Reaction mass of 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-{[hydroxy(phosphonooxy)phosphoryl]oxy}ethyl)-4-methyl-1,3-thiazol-3-ium chloride and 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-5-[2-(phosphonooxy)ethyl]-1,3-thiazol-3-ium chloride dihydrate

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Additional information

There is only limited data available for the environmental fate of the target substance Reaction mass of 3-[(4-Amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-{ 2-[hydroxy(phosphonooxy)-phosphinyl]oxyethyl]-thiazoliumchlorid and 3-[( 4-Amino-2-methyl-5-pyrimidinyl)methyl]-4-methyl-5-(2-phosphonooxyethyl)-thiazoliumchlorid-Dihydrat. Therefore, a read-across approach was pursued to compile relevant data from a structurally and chemically closely related source substance in order to fulfill the standard information requirements laid down by REACh Regulation (EC) No 1907/2006, Annex XI, 1.5. According to Article 13 (1) of the regulation, “information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In regard to the general rules for grouping of substances and the read-across approach, the regulation specifies (Annex XI, item 1.5) that substances may be predicted as similar provided that their physico-chemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

The target substance is a multi-constituent, mainly consisting of a diphosphate (CAS 154-87-0) and monophosphate (CAS 532-40-1) chloride salt of thiamine, which are both derivatives of the selected source substance 2-{3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl}ethyl hydrogen phosphate (CAS 10023-48-0). Based on the high degree of similarity between the physico-chemical properties of the target and source substances, the target substance is expected to have a similar environmental fate profile. Thus, the source substance is considered a suitable representative for the assessment of the stability and ready biodegradability of the target substance. A detailed read-across justification is provided in IUCLID section 13 of the technical dossier.

 

The target substance is ionisable and the two main constituents have very similar speciation and log D profiles. Since QSAR models cannot evaluate salts, the pKa values and log D profiles were estimated for the corresponding acid forms of the two constituents, i.e. for CAS 136-09-4 (diphosphate) and CAS 10023-48-0 (monophosphate), respectively. The calculated pKa values of the main constituent (CAS 154-87-0) are 0.95, 4.78, and 6.25 (SPARC v4.6), and the calculated pKa values of the second constituent (CAS 532-40-1) are 0.92, 4.76, and 6.22 (SPARC v4.6). For both main constituents a total of 12 chemical species were identified, three of which are relevant at environmentally relevant pH values from 4 to 9. The log D profiles show that the substance is generally hydrophilic between pH 0 and 14 and that its hydrophilicity increases with increasing pH values (SPARC v4.6).

The overall low log D profiles of both constituents (-3.8 to -13.3 (CAS 154-87-0) and -3.3 to -8.0 (CAS 532-40-1), pH 0 - 14), the low log Kow (-4.5 at 20 °C, OECD 105), high water solubility (312 g/L at 20 °C, OECD 105) and the low, calculated log Koc values (0.77 - 0.80, pH 7, pKa 6.25/6.22, ChemProp v6.5) indicate that water is the main compartment for environmental distribution. Furthermore, the substance is characterized by low vapor pressure (2.4E-09 hPa at 20 °C, OECD 104) and is therefore not expected to evaporate into the atmosphere. Experimental studies testing the closely related source substance (CAS 10023-48-0) indicate that the target substance is not readily biodegradable (39% ThODNH4 in 28 d/25% ThODNO3 in 28 d, OECD 301F) and hydrolytically stable for ≥ 30 d at environmentally relevant conditions (25 °C, pH 4.6 – 9.0). However, considering the low log Kow and low log D profiles, the potential for bioaccumulation is low.