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Toxicological information

Skin sensitisation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report date:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 442D (In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method)
GLP compliance:
yes (incl. QA statement)
Type of study:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
4'-anilinotoluene-4-sulphonanilide
EC Number:
202-902-1
EC Name:
4'-anilinotoluene-4-sulphonanilide
Cas Number:
100-93-6
Molecular formula:
C19H18N2O2S
IUPAC Name:
4'-anilinotoluene-4-sulphonanilide

Results and discussion

In vitro / in chemico

Results
Parameter:
other: CRFT
Value:
17.4
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Thisin vitrostudy was performed to investigate the potential ofN-(4-anilinophenyl)-4-methylbenzenesulfonamidetoactivate the Nrf2 transcription factor (sensitizing potential), by using the LuSens cell line.

A detailed listing of all measured and calculated values of the assay is given in Annex 2 (values of CRFT), Annex 3 (values of experiment I), and Annex 4 (values of experiment II). In addition, the final results of both experiments are summarized in table 8-a and 8-b and graphically illustrated in figure 8-a to 8-d.

The assay was performed in two independent experiments. 12concentrations of the test item were evaluated. The exposure time was 48 h. The following nominal concentrations of the test item were investigated in experiment I and II:

8.41 µM, 10.09 µM, 12.11 µM, 14.54 µM, 17.44 µM, 20.93 µM, 25.12 µM, 30.14 µM, 36.17 µM, 43.40 µM, 52.08 µM, 62.50 µM

None of the real treatment concentrations in both experiments deviated more than 10 % from the nominal concentration. At the end of treatmentprecipitates were visible in the CRFT at the concentrations15.63 µM to 2000 µM and in the experiments at the concentrations 17.44 µM to 62.50 µM.

EGDMA (120 µM) was used as positive control. The viability was above 70 % and a distinct increase in luciferase induction above 2.5 fold in comparison to the solvent control was detected. This luciferase induction is well within the historical data range of the positive control.

DL-lactic acid (5000 µM) was used as negative control. The viability was above 70 % and the induction of the luciferase was < 1.5 fold in comparison to the solvent control and well within the historical data range of the negative control (table 18-a).

The induction of the luciferase of the growth control (Medium no. 3) was < 1.5 fold.

Since all acceptability criteria of the assay were metthe study is valid.

In experiment I cytotoxic effects were observed at the concentration 17.44 µM as well as at the concentrations 25.12 µM to 62.5 µM. In experiment II cytotoxic effects were detected at the concentrations 14.54 µM to 62.5 µM.

Finally the following test item concentrations showed a viability ≥ 70 % and could therefore be evaluated for luciferase induction:

Experiment I: 8.41 µM, 10.09 µM, 12.11 µM, 14.54 µM, 20.93 µM

Experiment II: 8.41 µM, 10.09 µM, 12.11 µM

A substantial and reproducible dose dependent and statistically significantl (see Annex 8) increase in luciferase induction was measured in all non-cytotoxic test item concentrations. In those concentrations, the induction exceeded the threshold of 1.5 fold in comparison to the solvent control.

 

In conclusion, it can be stated that under the experimental conditions of this study, the test item,N-(4-anilinophenyl)-4-methylbenzenesulfonamide, was positive in the LuSens assay and is therefore considered to have the potential toactivate theNrf2transcription factor (sensitizing potential).

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Under the experimental conditions of this study, the test item, N-(4-anilinophenyl)-4-methylbenzenesulfonamide, was positive in the LuSens assay and is therefore considered to have the potential to activate the Nrf2 transcription factor (sensitizing potential).