2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonyl chloride

Endpoint summary

Description of key information

Skin sensitisation: sensitising based on weight of evidence from 2 in chemico/in vitro studies.

- positive in DPRA (OECD 442C, GLP)

- positive in KeratinoSens (OECD 442D, GLP)

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

In chemico/in vitro skin sensitisation

There are two studies available, in which the substance was tested in chemico and in vitro for potential induction of skin sensitisation. All three studies were conducted under GLP conditons and in accordance with OECD Guidelines 442C (DPRA) and 442D (KeratinoSens).

-         Direct Peptide Reactivity Assay (DPRA)

The objective of this study was to determine the reactivity of TA-2 towards model synthetic peptides containing either cysteine (SPCC) or lysine (SPCL).  After incubation of the test item with either SPCC or SPCL, the relative peptide concentration was determined by High-Performance Liquid Chromatography (HPLC) with gradient elution and photodiode array (PDA) detection at 220 nm and 258 nm.  SPCC and SPCL Percent Depletion Values were calculated and used in a prediction model which allows assigning the test item to one of four

reactivity classes used to support the discrimination between sensitizers and non-sensitizers. The study procedures described in this report were based on the most recent OECD guideline.

In the cysteine reactivity assay the test item showed 100.0% SPCC depletion while in the lysine reactivity assay the test item showed 23.4% SPCL depletion.  The mean of the SPCC and SPCL depletion was 61.7% and as a result the test item was considered to be positive in the DPRA and classified in the “high reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.

-         KeratinoSens™ Assay

The objective of this study was to evaluate the ability of TA-2 to activate the antioxidant/electrophile responsive element (ARE)-dependent pathway in the KeratinoSens™assay.

Cells were incubated with the test item in a concentration range of 0.98 – 2000 µM (2-fold dilution series) for 48 hours ± 1 h. The activation of the ARE-dependent pathway was assessed by measuring the luminescence induction compared to the vehicle control. In addition, the viability was assessed with an MTT assay.

TA-2 showed toxicity (IC 30  values of 1156 µM and 975 µM and IC 50  values of 1398 µM and 1031 µM in experiment 1 and 2, respectively).  A biologically relevant, dose-related induction of the luciferase activity (EC 1.5  values of 575 µM and 609 µM in experiment 1 and 2, respectively) was measured in both experiments.  The maximum luciferase activity induction (I max ) was 5.91-fold and 26.10-fold in experiment 1 and 2 respectively.  TA-2 is classified as positive in the KeratinoSens™assay since positive results (>1.5-fold induction)

were observed at biologically relevant concentrations (EC 50  value   < 1000 µM) with a cell viability of >70% compared to the vehicle control.

In  conclusion,  the  test  item  is  classified  as  positive  (activation  of  the  antioxidant/electrophile responsive element (ARE)-dependent pathway in keratinocytes) under the experimental conditions of the study.

Based on the weight of evidence from the two available in chemico/in vitro studies, the substance is considered to be skin sensitising.

Justification for classification or non-classification

The  available  data  indicate  that  the  substance  does  meet  the  classification  criteria  for  skin sensitisation in accordance with Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).