Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The test item does not indicate a potential for bioaccumulation based on its physical-chemical properties and available experimental data.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Toxicokinetic analysis of Phosphonic acid, (1-hydroxyethylidene)bis-, compd. with 2-aminoethanol (CAS 42220-47-3)

There are no studies available that experimentally investigated the toxicokinetic behaviour of the test item. Therefore, based on the molecular structure of its constituents and the test items physicochemical properties a toxicokinetic assessment is performed (please also refer to respective disseminated information of REACH Registration dossiers on ECHAs website for Etidronic acid (CAS 64-18-6) and 2-ethanolamine (monoethanolamine, MEA, CAS 141-43-5), respectively).

The test item is an organic multi-constituent substance appearing as white solid with tiny read spots on the surface, homogenously consisting of solid and liquid parts at ambient conditions. The mean molecular weight of the test item is 267.11 g/mol with a relative density of 1.532 at 20 °C. Melting point of the substance was determined to start at about ambient temperature ranging up to about 116 °C with a peak temperature at 81 °C. A normal boiling point could not be determined. At a pressure of 3000 hPa the boiling temperature was determined to be 92.9 °C. Vapour pressure was 15.6 hPa at 20 and 20.4 hPa at 25 °C. The test item is well soluble in water as indicated by solubility of > 70.5 g/100 and < 79.9 g/100g. The n-octanol/water partition coefficient was estimated to be < -5.

Absorption

Uptake of the test item in the intestine is expected based on its good water solubility and low molecular weight of the two main constituents (ECHA guidance R7c Table R.7.12-1). Even though, the logPow being < -5 is not within the favourable range for passive diffusion. The ingested phosphonic acid derivate as well as 2-ethanolamine is anticipated to at least partially dissociate in contact with gastrointestinal fluids. The small ionic structures formed may then be easily absorbed by aqueous pores or other carrier structures by means of bulk passaging water (ECHA guidance R7c, 2017).

 

The absorption of the test item via the GIT is well shown by the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test according to OECD 422 (BASF, 2018). Systemic effects were observed at the mid and high dose group (600 and 2000/1000 mg/kg bw/d), which indicates that the test item becomes bioavailable via the oral route.

 

Toxicokinetic behaviour of the constituent 2-ethanolamine was comprehensively investigated (please refer to disseminated dossier data on ECHA´s website). Topically applied it penetrates the skin very well. Thus, bioavailability via the GIT and the respiratory tract is considered likely as well.


The second constituent, etidronic acid, however, was found to be not well absorbed (less than 10 %).

Exposure to the test item and thus also absorption via the inhalation route cannot be ruled out based on the volatile character of the test item (vapor pressure 15.6 hPa).

Distribution

Based on systemic findings in the repeated dose toxicity study the test item is expected to be widely distributed through the body. Since the logPow of the test item is very low and does not exceed a value of 4 bioaccumulation is not anticipated (ECHA guidance R7c). The constituent 2-ethanolamine is an endogenously present molecule which is integrated in biosynthesis of phosphoglycerides of biological membranes. Therefore, incorporation mechanisms in cells of liver and kidney are assumed. Regarding the second constituent, phosphonic acid derivate, an expected absorption in bones at considerable amounts was not confirmed based on disseminated data on respective REACH Registration Dossier.

Metabolism

For etidronic acid no metabolites could be identified. Upon absorption, this constituent does probably not undergo further oxidation reactions by Phase I Cytochrome P450 enzymes. It is rather expected to be a potential substrate for phase II conjugation reactions such as glucuronidation or glutathione conjugation.

In contrast, extensive metabolism of 2-ethanolamine was indicated by the incorporation of radiolabelled carbon into hepatic amino acids, proteins and phospholipids. Urea and glycine were the major urinary metabolites of 2-ethanolamine.

Excretion

Ethanolamine is an endogenous breakdown product of cell membrane phospholipid phosphatidyl EA and commonly found in the gastrointestinal tract (Garsin, 2012). Thus, the substance may not be readily excreted but likely reabsorbed and utilized within endogenous anabolic pathways. Excretion of phosphonic acid derivate occurs slowly via the urine.

 

Uncertainties regarding toxicokinetics

Although no toxicokinetic data are available on the test item, there are no remaining uncertainties. Based on physico-chemical properties supported by experimental observations and information available on the two main constituents, the test item is expected to be absorbed via the oral, dermal and inhalation route. From observations in the OECD 422 main study with the test item it is concluded that at least a fraction is absorbed via the oral route. The observed systemic effects indicate a wide distribution of the components throughout the body. Based on the small molecular size of the two main constituents and their well solubility in water excretion via urine is most likely. Extensive metabolism of 2-ethanolamine is anticipated.

Conclusion on toxicokinetics

Based on the available data it can be concluded that the test item becomes bioavailable via the oral, dermal and inhalation route. It is further readily distributed among body compartments. Metabolic conversion is expected. Excretion is mainly accomplished via the urine. The test item does not indicate a potential for bioaccumulation based on its physical-chemical properties and available experimental data.