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EC number: 452-330-3 | CAS number: -
- 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
Oral: Discriminating dose = 300 mg/kg bw, female rat, OECD 420, Rattray 2004
Dermal: LD50 > 2000 mg/kg bw, male/female rat, OECD 402, Rattray 2004
Inhalation: LC50 >5.16 mg/L, male/female rat, OECD 403, Durando 2016
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:
- 30 July 2003 to 27 August 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- fixed dose procedure
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Alpk:APfSD (Wistar-derived)
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 186-245 g
- Fasting period before study: Rats were fasted overnight prior to dosing
- Housing: 5 per cage
- Diet: ad libitum
- Water: Mains water ad libitum
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 per hour minimum
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark
IN-LIFE DATES: From: 30 July 2003 To: 27 August 2003 - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5 % w/v (aqueous)
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: Doses were prepared by adjusting the concentration of the test material in the dosing preparations
- Amount of vehicle (if gavage): Each dose volume was calculated for animals individually based on its weight at the time of dosing.
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bodyweight was administered as a standard dose volume - Doses:
- Sighting study: 300 or 2000 mg/kg bodyweight
Main test: 300 or 2000 mg/kg bodyweight - No. of animals per sex per dose:
- Sighting study: one initially
Main test: A further four animals were tested from both dosing groups - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were examined for physical and behavioural abnormalities prior to dosing. Post dosing, animals were examined for systemic toxicity twice on day 1 and daily up to day 15 thereafter. All animals were weighed prior to fasting, immediately before dosing and on days 8 and 15.
- Necropsy of survivors performed: Animals were sacrificed by halothane vapour overdose followed by exsanguination. All animals were subject to a macroscopic examination of the thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination. - Sex:
- female
- Dose descriptor:
- discriminating dose
- Effect level:
- 300 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Following a single oral dose of 300 mg/kg, none of the animals died. Signs of slight systemic toxicity were seen in all animals, with complete recovery by day 2. Following a single oral dose of 2000 mg/kg four of the animals showed signs of toxicity including (in two animals) convulsions and were killed in extremis on day 1.
- Clinical signs:
- In the 300 mg/kg dose group, signs of slight systemic toxicity were seen in all animals, with complete recovery by day 2. Following a single oral dose of 2000 mg/kg four of the animals showed signs of toxicity including (in two animals) convulsions and were killed in extremis. The surviving animal in this group was fully recovered by day 2.
- Body weight:
- All animals initially lost weight due to the pre-dose fast but all surviving animals showed an overall bodyweight gain during the study.
- Gross pathology:
- One animal dosed with 300 mg/kg was found to have a speckled thymus at post mortem. This was a spontaneous finding and was not considered to be related to treatment. One of the animals killed in extremis after dosing with 2000 mg/kg had red staining around the nose and mouth. This was a non-specifiec finding related to treatment.
- Interpretation of results:
- Toxicity Category IV
- Remarks:
- Migrated information Classification derived using the criteria reported in Annex II of the OECD Guideline 420. Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the test, the highest fixed dose of the test material administered in this study without causing any lethality (i.e. the discriminating dose-level) was 300 mg/kg to female rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
- Executive summary:
The acute oral toxicity of the test material was determined in accordance with the standardised guideline OECD 420 using the fixed dose procedure. Single female rats initially received one oral dose of 300 or 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. From the results of the initial phase, fixed dose levels of 300 and 2000 mg/kg were selected for the main phase study. In the main phase, groups of four female rats were dosed and assessed for signs of toxicity for 14 days following dosing. Bodyweights were recorded at intervals during the study. Animals in extremis and those surviving to the end of the study were killed and, together with those found dead, were examined post mortem. The initial females were included in the main phase of the study, to give a total of five animals per group.
None of the animals in the 300 mg/kg group died. Signs of slight systemic toxicity were seen in all animals, all of which had fully recovered by day 2. All animals showed an overall bodyweight gain during the study. There were no treatment related abnormalities post mortem. Following a single oral dose of 2000 mg/kg, four of the animals showed signs of severe toxicity including (in two animals) convulsions and were killed in extremis on day 1. The surviving animal showed signs of toxicity following dosing but had recovered by day 2 and showed an overall body weight gain during the study. At examination post mortem one of the animals killed in extremis had red staining around the nose and mouth.
The highest fixed dose of the test material administered in the study without causing any lethality (i.e. the discriminating dose-level) was 300 mg/kg to female rats.
Reference
Table 1: Bodyweights of female rats dosed with 300 or 2000 mg/kg of test material
Dose |
Animal no. |
Day |
||||
Pre-dosing (day -1) |
Dosing (day 1) |
day 2 |
day 8 |
Terminal (day 15) |
||
300 mg/kg |
49 |
206 |
184 |
Not performed |
231 |
246 |
4 |
190 |
168 |
Not performed |
243 |
264 |
|
5 |
192 |
168 |
Not performed |
230 |
242 |
|
6 |
192 |
173 |
Not performed |
225 |
233 |
|
7 |
186 |
170 |
Not performed |
234 |
239 |
|
2000 mg/kg |
63 |
245 |
218 |
227 |
282 |
311 |
72 |
199 |
181 |
- |
- |
- |
|
73 |
209 |
191 |
- |
- |
- |
|
74 |
243 |
194 |
- |
- |
- |
|
75 |
202 |
188 |
- |
- |
- |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- 300 mg/kg bw
- Quality of whole database:
- The study presented to assess the acute toxicity of the test substance was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test substance.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Remarks:
- The acute inhalation toxicity study was conducted solely to comply with a non-EU national registration requirement, and has been provided here in accordance with REACH, Article 22(1)e.
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08 December 2015 to 30 December 2015
- 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:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1300 (Acute inhalation toxicity)
- Version / remarks:
- 1989
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF 12-Nousan-8147
- Version / remarks:
- 1999
- Deviations:
- no
- GLP compliance:
- yes
- 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: SAGE® Labs
- Age at study initiation: 10-11 weeks old
- Weight at study initiation: 333-386 g (males), 218-250 g (females)
- Fasting period before study: No
- Housing: Singly housed in suspended stainless steel caging which conforms to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals.
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Rodent Diet® #2016 ad libitum
- Water (e.g. ad libitum): Municipal water ad libitum
- Acclimation period: 22 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 43-58
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 h cycle
IN-LIFE DATES: From: 08 December 2015 To: 30 December 2015 - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- 2.15 µm
- Geometric standard deviation (GSD):
- 2.22
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber, the base unit terminates the chamber with a 0.5-inch diameter tube for discharged air.
- Exposure chamber volume: 6.7 L
- Method of holding animals in test chamber: Animals were individually housed in polycarbonate holding tubes which seal to the chamber with an "O" ring during exposure.
- Source and rate of air: Air compressor, 36.0 Lpm
- Method of conditioning air: Filtered generator air was supplied to the spray atomization nozzle by an air compressor, and measured with a Mass Flow Controller. Additional filtered mixing air from the same air compressor, measured with a Mass Flow Controller, was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Chamber airflow was monitored throughout the exposure period and recorded periodically. The exposure was conducted under slight negative pressure.
- System of generating particulates/aerosols: The test substance was aerosolized using a modified Wright Dust Generator. The test substance was packed into the dust container and compressed 1000 lbs/in^2 using a lab press. The container was then fitted with a cutting head. Compressed generator and mixing air were supplied to the dust generator. The aerosolized dust was then fed directly into the chamber through the dust outlet assembly.
- Method of particle size determination: An eight-stage 1 ACFM Andersen Ambient Particle Sizing Sampler. Samples were withdrawn from the breathing zone of the animals at two intervals. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined graphically using two-cycle logarithmic probit axes.
- Temperature, humidity, pressure in air chamber: 20-21°C, 35-39%
- Compressed generator / mixing air: 30/30 psi
- T90/T99: 0.43 min / 0.86 min
TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric samples were withdrawn at 6 intervals from the breathing zone of the animals. Samples were collected using 37 mm glass fiber filters (Whatman™ GF/B) in a filter holder attached by ¼ inch Tygon® tubing to a vacuum pump. Filter papers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine the chamber concentration. Sample airflows were measured using a Mass Flow Controller.
- Samples taken from breathing zone: yes - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- >= 4 h
- Concentrations:
- 5.16 mg/L
- 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:Observed for mortality during the exposure period. Examined for signs of gross toxicity, and behavioral changes upon removal from the exposure tube and at least once daily thereafter for 14 days. Individual body weights of the animals were recorded prior to test substance exposure (initial) and again on Days 1, 3, 7, and 14 (terminal).
- Necropsy of survivors performed: yes - Statistics:
- Not applicable (limit test, no mortalities).
- Preliminary study:
- Prior to initiation of the full inhalation study, pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the desired chamber concentration (5.0 mg/L) and desired particle size distribution (mass median aerodynamic diameter between 1 and 4 μm). The procedures and aerosolization equipment used in the full test were based on the results of pre-test trial number 3 which provided a gravimetric chamber concentration of 5.20 mg/L and a mass median aerodynamic diameter of 2.25 μm.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5.16 mg/L air
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- All animals survived.
- Clinical signs:
- other: Following exposure all rats exhibited irregular respiration. In addition, one male was hypoactive. All animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period.
- Body weight:
- All animals gained body weight during the study.
- Gross pathology:
- No gross abnormalities were noted.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats.
- Executive summary:
An acute inhalation toxicity test was conducted with rats to determine the potential of the test substance to produce toxicity from a single exposure via the inhalation (nose-only exposure) route.
After establishing the desired generation procedures during the pre-test trials, ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distributions of the test atmosphere were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for up to 14 days following exposure. Body weights were recorded prior to exposure (initial) and again on Days 1, 3, 7, and 14 (terminal). Necropsies were performed on all animals at terminal sacrifice.
The gravimetric chamber concentration was 5.16 mg/L. The average mass median aerodynamic diameter was estimated to be 2.15 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.22.
All animals survived exposure to the test atmosphere and gained body weight during the study. Following exposure, all rats exhibited irregular respiration. In addition, one male was hypoactive. However, all animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Therefore, under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats.
Reference
Table 1: Summary of acute study test atmosphere characteristics of CA3250
Test atmosphere characteristics |
||
Parameter |
Target concentration (mg/L) |
|
|
5.0 |
|
Gravimetric concentration |
5.16±0.11 mg/L (n=6) |
|
Nominal concentration |
9.49 mg/L |
|
Particle size MMAD; GSD |
2.12, 2.17 µm; 2.19, 2.25 |
|
|
(at 1.5 and 3 hours into exposure respectively) |
|
Particle size distribution |
% total particles captured (by weight) |
|
Size range (µm) |
Run 1 (1.5 hours into exposure) |
Run 2 (3 hours into exposure) |
Particles<9.0 µm (% w/w) |
2.4 |
3.2 |
Particles < 5.8 µm (% w/w) |
5.4 |
5.6 |
Particles< 4.7µm (% w/w) |
6.5 |
7.2 |
Particles<3.3 µm (% w/w) |
19.0 |
18.9 |
Particles < 2.1 µm (% w/w) |
26.6 |
27.5 |
Particles< 1.1µm (% w/w) |
25.1 |
21.1 |
Particles<0.7 µm (% w/w) |
8.4 |
7.8 |
Particles < 0.4 µm (% w/w) |
3.5 |
5.0 |
Particles < 0 µm (% w/w) |
3.2 |
3.6 |
Average total air flow |
36.0 L/min |
|
Air changes / hour |
322 |
|
Temperature (exposure chamber) |
20-21°C |
|
Humidity (exposure chamber) |
35-39% |
|
T99 |
0.86 m |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The study presented to assess the acute toxicity of the test substance was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test substance.
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:
- 10 September 2003 to 07 October 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was performed to GLP and in line with the standardised guideline OECD 402, EU Method B.3 and EPA OPPTS 870.1200 with no deviations thought to impact the reliability of the presented results.
- 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:
- other: Alpk:APfSD (Wistar-derived)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 255-276 g males, 190-207 g females
- Housing: Individually
- Diet: ad libitum
- Water: ad libitum, mains water
- Acclimation period: At least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 changes minimum
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark
IN-LIFE DATES: From: 10 September 2003 To: 7 October 2003 - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: Dorso-lumbar region of each animal (7 cm x 7 cm area was clipped free of hair with veterinary clippers to allow administration of the test material).
- Type of wrap if used: The test substance was applied to the shorn back of each animal and was kept in contact with the skin for approximately 24 hours using an occlusive dressing wrapped around the trunk. Each dressing consisted of a foil backed gauze patch to cover the treated area and was held in place by a cohesive bandage secured with two pieces of surgical tape.
REMOVAL OF TEST SUBSTANCE
- Washing: The dressings were carefully cut using blunt tipped scissors, removed and discarded. The skin at the site of application was cleansed of any residual test material using clean swabs of absorbent cotton wool soaked in clean warm water and then dried gently with clean tissue paper.
- Time after start of exposure: At the end of the 24 hour contact period.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The amount of test material applied was calculated for each animal according to its weight at the time of dosing.
- For solids, paste formed: The test material was moistened to a dry paste with a small amount (1 mL) of water. - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg body weight
- No. of animals per sex per dose:
- 5 males and 5 females per group
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Prior to the start of the study, all rats were examined for any physical or behavioural abnormalities. The animals were observed twice following application on day 1 (only gross abnormalities were noted at this time as the presence of the dressings may have affected the behaviour and movement of the rats). Subsequent observations for signs of systemic toxicity and skin irritation were made once daily up to day 15. The animals were weighed immediately before dosing (day 1) and on days 8 and 15 (termination).
- Necropsy of survivors performed: All animals were killed by an overdose of halothane vapour followed by exsanguination. All animals were examined post mortem. An external observation was performed and a detailed examination of all thoracic and abdominal viscera. All abnormalities were recorded but tissues were not submitted for histopathological examination. - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- None of the animals died during the course of the study. None of the animals exhibited signs of systemic toxicity.
- Clinical signs:
- All the animals were stained yellow by the test substance for up to 5 days. Signs of slight skin irritation were seen in all animals but had completely resolved by day 14.
- Body weight:
- All animals gained weight during the study.
- Gross pathology:
- There were no macroscopic abnormalities at examination post mortem.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information The test material failed to elicit any toxicological response in any animal during the course of the study. Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the test, the acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to male and female rats. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
- Executive summary:
The acute dermal toxicity of the test material was determined in accordance with the standardised guidelines OECD 402, EU Method B.3 and EPA OPPTS 870.1200. Five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. Signs of slight irritation were seen in all animals but had completely resolved by day 14. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.
Reference
Table 1: Body weights
Sex |
Animal no. |
Day |
||
Day of dosing (Day 1) |
Day 8 |
Terminal (Day 15) |
||
Male |
1 |
276 |
313 |
357 |
2 |
263 |
309 |
379 |
|
3 |
255 |
304 |
366 |
|
4 |
274 |
324 |
392 |
|
5 |
261 |
307 |
371 |
|
Mean |
265.8 |
311.4 |
373 |
|
S.D. |
8.9 |
7.8 |
13.3 |
|
Female |
6 |
203 |
227 |
264 |
7 |
190 |
195 |
218 |
|
8 |
197 |
215 |
242 |
|
9 |
207 |
222 |
227 |
|
10 |
195 |
206 |
222 |
|
Mean |
198.4 |
213.0 |
234.6 |
|
S.D. |
6.7 |
12.8 |
18.8 |
Table 2: Irritation observations
Sex |
Animal no. |
Observation |
Day |
|||||||||||
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
|||
Male |
1 |
Desquamation |
S |
S |
S |
S |
S |
S |
S |
|||||
Erythema |
S |
S |
S |
|||||||||||
Oedema |
S |
|||||||||||||
Scabs: small scattered |
P |
P |
P |
P |
P |
P |
P |
|||||||
2 |
Desquamation |
S |
S |
S |
S |
S |
S |
S |
||||||
Erythema |
S |
|||||||||||||
Scabs: small scattered |
P |
P |
P |
P |
P |
P |
P |
|||||||
3 |
Desquamation |
S |
S |
S |
S |
S |
||||||||
Oedema |
S |
|||||||||||||
Scabs: small scattered |
P |
|||||||||||||
Scab: edge of application area |
P |
P |
P |
|||||||||||
4 |
Desquamation |
S |
S |
S |
S |
S |
S |
S |
S |
S |
S |
S |
||
Oedema |
S |
|||||||||||||
Scabs: small scattered |
P |
P |
P |
P |
P |
P |
P |
P |
P |
P |
||||
5 |
Desquamation |
S |
S |
|||||||||||
Oedema |
S |
|||||||||||||
Scabs: small scattered |
P |
|||||||||||||
Scab: edge of application area |
P |
P |
||||||||||||
Female |
6 |
Desquamation |
S |
S |
S |
S |
S |
S |
S |
S |
||||
Erythema |
S |
S |
||||||||||||
Oedema |
S |
|||||||||||||
Scabs: small scattered |
P |
P |
P |
P |
P |
P |
P |
P |
||||||
7 |
Desquamation |
S |
S |
|||||||||||
Scab: edge of application area |
P |
P |
P |
P |
P |
P |
||||||||
8 |
Desquamation |
S |
S |
S |
S |
S |
S |
S |
||||||
Oedema |
S |
|||||||||||||
Scabs: small scattered |
P |
P |
P |
P |
P |
P |
P |
|||||||
Scab: edge of application area |
P |
P |
P |
|||||||||||
9 |
Desquamation |
S |
S |
|||||||||||
10 |
Oedema |
S |
||||||||||||
Scab: edge of application area |
P |
P |
P |
P |
P |
P |
P = Present
S = Slight
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The study presented to assess the acute toxicity of the test substance was performed in line with GLP and accepted standardised guidelines with a high standard of reporting. The study was assigned a reliability score of 1 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test substance.
Additional information
Oral
The acute oral toxicity of the test material was determined in accordance with the standardised guideline OECD 420 using the fixed dose procedure. Single female rats initially received one oral dose of 300 or 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. From the results of the initial phase, fixed dose levels of 300 and 2000 mg/kg were selected for the main phase study. In the main phase, groups of four female rats were dosed and assessed for signs of toxicity for 14 days following dosing. Bodyweights were recorded at intervals during the study. Animals in extremis and those surviving to the end of the study were killed and, together with those found dead, were examined post mortem. The initial females were included in the main phase of the study, to give a total of five animals per group.
None of the animals in the 300 mg/kg group died. Signs of slight systemic toxicity were seen in all animals, all of which had fully recovered by day 2. All animals showed an overall bodyweight gain during the study. There were no treatment related abnormalities post mortem. Following a single oral dose of 2000 mg/kg, four of the animals showed signs of severe toxicity including (in two animals) convulsions and were killed in extremis on day 1. The surviving animal showed signs of toxicity following dosing but had recovered by day 2 and showed an overall body weight gain during the study. At examination post mortem one of the animals killed in extremis had red staining around the nose and mouth.
The highest fixed dose of the test material administered in the study without causing any lethality (i.e. the discriminating dose-level) was 300 mg/kg to female rats.
Dermal
The acute dermal toxicity of the test material was determined in accordance with the standardised guidelines OECD 402, EU Method B.3 and EPA OPPTS 870.1200. Five male and female rats received a single dermal application of 2000 mg/kg of the test material and were assessed daily for the following 14 days for any signs of systemic toxicity. None of the animals died and there were no signs of systemic toxicity. Signs of slight irritation were seen in all animals but had completely resolved by day 14. All animals gained weight during the study. There were no macroscopic abnormalities at examination post mortem. The acute dermal median lethal dose of the test material was estimated to be in excess of 2000 mg/kg to both male and female rats.
The available data is considered to be complete and the results determined, oral discriminating dose of 300 mg/kg and the dermal LD50 ≥ 2000 mg/kg, were taken forward for risk assessment.
Inhalation
An acute inhalation toxicity test was conducted with rats to determine the potential of the test substance to produce toxicity from a single exposure via the inhalation (nose-only exposure) route in accordance with OECD TG 403 and following GLP. Ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. The gravimetric chamber concentration was 5.16 mg/L. The average mass median aerodynamic diameter was estimated to be 2.15 µm based on graphic analysis of the particle size distribution as measured with a 1 ACFM Andersen Ambient Particle Sizing Sampler with an average geometric standard deviation of 2.22. All animals survived exposure to the test atmosphere and gained body weight during the study. Following exposure, all rats exhibited irregular respiration. In addition, one male was hypoactive. However, all animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Therefore, under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats.
Justification for selection of acute toxicity – oral endpoint
Only one study available.
Justification for selection of acute toxicity – dermal endpoint
Only one study available.
Justification for selection of acute toxicity - inhalation endpoint
Only one study available.
Justification for classification or non-classification
Oral
In accordance with the criteria for classification as defined in Annex III of the OECD Guideline 420, the test material meets the criteria for classification as Acute toxicity oral category 4: Harmful if swallowed (H302) of Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2.
Dermal
In accordance with criteria for classification as defined in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2, the test material does not require classification for acute dermal toxicity as no signs of toxicity were noted during the course of the study.
Inhalation
In accordance with criteria for classification as defined in Regulation (EC) No. 1272/2008, Annex I, Part 3, 3.1.2, the test material does not require classification for acute inhalation toxicity as no signs of toxicity were noted during the course of the study.
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