(E)-N'-(2-cyano-4-(3-(1-hydroxy-2-methylpropan-2-yl)thioureido)phenyl)-N,N-dimethylformimidamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

activation of keratinocytes

Test material

Test material information

Constituent 1

Reference substance name:

E-N'-{2-cyano-4-[3-(2-hydroxy-1,1-dimethylethyl)-thioureido]-phenyl}-N,N-dimethylformamidine

Cas Number:

1429755-57-6

Molecular formula:

C15H12N5OS

IUPAC Name:

E-N'-{2-cyano-4-[3-(2-hydroxy-1,1-dimethylethyl)-thioureido]-phenyl}-N,N-dimethylformamidine

Results and discussion

In vitro / in chemico

Results

Key result

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

ARE-Nrf2 Luciferase Test (KeratinoSens™) – Results summary

Study Number: SQ46WL

Test Date: 13 August 2020

SPS 5290 Stage 3 Results

Test item conc. (µM)	0.98	1.95	3.91	7.81	15.63	31.25	62.5	125	250	500	1000	2000
Mean fold induction	0.78	0.81	3.76	1.02	1.02	0.92	1.08	1.19	1.63	2.21	3.40	9.24
Statistically significant	N/A	N/A	Yes	N/A	N/A	N/A	N/A	N/A	Yes	Yes	Yes	Yes
Viability (%)	115.80	105.40	108.22	99.99	99.27	101.07	93.85	90.68	104.03	93.78	91.76	38.41
Imax	9.24
EC1.5(µM)	214.03
IC30(µM)	1407.83
IC50(µM)	1782.70

Determination criteria for the skin sensitisation potential of the test item	Result
Is the Imax≥1.5 fold and statistically significant	Yes
Is the cellular viability >70% at the EC1.5determining concentration	Yes
Is the EC1.5value <1000 µM	Yes
Is there a dose-response increase for luciferase induction	Yes
KeratinoSens™ prediction	Positive

 

 

Positive Control (cinnamic aldehyde) Results

Positive control conc. (µM)	4	8	16	32	64
Mean fold induction	1.15	4.79	2.66	2.79	7.67
Statistically significant	N/A	Yes	Yes	Yes	Yes
Viability (%)	90.60	104.18	85.48	95.66	44.90
Imax	7.67
EC1.5(µM)	4.39
IC30(µM)	N/A
IC50(µM)	N/A

 

Test Acceptance Criteria	Result
Luciferase activity induction obtained with the positive control statistically significant above the threshold of 1.5 in at least one of the test concentrations	Yes	Pass
Average induction of positive control at 64 µM between 2 – 8	Yes (7.67)	Pass
EC1.5of positive control within two standard deviations of the historical mean (‑2.36 to 28.67)	Yes (4.39)	Pass
CV% of blank values < 20%	No (32.3%)	Fail

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

After 48h exposure of cells with 12 concentrations of the test item, Luciferase measurements and MTT viability testing were performed.
The test item was classified as Positive according to the KeratinoSens prediction model.