Vinylphosphonic acid

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Expert Statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert Statement, no study available

Principles of method if other than guideline:

Expert statement

GLP compliance:

no

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.

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.

Description of key information

Based on physico-chemical properties, oral absorption and distribution through-out the body is expected.These assumptions are supported by the results of single and repeated-dose toxicity studies in vivo. Absorption via the inhalation route is, due to physico-chemical properties of the substance, not expected. Bioaccumulation of Vinylphosphonic acid is not expected after continuous exposure. The test substance and/or its metabolites are expected to be predominantly excreted via urine and to a lower extent via faeces.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

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.

Distribution

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.

Metabolism

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.

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.