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EC number: 500-336-2 | CAS number: 157348-58-8
- 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
Under the conditions of the study in rats according to OECD 423 the acute toxicity after oral application is greater than 2000 mg/kg bw for the test item (BSL Bioservice, 2004). Furthermore, an acute inhalation toxicity study was conducted in rats according to OECD 403 revealed LC50 of greater than 5.03 mg test item/L air/4 hours (LPT, 2016). An acute dermal toxicity study is not available for the test substance.
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:
- 2004-07-05 to 2004-07-21
- 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)
- Version / remarks:
- 2001
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
- Specific details on test material used for the study:
- PREPARATION of the TEST ITEM
- In the first and second step 2000 mg of the test item were diluted in Cottonseed Oil (Sigma Chemicals Co., Lot 103K0064) ad 10 mL.
- The test substance was freshly mixed prior to administration and stirred troughout dose administration to guarantee stability and homogenicity.
The vehicle was chosen due to its non-toxic characteristics. - Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Rats (HsdBrlHan: WIST), Sex: female
- Step 1: Body weight at the commencement of the study: 150 - 153 g
Step 2: Body weight at the commencement of the study: 140 - 165 g
- Three female animals were used for each step
- The animals were derived from a controlled full barrier maintained breeding system (SPF)
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- According to Art. 9.2, No.7 of the Greman Act on Animal Welfare the animals were bred for experimental purposes.
ANIMAL HUSBANDRY
The animals were barrier maintained (semi-barrier) in an air conditioned room
- Temperature: 22 +/- 3 °C
- Rel. humidity: 55 +/- 10%
- Artificial change: 10 x / hour
- Feeding ad libitum, Altromin 1324 maintenance diet for rats and mice, totally-pathogen-free (TPF)
- Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- The animals were kept in Macrolon cages on Altromin saw fiber bedding
- Certificates of food, water and bedding are filed at BSL Bioservice
- Adequate acclimatization period
PREPARATION OF THE ANIMALS
- The animals were marked for individual identification by tail painting
- Prior to the adminstration a detailed clinical observation was made of all animals
- Prior to administration of the test item animals were fasted by withholding food overnight.
Following the period of fasting the animals were weighed and the test item was administered. Then the food was withheld for a further 3-4 hours. - Route of administration:
- oral: gavage
- Vehicle:
- cotton seed oil
- Details on oral exposure:
- ADMINISTRATION:
- The test item was aministered in a single dose by gavage using an intubation cannula.
- Volume of administration: The test item was administered according to body weight at a volume of 10 mL/kg bw. - Doses:
- The starting dose (step 1 and 2) was selected to be 2000 mg/kg body weight. According to the acute toxic class method regime no further testing was required since no compound-related mortality was found.
- No. of animals per sex per dose:
- 6 (step 1 and 2)
- Control animals:
- no
- Details on study design:
- OBSERVATION:
- Animals were observed for 14 days after dosing.
WEIGHT ASSESSMENT:
- The animals were weighed prior to the administration and once a week thereafter.
CLINICAL EXAMINATION:
- A careful clinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours post-dose.
Animals were observed once a day thereafter.
- Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
PATHOLOGY:
- At the end of the observation period - Statistics:
- EVALUATION OF RESULTS:
Individual reactions of each animal were recorded at each observation time. Toxic response data were recorded by sex and dose level. Nature, severity and duration of clinical observations were described. Body weight changes were summarized in tabular form. Necropsy findings were described. - Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No deaths occured.
- Clinical signs:
- No clinical signs of toxicity were observed throughout the observation period for any animals of step 1 and 2.
- Body weight:
- Throughout the 14-days observation period no weight loss was recorded in any animals of step 1 and 2 (see tables "Absolute body weights in g" below).
The weight gain was within the expected range. - Gross pathology:
- Beside acute injection of blood vessels in the adominal region, which is due to the euthanasia injection no special gross pathological changes were found in any animals of step 1 nad 2.
- Other findings:
- No other treatment related effects were observed.
- Conclusions:
- Under the conditions of this study the acute toxicity after oral application is greater than 2000 mg/kg bw.
- Executive summary:
In this study the acute toxic class method according to OECD 423 was performed with the test item.
In the first step the test item was given at the limit dose of 2000 mg/kg body weight to a group of 3 female rats (HsdBrlHan:WIST) as a single administration by oral gavage at the volumne of 10 mL/kg bw. In the second step the test item was given at the same dose and volume to a further group of 3 female rats (HsdBrlHan:WIST).
The dosage of 2000 mg/kg bw caused no compound-related mortality in any animals of step 1 and 2 within 14 days post-dose.
A careful cinical examination was made several times on the day of dosing. Part of this were at least three observations within the first four hours post-dose. Animals were observed once a day thereafter.
At the end of the observation period the surviving animals were sacrified. Necropsy of all animals was carried out to record gross pathological changes.
No clinical signs of toxicity were observed throughout the observation period for any animals of step 1 and 2.
Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection no special gross pathological changes were found in any animals of step 1 and 2.
Throughout the 14 -days observation period no weight loss was recorded in any animals of step 1 and 2. The weight gain was within the expected range.
No other treatment related effects were observed.
Therefore, under the conditions of this study the acute toxicity after oral application is greater than 2000 mg/kg bw.
Reference
Absolute Body Weights in g
Step 1 (2000 mg/kg bw)
Animal No./Sex | Day 0 | Day 7 | Day 14 |
1 / female |
150 | 167 | 182 |
2 / female | 153 | 179 | 193 |
3 / female | 151 | 182 | 203 |
Step 2 (2000 mg/kg bw)
Animal No./Sex | Day 0 | Day 7 | Day 14 |
1 / female | 147 | 164 | 167 |
2 / female | 140 | 160 | 162 |
3 / female | 165 | 176 | 188 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- The study is a guideline study with Klimisch score 1 (reliable without restrictions).
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2016-03-08 to 2016-05-03
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- adopted September 7, 2009
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Version / remarks:
- Acute Inhalation Toxicity, published in the Official Journal of the European Union L81, dated January 24, 2014.
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Rat / CD / Crl:CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS:
- Strain: Rat / CD / Crl: CD(SD)
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age: males: Approx. 8 weeks, females: approx. 10 weeks
- Weight at study initiation: males: 290 - 315 g, females: 250 - 290 g
- Number of animals: 3 males and 3 females
- Fasting period before study: 16 hours
- Housing: groups of three animals
- Diet: ad libitum, Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water: ad libitum, tab water
- Acclimatisation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3 °C
- Humidity (%): 55 + / - 15 %
- Photoperiod (hrs dark / hrs light): 12 hours darkness, 12 hours artifical light - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: compressed filtered air
- Mass median aerodynamic diameter (MMAD):
- 2.585 µm
- Geometric standard deviation (GSD):
- 2.85
- Remark on MMAD/GSD:
- The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis.
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Diluent: Dimethylsulfoxyd (DMSO), The test item is an emulsion with a high viscosity. Hence, a mixture of the test item with water (1 + 1, m/m) was the highest possible concentration to obtain an appropriate aerosol.
- Type of exposure: Using a dynamic inhalation chamber (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER .
- Method of holding animals in test chamber (volume 40 l): The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.
- Source of air: compressed filtered air
- Method of conditioning air: A manometer and an air-flow meter were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary.
- Oxygen content: The oxygen content in the inhalation chamber was 21% v/v. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081).
- Type or preparation of particles: The aerosol of the test item was obtained using a spray-jet. The spray-jet was fed with compressed air (5.0 bar) from a compressor and with the test item using a TSE infusion pump . At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
- Analysis of the aerosol concentration: The actual aerosol concentration in the inhalation chamber was measured 4 times gravimetrically with an air sample filter (Minisart SM 17598; 0.45 µm) and pump (Vacuubrand, MZ 2C ) controlled by a rotameter. Aerosol samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses in the inhalation chamber and air was sucked through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling on an analytical balance (accuracy 0.1 mg).
- Method of particle size distribution: An analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor according to MAY .
The impactor is a device that classifies particles present in a sample of air or gas into known size ranges. It does this by drawing the air sample through a cascade of progressively finer nozzles. The air jets from these nozzles impact on pre-weighed plane sampling surfaces (slides).
Each stage represents an aerodynamic size range and collects finer particles than its predecessor. Each successive stage represents a special aerodynamic cut off diameter.
The dust from the exposure chamber was drawn through the cascade impactor for 1 minute at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg).
The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 32 µm particle size range and the filter (particle size range < 0.5 µm) were not included in the determination of the MMAD in order not to give undue weight to these values.
The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis.
- Temperature, humidity: The temperature (22°C ± 3°C) and humidity was checked and noted once every hour during the exposure period of the experiment.
TEST ATMOSPHERE
- Concentrations: 5.03 mg/l
Air flow entrance (L/h): 900
Air flow exit (L/h): 800
Air change (changes per hour): 31,6
VEHICLE
compressed filtered air
TEST ATMOSPHERE
see table below
CLASS METHOD (if applicable)
Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis. - Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- The actual aerosol concentration in the inhalation chamber was measured 4 times gravimetrically with an air sample filter (Minisart SM 17598; 0.45 µm) and pump (Vacuubrand, MZ 2C ) controlled by a rotameter.
- Duration of exposure:
- 4 h
- Concentrations:
- The actual aerosol concentrations of 5.03 mg /L air was measured at the animals’ nose.
- No. of animals per sex per dose:
- 3
- Control animals:
- no
- Details on study design:
- EXAMINATIONS:
- Post dose observation period: 14 days
- body weights: Individual body weights of animals were determined 1 day before administration (acclimatisation period), on test day 1 prior to exposure and on test days 2, 4, 8 and 15.
- mortality: once per hour during, and once after treatment on day of exposure; thereafter twice daily
- clinical signs: . A careful clinical examination was made at least once daily until all symptoms subsided, thereafter each working day.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy: all animals was carried out and all gross pathological changes were recorded. In addition, the weight of the lungs was determined. - Statistics:
- not necessary
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5.03 mg/L air
- Based on:
- act. ingr.
- Exp. duration:
- 4 h
- Mortality:
- No animal died prematurely.
- Clinical signs:
- other: Slight ataxia and slight dyspnoea immediately until 30 minutes or 3 hours after end of exposure.
- Body weight:
- One of the 3 female animals appeared to be reduced in body weight gain since test day 8.
- Gross pathology:
- None findings
- Other findings:
- no other findings
- Conclusions:
- Under the present test conditions, LC50-value for CD rats following inhalation of the test item for 4 hours was determined as follows (actual concentration): LC50: exceeding 5.09 mg test item/L air.
- Executive summary:
The aim of the present experiment was to obtain information on the acute toxicity and respiratory irritation, following a single 4-hour inhalation exposure of rats to the test item in an acute inhalation toxicity study.
Under the present test conditions, a 4-hour exposure to test item at the concentration of 5.03 mg/L air revealed slight ataxia and slight dyspnoea on test day 1 in all 3 of 3 male and 3 of 3 female animals. No animal died prematurely. One of 3 male and 1 of 3 female animals appeared to be reduced in body weight gain. No pathological findings were noted at necropsy.
LC50value for males and females combined (14 days):
> 5.03 mg test item/L air/4 hours
The test item is a viscous liquid. A 50% (m/m) concentration of the test item in dimethylsulfoxyd (DMSO) was the most suitable concentration to obtain an appropriate aerosol.
All concentrations refer to the undiluted supplied test item.
Aerosol concentration and particle size distribution
The generated aerosol had mass median aerodynamic diameters (MMAD) of 2.585 µm as determined with a cascade impactor. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 2.85.
The actual aerosol concentrations of 5.03 mg test item/L air was measured at the animals’ nose.
The mean actual exposure concentration of test item was as follows:
actual concentration
nominal concentration
mass median aerodynamic diameter
respirable amount particle size
≤4 µm
[mg/L air]
[mg/L air]
[µm]
[mg/L air]
[%]
5.03
27.78
2.585
2.00
39.7
Conclusion
Under the present test conditions, the LC50value for rats following inhalation of test item for 4 hours was determined as follows (actual concentration, mean aerosol concentration):
LC50 males and females combined (14 days) > 5.03 mg test item/L air/4 hours (actual concentration).
Reference
The
mean actual exposure concentration, MMAD and GSD of the test item were
as follows:
actual concentration
|
nominal concentration |
mass median aerodynamic diameter |
respirable amount particle size ≤4 µm |
|
[mg/L air] |
[mg/L air] |
[µm] |
[mg/L air] |
[%] |
5.03 |
27.78 |
2.585 |
2.00 |
39.7 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 5 030 mg/m³
- Quality of whole database:
- The study is a guideline study with Klimisch score 1 (reliable without restrictions).
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
According to the EC Regulation 1272/2008 and subsequent regulations and based on the results of the acute oral and inhalation studies in rats the test substance must not be classified.
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