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EC number: 410-690-9 | CAS number: 103055-07-8 CGA 184699
- 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, males/females, rat, according to OECD TG 401, Hartmann, 1988.
- Inhalation: LC50 > 2350 mg/m3, males/female, rat, according to OECD TG 403, Hartmann, 1988.
- Dermal: LD50 > 2000 mg/kg bw, males/females, rat, equivalent to OECD TG 402, Hartmann, 1988.
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 Jan 1988 to 08 Feb 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- Feb 1987
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Tif: RAI f (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 7 - 8 weeks young adults
- Weight at study initiation: 169 - 204 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: housed in Macrolon cages type 4, with standardized soft wood, segregated by sex, group-housed (5 animals per cage)
- Diet: Rat chow, ad libitum
- Water: provided, ad libitum
- Acclimation period: minimum of 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 25 Jan 1988 To: 08 Feb 1988 - Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on oral exposure:
- The test substance was administered at a single dose volume of 10 mL/kg bw.
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations clinical signs: The animals were observed for signs of systemic toxicity twice (a.m. and p.m.) on working days, and once (a.m.) on weekend days
- The animals were weighed at the start and on day 7 and 14.
- The animals were submitted to a gross necropsy at the end of the observation period. - Statistics:
- From the body weights, the group means and their standard deviations were calculated.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality observed.
- Clinical signs:
- other: Ruffled fur, dyspnea, hunched posture, and exophthalmos were seen, being common symptoms in acute tests. The animals recovered within 11 days.
- Gross pathology:
- No deviations from normal morphology were found.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute oral LD50 of the test substance is estimated to be > 2000 mg/kg for both male and female rats.
- Executive summary:
Groups of 5 young adult male and 5 female Tif: RAI f (SPF) rats received a single oral (gavage) dose of 2000 mg/kg bw of the test substance in a study performed according to OECD TG 401 following GLP principles. Prior to dosing, the animals were fasted overnight. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals throughout the study. All animals were subjected to a complete gross necropsy following their sacrifice or spontaneous death. Ruffled fur, dyspnoea, hunched posture, and exophthalmos were observed, being common symptoms in acute tests. The animals recovered within 11 days. Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined for the test substance. The LD50 in both male and female rats was greater than 2000 mg/kg bw.
Reference
Table 1 Mean body weight and standard deviation
|
males |
females |
||||
Dose (mg/kg) |
Day 1 |
Day 7 |
Day 14 |
Day 1 |
Day 7 |
Day 14 |
2000 |
191/9.0 |
269/11.2 |
313/13.8 |
176/5.5 |
226/7.7 |
249/12.8 |
Table 2: Signs and symptoms
Observations | Exposure day (hours) | Days of post-exposure period | |||||||||||||||||
1 | 2 | 3 | 4 | 5 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | >13 | |
2000 mg/kg males |
|||||||||||||||||||
ruffled fur |
x | xx | xx | x | x | x | x | x | x | x | x | x | x | x | x | ||||
dyspnea | xx | x | x | x | x | x | x | x | x | x | x | ||||||||
body position curved | x | x | x | x | x | x | x | ||||||||||||
exophtalmos | x | x | x | x | x | x | x | x | x | x | |||||||||
2000 mg/kg females |
|||||||||||||||||||
ruffled fur | x | xx | xx | x | x | x | x | x | x | x | x | x | x | x | x | ||||
dyspnea | xx | x | x | x | x | x | x | x | x | x | x | ||||||||
body position curved | x | x | x | x | x | x | x | ||||||||||||
exophtalmos | x | x | x | x | x | x | x | x | x | x |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- > 2 000 mg/kg bw
- Quality of whole database:
- GLP compliant OECD TG 401 study.
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:
- 22 Mar 1988 to 12 Apr 1988
- 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:
- May 1981
- GLP compliance:
- yes
- Test type:
- traditional method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Tif: RAI f (SPF) hybrids of RII/1 x RII/2
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: age 7 - 8 weeks
- Weight at study initiation: 178 to 331 g
- Housing: Group of 5 (by sex); Macrolon cages, Type 4 with standardised soft wood bedding
- Diet: Rat diet, ad libitum.
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: 22 Mar 1988 To: 12 Apr 1988 - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Mass median aerodynamic diameter (MMAD):
- >= 1.9 - <= 2.8 µm
- Geometric standard deviation (GSD):
- >= 2.2 - <= 2.5
- Remark on MMAD/GSD:
- In of the vicinity of the animals, 84 to 95 % (weight) of the airborne particles had a diameter smaller than 7 μm during the exposure.
- Details on inhalation exposure:
- INHALATION EXPOSURE CHAMBER
All exposures were conducted in a nose-only exposure. The chamber was designed to ensure a rapid equilibration (internal active volume less than one litre) and a uniform exposure of all animals in the system. In order to avoid rebreathing of the exhaled air, "fresh" test substance (in first—pass chamber air) was supplied to each animal via individual delivery and exhaust tubes. In addition to the necessary animal and sampling ports, identical "void" outlets were opened in proportion to the total air flow through the chamber. Thus the flow in any individual aerosol delivery tube was standardized to 2 L/min (velocity 1.25 m/s).
For the inhalation period, the rats were placed in Macrolon animal holders positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at an exactly balanced pressure to prevent leakage of the test atmosphere from the system, as well as dilution with outside air. The exhaust air was decontaminated by subsequent passage through an absolute filter. The aerosol concentration in the chamber was determined gravimetrically 5 times during the exposure period. Samples of the test atmosphere (1 L) were passed through a GP 92 filter. The air flow rate for the sample collection was kept constant (2 L/min) by means of a Sierra Series 110 constant flow air sampler, regardless of filter loading. The mean and standard deviation of the aerosol concentrations for the exposure was calculated. Particle size analysis was conducted with an APS-33 Aerodynamic Particle Sizer, equipped with appropriate dilution systems to avoid coincidence counts. The number distribution in the 48 size classes was converted to a mass distribution, based on the bulk density of the test substance, which was determined separately. The following environmental parameters inside the inhalation chamber were monitored at approximately the same intervals as the concentration determinations:
- Temperature
- Relative humidity
- Oxygen content
AEROSOL
The aerosol was generated from the solid test material by means of a brush-feed micronizing jet mill. The aerosol generation system consists of a dual flexible brush dust-feed mechanism, modified from a design by Milliman, and a jet mill, to be aerodynamically compatible with the brush feed and the exposure system. In this instrument, powders are transferred from a hopper brush through a slit interface to the aspiration tube of the jet mill by means of a spiral feed brush driven by a stepping motor. In the mill, the material is micronized by impaction of particle against particle in two opposing air streams. A cyclone type classifier ensures that only particles of the desired diameter leave the jet mill, while the larger ones are re-entrained into the air stream for further milling. In a preliminary experiment, the appropriate interface slit size, brush speeds, and air pressures and flows were determined for the desired concentration. The dust generator was operated at a total airflow (through the aspiration tube and the two milling jets) of 37 L/min (input pressure 210/210 kPa), and the aerosol was diluted with filtered humidified air to yield a total flow of 48 L/min. Secondary agglomerates were removed from the aerosol by means of a glass cyclone. The throughput of the solid test material was determined by weighing the dust genera tor and the cyclone before and after aerosol generation. The control animals were exposed to filtered humidified air (32 L/min) under the same conditions as described above.
ANALYSIS OF INHALATION ATMOSPHERES
The air flow through the chamber was measured with flow meters. Adjustments to maintain a total flow of 48 L/min could be made with needle valves. However, no deviations were observed in any of the exposures, once the equilibrium was reached (within the first 10 minutes after beginning of exposure). - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 2350 ± 100 mg/m³
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Details on study design:
- OBSERVATIONS
MORBIDITY/MORTALITY
The animals were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days.
BODY WEIGHTS
Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period.
GROSS PATHOLOGY
Examinations were performed on all animals, which were killed after 14 days by ether anaesthesia. Particular attention was given to the respiratory tract - Statistics:
- Inhalation LC50 values (including their 95 % confidence limits) for a 4 hour treatment and a subsequent 14 day observation period could not be calculated, because no mortalities were elicited by the test substance at a concentration of 2350 ± 100 mg/m3 (limit test). The body weights of the treated animals and the controls were compared by analysis of variance.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 2 350 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- No mortality occurred.
- Clinical signs:
- other: The symptoms, piloerection, hunched posture, dyspnea, were seen and in similar extent in both sexes. These findings disappeared within 2 days.
- Body weight:
- The males exposed to the test article exhibited a significantly higher body weight increase during the second week after exposure
- Gross pathology:
- No treatment-related deviations from normal morphology were detected at necropsy.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute inhalation LC50 of the test substance in rats was found to be greater than 2350 mg/m3 for both males and females.
- Executive summary:
The acute inhalation toxicity of the test substance was evaluated in groups of 5 male and 5 female young adult albino rats (Tif: RAI f (SPF)), rats in accordance with OECD TG 403 following GLP principles. The animals were exposed to 0 (control – purified air) or 2350 mg/m³ test article in a nose-only exposure system and were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals, which were killed after 14 days by ether anaesthesia. Particular attention was given to the respiratory tract.
Upon a 4hour aerosol inhalation exposure and a 14 day post-treatment observation period, no mortalities were elicited by the test substance at a concentration of 2350 ± 100 mg/m3. Due to the properties of the test material, it was not possible to generate higher aerosol concentrations of the test substance. The mass median aerodynamic diameter (MMAD) of the particles was between 1.9 and 2.8 µm, with a geometric standard deviation (GSD) of 2.2 to 2.5. In the vicinity of the animals, 84 to 95 % of the airborne particle mass had a diameter smaller than 7 µm. The animals of both sexes exposed to the test substance experienced the symptoms piloerection, hunched posture and dyspnoea to a similar extent. They recovered within 2 days. From the absence of mortalities it can be assumed that the LC50 to male and female rats is greater than 2350 mg/m3 air.
In conclusion, the acute inhalation LC50 of the test substance in rats was found to be greater than 2350 mg/m3 for both males and females.
Reference
Table 1 Exposure atmospheres
Parameter |
1 - Control Group (air) |
2 – Exposure Group (test substance) |
Exposure day |
22 Mar 1988 |
12 April 1988 |
Nominal concentration (mg/m3) |
Control * |
3003 |
Mean exposure concentration ** (mg/m3) ± SD |
2350 ± 100 |
|
Mass median aerodynamic diameter (MMAD) (mm) |
1.9 – 2.8 |
|
Geometric standard deviation (GSD) |
2.2 – 2.5 |
|
Particles < 7 mm (% w/w) |
84 – 95 |
|
Particles < 3 mm (% w/w) |
52 – 73 |
|
Air flow (L/min) through generator |
32 |
37 |
Mean chamber temperature (ºC) *** ± SD |
22.3 ± 0.1 |
23.0 ± 0.1 |
Mean relative humidity (%) *** ± SD |
47 ± 1 |
38 ± 1 |
Mean oxygen content (%) *** ± SD |
21.0 ± 0 |
21.0 ± 0 |
* exposed to filtered humidified air
** determined gravimetrically 5 times during exposure period
*** determined 5 times during the exposure period
Table 2 Observation of symptoms
Observations |
Exp. day |
Day of post exposure period |
||||||||||
de |
ae |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
>9 |
|
Control males |
|
|
no effect observed in all animals |
|||||||||
Test article exposed males |
|
|
|
|
|
|
|
|
|
|
|
|
piloerection |
|
++ |
+ |
|
|
|
|
|
|
|
|
|
hunched post. |
|
+ |
|
|
|
|
|
|
|
|
|
|
dyspnoea |
|
++ |
+ |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Control females |
|
|
no effect observed in all animals |
|||||||||
Test article exposed females |
|
|
|
|
|
|
|
|
|
|
|
|
piloerection |
|
++ |
+ |
|
|
|
|
|
|
|
|
|
hunched post. |
|
+ |
|
|
|
|
|
|
|
|
|
|
dyspnoea |
|
++ |
+ |
|
|
|
|
|
|
|
|
|
Exp.day = exposure day (de = during, ae = after exposure)
+ = slight ++ moderate = +++ = severe
hunched post. = hunched posture
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating conc.
- Value:
- >= 2 350 mg/m³ air
- Physical form:
- inhalation: aerosol
- Quality of whole database:
- GLP compliant OECD TG 403 study
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:
- 16 Feb 1988 to 01 Mar 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- Feb 1987
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Tif: RAI f (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: Young adult of 7 to 8 weeks
- Weight at study initiation: 224 to 250 g
- Housing: Group of 5 (by sex); Macrolon cages, Type 3 with standardised soft wood bedding
- Diet: Rat diet, ad libitum.
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: 16 Feb 1988 To: 01 Mar 1988 - Type of coverage:
- occlusive
- Vehicle:
- arachis oil
- Details on dermal exposure:
- TEST SITE
- Area of exposure: an area on the back of the rat
- Pre-treatment: Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- % coverage: 10 % of the total body surface
- Type of wrap if used: The treated area was covered with a gauze-lined semi occlusive dressing fastened around the trunk with an adhesive elastic bandage
REMOVAL OF TEST SUBSTANCE
- Washing: After 24 hours, the dressings were removed and treated area was the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly.
TEST MATERIAL
- Amount applied: 4 mL/kg
- Concentration: 2000 mg/kg bw test substance suspended in Oleum arachidis
- Constant volume or concentration used: yes - Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- Remarks:
- A control gauze patch was applied to the contralateral flank.
- Details on study design:
- - Duration of observation period following administration: 14 days.
- Frequency of weighing: Individual body weights of the animals were recorded on Days 1, 7 and 14.
- Frequency of observations: Animals were observed daily; a.m. and p.m. on working days, a.m. on weekend days
- Necropsy of survivors performed: yes, on Day 15 and were subjected to gross necropsy at the end of the observation period.
- Clinical signs: Clinical signs were recorded daily. Ruffled fur, dyspnoea, abnormal body positions, and spontaneous activity were monitored. - Statistics:
- From the body weights, the group means and their standard deviations were calculated.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality occurred.
- Clinical signs:
- other: Not treatment-related observations: ruffled fur, dyspnea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days.
- Gross pathology:
- No deviations from normal morphology were found at autopsy.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The acute median lethal percutaneous dose (LD50) to rats of test substance was found to be greater than 2000 mg/kg bw.
- Executive summary:
An acute dermal study was performed in accordance with OECD TG 402 following GLP principles. The test was conducted with Tif: RAI f (SPF) rats to determine the potential for the test substance to produce toxicity from a single topical application. Approximately 24 hours before treatment, an area of at least 10 % of the body surface of the back of one group of 10 rats (5/sex) was shaved with an electric clipper. Test article was evenly dispersed on the skin at a dosage of 2000 mg/kg bw in Oleum arachidis in a dose volume of 4 mL/kg bw and covered with a semi-occlusive dressing. After an exposure period of 24 hours, the dressing was removed and the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly. Mortality, signs and symptoms were recorded daily, body weight at start and on days 7 and 14 of the study, and the animals were subjected to gross necropsy at the end of the 14-day observation period.
No mortality occurred; ruffled fur, dyspnoea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days. Body weight growth was observed and no deviations from normal morphology were found at autopsy. Upon an acute dermal application and a 14-day post-treatment observation period, the LD50 for the test substance in rats was greater than 2000 mg/kg bw in both sexes.
Reference
Table 1 Rate of deaths
Dose mg/kg |
Totals |
Hours aft. Treatment |
Day of post exposure period |
||||||||||||||||||
|
in grp |
Deaths |
1 |
2 |
3 |
5 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
>13 |
|
|
no |
% |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2000 mg/kg, males |
5 |
0 |
0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
2000 mg/kg, females |
5 |
0 |
0 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Table 2 Mean body weight and standard deviation
Males |
Females |
|||||
dose mg/kg |
day 1 |
day 7 |
day 14 |
day 1 |
day 7 |
day 14 |
2000 |
244/ 6.3 |
281/23.6 |
328/21.4 |
233/ 6.6 |
243/ 6.5 |
259/10.9 |
Table 3 Signs and symptons
Observations |
Exposure day: hours |
Day of post-exposure period |
||||||||||||||||
1 |
2 |
3 |
5 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
>13 |
|
2000 mg/kg, males |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
ruffled fur |
x |
x |
x |
x |
x |
x |
x |
x |
|
|
|
|
|
|
|
|
|
|
dyspnoea |
x |
x |
x |
x |
x |
x |
x |
|
|
|
|
|
|
|
|
|
|
|
hunched post. |
|
|
|
|
x |
x |
|
|
|
|
|
|
|
|
|
|
|
|
ventr.recumb |
x |
x |
x |
x |
x |
|
|
|
|
|
|
|
|
|
|
|
|
|
red.spont.act |
x |
x |
x |
x |
|
|
|
|
|
|
|
|
|
|
|
|
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2000 mg/kg, females |
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ruffled fur |
x |
x |
x |
x |
x |
x |
x |
x |
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dyspnoea |
x |
x |
x |
x |
x |
x |
x |
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hunched post. |
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x |
x |
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ventr.recumb |
x |
x |
x |
x |
x |
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red.spont.act |
x |
x |
x |
x |
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x = slight xx = moderate XXX = marked
hunched post. = hunched posture ventr.recumb. = ventral recumbency
red.spont.act = reduced spontaneous activity
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- discriminating dose
- Value:
- > 2 000 mg/kg bw
- Quality of whole database:
- GLP compliant OECD TG 402 like study
Additional information
All available data was assessed and the studies representing the worst-case effects were included as key or weight-of-evidence studies. Other studies are included as supporting information. Dosing with the test substance in rat and mouse results in low acute toxicity by the oral, dermal and inhalation routes of exposure. The key studies are considered to be worst-case and were selected for the CSA. Two acute toxicity studies with metabolites of the test substance are available with a combined male/female LD50 of 1273 and 2065 mg/kg bw.
Acute oral toxicity study in rats, Hartmann 1988
Groups of 5 young adult male and 5 female Tif: RAI f (SPF) rats received a single oral (gavage) dose of 2000 mg/kg bw of the test substance in a study performed according to OECD TG 401 following GLP principles. Prior to dosing, the animals were fasted overnight. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their body weights were recorded at intervals throughout the study. All animals were subjected to a complete gross necropsy following their sacrifice or spontaneous death. Ruffled fur, dyspnoea, hunched posture, and exophthalmos were observed, being common symptoms in acute tests. The animals recovered within 11 days. Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined for the test substance. The LD50 in both male and female rats was greater than 2000 mg/kg bw.
Acute inhalation toxicity study in rats, Hartmann 1988
The acute inhalation toxicity of the test substance was evaluated in groups of 5 male and 5 female young adult albino rats (Tif: RAI f (SPF)), rats in accordance with OECD TG 403 following GLP principles. The animals were exposed to 0 (control – purified air) or 2350 mg/m³ test article in a nose-only exposure system and were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals, which were killed after 14 days by ether anaesthesia. Particular attention was given to the respiratory tract.
Upon a 4 hour aerosol inhalation exposure and a 14 day post-treatment observation period, no mortalities were elicited by the test substance at a concentration of 2350 ± 100 mg/m3. Due to the properties of the test material, it was not possible to generate higher aerosol concentrations of the test substance. The mass median aerodynamic diameter (MMAD) of the particles was between 1.9 and 2.8 µm, with a geometric standard deviation (GSD) of 2.2 to 2.5. In the vicinity of the animals, 84 to 95 % of the airborne particle mass had a diameter smaller than 7 µm. The animals of both sexes exposed to the test substance experienced the symptoms piloerection, hunched posture and dyspnoea to a similar extent. They recovered within 2 days. From the absence of mortalities it can be assumed that the LC50 to male and female rats is greater than 2350 mg/m3 air.
In conclusion, the acute inhalation LC50 of the test substance in rats was found to be greater than 2350 mg/m3 for both males and females.
Acute dermal toxicity in rats, Hartmann 1988
An acute dermal study was performed in accordance with OECD TG 402 following GLP principles. The test was conducted with Tif: RAI f (SPF) rats to determine the potential for the test substance to produce toxicity from a single topical application. Approximately 24 hours before treatment, an area of at least 10 % of the body surface of the back of one group of 10 rats (5/sex) was shaved with an electric clipper. Test article was evenly dispersed on the skin at a dosage of 2000 mg/kg bw in Oleum arachidis in a dose volume of 4 mL/kg bw and covered with a semi-occlusive dressing. After an exposure period of 24 hours, the dressing was removed and the skin was cleaned with lukewarm water. Thereafter, the skin reaction was appraised repeatedly. Mortality, signs and symptoms were recorded daily, body weight at start and on days 7 and 14 of the study, and the animals were subjected to gross necropsy at the end of the 14-day observation period.
No mortality occurred; ruffled fur, dyspnoea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 5 days. Body weight growth was observed and no deviations from normal morphology were found at autopsy. Upon an acute dermal application and a 14-day post-treatment observation period, the LD50 for the test substance in rats was greater than 2000 mg/kg bw in both sexes.
Justification for classification or non-classification
Based on the result of the acute oral, acute dermal and acute Inhalation toxicity study classification for acute toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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