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Administrative data

Description of key information

The acute oral LD50 of the test substance in rats of both sexes observed over a period of 7 days is greater than 6000 mg/kg bw.

The LC50 of a 4 hour dust exposure for rats of both sexes is greater than 9500 mg/m3 air, when evaluated for a 14 day post-treatment observation period.

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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-Geigy, Basel, Switzerland
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 160-180 g
- Fasting period before study: yes (1 night)
- Housing: in groups of 5
- Diet: NAFAG (Gossau SG, rat food) ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): approx. 50
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2 %
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 and 30 %

MAXIMUM DOSE VOLUME APPLIED: 6000 mg/kg bw (no higher doses were possible)
Doses:
1000 mg/kg
3170 mg/kg
6000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occured
Clinical signs:
Within 2 hours after treatment the rats in all dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 5 days.
Body weight:
no data
Gross pathology:
No substance related gross organ changes were found.
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:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-Geigy, Basel, Switzerland
- Weight at study initiation: 195-200 g
- Housing: The males and females were segregated and kept in Macrolon cages, type 4, (9 animals to a cage).
- Diet: rat food - NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 1
- Humidity (%): 55+/- 5
- Photoperiod (hrs dark / hrs light): 10/14
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the dust.
- Rate of air: 20 L/min.
- System of generating particulates/aerosols: The dust was generated by injecting the test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm.
- Method of particle size determination: The size distribution of the dust particles was measured with a 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.

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration and the particle size distribution of the dust in the vicinity of the animals was monitored at 1 hour intervals throughout the dust exposure. The concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 nm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the dust particles was measured with a 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.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution: ca. 42 % particles > 7 µm, ca. 45 % particles of 3-7 µm, ca. 10 % particles of 1-3 µm and ca. 3 % particles of <1 µm
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
9465 ± 632 mg/m3
No. of animals per sex per dose:
9
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
discriminating conc.
Effect level:
9 465 mg/L air
Based on:
test mat.
95% CL:
> 8 833 - < 10 097
Exp. duration:
4 h
Mortality:
no mortality occured
Clinical signs:
other: no clinical signs were found
Body weight:
no abnormal changes were detected
Gross pathology:
no gross pathology findings were detected
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
9 500 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

oral route:

The compound was tested on 30 Tif. RAI rats (15 males/ 15 females; CIBA-Geigy, 1973). The substance was suspended at 10 and 30 % with carboxymethyl cellulose 2 % and administered by oral intubation. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer. Three concentrations were tested: 1000, 3170 and 6000 mg/kg bw. Within 2 hours after treatment the rats in all dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 5 days. They were killed and autopsied after an observation period of 7 days. No substance related gross organ changes were seen. Therefore, the LD50 value was determined to be greater than 6000 mg/kg bw.

inhalation route:

A test was performed with 9 male and 9 female rats of the Tif: RAIf (SPF) strain (CIBA-Geigy, 1976). The dust was generated by injecting the test material into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min. For inhalation the rats were kept on separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the dust. The exposure was started 15 minutes after onset of the dust production, when the dust had reached an even dispersal throughout the chamber. After a 4 hour inhalation the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days. During the 4-hour exposure and the subsequent 14-day observation period no deaths and no toxic symptoms were observed. The animals were submitted to a necropsy at the end of the observation period. No substance related gross organ changes were seen. Therefore, the LC50 value was determined to be greater than 9500 mg/m3 air.

Justification for classification or non-classification

Based on the available information classification for acute oral or inhalation toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.