Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Oral: evidence presented by the combined 28-day oral toxicity/reproductive toxicity study indicates that the substance is absorbed following administration in aqueous suspension; this is despite of the very low water solubility (0.145 mg/L @pH4) and lipophilic partition co-efficient (4.9). Fetal/embryonic effects( decreased weight gain) also indicate that the substance is readily distributed once absorbed. 
Inhalation: Particle size (<45µm) would indicate that the substance is potentially respirable with the low water solubility likely to enhance the penetration to the lower respiratory tract. Given that oral absorption of the substance has been demonstrated in the 28 repeat dose study, it can be expected that absorption by the inhalation route is also likely.

Dermal absorption: based upon the physical properties of water solubility and partition coefficient- dermal uptake is expected to be low, the log Pow would indicate that the absorption to the lipophilic stratum corneum would be high, however the transfer into the epidermis will be low.

Metabolism: evidence from the 28 day study showing hepatocyte hypertrophy as an adaptive change to substance exposure would indicate that the substance is undergoing hepatic metabolism, however the identity of chemical species and extent of biotransformation is unknown.
Excretion: Evidence from the 28-day study, alpha2µglobulin secretion in male kidney, indicates some degree of excretion of the substance or its metabolites.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - dermal (%):
10

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 inhalation routes. Uptake is unlikely by the dermal route, a default value of 10% is assigned based upon the physical properties of the substance. Hepatic and renal effects noted at all dose levels indicate that some degree of metabolism and excretion of the substance is taking place.