Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Physical-chemical data suggest that the registered substance will be poorly absorbed by oral, dermal and inhalation routes of exposure, and toxicological data support minimal, if any, absorption. There is no evidence for metabolic bioactivation, based on the absence of target organ toxicity in-vivo, and on the absence of genotoxicity in the bacterial reverse mutation assay and in the in-vitro mammalian cytogenetic test in Chinese hamster ovary cells (CHO), both conducted in the presence and absence of a mammalian metabolic activation system.

Key value for chemical safety assessment

Additional information

Although no specific toxicokinetic data are available for the registered substance, physical-chemical as well as toxicology data provide useful pieces of information.

The registered substance is described as a solid brown powder, with low vapour pressure (less than 2.6 x 10^-4 Pa at 25 °C) and mass median and mean diameters of 175 µm (SD 8.1) and 199 µm (SD 4.5), respectively. These data indicate that respiratory exposure is unlikely to occur under normal conditions, and that in any case the inner tract of the respiratory system would hardly be reached even in case of generation of airborne dusts or aerosol.

The registered substance is highly lipophilic (log Pow> 7.8) but the extremely low water solubility (below the instrumental detection limit of 0.05 mg/L) is expected to limit the extent of absorption from the gastrointestinal tract. The results obtained in the toxicity studies confirm this assumption, because no evidence of systemic toxicity, organ toxicity or neurobehavioural changes could be noted following 28-days of continuous exposure via the diet, at dosages exceeding the limit dose of 1000 mg/kg bw/day (i.e. up to more than 1300 mg/kg bw/day during the first week of the study, when the animals were younger and lighter).

The large molecular weight (more than 500) and high log Pow (> 7.8) infer dermal permeability and percutaneous absorption to be low. Toxicological studies again confirm this assumption, because no signs of systemic toxicity were observed at the limit dose of 2000 mg/kg bw in an acute dermal study, and no signs of irritation followed the application of 0.5 g of the substance to the skin of rabbits. In addition, no skin sensitisation potential was detected in a fully compliant Local Lymph Node Assay.

In summary: physical-chemical data suggest that the registered substance will be poorly absorbed by oral, dermal and inhalation routes of exposure, and toxicological data support minimal, if any, absorption. There is no evidence for metabolic bioactivation, based on the absence of target organ toxicity in-vivo, and on the absence of genotoxicity in the bacterial reverse mutation assay and in the in-vitro mammalian cytogenetic test in Chinese hamster ovary cells (CHO), both conducted in the presence and absence of a mammalian metabolic activation system.