Registration Dossier

Diss Factsheets

Administrative data

basic toxicokinetics, other
Type of information:
other: Expert Statement
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Expert Statement, no study available

Data source

Reference Type:
other: Expert Statement
Report date:

Materials and methods

Principles of method if other than guideline:
Expert statement
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Vinylphosphonic acid
EC Number:
EC Name:
Vinylphosphonic acid
Cas Number:
Molecular formula:
vinylphosphonic acid
Test material form:
other: Liquid: Clear colourless

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorption is a property of a substance to diffuse across biological membranes. Generally, oral absorption is favored for molecular weights below 500 g/mol and log Pow values between -1 and 4. In the GI tract absorption of small water-soluble molecules (molecular weight up to around 200 g/mol) occurs through aqueous pores or carriage of such molecules across membranes with the bulk passage of water. Therefore, it can be considered as likely that Vinylphosphonic acid becomes bioavailable following the oral route, as indicated by its physicochemical properties.
This assumption is supported by the results of acute oral and repeated dose oral toxicity studies where clinical signs and macroscopic changes at necropsy concerning liver, stomach, pancreas, small intestine and peritoneum were observed indicating systemic bioavailability.

Absorption via the respiratory route also depends on physico-chemical properties like vapour pressure, log Pow and water solubility. In general, highly volatile substances are those with a vapour pressure greater than 25 kPa or boiling point below 50°C. Substances with log Pow values between -1 and 4 are favored for absorption directly across the respiratory tract epithelium by passive diffusion. Due to its low vapour pressure of 3.15E-5 Pa at 20 °C and 5.39E-5 Pa at 25 °C Vinylphosphonic acid is unlikely to be available as a vapour and exposure and uptake via inhalation is considered as negligible. Furthermore, the substance is a solidified melted mess and no production of dust is expected.

In general, dermal absorption is favored by small molecular weights and high water solubility of the substance. Log Pow values between 1 and 4 favor dermal absorption, particularly if water solubility is high. However, if water solubility is above 10 g/L and the log Pow value below 0 the substance may be too hydrophilic to cross the lipid rich stratum corneum and dermal uptake will be low. Therefore, for Vinylphosphonic acid low dermal absorption is predicted because of its high water solubility and an estimated log Pow value of -1.69. As the substance is corrosive to skin causing erythema, encrustation and dry skin the damage to the skin may rather enhance the penetration.
Details on distribution in tissues:
In general, the smaller the molecule the broader is its distribution. Small water-soluble molecules and ions will diffuse through aqueous channels and pores in the membranes. After being absorbed into the body, Vinylphosphonic acid is expected to distribute through-out the body water. In the repeated dose toxicity study described above various clinical signs in different organs were observed indicating a broad distribution of the substance. Due to its low log Pow the test item is unlikely to bioaccumulate in tissue, and there are no other physicochemical properties indicating bio-accumulating properties.
Details on excretion:
In general, urinary excretion is favored by low molecular weight (below 300 g/mol in the rat) and good water solubility. Therefore, Vinylphosphonic acid and its metabolites are expected to be excreted mostly via urine.

Metabolite characterisation studies

Details on metabolites:
Vinylphosphonic acid dissociates in aqueous solution to render phosphonic acid anion and ethen (vinyl) cation. Ethen is described to undergo epoxidation via cytochrome P-450 enzymes and further conjugation of glutathione via Glutathione-S-transferase or hydration via epoxide hydrolase which results in excretion of these metabolites mostly via urine. From the in vitro genotoxicity studies no remarkable differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic S9 Mix could be detected, which might indicate that no metabolic activation of the substance occurs in vitro and probably also in vivo.

Applicant's summary and conclusion