Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The acute oral LD50 of the test material in rats is > 6000 mg/kg bw.

The acute oral LD50 of the test material in hamsters is > 3000 mg/kg bw.

The inhalation LC50 of the test material in rats is > 2119 mg/m³ air.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: LV 86
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: raised on the premises
- Age at study initiation: 7 to 8 weeks old
- Weight at study initiation: males: 165-179 g; females: 164-169 g
- Fasting period before study: overnight
- Housing: the animals were housed in groups of 5 in Macrolon cages (type 3)
- Diet (e.g. ad libitum): ad libitum rat food - NAFAG, Gossau SG
- Water (e.g. ad libitum): ad libitum water
- Acclimation period: a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): a 10 hours light cycle day
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2%
Details on oral exposure:
DOSE VOLUME APPLIED: 20 mL/kg

DOSAGE PREPARATION (if unusual):
The test substance was suspended. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Rationale for dose selection: no higher doses were possible
Doses:
4000, 5000, 6000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days; physical condition and rate of deaths were monitored throughout the whole observation period
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
Sedation, Dyspnoea, exopthalmos, ruffled fur, body position (curved).
The surviving animals recovered within 10 days.
Body weight:
Normal weight gain.
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
6 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: EN 63699.02

Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Raised on the premises
- Weight prior to exposure: average for males: 207-235 g; average for females: 188-212 g
- Housing: The males and females were segregated and kept in Macrolon cages, type 4 (10 animals to a cage)
- Diet: ad libitum rat food - NAFAG, Gossau SG, Switzerland
- Water: ad libitum water
- Acclimation period: a minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): 55 ± 10
- Photoperiod (hrs dark / hrs light): 10 hour light cycle day.

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
TESTING PROCEDURE:
For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snouts and nostrils of the animals only were exposed to the aerosol.

During the exposure period at approximately the same times as chamber concentration was measured, the following parameters were determined inside the inhalation cylinder: temperature (with a THERM 2104 contact thermometer, Ahlborn Mess- und Regeltechnik, 815 Holzkirchen, Germany), relative humidity (with a VÆSALA Humidity Indicator HMI 11, Kelag AG, 8057 Zurich, Switzerland) and oxygen content (with a DRAEGER E 15 stationary control system, Draegerwerk AG, Lübeck, Germany).

After a 4 hour inhalation exposure the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days.

GENERATION OF TEST ATMOSPHERE
The aerosol was generated by injecting two different concentrations of the solid test material with the help of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream which was discharged into the exposure chamber at a rate of 10 L/min.

The control animals were exposed to filtered air under the same conditions as described above.

The concentration and the paricle size distribution of the aerosol in the breathing zone vicinity of the animals were monitored at regular intervals throughout the aerosol exposure. The concentration was determined 5 times gravimetrically by sampling the test atmosphere though a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured twice with a 4 stage Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2119±168 and 1365±47 mg/m³
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded immediately prior to exposure (control weights) and at day 7 and 14; physical condition and incidence of death were monitored throughout an observation period of 14 days
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 119 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No deaths occurred in the control group or the 1365 and 2119 mg/m³ exposure groups.
Clinical signs:
other: The surviving animals recovered within 7 to 8 days after the exposure period. Slight dyspnoea, exophthalmus,ruffled fur,and curved body position were noted during and after exposure to 1365 and 2119 mg/m³ of the test material.
Body weight:
Overall body weights and weight gains were within normal limits when measured at day 7 and 14 of the observation period.
Gross pathology:
No gross pathology was noted in the control or either treatment groups at necropsy.
Other findings:
Particle size distribution analysis of the chamber airborne particles showed that 80% were smaller than 7 µm in diameter.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

Two acute oral toxicity studies were performed.

- In an acute oral toxicity study comparable to OECD guideline 401 (CIBA-GEIGY, 1978) the test material was evaluated in (7 to 8 weeks old) healthy random bred rats of the Tif: RAIf (SPF) strain. Animals fasted overnight were treated by oral intubation, in groups of five per dose level (4000, 5000, 6000 mg/kg bw). Physical condition and rate of deaths were monitored throughout a 14-day observation period. Animals in all three dose groups showed sedation, dyspnoea, exopthalmos, ruffled fur, body position (curved) and recovered within 10 days. No death occurred and no substance related gross organ changes were seen. The acute oral LD50 of the test material is > 6000 mg/kg bw. The test material has therefore practically no acute toxicity to the rat by this route of administration.

- In an acute oral toxicity study comparable to OECD guideline 401 (CIBA-GEIGY, 1981) the test material was evaluated in 9-11 week old Chinese hamsters of both sexes. Animals fasted overnight were treated orally, with a single dose (3000 mg/kg), by means of a stomach tube. Physical condition and rate of deaths were monitored throughout a 14 day observation period. No deaths occurred. Animals were slightly sedated, showed slight dyspnoea, ruffled furr and body position (curved). The animals recovered within 6 days. All animals were submitted to a necropsy, no gross organ changes were seen. The acute oral LD50 is greater than 3000 mg/kg. The test material has therefore practically no acute toxicity to the Chinese hamster by this route of administration.

Inhalation:

In an inhalation study comparable to OECD guideline 403 (CIBA-GEIGY, 1980) rats of the Tif: RAIf (SPF) strain (10/sex/dose) were administered the test material (1365± 47 mg/m³, 2119±168 mg/m³) by inhalation for 4 hours followed by a 14-day observation period. No death occurred. Overall body weights and weight gains were within normal limits when measured at day 7 and 14 of the observation period. The surviving animals recovered within 7 to 8 days after the exposure period. Slight dyspnoea, exophthalmus, ruffled fur, and curved body position were noted during and after exposure to 1365 and 2119 mg/m³ of the test material. No gross pathology was noted in the control or either treatment groups at necropsy. The LC50 was > 2119 mg/m³ air.

Justification for classification or non-classification

                       

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008.