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EC number: 256-050-0 | CAS number: 43035-18-3
- 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
Acute oral toxicity:
Female Wistar-rats were subjected to test acute oral toxicity. The test
substance was administered by gavage at a dose of 10000 mg/kg bw (25% in demineralized water). No animal died during the 14 day observation period, resulting in a LD50 >10000 mg/kg bw.
LD50, oral: >10000 mg/kg bw
Acute dermal toxicity:
Single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. The dermal LD50 was determined to be > 2000 mg / kg body weight.
LD50, dermal: >2000 mg/kg bw, RA from source substance PR 170
Acute inhalation toxicity:
Male and female Sprague Dawley rats were subjected to test acute inhalation toxicity. The test
substance was administered for 4 h at a dose of 5.04 mg/L air. No animal died during the 14 day observation period, resulting in a LC50 > 5.04 mg/L air.
LC50, inhalation > 5.04 mg/L air
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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: WISKf(SPF71), Hoechst AG, breeding colony
- Weight at study initiation: 172 g +/- 3.39 g
- Fasting period before study: 16 h
- Housing: grouped, plastic cages
- Diet: Altromin 1324 (Altromin GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- demineralised
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 25 % - Doses:
- 10000 mg/kg bw
- No. of animals per sex per dose:
- 10
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes - Key result
- Sex:
- female
- Dose descriptor:
- LD0
- Effect level:
- > 10 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- - no deaths occurred
- Clinical signs:
- other: - no animal showed any clinical symptoms - faeces was red-coloured
- Gross pathology:
- - animals killed at the end of the observation period showed no macroscopically visible changes
- Interpretation of results:
- not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- Single application of 10000 mg test substance per kg bw did not cause lethality in female Wistar-rats during the 14 day observation period, resulting in a LD50 > 10000 mg/kg bw.
- Executive summary:
Female Wistar-rats were subjected to test acute oral toxicity. The test substance was administered by gavage at a dose of 10000 mg/kg bw (25% in demineralized water). No animal died during the 14 day observation period, resulting in a LD50 >10000 mg/kg bw.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 10 000 mg/kg bw
- Quality of whole database:
- adequate reliability
LD50: >10000 mg/kg bw
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:
- 10 November 2022 to 01 December 2022
- 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:
- OECD Guidelines for Testing of Chemicals No. 403 – Traditional Protocol “Acute Inhalation Toxicity” adopted on 07 September 2009
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- traditional method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: In-house bred
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Weight at study initiation: Males: 182.12 g to 191.26 g; Females: 166.18 g to 179.49 g
- Housing: Three animals per sex were housed in a standard polycarbonate cage (size: L 430 × B 280 × H 210 mm) with stainless steel mesh top grill having facilities for holding pelleted feed and drinking water in water bottle fitted with stainless steel sipper tube
- Diet (e.g. ad libitum): yes and Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG)
- Water (e.g. ad libitum): yes and Deep bore-well water passed through reverse osmosis unit
- Acclimation period: 11 November 2022 to 16 November 2022
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9°C to 22.6°C
- Humidity (%): 43% to 66%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle
IN-LIFE DATES: From: 11 November 2022 To: 01 December 2022 - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- clean air
- Mass median aerodynamic diameter (MMAD):
- > 2.98 - <= 3.23 µm
- Geometric standard deviation (GSD):
- > 2.71 - <= 2.77
- Remark on MMAD/GSD:
- within the specified range as per guideline
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only dynamic inhalation exposure system
- Exposure chamber volume: 0.76
- Method of holding animals in test chamber: Restrainers
- Source and rate of air (airflow): 20 lt per minute
- Method of conditioning air: filtered air
- System of generating particulates/aerosols: Rotating Brush Generator (Palas RBG 1000 - supplied by Palas GmbH)
- Method of particle size determination: Gravimetric method
- Treatment of exhaust air: NaOH
- Temperature, humidity, pressure in air chamber: 22.3°C to 22.8°C, 52.9% to 56.5%, 60 psi
TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- Time needed for equilibrium of exposure concentration before animal exposure:
t95 (min) = 3× Chamber Volume / Chamber airflow
= 3× 0.76 L / 20 L/min
= 0.11 minutes
CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: As per guidelines the limit concentration was 5 mg/L of air. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- > 0 - <= 240 min
- No. of animals per sex per dose:
- Limit Test - 3 Males and 3 Females
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once daily for clinical signs and twice daily for mortality and weighing of animals on day 1, 3, 7 and 14
- Necropsy of survivors performed: yes - Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5.04 mg/L air
- Based on:
- test mat.
- Mortality:
- No mortality
- Clinical signs:
- other: No treatment related clinical signs and mortality were observed at the mean limit concentration of 5.04 mg/L of air. Post exposure observation, i.e., on day 2 and day 3 test item color feces was noted
- Body weight:
- No treatment related changes were observed in body weight and percent change in body weight with respect to day 1 at the mean limit concentration of 5.04 mg/L of air. However, all animals showed slight decrease in body weight on day 2 due to exposure and increased in body weight from day 4 onwards
- Gross pathology:
- No treatment related gross pathological findings were observed at the mean limit concentration of 5.04 mg/L of air
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Based on the results of this study the test item has not to be classified for acute inhalation toxicity according to Regulation (EC) No 1272/2008.
- Conclusions:
- Under the experimental conditions employed and based on the above results of experiment, there were no clinical signs and mortality observed at the mean limit concentration of 5.04 mg/L of air. Hence, the LC50 of the test item is > 5.04 mg/L of air.
- Executive summary:
The test item was evaluated for acute inhalation toxicity in Sprague Dawley rats.
The objective of the study was to assess the toxic potential and to determine the LC50 of test item when administered by inhalation route through flow-past nose-only dynamic inhalation equipment for a single 4 hours exposure to rats. Three male and three female rats were used for conducting the acute inhalation toxicity study.
As such test item was used during technical pre-test and limit test to generate the dust aerosols through rotating brush generator. The technical pre-test was carried out without animals. During the technical pre-test, the target concentration i.e. 5.04 mg/L of air was achieved at the feed rate of 30 mm/hour with a rotation of 600 RPM.
During the exposure period, the temperature, relative humidity, oxygen and carbon dioxide concentration of the chamber was found within the acceptable limits. The particle size MMAD and GSD values were within the acceptable limits, at the mean limit concentration of 5.04 mg/L of air.
All animals were observed for clinical signs of toxicity and mortality during exposure and post exposure on day 1 and once daily thereafter for clinical signs and twice daily for mortality for 14 days for post exposure period. Individual animal body weight was recorded on day 1 (on the day of exposure) prior to the exposure and on day 2, 4, 8 and 15. All the rats were euthanized after 14 days post exposure by intraperitoneal administration of sodium thiopentone and they were subjected to gross necropsy.
No treatment related clinical signs of toxicity and mortalities were observed. Slight decrease in body weight was noted on Day 2 due to exposure. All animals showed increase in body weight on day 4, 8 and 15.
No treatment related gross pathological findings were observed at the mean limit concentration of 5.04 mg/L of air.
Reference
Group & Concentration (mg/L of air) | Animal No. | Sex | Day 1 | Days | ||||||||||||||||||
During Exposure | Post exposure | |||||||||||||||||||||
1 hr* | 2 hrs* | 3 hrs* | 4 hrs* | 30-40 min | 1 hr* | 2# | 3# | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | |||
Limit Test & 5.04 | Rh7081 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N |
Rh7082 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh7083 | M | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh7084 | F | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh7085 | F | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | |
Rh7086 | F | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N | N |
*: ± 10 minutes; N: Normal; M: Male; F: Female; min: minute; hr(s): hour(s); #Test item color feces noted
Group & Concentration (mg/L of air) | Animal No. | Sex | Body Weight (g) on Days |
| Percent Change in Body Weight with Respect to Day 1 | |||||||
1# | 2 | 4 | 8 | 15 |
| 1-2 | 1-4 | 1-8 | 1-15 | |||
Limit Test & 5.04 | Rh7081 | M | 203.36 | 200.65 | 204.77 | 217.17 | 239.19 |
| -1.33 | 0.69 | 6.79 | 17.62 |
Rh7082 | M | 211.19 | 209.39 | 213.39 | 228.24 | 252.32 |
| -0.85 | 1.04 | 8.07 | 19.48 | |
Rh7083 | M | 208.93 | 205.49 | 209.42 | 223.46 | 246.25 |
| -1.65 | 0.23 | 6.95 | 17.86 | |
Mean |
| 207.83 | 205.18 | 209.19 | 222.96 | 245.92 |
| -1.28 | 0.66 | 7.27 | 18.32 | |
(±) SD |
| 4.03 | 4.38 | 4.31 | 5.55 | 6.57 |
| 0.40 | 0.40 | 0.70 | 1.01 | |
n |
| 3 | 3 | 3 | 3 | 3 |
| 3 | 3 | 3 | 3 | |
Rh7084 | F | 182.41 | 180.82 | 183.58 | 192.61 | 211.67 |
| -0.87 | 0.64 | 5.59 | 16.04 | |
Rh7085 | F | 187.05 | 186.66 | 188.15 | 199.82 | 214.70 |
| -0.21 | 0.59 | 6.83 | 14.78 | |
Rh7086 | F | 195.88 | 193.71 | 196.21 | 206.09 | 223.52 |
| -1.11 | 0.17 | 5.21 | 14.11 | |
Mean |
| 188.45 | 187.06 | 189.31 | 199.51 | 216.63 |
| -0.73 | 0.47 | 5.88 | 14.98 | |
(±) SD |
| 6.84 | 6.45 | 6.39 | 6.75 | 6.16 |
| 0.47 | 0.26 | 0.84 | 0.98 | |
n |
| 3 | 3 | 3 | 3 | 3 |
| 3 | 3 | 3 | 3 |
#: Prior to exposure; M: Male; F: Female; SD: Standard Deviation; n; Number of animals
Technical Pre-test:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) |
Mean BZC (mg/L of Air) |
1 | 30 | 600 | 345.71 | 353.34 | 7.63 | 1.52 | 1 | 5.02 | 5.03 |
2 | 30 | 600 | 350.65 | 358.31 | 7.66 | 1.52 | 1 | 5.04 |
Limit Test:
Sl. No. | Feed rate (mm/hour) | Rotation (rpm) | Initial weight (mg) (a) | Final weight (mg) (b) | Difference (mg) (c) = (b) – (a) | Air Flow Rate (L/min) (d) | Time (min) (e) | BZC (mg/L of air) | Mean BZC (mg/L of Air) |
1 | 30 | 600 | 350.05 | 357.69 | 7.64 | 1.52 | 1 | 5.03 | 5.04 |
2 | 30 | 600 | 356.09 | 363.78 | 7.69 | 1.52 | 1 | 5.06 | |
3 | 30 | 600 | 349.86 | 357.53 | 7.67 | 1.52 | 1 | 5.05 |
BZC: Breathing Zone Concentration; Sampled volume: 1.52 L/min; Sampling time: 1 minute
Mass of test item collected on the filter paper (c) | |
Volume of air passed through the filter paper (d) X time (e) |
Technical Pre-test:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) | Air Flow (L/min) |
5.03 | 1 | 30 | 600 | 22.4 | 54.6 | 20.5 | 616 | 20 |
2 | 30 | 600 | 22.3 | 53.5 | 20.6 | 625 | 20 |
Limit Test:
Concentration (mg/L of air) | SL. No. | Feed rate (mm/hour) | Rotation (rpm) | Temperature (°C) | Relative Humidity (%) | Oxygen Concentration (%) | Carbon dioxide Concentration (ppm) | Air Flow (L/min) |
5.04 | 1 | 30 | 600 | 22.8 | 52.9 | 20.3 | 613 | 20 |
2 | 30 | 600 | 22.4 | 54.5 | 20.6 | 621 | 20 | |
3 | 30 | 600 | 22.5 | 56.5 | 20.3 | 619 | 20 | |
4 | 30 | 600 | 22.3 | 55.8 | 20.4 | 615 | 20 |
Note: 1% Carbon dioxide = 10000 ppm
Technical Pre-Test | |
Chamber Conditions | Range |
Feed Rate (mm/hour) and Speed (RPM) | 30 and 600 |
Temperature (°C) | 22.3 to 22.4 |
Relative humidity (%) | 53.5 to 54.6 |
Oxygen concentration (%) | 20.5 to 20.6 |
Carbon dioxide concentration (ppm) | 616 to 625 |
Air Flow (L/min)* | 20 |
BZC (mg/L) | 5.02 to 5.04 |
MMAD (µm) | 3.06 # |
GSD | 2.71 # |
Limit Test | |
Feed Rate (mm/hour) and Speed (RPM) | 30 and 600 |
Temperature (°C) | 22.3 to 22.8 |
Relative humidity (%) | 52.9 to 56.5 |
Oxygen concentration (%) | 20.3 to 20.6 |
Carbon dioxide concentration (ppm) | 613 to 621 |
Air Flow (L/min)* | 20 |
BZC (mg/L) | 5.03 to 5.06 |
MMAD (µm) | 2.98 to 3.23 |
GSD | 2.71 to 2.77 |
*: Values were constant throughout the exposure; #: Individual value; BZC: Breathing Zone Concentration (Actual Concentration), MMAD: Mass Median Aerodynamic Diameter, GSD: Geometric Standard Deviations.
Group & Concentration (mg/L of air) | Animal No. | Sex | Fate | Gross Pathology Findings | |
External | Internal | ||||
Limit Test & 5.04 | Rh7081 | M | TS | NAD | NAD |
Rh7082 | M | TS | NAD | NAD | |
Rh7083 | M | TS | NAD | NAD | |
Rh7084 | F | TS | NAD | NAD | |
Rh7085 | F | TS | NAD | NAD | |
Rh7086 | F | TS | NAD | NAD |
NAD: No Abnormality Detected; M: Male; F: Female; TS: Terminal Sacrifice
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- > 5.04 mg/L air
- Physical form:
- inhalation: aerosol
- Quality of whole database:
- reliable without restriction
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- see Rationale and Justification for the Analogue Read-Across Approach - Nanoforms and Bulk Forms (Chapter 13)
- Reason / purpose for cross-reference:
- read-across source
- Limit test:
- yes
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- other: Content C.I.
- Remarks on result:
- other: no animal died within 14 d observation period
- Mortality:
- No mortality was observed
- Clinical signs:
- other: No treatment-related effects were observed
- Gross pathology:
- No treatment-related effects were observed
- Other findings:
- No erythema or oedema was observed. Scratches were observed in 1 of 5 male animals.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. In one male animal scratches were observed from day 6 until the end of the observation period which might be caused by scratching activities of the animal. The dermal LD50 was determined to be > 2000 mg / kg body weight.
- Executive summary:
Acute toxicity after dermal application was investigated in Wistar rats according to an OECD 402 limit test. Animals (5 males and 5 females) were applied 2000 mg/kg bw in cottonseed oil for 24 hours. No animal died during the observation period.
Table1: Results per Step
Sex
Dose
(mg/kg bw)Number
of AnimalsNumber
of Intercurrent Deathsmale
2000
5
0
female
2000
5
0
Signs of toxicity related to dose level used, time of onset and duration:
No treatment-related effects were observed
Effect on organs (related to dose level):
No treatment-related effects were observed.
Signs of irritation:
No erythema or oedema was observed. Scratches were observed in 1 of 5 male animals.
Conclusion
Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. In one male animal scratches were observed from day 6 until the end of the observation period which might be caused by scratching activities of the animal.
The dermal LD50 was determined to be > 2000 mg / kg body weight.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Reliability of the original study (GLP compliant guideline study) as such was 1 (reliable without restrictions). Downgrading on reliability 2 is owed to the read across application. Due to their similar physicochemical properties it can reasonably be assumed that the target substance and the source substances used also reveal comparable toxicological properties and that the available toxicological data from the source substances can easily and reliably be used to predict specific properties of the target substance.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1200 (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:
- - Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1114)
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8
(drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin
saw fibre bedding (lot no. 110811)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions - Type of coverage:
- semiocclusive
- Vehicle:
- cotton seed oil
- Details on dermal exposure:
- Preparation of the Animals:
The animals were marked for individual identification by tail painting.
Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk using an electric clipper.
Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used.
No less than 10% of the body surface was cleared for the application.
Prior to the application a detailed clinical observation was made of all animals.
Application:
The test item was applied at a single dose, uniformly over an area which was approximately 10% of the total body surface. In order to ensure good skin contact the test item was moistened with the vehicle.
The test item was held in contact with the skin by a dressing throughout a 24-hour period.
The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner. - Duration of exposure:
- The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period the residual test item was removed using cottonseed oil.
- Doses:
- The test item was applied at a single dose of 2000 mg/kg body weight to each animal.
- No. of animals per sex per dose:
- 5 male and 5 female
- Control animals:
- not required
- Details on study design:
- Observation period:
All animals were observed for 14 days after dosing
Weight Assessment:
The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
Clinical Examination:
careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes
and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded.
Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities
were recorded. 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. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea,
lethargy, sleep and coma.
Pathology:
At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected
intraperitoneally (Narcoren®, Merial) at the dosage of approximately 8 mL/kg bw. All animals were subjected to gross necropsy.
All gross pathological changes were recorded and in case of findings the tissues were preserved for a possible
histopathological evaluation. The preserved tissues of which no histopathological evaluation was made will be discarded
3 months after the release of the final report unless otherwise agreed upon with the sponsor.
Evaluation of Results:
Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by sex and dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described. - Statistics:
- According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- other: Content C.I.
- Remarks on result:
- other: no animal died within 14 d observation period
- Mortality:
- No mortality was observed
- Clinical signs:
- other: No treatment-related effects were observed
- Gross pathology:
- No treatment-related effects were observed
- Other findings:
- No erythema or oedema was observed. Scratches were observed in 1 of 5 male animals.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. In one male animal scratches were observed from day 6 until the end of the observation period which might be caused by scratching activities of the animal. The dermal LD50 was determined to be > 2000 mg / kg body weight.
- Executive summary:
Acute toxicity after dermal application was investigated in Wistar rats according to an OECD 402 limit test. Animals (5 males and 5 females) were applied 2000 mg/kg bw in cottonseed oil for 24 hours. No animal died during the observation period.
Table1: Results per Step
Sex
Dose
(mg/kg bw)Number
of AnimalsNumber
of Intercurrent Deathsmale
2000
5
0
female
2000
5
0
Signs of toxicity related to dose level used, time of onset and duration:
No treatment-related effects were observed
Effect on organs (related to dose level):
No treatment-related effects were observed.
Signs of irritation:
No erythema or oedema was observed. Scratches were observed in 1 of 5 male animals.
Conclusion
Under the conditions of the present study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity. In one male animal scratches were observed from day 6 until the end of the observation period which might be caused by scratching activities of the animal.
The dermal LD50 was determined to be > 2000 mg / kg body weight.
Referenceopen allclose all
Table Absolute Body Weights in g and Body Weight Gain in %:
Dose: 2000 mg/kg body weight |
||||
Animal No. / Sex |
g |
g |
g |
% |
21 / male |
227 |
242 |
276 |
22 |
22 / male |
236 |
251 |
277 |
17 |
23 / male |
229 |
248 |
278 |
21 |
24 / male |
230 |
241 |
274 |
19 |
25 / male |
245 |
260 |
280 |
14 |
26 / female |
216 |
220 |
223 |
3 |
27 / female |
213 |
214 |
221 |
4 |
28 / female |
218 |
215 |
217 |
-0.50 |
29 / female |
215 |
218 |
223 |
4 |
30 / female |
207 |
211 |
220 |
6 |
Table LD50:
Dose (Unit)
|
Number of Animals Investigated |
Number of Intercurrent Deaths |
LD50 |
2000 mg/kg bw |
5 males |
0 |
> 2000 mg/kg bw |
2000mg/kg bw |
5 females |
0 |
> 2000 mg/kg bw |
bw = body weight
Table Absolute Body Weights in g and Body Weight Gain in %:
Dose: 2000 mg/kg body weight |
||||
Animal No. / Sex |
g |
g |
g |
% |
21 / male |
227 |
242 |
276 |
22 |
22 / male |
236 |
251 |
277 |
17 |
23 / male |
229 |
248 |
278 |
21 |
24 / male |
230 |
241 |
274 |
19 |
25 / male |
245 |
260 |
280 |
14 |
26 / female |
216 |
220 |
223 |
3 |
27 / female |
213 |
214 |
221 |
4 |
28 / female |
218 |
215 |
217 |
-0.50 |
29 / female |
215 |
218 |
223 |
4 |
30 / female |
207 |
211 |
220 |
6 |
Table LD50:
Dose (Unit)
|
Number of Animals Investigated |
Number of Intercurrent Deaths |
LD50 |
2000 mg/kg bw |
5 males |
0 |
> 2000 mg/kg bw |
2000mg/kg bw |
5 females |
0 |
> 2000 mg/kg bw |
bw = body weight
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- adequate reliability
Additional information
Justification for classification or non-classification
Available LD50 values of >10000 mg/kg bw (oral), >2000 mg/kg bw (dermal, RA from source substance PR 170) and the LC50 value of Y5.04 mg/L air exceed the respective threshold for classification. Thus the substance subject to registration does not meet criteria for classification according to REGULATION (EC) No 1272/2008.
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