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EC number: 224-207-2 | CAS number: 4246-51-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- 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
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- 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
similar to OECD 401, LD50 oral, rat = 3160 mg/kg (1984, no GLP, reliability 2)
similar to OECD 402, LD50 dermal, rat > 2150 mg/kg bw (1984, no GLP, reliability 2)
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:
- October 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- non-GLP
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- GLP compliance:
- no
- Test type:
- standard acute method
- Specific details on test material used for the study:
- - Physical state/appearance: yellowish liquid
- Purity: min 95%
- Expiration date of the lot/batch: July 1985 - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Weight at study initiation: mean males: 182 g; mean females: 171 g
- Fasting period before study: 16 hours
- Housing: 5 animals per cage (type DK-III, Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiaet (Klingentalmuehle AG, Kaiseraugst, CH) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- (aqua dest.)
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 14.7%, 21.5%, 31.6%
- Justification for choice of vehicle: aqueous preparation corresponds to physiological medium
DOSE VOLUME APPLIED: 10 ml/kg - Doses:
- 1470, 2150, 3160 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: check for mortality twice per day on working days and once per day on weekends/public holidays; clinical observation several times on the day application, afterwards at least once per day on working days; weighing on the day of application and on days 2, 7 and 12
- Necropsy of survivors performed: yes - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- ca. 3 160 mg/kg bw
- Based on:
- test mat.
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- ca. 2 850 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: value from interpolation
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- ca. 3 160 mg/kg bw
- Based on:
- test mat.
- Mortality:
- The highest applied dosage caused mortality (80%, 40% mortality for male and female rats, respectively) See table1 ("Any other information on results incl. tabeles")
- Clinical signs:
- other: Clinical signs included dyspnoea, rattling breath, apathy, agitation, abnormal position, staggering, tremble, tremor, spastic gait, piloerection, poor general state
- Gross pathology:
- Animals that died: general congestive hyperemia; stomach: bloody gastritis in glandular stomach; intestine: atonic, reddened diarrheal content.
Sacrificed animals: No abnormalities. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The aute oral toxicity study revealed a LD50 of 2850 mg/kg bw for male rats and a LD50 of 3160 mg/kg bw for female rats as well as males/females.
- Executive summary:
In an acute toxicity study similar to OECD guideline 401 (non-GLP, reliability 2) 5 rats/sex were exposed to 1470, 2150, 3160 mg/kg bw of the test substance per gavage. No mortality was observed the low- and mid-dose group. The dosage of 3160 mg/kg bw caused 60% mortality in the rats (80% mortality for males, 40% mortality for females). Therefore, the LD50 for male and female rats was 3160 mg/kg bw (LD50males = 2850 mg/kg bw, LD50females = 3160 mg/kg bw). Clinical observations revealed dyspnoea, rattling breath, apathy, agitation, abnormal position, staggering, tremble, tremor, spastic gait, piloerection, poor general state. Animals wich died after oral exposure had general congestive hyperemia as well as pathological findings in the stomach and intestine (bloody gastritis in glandular stomach, atonic, reddened diarrheal content). All other sacrifieced anilmals did not show abnormalities and gained bodyweight during the study.
Reference
Tab. 1: Mortality:
Dose (mg/kg) |
3160 |
2150 |
1470 |
|
Males |
||||
Dead animals/total animals after |
1 h |
0/5 |
0/5 |
0/5 |
1 d |
4/5 |
0/5 |
0/5 |
|
2 d |
4/5 |
0/5 |
0/5 |
|
7 d |
4/5 |
0/5 |
0/5 |
|
14 d |
4/5 |
0/5 |
0/5 |
|
Females |
||||
Dead animals/total animals after |
1 h |
0/5 |
0/5 |
0/5 |
1 d |
2/5 |
0/5 |
0/5 |
|
2 d |
2/5 |
0/5 |
0/5 |
|
7 d |
2/5 |
0/5 |
0/5 |
|
14 d |
2/5 |
0/5 |
0/5 |
Tab. 2: Mean body weights (g):
|
Dose (mg/kg) |
Weight day |
|||
0 |
2 |
7 |
12 |
||
Males |
3160 |
179 |
186 |
213 |
253 |
2150 |
180 |
204 |
238 |
263 |
|
1470 |
188 |
219 |
251 |
278 |
|
Females |
3160 |
171 |
169 |
189 |
201 |
2150 |
167 |
186 |
199 |
211 |
|
1470 |
176 |
196 |
212 |
225 |
Tab. 3: Symptoms (cageside observations):
Dose (mg/kg) |
3160 |
2150 |
1470 |
Males |
|||
Dyspnoea |
1H-2D |
|
|
Apathy |
1H-4H |
|
|
Agitation |
1D-2D |
|
|
Staggering |
1H-2D |
|
|
Piloerection |
1H-6D |
|
|
Poor general state |
1H-2D |
|
|
|
|||
Females |
|||
Dyspnoea |
1H-2D |
|
|
Rattling breath |
4H-2D |
|
|
Apathy |
1H-2D |
|
|
Abnormal position |
4H |
|
|
Staggering |
1H-2D |
|
|
Tremble |
4H |
|
|
Tremor |
4H |
|
|
Spastic gait |
2D |
|
|
Piloerection |
4H-6D |
|
|
Poor general state |
1H-2D |
|
|
H: Hour; D: Day
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 160 mg/kg bw
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:
- November 1983
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- non-GLP
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- - Physical state/appearance: yellowish liquid
- Purity: min 95%
- Expiration date of the lot/batch: July 1985 - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Weight at study initiation: mean males: 259 g; mean females: 218 g
- Housing: single housing (type DK-III, Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiaet (Klingentalmuehle AG, Kaiseraugst, CH) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: ca. 50 cm² of shaved dorsal/dorsolateral skin
- Type of wrap if used: semiocclusive
REMOVAL OF TEST SUBSTANCE
- Washing: with warm water
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount applied: 2.15 mL/kg
- Concentration: undiluted - Duration of exposure:
- 24 hours
- Doses:
- 2150 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: check for mortality/moribund animals twice per day on working days and once per day on weekends/public holidays; clinical observation several times on the day application, afterwards at least once per day on working days; weighing on the day of application and on days 2, 6 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: assessment of local effects (30 - 60 min after removal of semiocclusive coverage and afterwards at least once per week) - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 150 mg/kg bw
- Based on:
- test mat.
- Mortality:
- One male animal died 2 days after application of the test substance.
- Clinical signs:
- other: Clinical signs included dyspnoea, apathy, aggressiveness, staggering, poor general state
- Gross pathology:
- Animal that died: lungs: severe edema
Sacrificed animals: no abnormalities in organs observed - Other findings:
- Local skin effects: 1 male animal moderate, 1 male animal superficial erosions with crust formation; other animals: profound necrosis
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The aute dermal toxicity study revealed a LD50 > 2150 mg/kg bw for male and female rats.
- Executive summary:
In an acute dermal toxicity study similar to OECD guideline 402 (non-GLP, reliability 2) 5 rats/sex were exposed to a single dose of 2150 mg/kg bw of the test substance in a semiocclusive manner. Therefore, 2.15 mL/kg of the undiluted test substance were applied to 50 cm² of the shaved dorsal/dorsolateral skin for 24 hours. Washing with warm water was performed after exposure. One male animal died 2 days after application of the test substance and showed severe edema of the lung. Clinical signs of the surviving animals included dyspnoea, apathy, aggressiveness, staggering, poor general state. No abnormal organs were observed in these rats. Exposure caused severe skin reactions as 1 male animal had moderate, 1 male animal superficial erosions with crust formation and all other animals profound necrosis. Due to the mortality of 1/10 animals in this study a LD50 was set to be greater than the tested limit dose of 2150 mg/kg bw.
Reference
Tab. 1: Mortality:
Dose (mg/kg) |
2150 |
|
Males |
||
Dead animals/total animals after |
1 h |
0/5 |
1 d |
0/5 |
|
2 d |
1/5 |
|
7 d |
1/5 |
|
14 d |
1/5 |
|
Females |
||
Dead animals/total animals after |
1 h |
0/5 |
1 d |
0/5 |
|
2 d |
0/5 |
|
7 d |
0/5 |
|
14 d |
0/5 |
Tab. 2: Mean body weights (g):
|
Dose (mg/kg) |
Weight day |
|||
0 |
2 |
6 |
13 |
||
Males |
2150 |
259 |
241 |
263 |
292 |
Females |
2150 |
218 |
241 |
211 |
231 |
Tab.3: Symptoms (cageside observations):
Dose (mg/kg) |
2150 |
Males |
|
Dyspnoea |
2D-5D |
Apathy |
2D-5D |
Agressiveness |
8D-9D |
Staggering |
2D-5D |
Poor general state |
2D-5D |
Females |
|
Dyspnoea |
2D-6D |
Apathy |
2D-5D |
Agressiveness |
6D-9D |
Staggering |
2D-6D |
Poor general state |
2D-6D |
D: Day
Tab. 4: Local effects
Dose (mg/kg) |
2150 |
Males |
|
Profound necrosis |
1D-14D |
Edema |
1D-14D |
Females |
|
Profound necrosis |
1D-14D |
Edema |
1D-14D |
D: Day
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 2 150 mg/kg bw
Additional information
Acute oral toxicity:
The acute oral toxicity of the test substance was assessed similar to OECD401 (BASF, 1984). Five rats per dose (1470, 2150, 3160 mg/kg) were given the test item at aqueous solution (14.7%, 21.5%, 31.6%) once per oral gavage. Animals were observed for 14 days and mortality as well clinical signs were monitored. None of the animals died following application of the two lowest doses (i.e. 1470 and 2150 mg/kg). At the highest dose (3160 mg/kg) 4/5 males and 2/5 female died. Clinical signs included dyspnoea, rattling breath, apathy, agitation, abnormal position, staggering, tremble, tremor, spastic, gait, piloerection and poor general state. In decedent animals gross pathology findings included general congestive hyperemia, bloody gastritis in glandular stomach; atonical intestine and reddened diarrheal content. Surviving animals showed no abnormalities at sacrifice.
Based on these results, the oral LD50 was calculated as ca. 3160 mg/kg for females and as ca. 2850 mg/kg for males. The combined oral LD50 was 3160 mg/kg (males and females). The study is regarded as acceptable (key study).
Additionally, Smyth et al. (1969) reported an oral LD50 value of 4333 mg/kg bw for male rats. The study is classified as acceptable (supporting studies).
Acute inhalation toxicity:
In an acute inhalation toxicity study with whole body exposure (Smyth et al., 1969), six albino rats were exposed to a vapour atmosphere of the test substance for a series of time periods ranging from 15 minutes up to 8 hours and observed for 14 days. A 4 hours exposure to a flowing stream of vapor-ladened air with the test substance resulted in no mortality, whereas after 8 h exposure mortality occurred. This study is not valid and therefore disregarded because the vapor concentration is unknown and co-exposure via inhalation, oral and dermal route occurred.
Acute dermal toxicity:
In a single dose study (BASF, 1984) the acute dermal toxicity of the test substance was assessed according to OECD402. The test substance was administered to about 50 cm² (corresponds to at least 10 % of the body surface area) of the previously clipped skin (dorsal and dorsolateral parts of the trunk) of five Wistar rats and semi-occlusive covered. 24 h later, the dressing was removed and the application site rinsed with warm water to remove residual amounts of the test substance. Animals were observed for 14 days. One male animal died two days after application of the test substance. Clinical signs included dyspnoea, apathy, aggressiveness, staggering and poor general state. The Animal that died had severe edema in the lungs. No abnormalities were observed in organs of all other animals sacrificed at the end of the study. Moderate local skin effects were observed in one male, another male developed superficial erosions with crust formation, whereas the other animals showed profound necrosis. Taken together, the test item does not depict any risk of dermal toxicity and the LD50 is > 2150 mg/kg in males and females. The study is regarded as acceptable (key study).
Justification for selection of acute toxicity – oral endpoint
Most reliable study (key study).
Justification for selection of acute toxicity – dermal endpoint
Most reliable study (key study).
Justification for classification or non-classification
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008.
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