 an
- 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. - 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:
- other: 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:
- other: 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.
Referenceopen allclose all
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 Number |
162 3.6 5 |
213 4.2 5 |
280 10.4 5 |
1000 |
Mean Number |
163 6.5 5 |
210 31.8 2 |
282 26.2 2 |
|
1400 |
Mean Number |
163 1.3 5 |
204 0.7 2 |
265 9.2 2 |
|
2000 |
Mean Number |
163 5.8 5 |
189 14.8 2 |
266 15.6 2 |
|
female |
500 |
Mean Number |
120 4.7 5 |
160 8.6 5 |
187 14.7 5 |
700 |
Mean Number |
120 6.6 5 |
157 10.2 5 |
181 13.0 5 |
|
1000 |
Mean Number |
119 4.3 5 |
150 5.7 2 |
170 6.4 2 |
|
1400 |
Mean Number |
122 6.9 5 |
156 19.1 2 |
188 17.7 2 |
|
2000 |
Mean 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.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 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
- 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:
- other: - 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
- 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. - 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).
Referenceopen allclose all
Under test conditions, the acute inhalation LC50 value was found to be 159 mg/m3 (0.159 mg/L; 18.9 ppm) in rats.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 159 mg/m³ air
- 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
- 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:
- other: 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).
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 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.
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