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EC number: 613-145-5 | CAS number: 63139-21-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
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- Endpoint summary
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- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
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- Acute Toxicity
- Irritation / corrosion
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- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Based on the results of an acute oral toxicity study according to OECD guideline 423, the LD50 value of the test item is expected between 300 - 2000 mg/kg bw. Based in GHS criteria, the test item is classified for acute oral toxicity, category 4. Based on the result of a acute dermal toxicity study according to OECD guideline, the test item can be considered to have no acute toxic potential to skin. The LD50 value was higher than 2000 mg/kg bw after dermal application to rats (reference 7.2.1-1 and 7.2.3-1).
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:
- 2006-10-16 to 2007-08-02
- 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)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: The mean initial body weight at the start of the study was 164 g (range from 156 to 175 g).
- Fasting period before study: Diet was withheld from 17 hours before until up to 4 hours after treatment.
- Housing: Separately in type III Makrolon cages, Conventional softwood granulate was used as the bedding.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 7 days before dosing
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22
- Humidity (%): 47 to 60
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- methylcellulose
- Remarks:
- Methocel K4M Premium solution
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 15 g/L and 100 g/L
- Amount of vehicle: 20 mL/kg bw
MAXIMUM DOSE VOLUME APPLIED: 20 mL of 100 g/L test item
CLASS METHOD
- Rationale for the selection of the starting dose: Limit dose - Doses:
- 2000 mg/kg bw and 300 mg/kg bw
- No. of animals per sex per dose:
- 300 mg/kg bw: 3 males and 3 females
2000 mg/kg bw: 3 females - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and general condition of all rats were monitored for at least 6 hours after administration and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: Yes - Statistics:
- The body weight data were recorded with the PC-program "AKUDAT". The statistical evaluations of the body weight were carried out with the PC-program "TOX 511 A", developed by the Institute of Toxicology of Merck KGaA, Darmstadt. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement.
- Preliminary study:
- Males treated with 2000 mg/kg bw. Signs of toxicity were seen immediately up to 6 hours after oral administration (locomotor disturbance, dyspnea).
- Key result
- Sex:
- female
- Dose descriptor:
- approximate LD50
- Effect level:
- > 300 - < 2 000 mg/kg bw
- Based on:
- not specified
- Mortality:
- 300 mg/kg bw: 0/3 males and 0/3 females;
2000 mg/kg bw: 3/3 females - Clinical signs:
- other: In rats treated with 2000 mg/kg, clinical signs were seen immediately up to 3 hours after oral administration. They consisted of salivation, abdominal position, locomotor disturbance, and dyspnea. Signs of toxicity were seen in the rats treated with 300 m
- Gross pathology:
- Gross pathology of two animals treated with 2000 mg/kg revealed in the stomach gas and fluid content. Histology examination revealed no corresponding changes. In all other animals that died or were sacrificed as planned, no macroscopic changes were detected.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- According to the results of this study with the test item, the LD50 value is expected to be between 300 - 2000 mg/kg.
- Executive summary:
The test material was tested for acute toxicity in rats after single oral administration of 300 and 2000 mg/kg body weight. The test material was suspended with aqueous Methocel® K4M Premium solution as vehicle.This study was performed according to the "Acute toxic class method" (ATC) as described in the OECD Guideline 423. The rats treated with 300 mg/kg bw survived until the end of the observation period, whereas all rats treated with 2000 mg/kg bw died within 45 minutes and 3 hours after dosing. Signs of toxicity were seen in the rats treated with 300 mg/kg bw immediately up to 6 hours after oral administration. They consisted of locomotor disturbance, dyspnea and one female rat showed temporarily abdominal position. The body weight development of the rats was inconspicuous. In rats treated with 2000 mg/kg bw, clinical signs such as salivation, abdominal position, locomotor disturbance and dyspnea were seen immediately after oral administration. Gross pathology of two animals treated with 2000 mg/kg bw revealed gas and fluid content in the stomach. Histology examination revealed no corresponding changes. In all other animals that died or were sacrificed as planned no macroscopic changes were detected.
Reference
Table 1: Mortality
Dose mg/kg bw |
Dead/ treated animals |
|
Males |
Females |
|
300 |
0/3 |
0/3 |
2000 |
- |
3/3 |
Table 2: Clinical findings (summary) for 300 mg/kg bw in male rats
Symptoms of intoxication at time after treatment |
Minutes |
Hours |
Day |
|||||||||||||||||||
1-15 |
15-60 |
1-2 |
2-3 |
3-4 |
4-5 |
5-6 |
6-24 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
|
Sex: Male, Dose: 300 mg/kg bw |
||||||||||||||||||||||
Number of animals observed |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
Abdominal position |
/ |
1 |
1 |
1 |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Locomotor disturbance |
2 |
3 |
3 |
3 |
3 |
3 |
3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Dyspnea |
2 |
2 |
1 |
1 |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
No abnormal symptoms |
1 |
|
|
|
|
|
|
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
Sex: Male, Dose: 2000 mg/kg bw |
||||||||||||||||||||||
Number of animals observed |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
/ |
Table 3: Clinical findings (summary) for 300 mg/kg bw and 2000 mg/kg bw in female rats
Symptoms of intoxication at time after treatment |
Minutes |
Hours |
Day |
|||||||||||||||||||
1-15 |
15-60 |
1-2 |
2-3 |
3-4 |
4-5 |
5-6 |
6-24 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
|
Sex: Female, Dose: 300 mg/kg bw |
||||||||||||||||||||||
Number of animals observed |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
No abnormal symptoms |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
3 |
Sex: Female, Dose: 2000 mg/kg bw |
||||||||||||||||||||||
Number of animals observed |
3 |
3 |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Salivation |
3 |
3 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Abdominal position |
3 |
3 |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Locomotor disturbance |
3 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Dyspnea |
3 |
3 |
1 |
1 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Table 4: Body weights in grams (300 mg/kg bw, males and females)
|
|
|
Day |
|||||||
Dose |
Sex |
Animal No |
1 |
2 |
4 |
6 |
8 |
11 |
13 |
15 |
300 mg/kg bw |
Male
|
1 |
164 |
187 |
204 |
219 |
236 |
258 |
270 |
280 |
|
Male |
2 |
175 |
207 |
220 |
239 |
256 |
278 |
294 |
305 |
|
Male |
3 |
156 |
172 |
192 |
203 |
218 |
234 |
242 |
250 |
|
Female |
4 |
163 |
179 |
179 |
187 |
188 |
197 |
198 |
203 |
|
Female |
5 |
163 |
180 |
183 |
194 |
196 |
208 |
214 |
218 |
|
Female |
6 |
162 |
178 |
178 |
185 |
181 |
198 |
201 |
203 |
Table 5: Body weights in grams (2000 mg/kg bw, females)
|
|
|
Day |
|||||||
Dose |
Sex |
Animal No |
1 |
2 |
4 |
6 |
8 |
11 |
13 |
15 |
2000 mg/kg bw |
Female
|
7 |
160 |
|
|
|
|
|
|
|
|
Female |
8 |
161 |
|
|
|
|
|
|
|
|
Female |
9 |
170 |
|
|
|
|
|
|
|
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 300 mg/kg bw
- Quality of whole database:
- Guideline study under GLP conditions.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2006-10-16 to 2006-12-01
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: Approx. 7 to 11 weeks
- Weight at study initiation: Range from 214 to 244 g (mean: 230 g)
- Housing: Separately in type IE Makrolon cages with a shelter and softwood granulate as bedding.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22
- Humidity (%): 48 to 66
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: Day 0 To: Day 14 - Type of coverage:
- semiocclusive
- Vehicle:
- paraffin oil
- Details on dermal exposure:
- TEST SITE
- Area of exposure: 6 x 6 cm
- Type of wrap: Gauze patch + self-adhesive fabric
REMOVAL OF TEST SUBSTANCE
- Washing: The remaining test material was wiped off.
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount applied: 3.52 g test item preparation/kg bw
- Concentration: 569 g/L
- Constant volume or concentration used: Yes
VEHICLE
- Lot/batch No: K32250274 333 - Duration of exposure:
- 24 hours
- Doses:
- - 2000 mg/kg bw
- No. of animals per sex per dose:
- 5 males and 5 females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and general condition of all rats were monitored for at least 6 hours after administration and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: Yes
- Other examinations performed: All animals were subjected to a gross pathological investigation. - Statistics:
- Not performed
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- no indication of skin irritation up to the relevant limit dose level
- Mortality:
- All rats survived the observation period.
- Clinical signs:
- other: No signs of toxicity were detected in the 5 male and 5 female rats after dermal treatment with 2000 mg/kg of the test item.
- Gross pathology:
- At necropsy, no organ alterations were seen.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg bw after dermal application to rats.
- Executive summary:
The test material was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration, the test material was moistened with liquid paraffin, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric. The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations.
Reference
Table 1: Individual body weights in grams
|
|
|
Day |
|||||||
Dose |
Sex |
Animal No |
1 |
2 |
4 |
6 |
8 |
11 |
13 |
15 |
2000 mg/kg bw |
male |
1 |
244 |
236 |
248 |
259 |
273 |
291 |
296 |
312 |
male |
2 |
220 |
206 |
217 |
224 |
234 |
246 |
249 |
256 |
|
male |
3 |
233 |
231 |
244 |
260 |
269 |
285 |
295 |
303 |
|
male |
4 |
240 |
238 |
247 |
256 |
270 |
285 |
292 |
302 |
|
male |
5 |
243 |
235 |
251 |
264 |
275 |
292 |
300 |
311 |
|
female |
6 |
220 |
218 |
226 |
226 |
233 |
235 |
233 |
241 |
|
female |
7 |
227 |
208 |
226 |
221 |
229 |
232 |
234 |
236 |
|
female |
8 |
235 |
220 |
221 |
235 |
226 |
236 |
236 |
242 |
|
female |
9 |
224 |
224 |
230 |
233 |
238 |
242 |
232 |
239 |
|
female |
10 |
214 |
204 |
210 |
217 |
218 |
218 |
227 |
224 |
|
male |
N |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
Mean |
236 |
229 |
241 |
253 |
264 |
280 |
286 |
297 |
||
Gain (%) |
**** |
-3 |
2 |
7 |
12 |
19 |
21 |
26 |
||
female |
N |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
Mean |
224 |
215 |
223 |
226 |
229 |
233 |
232 |
236 |
||
Gain (%) |
**** |
-4 |
-1 |
1 |
2 |
4 |
4 |
6 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Guideline study under GLP conditions
Additional information
Acute oral toxicity, key study
The test material was tested for acute toxicity in rats after single oral administration of 300 and 2000 mg/kg body weight. The test material was suspended with aqueous Methocel® K4M Premium solution as vehicle.This study was performed according to the "Acute toxic class method" (ATC) as described in the OECD Guideline 423. The rats treated with 300 mg/kg bw survived until the end of the observation period, whereas all rats treated with 2000 mg/kg bw died within 45 minutes and 3 hours after dosing. Signs of toxicity were seen in the rats treated with 300 mg/kg bw immediately up to 6 hours after oral administration. They consisted of locomotor disturbance, dyspnea and one female rat showed temporarily abdominal position. The body weight development of the rats was inconspicuous. In rats treated with 2000 mg/kg bw, clinical signs such as salivation, abdominal position, locomotor disturbance and dyspnea were seen immediately after oral administration. Gross pathology of two animals treated with 2000 mg/kg bw revealed gas and fluid content in the stomach. Histology examination revealed no corresponding changes. In all other animals that died or were sacrificed as planned no macroscopic changes were detected.
Acute dermal toxicity study, key study
The test material was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration, the test material was moistened with liquid paraffin, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric. The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations.
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No 1272/2008
The available test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Thus, the test item is considered to be classified for acute oral toxicity (category 4) but not for acute dermal toxicity under Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/217.
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