Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

oral: clinical signs witnessed in the repeat dose oral toxicity study indicates that the substance is absorbed following administration in polyethylene glycol with systemic effects noted: clinical chemistry,thyroid, liver and kidney following exposure to all dose levels. NO toxicologically significant effects were observed on reproductive or developmental parameters in the exposed animals.

The water solubility, partition coefficient and molecular mass all indicate that this substance will be bioavailable via the oral route.

Inhalation: The particle size distribution indicates that there is limited potential for exposure by this route.

Dermal absorption:  the physical parameters of the substance: molecular weight and log Pow, indicate that the substance may penetrate the stratum corneum and be systemically available from dermal exposure.

Metabolism: There is significant evidence from the 28 day study to indicate that the substance is undergoing extensive hepatic metabolism (adaptive hepatic hypertrophy at all dose levels with diffuse midzonal/centilobular hypertrophy; increases in serum cholesterol and ALAT).

Excretion: There is limited evidence from the oral toxicity studies conducted ( significant increases in calcium and inorganic phosphorus, presence of hylaine droplets and  increases in absolute and relative kidney weights in both sexes  in repeat dose studies) that the substance may interact with the kidneys.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
100

Additional information

Based upon the results of repeat dose toxicity testing and the physical properties of the substance, it can be predicted that absorption and distribution can be expected by the oral and dermal routes. Default absorption rates of 100% are assigned to these routes based upon the relevant physical properties of molecular weight, log Kow and water solubility. Uptake is unlikely by the inhalation route, given the particle size distribution of the substance and a default absorption rate of 0% is assigned.

There is little to no evidence of the metabolic or excretion profile of the substance however the effects on the liver, kidneys and clinical chemistry observed in the repeat dose study is indicative of a metabolic/excretion pathway.