Phosphoric acid, P,P'-[2,2-bis(chloromethyl)-1,3-propanediyl] P,P,P',P'-tetrakis(2-chloro-1-methylethyl) ester

Endpoint summary

Additional information

Based on Read-Across with 2,2-Bis(chloromethyl)trimethylene bis[bis(2-chloroethyl)phophate

The ADME characteristics were investigated by the oral and IV routes in the rat. The bioavailability after the oral low and high doses were > 100% and approximately 50%, respectively. However, the bioavailability for the high dose was calculated using a lower IV dose. In addition, less than 1% of the parent compound was found in the faeces after the oral high dose, indicating practically complete absorption from the gastrointestinal tract. Therefore, 100% absorption by the oral route is assumed and is taken forward to risk characterisation. No sex difference was observed in blood kinetics at the low dose, however, in the high dose group, Cmax and AUC were higher in females than males. The elimination half life was 99-113 hours, irrespective of the dose, route or sex. The retention of radioactivity was low, with the majority (60%) of the radioactivity excreted by biliary route within 3 days of dosing. Approximately 20% was excreted in urine and a small amount of radioactivity exhaled as¹⁴CO₂. [¹⁴C]-radiolabelled test substance or its metabolites were distributed all over the body, but no target organs, other than organs of elimination were identified. The major metabolites which could be identified were found in the faeces.

 

An in vitro percutaneous absorption study using human skin membranes in flow-through diffusion cells was conducted to determine the rate and extent of absorption following topical application [¹⁴C] radiolabelled material, either “neat” or in an ethanol vehicle, to human skin. The skin membranes were exposed for 8 hours, mimicking a normal working day. The dermal delivery for the test substance and the substance in ethanol (0.2 mg/cm²) was 0.51 % and 6 %, respectively.