Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The available experimental data in animals show evidence of oral absorption and systemic distribution of the test substance since (no adverse) effects were reported in the liver and kidney of rodents following repeated exposures. No systemic effects were observed when the test substance was dermally applied in the acute dermal toxicity study.

No indication on the test substance excretion was obtained.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
10
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
10

Additional information

No specific toxicokinetic studies are available on Triethyl phosphonoacetate. A toxicokinetic assessment was made, based on the physico-chemical properties of the test substance, QSAR model and the results of toxicity studies (acute oral and dermal toxicity, skin sensitisation, in vitro genotoxicity studies and repeat dose toxicity study).

Physico-chemical properties :

Water solubility: miscible in all proportions with water (at 20°C)

Partition coefficient in octanol/water:1.13 (at 30°C)

Vapour pressure: 0.61 Pa (at)

Boiling point:: 269°C at 99.7 kPa

Density: 1.12 (at 20°C)

 

Absorption :

Inhalation:

No data were available for this route of exposure. However, the submitted substance is a liquid with a low volatility, as evidenced by the low vapour pressure and the elevated boiling point. Therefore it can be considered that the absorption by the inhalation route is limited.

 

Oral:

There was no mortality or evidence of systemic toxicity in the acute oral toxicity study in rats at the dose of 2000 mg/kg bw during the 14-day observation period. It is not possible to determine from this study whether the absence of effects was due to inherent low toxicity or to low absorption from the gastrointestinal tract.

In an oral repeated dose toxicity study performed in rat, the NOAEL was determined to be of 1000 mg/kg bw. No adverse systemic effects were observed, but effect on the organ weight of kidney and liver showed that the submitted substance is absorbed by this route of exposure and then distributed.

 

Dermal route:

There was no evidence of systemic toxicity in the acute dermal toxicity study in rabbits at the dose of 2000 mg/kg bw. There were neither any signs of toxicity or sensitisation effects after cutaneous exposure on the mouse ears in the LLNA assay.

In addition, although the molecular weight is relatively small (224.2 g/mol), the log Po/w of 1.13, the highly solubility in water and the low estimated dermal permeability coefficient (0.000487 cm/hr based on DERMWIN model) tend to support a limited capacity for absorption through the skin.

 

Distribution:

No specific toxicological effects were observed in the acute and/or repeated dose toxicity studies in rodents. However, the increase in liver weight in males in the 28-day rat toxicity study (with no histopathological correlation) and the increase of the kidney weight in males and females (with the presence of hyaline droplets in males only), support a systemic distribution of the submitted substance.

 

Metabolism:

Three in vitro studies assessed the potential genotoxicity of Triethyl phosphonacetate. An Ames test (Thompson, 2000), a chromosome aberration test in V79 cells (Hopker, 2007) and a mouse lymphoma assay (Wollny, 2006) all gave negative results with no indication of cytotoxicity either with or without metabolic activation. As such, these studies confirmed that Triethyl phosphonacetate does not have genotoxic potential but did not provide any information on possible metabolism.

Adaptive effects in the liver of males exposed to 1000 mg/kg bw/day were reported in the oral repeat dose toxicity study in the rat (Bentz, 2012). These effects suggest that the Triethyl phosphonacetate may be metabolised in this organ, however no studies to identify metabolites have been carried out.

Elimination

There is no information to indicate a route of excretion for Triethyl phosphonacetate but its high water and relatively fat solubility indicate that excretion of unchanged parent substance and/or metabolites could occur by renal or biliary routes and that bioaccumulation is unlikely. The parent substance could not be eliminated via the lungs in expired air due to its low volatility.