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EC number: 222-883-3 | CAS number: 3648-18-8
- 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
Oral
LD50 > 2000 mg/kg bw, rat (female), OECD 423, EU Method B.1 tris. Dreher (2013)
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:
- 25 March 2013 to 11 April 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Deviations:
- yes
- Remarks:
- (On one occasion the relative humidity was recorded below the protocol range with a recording of 44 %. This study deviation neither affected the overall interpretation of study findings nor compromised the integrity of the study.)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Deviations:
- yes
- Remarks:
- (On one occasion the relative humidity was recorded below the protocol range with a recording of 44 %. This study deviation neither affected the overall interpretation of study findings nor compromised the integrity of the study.)
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: HsdHan™:WIST
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan UK Limited, Bicester, UK
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 179 - 196 g
- Fasting period before study: animals were fasted from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: animals were housed in groups of up to five during the acclimatisation period in cages that conform to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet: SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham, UK, ad libitum
- Water: mains water, ad libitum
- Acclimation period: 7 - 9 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 45 - 65 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
In order to enrich both the environment and the welfare of the animals, they were provided with wooden Aspen chew blocks, nesting materials and rodent retreats. Environmental enrichment materials were removed during the period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing. - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- - Individual doses
Individual doses (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the specific gravity for the neat material.
- Dose volume
The test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.
During the study, the animals were treated with a dose volume of 1.87 mL/kg - Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 3 animals initially then a further 3 animals once the survival of the previously treated animals was confirmed.
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations: All animals were examined at the beginning and end of the working day throughout the acclimatisation and study periods to ensure they were in good health. Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
- Frequency of weighing: Individual body weights were recorded on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes. A full macroscopic necropsy was performed and all lesions were recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines. No tissue preservation or histopathological assessment of tissues was undertaken.
- Other examinations performed: yes (gene analysis)
Blood samples for gene analysis (0.5 mL nominal) were taken from all animals on Day -1 and Day 1 (24 hours after dosing).
Samples were taken from jugular vein into into trisodium citrate anticoagulant. Samples were mixed gently by hand then continuously for at least 2 minutes on automatic mixer. Once mixed the 3 samples from each group, at each timepoint, were pooled together and placed in a cooled Kryorack. The resultant plasma was separated, transferred to uniquely labelled clear polypropylene tubes and frozen immediately at <–50 °C. - Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- None of the animals died during the study.
- Clinical signs:
- other: No clinical signs were seen during the study.
- Gross pathology:
- No abnormalities were noted at necropsy.
- Other findings:
- Gene analysis findings were not reported.
- Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.
- Executive summary:
The acute oral toxicity of the test material was investigated in a GLP study which was conducted in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris, following the Acute Toxic Class method.
During the study two groups of 3 female rats were sequentially treated with test material at dose level of 2000 mg/kg bw. The test material was administered orally, by gavage, without dilution. All animals were killed on Day 15 and subsequently underwent a full necropsy.
There were no deaths and no signs of toxicity. All rats achieved body weight gains during the first and second weeks of the study. No abnormalities were noted at necropsy. Therefore, under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The key study was assigned a reliability score of 1 according to the criteria of Klimisch. Supporting data were assigned a reliability score of 4. Overall, the quality of the database is good.
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:
- 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- tudy conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- additional blood sampling for determination of absorption
- Principles of method if other than guideline:
- Blood samples for toxicokinetics (0.5 mL nominal) were taken from all animals on Day 1 at 3 and 24 hours after dosing.
- GLP compliance:
- yes
- Test type:
- fixed dose procedure
- Limit test:
- yes
- Species:
- rat
- Sex:
- male/female
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Duration of exposure:
- 24 h
- Doses:
- 2000 mg / kg bw
- No. of animals per sex per dose:
- 5 male and female
- Control animals:
- not required
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- >= 2 000 mg/kg bw
- Based on:
- test mat.
- Interpretation of results:
- study cannot be used for classification
- Remarks:
- Migrated information
- Conclusions:
- The acute median lethal dermal dose of TIB KAT 216 to rats was found to exceed 2000 mg/kg.
Reference
Clinical signs following treatment
Dose level: 2000 mg/kg
Clinical sign |
Animal number and sex |
||||
29M |
30M |
31M |
32M |
33M |
|
No observations |
ü |
ü |
ü |
ü |
ü |
Clinical sign |
Animal number and sex |
||||
34F |
35F |
36F |
37F |
38F |
|
No observations |
ü |
ü |
ü |
ü |
ü |
Dermal reactions
Dose level: 2000 mg/kg
Day |
Dermal reaction |
Animal number and sex |
||||
29M |
30M |
31M |
32M |
33M |
||
2 to 15 |
Erythema Oedema |
0 0 |
0 0 |
0 0 |
0 0 |
0 0 |
Day |
Dermal reaction |
Animal number and sex |
||||
34F |
35F |
36F |
37F |
38F |
||
2 to 15 |
Erythema Oedema |
0 0 |
0 0 |
0 0 |
0 0 |
0 0 |
Individual body weights and weekly increments
Dose level (mg/kg) |
Animal number and sex |
Body weight (g) at: |
Increment (g) |
|||||
Day -1 |
Day 1 |
Day 4 |
Day 8 |
Day 15 |
Day 1 to 8 |
Day 8 to 15 |
||
2000 |
29M |
257 |
266 |
273 |
279 |
308 |
13 |
29 |
30M |
260 |
269 |
269 |
279 |
294 |
10 |
15 |
|
31M |
279 |
286 |
284 |
289 |
307 |
3 |
18 |
|
32M |
268 |
271 |
272 |
281 |
294 |
10 |
13 |
|
33M |
269 |
281 |
283 |
293 |
306 |
12 |
13 |
|
2000 |
34F |
181 |
188 |
195 |
189 |
203 |
1 |
14 |
35F |
201 |
207 |
203 |
213 |
216 |
6 |
3 |
|
36F |
180 |
183 |
179 |
190 |
202 |
7 |
12 |
|
37F |
178 |
186 |
178 |
191 |
200 |
5 |
9 |
|
38F |
195 |
202 |
202 |
210 |
222 |
8 |
12 |
Necropsy findings
Dose level:2000 mg/kg
Animal number and sex |
Time and manner of death (Day) |
Necropsy comments |
29M |
15T |
No macroscopic changes
|
30M |
15T |
No macroscopic changes
|
31M |
15T |
No macroscopic changes
|
32M |
15T |
No macroscopic changes
|
33M |
15T |
No macroscopic changes
|
34F |
15T |
No macroscopic changes
|
35F |
15T |
No macroscopic changes
|
36F |
15T |
Liver: raised area, right median lobe - 9 mm diameter raised area protruding into thoracic cavity - moderate # |
37F |
15T |
No macroscopic changes
|
38F |
15T |
No macroscopic changes
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- The key study was assigned a reliability score of 1 according to the criteria of Klimisch. Supporting data were assigned a reliability score of 4. Overall, the quality of the database is good.
Additional information
Oral
In the key study (Dreher, 2013), the acute oral toxicity of the test material was investigated under GLP conditions, and in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris, following the Acute Toxic Class method. During the study two groups of 3 female rats were sequentially treated with test material at dose level of 2000 mg/kg bw. The test material was administered orally, by gavage, without dilution. All animals were killed on Day 15 and subsequently underwent a full necropsy. There were no deaths and no signs of toxicity. All rats achieved body weight gains during the first and second weeks of the study. No abnormalities were noted at necropsy. Therefore, under the conditions of the study, the acute median dose level of the test material was found to exceed 2000 mg/kg.
Supporting information is available in the form of an abstract of an internet source with no reported methodology which reported the LD50 of the test material to be 6450 mg/kg (WHO, 1980). Data from an abstract of a journal with limited information regarding the methodology (Klimmer, 1969) reported the LD50 of the test material to be 6450 mg/kg. Furthermore, Smith (1978) cited LD50 values from secondary sources; in the first (cited from Barth et al, 1964), the LD50 value was reported to be 600 – 6450 mg/kg, and in the second (cited from Schering) the LD50 value was reported to be in excess of 4000 mg/kg. The supporting data all support the findings of the key study.
Inhalation
In accordance with point 8.5.2, Column 2 (Specific rules for adaptation from Column 1), Annex VIII of Regulation (EC) No. 1907/2006, an acute inhalation study does not need to be performed as the substance has a low vapour pressure (less than 2.2 x 10^-3 Pa at 25 ºC) and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral route, which is more appropriate when considering the properties of this substance.
Justification for selection of acute toxicity – oral endpoint
Dreher (2013) was selected as the key study since it was performed under GLP conditions and in accordance with standardised guidelines. Supporting data are taken from publications with limited detail on experimental materials and methods.
Justification for selection of acute toxicity – inhalation endpoint
A data waiver has been submitted to address this endpoint.
Justification for selection of acute toxicity – dermal endpoint
Dreher (2013) was selected as the key study since it was performed under GLP conditions and in accordance with standardised guidelines. Supporting data are taken from publications with limited detail on experimental materials and methods.
Justification for classification or non-classification
Oral
In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for acute oral toxicity as no signs of toxicity were noted during the course of the key study.
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