[No public or meaningful name is available]

Endpoint summary

Description of key information

Skin sensitisation (OECD 429), LLNA, mouse: not sensitising

Read-across from Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid (CAS 2241455 -89 -8).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Parameter:

SI

Value:

1.1

Variability:

± 0.4

Test group / Remarks:

6.25%

Key result

Parameter:

SI

Value:

0.9

Variability:

± 0.3

Test group / Remarks:

12.5%

Key result

Parameter:

SI

Value:

0.7

Variability:

± 0.2

Test group / Remarks:

25%

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

The read-across approach is detailed in the analogue justification. The target and source substances are considered unlikely to differ in their skin sensitisation potential. The available skin sensitization (LLNA) study in mice with the source substance (CAS 2241455-89-8) did not reveal a skin sensitising potential. Applying the read-across approach, the target substance reaction mass of dipotassium 2-(3,4-dimethyl-1H-pyrazol-1-yl) succinate and dipotassium 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinate (EC 950-225-1) is not expected to be a skin sensitiser.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no experimental data available regarding the skin sensitization potential of Reaction mass of dipotassium 2-(3,4-dimethyl-1H-pyrazol-1-yl) succinate and dipotassium 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinate (EC 950-225-1). Thus, read-across from an appropriate analogue substance Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid (CAS 2241455-89-8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 in order to fulfil the standard information requirements defined in Regulation (EC) No 1907/2006, Annex VII , 8.3.The read-across is based on common (bio)transformation compounds of source and target substance.A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

A skin sensitization study with the analogue substance Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid was performed according to OECD guideline 429 and in compliance with GLP (2012). In this study five CBA mice per dose were treated with 25 µL of 6.25%, 12.5%, and 25% test substance (diluted in DMSO) once daily for 3 consecutive days. The dosing concentrations were determined in a range-finder assay. No signs of systemic toxicity or signs of irritation at the application site were detected after treatment of the animals with up to 25% test item solution. 25% was the maximum technically applicable concentration determined in a solubility test. Five days after the first topical application all mice were dosed with 250 µL 3H-methyl thymidine (corresponding to 20 µCi) by intravenous injection (tail vein). Approximately 5 hours after the injection of 3H-methyl thymidine all mice were sacrificed by cervical dislocation. The draining auricular lymph nodes were excised, individually pooled for each animal (2 lymph nodes per animal) and collected with phosphate buffered saline (PBS). A single cell suspension of pooled lymph node cells was prepared and washed. After precipitation of macromolecules with TCA, scintillation fluid was added and the 3H-methyl thymidine–incorporation was measured in a ß-counter and expressed as the number of disintegrations per minute (DPM). Similarly, background 3H-methyl thymidine levels were also measured (5% TCA). Determination of radioactivity was performed individually for each animal.

The DPM were 3392±1024, 3848±1312, 2988±920, and 2268±574 for the control, 6.25%, 12.5%, and 25% dose group, respectively. The resulting stimulation indices were 1.1 ± 0.4, 0.9 ± 0.3 and 0.7 ± 0.2 for the 6.25%, 12.5%, and 25% dose group, respectively. In addition, no signs of systemic toxicity or signs of irritation at the application site were detected. In conclusion, as the stimulation index after treatment with Reaction mass of 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid and 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinic acid was smaller than three, the test item was not sensitising under the conditions of the test.

 

The target and source substances are considered unlikely to differ in their sensitisation potential. Therefore, an stimulation index smaller than three, indicating no sensitising potential was considered for the hazard assessment and Classification and labelling purposes for the target substance Reaction mass of dipotassium 2-(3,4-dimethyl-1H-pyrazol-1-yl) succinate and dipotassium 2-(4,5-dimethyl-1H-pyrazol-1-yl)succinate (EC 950-225-1).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on read-across, the available data on skin sensitisation do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and is therefore conclusive but not sufficient for classification.