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Categories

Category name:
Category of four Sulphenamides (TBBS, CBS, DCBS, MBS)

Justifications and discussions

Category definition:
The read-across document attached in chapter 13 of the TBBS data set describes the use of a read-across approach for four mono-constituent sulphenamides of similar chemical structure as a group: N-tert-butylbenzothiazole-2-sulphenamide (TBBS, CAS 95-31-8), N-cyclohexylbenzothiazole-2-sulphenamide (CBS, CAS 95-33-0) and N,N-dicyclohexylbenzothiazole-2-sulphenamide (DCBS, CAS 4979-32-2). Additional existing data was taken into account from 2-(morpholinothio)benzothiazole (MBS, CAS 102-77-2) which has currently no active registrations. As a result the proposed category consists of four members.
The ECHA Read-Across Assessment Framework Guidance is followed and scenario 6 is selected to predict potential effects on fertility (EOGRT) and developmental toxicity to rabbits for all group members based on reliable data available for DCBS (RAAF Scenario 6)
Category rationale:
The category consists of four benzothiazole-2-sulphenamides with a variation the chemical structure of amines bound to the mercapto group. Primarily, the lipophilicity is the leading property for determining the (eco-)toxicity with MBS showing the lowest and DCBS the highest toxicity with TBBS and CBS in between. This trend is based on the fact that the log Kow as a main driver for toxicity is increasing within the category from MBS over TBBS and CBS to DCBS.

Since the substances 2-(morpholinothio)benzothiazole, CAS 102-77-2 (MBS), N-tert-butylbenzothiazole-2-sulphenamide, CAS 95-31-8 (TBBS), N-cyclohexylbenzothiazole-2-sulphenamide, CAS 95-33-0 (CBS) and N,N-dicyclohexylbenzothiazole-2-sulphenamide, CAS 4979-32-2 (DCBS) show structural similarity and have intrinsic properties which follow a similar pattern, it is considered that all pre-requisites for grouping and read-across are fulfilled:
All four substances consist of the identical basic molecular structure with the common functional group of a benzothiazole-2-sulphenamide moiety and differ only in one structural feature, the substituent bound to the mercapto group. It can be shown that the difference in the chemical nature of the substituent is responsible for the quantitative variation in the strength of observed effects.
Evaluation of available physio-chemical, environmental fate & pathways data, eco-toxicological, toxicological show a consistent pattern of substance properties in line with the proposed read across strategy. In light of this provided rationale these four substances are considered as a group (category). It can be shown that qualitatively similar effects following a certain pattern are caused by the common moiety within the benzothiazole-2-sulphenamide. The potency and strength of the effects (water solubility, partition coefficient, aquatic toxicity) vary quantitatively in a predictable manner throughout the category due to the variation of the substituents bound to the mercapto group. Regarding toxicity, similar toxicological effects and effect levels are observed.

Thus, the human health properties of the target substance(s) may be predicted within the category by interpolation from information of tests conducted on the source substances. All available data of physiologically relevant physicochemical parameters as well as toxicological properties are scrutinized by a trend analysis within the group in order to evaluate which substance of the sulphenamides family represents the ‘worst case’ in order to serve as a potential source substance. In the context of read-across, a worst-case approach means that the strength of effect(s) in the target substance(s) is actually expected to be lower than the strength of effect(s) observed for the source substance. Using the values obtained from the source substance, the prediction constitutes a worst case that will not lead to an underestimation of the effect(s) that would be observed in a study with the target substance(s) if it were to be conducted.

Under consideration of the REACH information requirements this approach aims at the prediction of human health properties from DCBS as source substance to CBS and TBBS as target substances for the endpoints Developmental Toxicity Study in a second species (OECD 414 in rabbits) and Extended One-Generation Reproductive Toxicity Study (EOGRTS, OECD 443). This consideration is done to avoid unnecessary vertebrate animal testing with respect to animal welfare.