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Description of key information

No toxicokinetics studies are available for either HMDTMP (4 -7Na). An assessment has been made with reference to relevant chemical properties and read-across evidence.

Key value for chemical safety assessment

Additional information

Oral

The physicochemical properties of phosphonic acid compounds, notably their high polarity, charge and complexing power, suggests that they will not be readily absorbed from the gastrointestinal tract. This is supported by experimental data on other phosphonates such as DTPMP and ATMP, which are also members of the aminomethylenepphosphonates analogue group. The data confirm that absorption after oral exposure is low, averaging 2-7% in animals and 2-10% in humans. Gastrointestinal pH is a major determinant influencing uptake, and is relatively acidic in the stomach (range: pH 1 - 4) and slightly more alkaline in the intestine (pH 4 - 7). The number of ionisations of the phosphonic acid moiety increases with increasing pH, rising from 1 - 2 at low pH (i.e. stomach) to 4 - 6 at more neutral pH (reflective of conditions in the intestine). The negative charge on each molecule also increases with each ionisation, further reducing the already low potential for uptake. Stability constants for the interaction of phosphonic acids with divalent metal ions are high, and indicate strong binding, especially at lower pHs.

Complexation of a metal with a phosphonic acid would produce an ion pair of charge close to neutral which might favour absorption; however the overall polarity of the complex would remain high thereby counteracting this potential. Overall, these considerations indicate that ingested phosphonic acid compounds will be retained within the gut lumen.

Dermal

Based on the very low log Kowvalue (-4) HMDTMP potassium salt and HMDTMP sodium salts would be too hydrophilic to cross the stratum corneum. Dermal absorption is therefore likely to be very low. An acute toxicity study by dermal routs reveals no effect of HMDTMP sodium salt.

Inhalation

The vapour pressure of HMDTMP potassium salt and HMDTMP sodiumis extremely low. Consequently, inhalation ofHMDTMP saltsvapour is not possible. It is possible that an aerosol (from aqueous solution) of eitherHMDTMP potassium salt and HMDTMP sodiumcould be inhaled. The potential aerosol droplet size that workers and consumers could be exposed to for these forms ofHMDTMP potassium salt and HMDTMP sodium salts arenot currently known. However, the very high water solubility of these substances suggests that absorption by this route would be low. Anyinhaled material would be expected to partition readily to mucus in the lungs, and hence be expectorated or ingested.

Distribution

There are no data on the distribution of either HMDTMP potassium salt or HMDTMP sodium salt. Due to the hydrophilic nature of these two substances, it is expected that the rate of diffusion across the membranes would limit their distribution. However, based on studies on other similar phosphonic acids such as EDTMP, bone appears to be a specific site for deposition of phosphonic acids in vivo. In a reliable study where two groups of male rats and mice were orally dosed with14C-labelled EDTMP (15 and 150 mg/kg bw respectively). The autoradiographs indicated that after one and fourteen days of dosing, radioactivity was localised mainly in the bone for both species and dose levels. (Wilson A.G.E 1989). The binding strength among phosphonates varies and it is reversible to different degrees.

Based on the very low lipophilicity, distribution into fatty tissues is unlikely.

Metabolism

There are no data on the metabolism ofHMDTMP potassium salt or HMDTMP sodium salt.Genetic toxicity testsin vitroshowed no observable differences in effects with and without metabolic activation for these substances.

Excretion

There are no data on the excretion of HMDTMP potassium salt or HMDTMP sodium salt.

In a well conducted (reliability 2) study in rats where14C-labelled EDTMP was dosed by gavage, 77% was excreted in faeces (i.e. gut absorption is poor). Small quantities were absorbed as indicated by 1% of dose in expired air, in urine (1%) and carcass contained less than 0.2%. (Kamatet al.1983) In a Toxicokinetics screening study (Rel. 4 due to limited reporting) where 3.97 mg/kg14C-labelled EDTMP was orally dosed to rats. 92.9% of the dose was found in the faeces. Most (83.8%) of this was in the 0-24 hour fraction. Approximately 1% of the dosed radioactivity was contained in the carcass and tissues at sacrifice (72 hr). The urine contained 1.78% of the dose and the CO2contained 2.03% after 72 hours. These data suggests minimal absorption of the test material. (Gibson W.B, 1979)