Dimethyl itaconate

Partition coefficient

Description of key information

Low lipophilicity, independent from pH (no ionisation, Kow = Pow = Dow = 7.2), no potential for bioaccumulation; Koa derived in the chapter on terrestrial bioaccumulation; Kaw derived in chapter on Henry's Law constant.

Key value for chemical safety assessment

Log Kow (Log Pow):

0.86

at the temperature of:

25 °C

Additional information

The partition coefficient between water and n-octanol of the submission item Dimethyl itaconate (CAS 617-52-7) was investigated in a GLP-compliant study (Brekelmans 2010, NOTOX Report no. 492870) using HPLC comparison according to the OECD TG 117 (2004) and EU A.8 (2008) protocols. The experiment can be considered relevant and adequate for the endpoint. Therefore it is deemed conclusive and was rated „reliable without restrictions“, i.e. “Klimisch 1” according to the scale of Klimisch et al. (1997).

By means of Quantitative Structure-Property Relationships (QSPR) the presence of pKa in the range of pH 1 to 14 was excluded and thus neutral pH conditions were chosen. No pH measurement was made and no buffers were used. Ethylmethylketone (CAS 78-93-3, Log Kow 0.3), Benzylalcohol (CAS 100-51-6, Log Kow 1.1), Nitrobenzene (CAS 98-95-3, Log Kow 1.9), Toluene (CAS 108-88-3, Log Kow 2.7), Bromobenzene (CAS 108-86-1, Log Kow 3.0), 1,4-Dichlorobenzene (CAS 106-46-7, Log Kow 3.4) were used as standard references considering the Log Kow values as given in the test guidance. The correlation coefficient (r) of the calibration curve was 0.9992 and the coefficient of determination (r²) was 0.9984 demonstrating the reliability of the method in the calibration range from Log Kow (i.e. Log Pow) 0.3 to 3.4. The column temperature was 25 °C.

In the chromatogram of the test item solution, one large test substance peak and one small test substance peak were observed. The large peak was considered to derive from the major component of the test substance and the small peak was probably from an impurity or hydrolysis product. This assumption is supported by the QSPR result of the Rekker calculation method as the HPLC comparison result differ less than 0.3 Log units for the test item. The peak area share of test item and impurity was calculated 92 % versus 7.9 %.

It can be concluded from the calibration cure function that the experimental lipophilicity of the test item is described by Log Kow 0.86 (Kow 7.2) at 25 °C, while the Log Kow of the impurity is ca. -0.616 (extrapolated), which indicates a higher polarity (hydrophilicity) and thus supports the assumption that it is an hydrolysis product.

Company data suggest that the impurity is one to the half acids of the submission item called Monomethyl Itaconate (MMI, i.e. either 4 -Methyl Itaconate, CAS 7338-27-4, or 1 -Methyl Itaconate).

Low lipophilicity, as expressed by a Log Kow of 4.5 or lower, is expected to indicate absence of potential for bioaccumulation in the aquatic environment (ECHA R. 11, 2014, Figure R.11-4: Integrated testing strategy for B-assessment, p 58). In accordance with REACH regulation (EC No 1907/2006 as published 29.5.2007 in the Official Journal of the European Union, page L 136/115) Annex IX column 2, testing of Bioaccumulation in aquatic species, preferably fish (9.3.2.) does not need to be conducted if the substance has a Log Kow ≤ 3. According to Gobas et al. (2009, p 634) substances with Log Kow ≥ 2 are eliminated slowly by urinary excretion, and may have however have an inherent biomagnification potential in air-respiring organisms depending on the Log Koa (i.e. n-octanol/water partition coefficient, derived in the chapter on terrestrial bioaccumulation). A third partition coefficient used to describe fugacity properties is the air/water partition coefficient Kaw, which represents the dimensionless Henry's Law constant and is derived and discussed in the respective chapter.

In conclusion the Log Kow of the submission item falls below all levels of concern. It can thus be safely concluded that the submission item lacks any potential for bioaccumulation in aquatic or terrestrial food chains.

• Klimisch HJ, Andreae M, Tillmann U (1997). A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data. DOI 10.1006/rtph.1996.1076 PMID 9056496 Regul Toxicol Pharmacol 25:1-5.
• ECHA R.11: European Chemicals Agency (2014). Guidance on information requirements and chemical safety assessment. Chapter R.11: PBT/vPvB assessment. Version 2.0. Reference ECHA-14-G-07-EN ISBN 978-92-9244-760-1. Self-published, Helsinki, Finland, in November. 119 p.
• Gobas FAPC, de Wolf W, Burkhard LP, Verbruggen E, Plotzke K (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments. DOI 10.1897/IEAM_2008-089.1 PMID 19552497 Online ISSN 1551-3793 Integrated Environmental Assessment and Management 5(4):624-37.