1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt

Endpoint summary

Description of key information

Key Study:

log Koc = 1.9 or Koc = 79 L/kg; OECD 121 (Currenta 2011), read-across from 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione (MB2)

 

Supporting Study:

log Koc = 1.19 or Koc = 15.4 L/kg; OECD 121 (Harlan 2013), study performed with zinc 4-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide 7-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide (ZMB2)

Additional information

The log Koc for zinc 4-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide 7-methyl-2-thioxo-2,3-dihydrobenzimidazol-1-ide (ZMB2) was determined with 1.19 in this study (OECD 121). In the HPLC-UV analysis performed in this study, a mobile phase consisting of methanol:water (55:45 v/v) at a pH of 7.42 was applied. Under these aqueous conditions, it is expected that ZMB2 will instantly dissociate to/dissolve as MB2 and zinc ions (LANXESS, 2018). Thus, in this study it should not have been possible to detect ZMB2 in undissociated form.

 

However, in the discussion section of the report the authors assume ZMB2 to be present in the unionized form at approximately pH 7 and state “The testing for adsorption coefficient was therefore performed at approximately neutral pH on the molecular form” and “Based on the chromatographic data, the test item was considered to be stable during the test procedure” . Based on the weight of evidence presented in the read-across document (refer to Section 13.2), this statement must be considered to represent a misinterpretation.

This is further supported by the following considerations:

The following experimental log Koc results were obtained:

Log Koc(ZMB2) = 1.19 (OECD 121, Harlan 2013)

Log Koc(MB2) = 1.9 (OECD 121, Currenta 2011).

Based on the experimental log Kow values determined for both compounds,

Log Kow(ZMB2) = 3.07 (OECD 107, SafePharm 2004)

Log Kow(MB2) = 0.3-0.4 (OECD 117, Currenta 2011)

ZMB2 would be expected to be more adsorptive than 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione (MB2). This assumption is confirmed when applying the regressions developed by Franco and Trapp (2008) for predicting the Koc’s for electrolytes, i.e. acids, bases and amphoters (ECETOC Technical Report 123, p. 46 ff.) for estimating log Koc’s of MB2 and ZMB2 assuming both are present in their neutral, non-dissociated/non-deprotonated state:

Log Koc(ZMB2) = 2.68 (equation for organic bases used)

Log Koc(ZMB2) = 2.63 (equation for amphoters used)

Log Koc(MB2) = 2.17 (equation for organic acids used)

Estimations of log Koc’s using the regressions by Franco and Trapp (2008) confirm the trends as expected, i.e. ZMB2 is predicted to be more adsorptive than MB2 if both are present in neutral form.

Based on the weight of evidence as presented in the read-across document (refer to Section 13.2), in conclusion in the study report by Harlan (2013, Study Number 41206094), the adsorption coefficient for MB2, rather than intact ZMB2 was determined [LogKoc: 1.19; this value being lower than that that of the reference standard with the lowest log Koc used (acetanilide, log Koc = 1.25)]. However, this measured value appears to be quite low when comparing with the above respective regressions by Franco and Trapp for the log Koc’s. On the other hand, the adsorption coefficient of 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione (MB2) was tested according to OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC)). The adsorption coefficient of the test item was determined to be log Koc = 1.9 or Koc = 79 L/kg, this value being higher than that of the reference standard with lowest log Koc used (2-Nitrobenzamide, log Koc = 1.45). As both log Koc studies (on MB2 and ZMB2) were performed according to OECD 121 under GLP, based on the read-across justification document (refer to Section 13.2) and the above discussion, the study on MB2 (log Koc = 1.9) is used as the key study for the adsorption / desorption endpoint.