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Description of key information

- Oral: similar to OECD guideline 401, prior GLP, LD50 (rat) >5000 mg/kg bw (no mortality or signs of toxicity)


- Inhalation: similar to OECD guideline 403, prior GLP, LC50 (rat) >1.04 mg/L (no mortality or signs of toxicity)


- Dermal: read across to CAS 30125-47-4, similar to OECD guideline 402, prior GLP, LD50 (rat) >2500 mg/kg bw (no mortality or signs of toxicity)

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
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
unknown concentration in vehicle, uncommon dose selection, high dose volume in PEG
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Physical state: solid
- Analytical purity: no data
Species:
rat
Strain:
other: Tif: RAif (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 to 8 weeks
- Mean weight at study initiation per treatment group: males 193-208 g (maximum SD: 13.4 g); females 172-188 g (maximum SD: 9.4)
- Fasting period before study: overnight
- Housing: groups of 5 in Macrolon cages (type 3)
- Diet (e.g. ad libitum): NAFAG, Gossau SG, CH; ad lib.
- Water (e.g. ad libitum): not specified; ad lib.
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-2
- Humidity (%):55+-10
- Photoperiod (hrs dark / hrs light): 10/14
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 and 20 mL/kg bw
Doses:
2000, 3000, 4000 and 5000 mg/kg bw (5000 mg/kg bw was reported to be the highest possible dose)
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: Physical condition and rate of deaths were monitored throughout the whole observation period. Bodyweights were recorded immediately prior to dosing (control weights) and at 7 and 14 days.
- Necropsy of survivors performed: yes. The animals were submitted at random to a necropsy at the end of the observation period.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality observed.
Mortality:
No mortality observed.
Clinical signs:
other: Dyspnoea, exophthalmus, curved position and ruffled fur were observed in all treatment groups and were reversible within at least 8 days (2000-3000 mg treatment) or 9 days (>=4000 mg).
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:
5 000 mg/kg bw
Quality of whole database:
Similiar to OECD 401, pre-GLP, Klimisch 2

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
Remarks:
no data on purity
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
K. Sachsse, L. Ullmann, G. Voss and R. Hess: Measurement of inhalation toxicity of aerosols in small laboratory animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity. Vol. XV, pp. 239-251, Zurich, June 1973
GLP compliance:
no
Test type:
traditional method
Limit test:
yes
Specific details on test material used for the study:
- Physical state: solid
- Analytical purity: no data
Species:
rat
Strain:
other: Tif:RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 185-190 g
- Housing: 9 per cage (Macrolon, Type 4)
- Diet (e.g. ad libitum): NAFAG, Gossau SG, CH; ad lib.
- Water (e.g. ad libitum): unspecified; ad lib.
- 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:
air
Details on inhalation exposure:
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. at a rate of 20 L/min. The concentration and the particle size distribution of the dust in the vicinity of the animals were 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 µm (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.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1.04 +/- 0.07 mg/L ( original data: 1041 +/- 69 mg/m^3)
No. of animals per sex per dose:
9
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation intervals were not reported; weighing was not performed
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.04 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality and no clinical signs were observed.
Mortality:
No mortality observed
Clinical signs:
other: No signs of toxicity observed
Body weight:
Not measured
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Executive summary:

No mortality and clinical signs were observed at the highest technically attainable concentration.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
1 041 mg/m³ air
Physical form:
inhalation: dust / mist
Quality of whole database:
Similiar to OECD 403, pre-GLP, Klimisch 2

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
please refer to the attached read-across justification
Reason / purpose for cross-reference:
read-across source
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no clinical signs were observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 500 mg/kg bw
Quality of whole database:
Read across to CAS 30125-47-4, similiar to OECD 402, pre-GLP, Klimisch 2

Additional information

Oral:


In the course of the key study, acute oral toxicity was examined by single oral (gavage) administration of the test material dissolved in polyethylene glycol at doses of 2000, 3000, 4000 or 5000 mg/kg bw to male and female Tif: RAif rats (5/sex/dose, fasted overnight). 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. All animals survived until the scheduled day of necropsy, no substance related gross organ changes were seen. Therefore, the LD50 was >5000 mg/kg bw.


 


Next to the key study mentioned above, several other acute oral toxicity studies in rats and mice were performed. All of the animals received single doses of the test substance up to 5000 or 7000 mg/kg bw, respectively, and were observed for a minimum of 8 days. Mortality did not occur in any of the studies; clinical signs or organ changes were also not observed. In two of the studies dyspnoe, curved position and ruffled fur were recorded; these symptoms were reversible within the post observation period.


 


Inhalation:


Acute inhalation toxicity was examined by a 4h dust exposure (1000 mg/m³ (highest technically attainable conc., nose only) to 9 male and female Tif: RAif rats. 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 conditions and incidence of death were monitored throughout an observation period of 14 days. None of the animals died, organ changes or clinical signs of toxicity were not observed. The LC50 was considered to be greater than 1.04 mg/L air.


 


Dermal:


Acute toxicity after dermal application of the test item was not evaluated. However, experimental data of a structural analogue (CAS 30125-47-4) are available.


To determine acute dermal toxicity of an analogue substance, 2500 mg/kg bw of the material was applied onto dorsal skin of male and female rats for 24h under occlusive conditions. The animals were observed for 14 days and checked daily for mortality and clinical signs of toxicity. None of the rats died; yellowish staining of the treatment site was observed. The LD50 was set >2500 mg/kg bw. 


Based on the physico-chemical, structural as well as toxicoligical similarities, the same outcome is assumed for the actual substance.

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. No mortality occurred. As a result, the substance is not considered to be classified for acute oral, inhalation or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.