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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in chemico
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April to May 2019
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))
GLP compliance:
yes (incl. QA statement)
Type of study:
direct peptide reactivity assay (DPRA)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,6-bis[[bis(2-hydroxyethyl)amino]methyl]-4-nonylphenol
EC Number:
243-500-6
EC Name:
2,6-bis[[bis(2-hydroxyethyl)amino]methyl]-4-nonylphenol
Cas Number:
20073-51-2
Molecular formula:
C25H46N2O5
IUPAC Name:
2,6-bis{[bis(2-hydroxyethyl)amino]methyl}-4-nonylphenol
Test material form:
liquid: viscous
Specific details on test material used for the study:
The Poliol MB 600 was found to be soluble in acetonitrile at 100 mM, therefore, acetonitrile was selected as the vehicle for this study.

Results and discussion

In vitro / in chemico

Resultsopen allclose all
Key result
Parameter:
other: Depeletion Cysteine
Remarks:
%
Value:
49
Positive controls validity:
valid
Remarks on result:
positive indication of skin sensitisation
Key result
Parameter:
other: Depletion Lysine
Remarks:
%
Value:
0
Positive controls validity:
valid
Remarks on result:
positive indication of skin sensitisation
Key result
Parameter:
other: Mean depletion (Cysteine and Lysine)
Remarks:
%
Value:
24.5
Positive controls validity:
valid
Remarks on result:
positive indication of skin sensitisation
Key result
Parameter:
other: Maximum standard deviation (cysteine)
Value:
4.69
Positive controls validity:
valid
Remarks on result:
positive indication of skin sensitisation
Key result
Parameter:
other: Maximum standard deviation (lysine)
Value:
0.05
Positive controls validity:
valid
Remarks on result:
positive indication of skin sensitisation
Other effects / acceptance of results:
Results of the present study indicate that, Poliol MB 600 met all the evaluation criteria to conclude as sensitisers in DPRA assay. Reference controls and positive controls met all the acceptance criteria for the controls. The cysteine peptide, used for the study, was stable throughout the study. This showed the suitability of test system and procedures used in the test facility.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
From the results of this study, under the specified experimental conditions, Poliol MB 600 was concluded as sensitizer in DPRA assay.
Executive summary:

EXECUTIVE SUMMARY:This study was conducted to evaluate the skin sensitisation potential of
Poliol MB 600using synthetic heptapeptides. The method followed was as per the OECD TG 442C.

Poliol MB 600was found to be soluble in acetonitrile at 100 mM.Thereforeacetonitrilewas selected as vehicle for this study.

Synthetic heptapeptides containing Lysine (Ac-RFAAKAA-COOH) or Cysteine (Ac-RFAACAA-COOH) were used as the test system in this assay.Cysteine and lysine containing peptides were incubated with positive control and test item for 24 ± 2 hours at 25 ± 2.5 ºC (in dark), separately.Relative peptide concentration was measured by high-performance liquid chromatography (HPLC) with gradient elution and UV detection at 220 nm. Cysteine and lysine peptide percent depletion values were calculated and used in a prediction model which allow assigning the test item to one of four reactivity classes used to support the discrimination between sensitisers and non-sensitisers (OECD, 2015).

HPLC system suitability was determined by the standard calibration curve and value of r2obtained was 0.99974 for cysteine and 0.99994 for lysine peptides, against set standard of r2> 0.99. The mean percent peptide depletion value of positive control,viz., cinnamic aldehyde was 72% for cysteine peptide and 41 % for lysine peptide. The Relative Coefficient of Variability (RCV) for the reference control B was 1.67 for cysteine peptide and 0.63 for lysine peptide. The mean peptide concentration of reference control A and B was 0.50 ± 0.05 mM. The relative coefficient of variability (RCV) for the stability of cysteine peptide in acetonitrile was 3.52 against set standard of <15%, indicating that cysteine is stable in acetonitrile. Percent peptide depletion values of Poliol MB 600 for cysteine and lysine were 49% and 0%, respectively. Mean percent depletion for Poliol MB 600 was 24.5%.

From results of this study, under specified experimental conditions, Poliol MB 600 was positive (moderate reactivity) in the DPRA assay. 

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