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Administrative data

Description of key information

Suitable acute toxicity studies were only available for oral and dermal adminisration of the test substance. As the study regarding acute inhalation toxicity obtained methodological deficincies, read across on reliable data from an analogue substance was performed.


 


- Oral: similar to OECD guideline 401, prior GLP, LD50 (rat) >10000 mg/kg bw (no mortality or signs of toxicity)


- Inhalation: read across to CAS 106276-80-6, similar to OECD guideline 403, prior GLP, LC50 (rat) >1.04 mg/L (no mortality or signs of toxicity)


- Dermal: 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
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
very brief documentation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
application volume exceeds 20 mL/kg bw; 7 days observation period
GLP compliance:
no
Remarks:
performed prior to the implementation of GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gassner
- Mean weight at study initiation: males: 229 g (208-246 g); females: 170 g (165-171 g)

ENVIRONMENTAL CONDITIONS: Not reported
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% aqueous solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 35 % suspension in 0.5 % aqueous CMC solution
Doses:
10000 mg/kg bw (28.5 mL/kg bw)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of weighing: day 1, 5 and 8
- Observation of clinical signs: on the day of administration and once daily afterwards (on working days)
- Necropsy of survivors performed: yes
Statistics:
not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality was observed
Clinical signs:
other: Yellow faeces
Gross pathology:
No abnormalities were observed
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 mg/kg bw
Quality of whole database:
Similar to OECD TG 401, pre-GLP, Klimisch 2

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please see the attached justification.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
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 aup to and including 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:
Read across to CAS 106276-80-6: similiar to OECD TG 403, pre-GLP, Klimisch 2

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
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:
incomplete documentation; occlusive treatment; 24 h exposure
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
occlusive treatment; 24 h exposure
GLP compliance:
no
Remarks:
performed prior to the implementation of GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Wiga, Ottobrunn, Germany
- Mean weight at study initiation: males 136 g, females 119 g

ENVIRONMENTAL CONDITIONS: Not reported
Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% solution in water
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal, p.c., 50 cm²
- % coverage: considered to be > 10 % (mean bw of 136 g, calculated with the formula " surface area = 9.1 x bw (exp) 0.67"
- Type of wrap if used: no data
- Site of exposure: dorsal

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water containing mild detergent
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 g/kg bw (5mL/kg bw)
- Concentration (if solution): 50 % suspension solution (in water 0.5% CMC)
- For solids, paste formed: yes
Duration of exposure:
24 h
Doses:
2500 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 weighing: before application
- Frequency of observations: daily (on working days: day 1, 2, 5, 6, 7, 8, 9, 12, 13 and 14)
- Necropsy of survivors performed: yes
Statistics:
not performed
Preliminary study:
no data
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.
Mortality:
No mortality ocurred.
Clinical signs:
other: No clinical signs were observed.
Gross pathology:
No abnormalities were observed.
Other findings:
After 24 h and 8 days: local yellow substance residues
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 500 mg/kg bw
Quality of whole database:
similiar to OECD TG 402, pre-GLP, Klimisch 2

Additional information

Oral:


Acute oral toxicity of the test item (purity 100%), dissolved in an aqueous solution 0.5% CMC, was determined by single oral (gavage) administration to male and female rats at a concentration of 10000 mg/kg bw. The animals were observed for 7 days and checked for mortality, body weight change and clinical signs of toxicity. All animals survived until scheduled day of necropsy which did not reveal any findings. Excretion of yellowish feces was reported. The LD50 after oral application is therefore considered to be higher than 10000 mg/kg bw.


 


Inhalation:


Acute inhalation toxicity was examined for the test substance itself. Exposure of 12 rats for 8h to an atmosphere enriched with the test material did not cause mortality or findings in necropsy. However, due to an unsuitable test method for non-volatile or non-dusty solids, the study is regarded as invalid and read across to CAS 106276-80-6 was performed.


 


Acute inhalation toxicity of the analogue substance was examined after 4h dust exposure of 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. Therefore, the LC50 is considered to be greater than 1.04 mg/L air.


In an inhalation hazard test with the thermal decomposition products of the analogue substance,  nine male and nine female rats of the Tif: RAIf (SPF) strain were exposed for 30 minutes (snouts and nostrils only) to the fumes produced upon thermal decomposition of the test material at a temperature of 300° C. Exposure to the fumes was tolerated by all animals. No mortality and signs of toxicity were observed after 30 min exposure to the vapour/ fume of the thermal decomposition products of the test substance at 300°C.


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


 


Dermal:


To determine acute dermal toxicity of the test substance, 2500 mg/kg bw of the material (purity 100%) 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 after dermal application is therefore considered to be higher than 2500 mg/kg bw.


 


Other routes:


Intraperitoneal injection of an aqeous solution of the test substance (10.000 mg/kg bw) into mice did not result in mortalities. Intra-abdominal deposits of test substance and conglutinations were observed during necropsy.

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.