Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea

Endpoint summary

Description of key information

Systemic bioavailablitity is limeted because of the mode of action: direct chemically reactivity. Local effects are expected to constitute primary toxicity. Bioavailability is unlikely from an in-vitro/in vivo assessment of genetic toxicity (see IUCLID chapter 7.6). Bioaccumulation is unlikely because of the low log Kow  < -2.8 (see IUCLID chapter 4.7).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea, like its parent THPC, is characterised by primary local toxicity (cyctotoxicity, irritation/corrosion, sensitisation) depending on the concentration applied. Systemic impairment is considered to be secondary to severe or/and repeated local toxicity. Genetic toxicity data (in vitro: positive; in vivo: negative) suggest bioavailablity of this reactive substance is limited.

In some older oral toxicity test the local toxicity have not been identified or considered (Aoyama 1975,..., NTP 1987). So, systemic endpoints have been identified and attributed to THPC. The substance, THPC-oliomeric reaction products with urea when tested in animals showed local and/or moderate signs of toxicity. The polymer of the substance (on treated fabric) is not expected to penetrate the skin in appreciable amounts due to its size and lack of solubility.

Mode of action:direct chemical reactivity.

Tris(hydroxymethyl)phosphine is the common (reactive) metabolite of the substance as well as related substances containing the Tetra(methylol)phosphonium cation, e.g. Tetrakis(hydroxymethyl)phosphonium chloride (THPC, CAS 124-64-1) and Tetrakis(hydroxymethyl)phosphonium sulphate (THPS, CAS 55566-30-8). Tris(hydroxymethyl)phosphine is formed spontaneously is aqueous matrix especially at alkaline pH.

The substance mode of action is direct chemical reactivity (cytotoxicity). This makes a systemic absorption of parent or the common reactive metabolit Tri(hydroxymethyl)phosphine unlikely. Results of genetic toxicity testing provide evidence for rather limited (systemic) bioavailability of the substance:

Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea was found positive for chromosomal aberrations in primary cultivated human lymphcytes (in vitro). In vivo,no indications for genotoxicity were found with the substance (Proban CC) in the mouse micronucleus test. This in vivo-result is further supported as no indications for genotoxicity were found with a close related substance (THPS) in the followingin-vivotests: two (oral) tests for micronuclei (MN-PCE) and for chromosomal aberrations (CA) in bone marrow cells of orally treated mice and two (dermal) tests for micronuclei (MN-PCE) and for chromosomal aberrations (CA) in bone marrow of dermally treated mice.

Bioavailability of the substance is unlikely because of the direct chemical reactivity of the substance with regard to demethylolation and oxidation converting a P(III)- into a P(V)-species (see biocide mode of action of structurally related THPS, in Paulus 2005). In consequence, parent and metabolites are water soluble and do not exhibit bioaccumulative potential. Metabolites are likely to be eliminated rapidly via urine.

The substance is characterized by primary local toxicity (cytotoxicity, irritation/corrosion, sensitisation) depending on the concentration applied. Genetic toxicity data (in vitro/in vivo) suggest bioavailablity of this reactive substance is limited. Toxicokinetic, eg adsorption, metabolism or distribution/excretion have no role.

In view of the excellent water solubility, its log Kow <-2.8 and its primary local toxicity the substance is not expected to be bioaccumulative.