Disodium piperazine-1,4-diethanesulphonate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Justification for type of information:

QSAR was performed in accordance with Section 8.3 of Annex VII of Regulation (EC) No 1907/2006 as amended in Commission Regulation (EU) 2016/1688 of 20 September 2016 and the strategy presented in ECHA
Guidance on information requirements and chemical safety assessment Chapter R.7a.

Qualifier:

according to guideline

Guideline:

other: DEREK NEXUS version 5.0.2

GLP compliance:

yes

Interpretation of results:

other: no alerts for skin sensitisation

Executive summary:

According to DEREK NEXUS version 5.0.2, 1,4 piperazinediethanesulfonic acid disodium salt is predicted to be not sensitizing to the skin

Reference 2

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)

GLP compliance:

yes

Type of study:

direct peptide reactivity assay (DPRA)

Specific details on test material used for the study:

Chemical name 1,4 piperazinediethanesulfonic acid disodium salt
CAS number 76836-02-7
Purity/Composition ≥ 98%
UVCB: No

Details on the study design:

For the DPRA assay, 1,4 piperazinediethanesulfonic acid disodium salt dissolved completely in milli-Q, no precipitate was observed in any of the samples. Furthermore, no co-elution of the test item and the peptides occurred.

Parameter:

other: Cystine Reactivity Assay

Value:

0.1

Remarks on result:

no indication of skin sensitisation

Parameter:

other: lysine reactivity assay

Value:

0.8

Parameter:

other: mean of the synthetic peptides containing either cysteine (SPCC) or lysine (SPCL) depletion

Value:

0.5

In the cysteine reactivity assay the test item showed 0.1 ± 0.2% SPCC depletion while in the lysine reactivity assay the test item showed 0.8 ± 1.2% SPCL depletion. The mean of the synthetic peptides containing either cysteine(SPCC) or lysine (SPCL) depletion was 0.5% and as a result the test item was considered to be negative in the DPRA and classified in the “no or minimal reactivity class”when using the Cysteine 1:10 / Lysine 1:50 prediction model.

Interpretation of results:

GHS criteria not met

Executive summary:

The objective of this study was to reach an overall conclusion on the endpoint skin sensitization based on all available relevant information, including in silico/in chemico/in vitro data. A DPRA assay assay were performed in accordance with Section 8.3 of Annex VII of Regulation (EC) No 1907/2006 as amended in Commission Regulation (EU) 2016/1688 of 20 September 2016 and the strategy presented in ECHA Guidance on information requirements and chemical safety assessment Chapter R.7a. The test item 1,4 piperazinediethanesulfonic acid disodium salt was negative in the DPRA, therefore it can be concluded that the substance will not interfere with protein moieties. Based on the current data-set it is concluded that there are no indications that 1,4 piperazinediethanesulfonic acid disodium salt has skin sensitizing properties. The data are considered sufficient to conclude that the substance does not have to be classified for skin sensitizing properties

Reference 3

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)

GLP compliance:

yes

Type of study:

activation of keratinocytes

Specific details on test material used for the study:

Chemical name 1,4 piperazinediethanesulfonic acid disodium salt
CAS number 76836-02-7
Purity/Composition ≥ 98%
UVCB: No

Details on the study design:

A valid KeratinoSensTM assay was performed according to OECD 442D and GLP. For the KeratinoSensTM assay, 1,4 piperazinediethanesulfonic acid disodium salt was dissolved in dimethyl sulfoxide to a final concentration of 200 mM. The final test concentrations in DMEM were 0.98 – 2000 µM and 1.0 – 2104 µM in experiment 1 and 2, respectively (2-fold dilution series). No precipitate was observed at any dose level tested. Two independent experiments were performed.

Run / experiment:

other: Experiment 1

Parameter:

other: Release of pro-inflammatory cytokines and induction of cyto-protective pathways in keratinocytes

Value:

1.04

Vehicle controls validity:

valid

Remarks on result:

no indication of skin sensitisation

Run / experiment:

other: Experiment 2

Parameter:

other: Release of pro-inflammatory cytokines and induction of cyto-protective pathways in keratinocytes

Value:

1.15

Vehicle controls validity:

valid

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is classified as negative in the KeratinoSensTM assay since negative results (<1.5-fold induction) were observed at test concentrations with a cell viability of >70% compared to the vehicle control.

Executive summary:

A valid KeratinoSensTM assay was performed according to OECD 442D and GLP. For the KeratinoSensTM assay, 1,4 piperazinediethanesulfonic acid disodium salt was dissolved in dimethyl sulfoxide to a final concentration of 200 mM. The final test concentrations in DMEM were 0.98 – 2000 µM and 1.0 – 2104 µM in experiment 1 and 2, respectively (2-fold dilution series). No precipitate was observed at any dose level tested. Two independent experiments were performed. The test item showedno toxicity (no IC30 and IC50 value) and no biologically relevant induction of the luciferase activity (no EC1.5 value) was measured at any of the test concentrations in both experiments. The maximum luciferase activity induction (Imax) was 1.04-fold and 1.15-fold in experiment 1 and 2, respectively. The test item is classified as negative in the KeratinoSensTM assay since negative results.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The objective of this study was to reach an overall conclusion on the endpoint skin sensitization based on all available relevant information, includingin silico/in chemico/in vitrodata.

A DEREK assessment, DPRA assay and KeratinoSens^TMassay were performed in accordance withSection 8.3 of Annex VII of Regulation (EC) No 1907/2006 as amended in Commission Regulation (EU) 2016/1688 of 20 September 2016 andthe strategy presented in ECHA Guidance on information requirements and chemical safety assessment Chapter R.7a.

According to DEREK NEXUS version 5.0.2, 1,4 piperazinediethanesulfonic acid disodium salt is predicted to be not sensitizing to the skin.

The test item 1,4 piperazinediethanesulfonic acid disodium salt was negative in the DPRA, therefore it can be concluded that the substance will not interfere with protein moieties. Furthermore, 1,4 piperazinediethanesulfonic acid disodium salt is found not to activate the antioxidant/electrophile responsive element (ARE)-dependent pathway in keratinocytes according to the results of a KeratinoSens^TMassay.

Based on the current data-set it is concluded that there are no indications that 1,4 piperazinediethanesulfonic acid disodium salt has skin sensitizing properties. The data are considered sufficient to conclude that the substance does not have to be classified for skin sensitizing properties.