Reaction product of a ((2S)-2, 6-diaminohexanoic acid hydrochloride salt, phosphonic acid and methanal) with a 1,2-disubstituted alkane and sodium hydroxide.

Endpoint summary

Additional information

TOXICOKINETIC BEHAVIOUR

 

The substance is a UVCB which consists of the partial salt of a complex mixture of aminophosphonate species.

 

Physico-chemical properties:

The substance is very soluble in water (70.0 to 80.0% w/w at 20 degC). The log P at 23 degC and pH 5 is less than -2.0. The vapour pressure is 0.0095 Pa at 25 degC.

 

Absorption

 

Oral: There is no study data on oral absorption available for SPE1415. The physicochemical properties of aminophosphonates, notably their high polarity, charge and complexing power, suggests that they will not be readily absorbed from the gastrointestinal tract. In an acute oral toxicity study, the LD50 of the substance is >2000mg/kg and there were no signs of systemic toxicity. This is consistent with poor oral absorption of SPE1415 and other structurally similar aminophosphonates. In a toxicokinetics study on the structurally related substance ATMP, absorption following oral administration was shown to be approximately 2.2%.

 

Inhalation: The vapour pressure of SPE1415 is extremely low (<10E-02 Pa). Consequently, inhalation of vapour is not possible to any significant extent.

 

Dermal: Based on the physico-chemical properties (LogP of < -2), the substance would not be expected to penetrate the skin to any significant extent.

 

Distribution

 

There is no study data on distribution available for SPE1415. In a toxicokinetics study on the structurally related substance ATMP, approximately 0.06% of the dose was found in the bone (femur, tibia and sternum) and 0.21% of the dose was found in the carcass. The overall tissue distribution confirmed that the highest levels of radioactivity were in the bone. No significant signs of localisation in other tissues were evident ten days after administration. The bone appeared to be the only tissue that demonstrated any significant amount of accumulation of ATMP-derived radioactivity.

 

Metabolism

 

There is no study data on metabolism available for SPE1415. In a toxicokinetics study on the structurally related substance ATMP, analysis of urine samples collected 24 hours after administration revealed the presence of the parent compound (25.1%), the N-methyl derivative (45.9%) and an unidentified metabolite (28.6%).

 

Excretion

 

There is no study data on excretion available for SPE1415. In a toxicokinetics study on the structurally related substance ATMP, faecal excretion was the principal route of elimination following oral gavage administration; 74% of the dose eliminated in 24 hr, 83% at 48 hr, up to a maximum 84% at 10 d. Trace amounts of radioactivity were present in urine (approx. 1% of dose) and blood, tissues and carcass (total approx. 0.3%) but not in exhaled air. Overall mean recovery from all sources was 85.9%.