Dimethyl phosphonate

Endpoint summary

Description of key information

STUDIES IN ANIMALS
Toxicokinetics
Information on toxicokinetics is available from one study where Fischer 344 rats and B6C3F1 mice were administered once orally 10 - 200 mg/kg 14C-labelled dimethyl phosphonate by gavage. Furthermore, rats were treated repeatedly for 5 days with an oral dose of 200 mg/kg bw 14C labelled dimethyl phosphonate
Absorption
From the studies on metabolism it can be concluded that dimethyl phosphonate was readily and near completely absorbed from the gastrointestinal tracts of rats and mice.
Distribution
Dimethyl phosphonate derived radioactivity was widely distributed in tissues of rats and mice 24 h after dosing. The radioactivity in the tissues was approximately proportional to the dose. The highest concentrations were observed in liver, kidney, spleen, lungs, and forestomach, and the lowest in brain, skeletal muscle, adipose tissue, and testes. Concentration of dimethyl phosphonate derived radioactivity in all tissues increased as the number of daily doses increased. The pattern of tissue distribution in mice was similar to that observed in rats but the radioactivity measured in mice tissues after the administration of labeled dimethyl phosphonate was lower.
Elimination
In rats 49 - 57 % of radioactivity was recovered as expired air (nearly complete after 12 hours), 28 - 38 % was found in urine (after 24 hours) and 2.5 % as organic volatiles. In mice approximately 44 % of radioactivity was eliminated via CO2 after 12 hours and approximately 49 % was found in urine after 24 hours. About 1 to 2 % of the radioactivity was found in the faeces in both species. The rate, extent and pattern of elimination of radioactivity were unaffected by dose over the range studied and by repeated administration.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Dimethyl phosphonate administered at a range of dose of 10-200 mg/kg was readily and near completely absorbed from the gastrointestinal tracts of rats and mice. Dimethyl phosphonate was eliminated primarily as CO₂ in the expired air, 44-57%, and urine 28-49%, and very little was collected in feces, 1-2%, or as volatile organics, 2-3%. Dimethyl phosphonate derived radioactivity was widely distributed in tissues of rats and mice, with the highest concentrations observed on the liver, kidneys, spleen, lungs and forestomach, and the lowest in brain, skeletal muscle, and adipose tissue. The disappearance of radioactivity from mouse tissues was approximately twice as rapid as from rat tissues. In vitro, dimethyl phosphonate was metabolized to formaldehyde by the microsomal fraction of liver, lungs, kidneys, forestomach, and glandular stomach. In vivo, dimethyl phosphonate was metabolized to the product of demethylation, monomethyl hydrogen phosphite (MMHP), which was excreted in urine.