Registration Dossier

Environmental fate & pathways

Endpoint summary

Administrative data

Description of key information

Additional information

Stability

Hydrolysis:

In a 5 day preliminary hydrolysis study conducted according to OECD 111, ZMB2 showed <10% hydrolysis with an equivalent half life of >1 year at 25 deg C. ZMB2, therefore, is not expected to hydrolyse within the environmental compartment (Harlan Laboratories, 2013).

When considering the results of the investigations carried out to support the read-across from 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione (MB2) to 2H-Benzimidazole-2-thione, 1,3-dihydro-4(or 5)-methyl-, zinc salt (2:1) (ZMB2) (LANXESS, 2018), the results of the hydrolysis as a function of pH study conducted with this substance must be reconsidered in light of new information.  The overall conclusion in LANXESS (2018) is that ZMB2 exhibits its salt characteristic in aqueous solution, i.e., dissolving in water to MB2 and zinc ions in a matter of seconds.  For full details of the investigations conducted relating to hydrolysis, refer to Section 13.2 of IUCLID.

In the HPLC-UV analysis performed in this study, a mobile phase consisting of acetonitrile:water (30:70 v/v) was applied. Under these aqueous conditions, based on the weight of evidence presented in this document, it is clear that ZMB2 will instantly dissociate to MB2 (LANXESS, 2018). Thus in this study it would not have been possible to detect ZMB2 in undissociated form, only MB2 was observable at pHs 4-9.

 

Biodegradation

Biodegradation in water (screening test):

Ready biodegradation:

Key study:

Conducted under GLP conditions, ZMB2 attained 27% degradation after 28 days and therefore cannot be considered to be readily biodegradable under the strict terms and conditions of OECD Guideline 301B (Safepharm Laboratories, 2003).

 

Supporting study:

In accordance with OECD Guideline 301 F (Ready Biodegradability: Manometric Respirometry Test), during the test period of 28 days ZMB2 provides a breakdown rate of 0%. ZMB2 is considered as "not readily biodegradable" (Bayer AG, 1992).

 

Biodegradation in water and sediments (simulation test):

In accordance with OECD 309 Guideline (Aerobic Mineralisation in Surface Water- Simulation Biodegradation Test), [14C-phenyl]-ZMB2 was applied to natural surface water containing suspended sediment under controlled labratory conditions and incubated in the dark for 64 days. Four major transformation products were observed at concentrations exceeding 10% of applied radioactivity and were identified by LC/MS; MB2, desthio-MB2, MB2 -sulfonic acid and MB2 -acetic acid. No residues of ZMB2 were detected during the test, including 0 h samples. It was concluded that ZMB2 dissociated upon contact with the surface water to form the primary transformation product MB2. The formation and decline of MB2 residues was best described using a SFO kinetic model where its DT50 was established at 17.8 days. The DT50 of the other three transformation products; desthio-MB2, MB2 -sulfonic acid and MB2 -acetic acid could not be established as an obvious decline in residue concentrations was not apparent.

 

Biodegradation in soil:

Based on the use pattern of the substance, intentional releases to the soil compartment are not expected.  In accordance with Column 2 of Annex IX of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation, if direct and indirect exposure of soil is unlikely, a biodegradation in soil study does not need to be conducted, therefore the endpoint has been waivered.

In addition, in a biodegradation screening study (Safepharm, 2003) ZMB2 did not meet the criteria of readily biodegradable.

 

Bioaccumulation

In accordance with REACH Annex IX, Section 9.3.2, Column 2, bioaccumulation testing need not be conducted if: the substance has a low potential for bioaccumulation.  LANXESS (2018 - see Section 13.2 of IUCLID) clearly shows that 2H-Benzimidazole-2-thione, 1,3-dihydro-4(or 5)-methyl-, zinc salt (2:1) (ZMB2), i.e. the registered substance, exhibits its salt characteristic in aqueous solution, i.e., dissolving in water to 1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione (MB2) and zinc ions in a matter of seconds.  Therefore, the measured log Pow value for ZMB2 is not considered relevant for bioaccumulation assessment as it will never exist in the aquatic environment.  Instead, the data presented for MB2 (log Pow = 0.3 - 0.4) is most relevant for bioaccumulation potential.  The low partitioning behaviour of MB2 is consistent with a conclusion of low bioaccumulation potential, and therefore bioaccumulation testing with the registered substance is not considered necessary.

The bioaccumulation potential of desthio-MB2, MB2-sulfonic acid and MB2-acetic acid, major transformation products of ZMB2 identified in an OECD 309 simulation test, were addressed.in Silicodata for the three substances and structural analogues was evaluated (Anderson, C. (2019). In addition, a literature search of the three substances was performed and suitable literature evaluated (Marczewski-Newman, T. (2019)). The data from the two sources was evaluaed and reported in a PBT assessment report (Anderson, C. (2019)) which is attached in Section 13.2 of this dossier. For the in silico assessment, a number of physical chemical and environmental fate properties based on (Q)SAR predictions and experimental data was compared and contrasted between the target substances (desthio-MB2, MB2 -sulfonic acid and MB2 -acetic acid) and their respective source substances. Endpoint data relating to the bioaccumulation potential of the substances was investigated thoroughly. For each substance, the log Kow, a key indicator endpoint for bioaccumulation potential, was predicted to be < 2 (actual: desthio-MB2 = 1.78, MB2-sulfonic acid = -1.38 and MB2-acetic acid = -2.45 to -1.2). Further, BCF values for each of the major transformation products was predicted to be <2000 L/kg wet wt (actual: desthio-MB2= 6.9 L/kg wet-wt, MB2-sulfonic acid and MB2-acetic acid = 3.2 L/kg wet-wt).  No relevant literature was available from the Marczewski-Newman, T. (2019)) literature search. It was concluded that desthio-MB2, MB2-sulfonic acid or MB2-acetic acid did not meet the criteria for bioaccumulation (B).

 

Trasnsport and distribution

Adsorption / desorption:

The log Koc of 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 this document, 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 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 this document, in conclusion in the study report by Harlan (2013, Study Number 41206094), the adsorption coefficient for MB2, rather than intact ZMB2 was determined.