Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: assessment
Adequacy of study:
weight of evidence
Study period:
2010
Reliability:
1 (reliable without restriction)

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Conclusions:
The results of the toxicity studies conducted with the test substance by gavage showed that it was not absorbed and distributed systemically, lack of absorption did not lead to any toxic effect. Lungs effect were considered local effects due to chemical pneumonitis and not specific target organ toxicity.
Excretion in urine is not deemed to be realistic as the substance is not absorbed sistematically.
Executive summary:

The present assessment of the absorption, distribution, metabolism and excretion of the studies substance is derived from experimental data produced to register the substance.

Toxicity                            

Acute oral and dermal toxicity studies in rats: in the limit test at a fixed dose of 2000 mg/kg no significant treatment related effects were seen. In such studies LD50 was higher than 2000 mg/kg.                                                

The repeated administration in the 13-week toxicity combined with reproductive endpoint study in rodent by oral did not showed any adverse systemic effects. NOAEL is considered to be 1000 mg/kg/day for males and females. Local effect were seen in lungs but considered an un-direct effect due to suspected chemical pneumonitis. It is known that low viscosity chemical can generate residues in the esophagus that can be aspired in the trachea and deposited in lungs creating such local inflammation. Dark material (the test material) seen in some animals in lung histiocytes support such conclusion.                                          

The lack of general effects and of the target organ toxicity does not lead to conclude that the test item is adsorbed and distributed systemically.

No effect were seen for reproductive end-points up to 1000 mg/kg/day, NOAEL for reproduction is therefore set at > 1000 mg/kg/day.

No information are available concerning excretion rates.          

Skin and eye irritation did not show any local or systemic toxicity.

In the skin sensitisation study, the test item showed a potential to sensitisation; the substance is therefore considered a skin sensitizer.                 

 

Mutagenicity

The test substance was not mutagenic in the bacterial mutation assay and in the "in vitro" chromosome aberration study using CHO, with and without metabolic activation system as well as in the mouse lymphoma test. These studies also demonstrated that no difference of behaviour has been showed after metabolic activation of the substance with S9mix. Toxicity is therefore not induced or enhanced by the metabolism of the substance.                                     

Assessment                                                 

The effects seen do not suggest a possible absorption by GI tract at given doses ; the bioaccumulation evaluation done (see previous paragraph) suggests that the test substance will not

bioaccumulate in aquatic organisms and that no secondary poisoning through the food chain may be realistic.    

No skin absorption was observed when applied during the acute toxicity studies as no systemic effect were observed..

The test substance is not absorbed systemically and hence could not show toxic potential.

Skin sensitisation study showed a sensitisation potential.