Registration Dossier

Administrative data

Description of key information

The toxicity of the substance has been assessed  by the repeated exposure over a period of 28-days by the three routes of exposure, oral, dermal and inhalation using read across studies .

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
There are two Klimisch score 1 read across studies avaiable.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
49.5 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
The read across study has a Klimisch score of 1.

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The NOEAL was selected from a Klimisch score 1 study. A lower quality study is also available.

Additional information

The repeat dose toxicity has been determined by subacute 28-day toxicity studies by oral, dermal and inhalation exposure. Based on the data available, the substance may have the potential for haemotological effects with a reduction in cholesterol observed in one of the studies by oral exposure. Affects observed in the repeat dose inhalation toxicity study available demonstrated enlarged lungs in high and intermediate dose animals which are likely to be physical effects due to the inhalation of mineral oil and not necessarily a direct toxicological effect of the registered substance.

Furthermore, one dermal repeat dose study exists noting effects which resulted in the Study Director being unable to assign a NOAEL. Due consideration of these data has been taken, but the results are considered not representative of the toxicological effects of the substance since the observations have not been repeated in the remaining study with dermal exposure, nor following exposure by oral and inhalation routes which are generally considered to represent greater systemic exposure routes. Furthermore, effects to the testes of male rats were not been observed in the reproductive toxicity study. In consequence, although data are not available to adequately determine the cause of these effects, the fact that no similar observations have been found in any other study undertaken is considered adequate justification to regard these data as not representative of the toxicological profile of the registered substance.

Notwithstanding these effects, no further effects were observed in the studies and each study achieved a NOAEL. The data are therefore considered adequate to assess the toxicological profile of the substance and for the purposes of classification.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The NOAEL was selected from the most conservative value of the two available read-across studies.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
There is only one read across study available.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Any local effects will be covered in the NOAEL for systemic effects.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The NOAEL was selected from the higher quality subacute dermal study.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
All local effects will be covered in the NOAEL for systemic effects.

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: other

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: lung

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for repeated dose toxicity.