Tetramethylammonium hydrogen phthalate

Endpoint summary

Description of key information

A toxicokinetic assessment was performed based on the available data of the substance.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

A substance can enter the body via the lungs, the gastrointestinal tract, and the skin. In general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract after oral administration. Two characteristics of TMHP favor uptake via passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water): (a) TMHP is highly soluble in water (> 1000g/L) which indicates that the substance will dissolve into the gastrointestinal fluids; (b) TMHP has a moderate molecular weight (approximately 239.27), thus its size will not obstruct uptake via diffusion. On the other hand, TMHP is a slightly hydrophilic compound with a partition coefficient below 0 (log Pow < -1.24), which can hamper penetration through lipid membranes. Furthermore, TMHP dissociates as soon as it comes in contact with the fluids of the gastro-intestinal tract to form a phthalate ester ion and a quaternary ammonium ion. It is generally recognised that ionized substances do not readily diffuse across biological membranes.

Based on these data, for risk assessment purposes oral absorption of TMHP is set at 50%, based on its water solubility and its moderate molecular weight. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

Once absorbed, wide distribution of the test substance throughout the body is expected based on its high water solubility and moderate molecular weight. Absorbed TMHP is most likely excreted via urine or bile. Based on the moderate partition coefficient of < -1.24, it not very likely that TMHP will accumulate in adipose tissue.

The vapour pressure of TMHP is very low (0.00001 Pa at 25°C), but no information on the particle size distribution is available. If TMHP reaches the tracheobronchial region, it is likely to be dissolved within the mucus lining the respiratory tract and to get absorbed due to its high water solubility and low molecular weight. Based on the above data, for risk assessment purposes the inhalation absorption of TMHP is set at 100%.

TMHP is a white, slightly lumpy, crystalline powder. Given the fact that TMHP is very hygroscopic, it will take up water and/or dissolve into the surface moisture of the skin, which will enhance uptake via the skin. The first layer of the skin, the stratum corneum, is a barrier for hydrophilic compounds. The ions formed after TMHP dissociates may influence its adsorption, since they may bind to skin components which would slow the uptake. The surface tension of the substance (72.1 mN/m at 20°C) is not expected to influence uptake via the dermal route.

According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of TMHP do not meet the criteria for limited dermal absorption (MW ca. 239.27 and log Pow -1.24), for risk assessment purposes dermal absorption should be set at 100%.

However, as it is generally accepted that dermal absorption does not exceed oral absorption, 50% dermal absorption is considered to be a more realistic dermal absorption factor. Based on these considerations, for risk assessment purposes the dermal absorption of TMHP is set at 50%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.