Magnesium dipropan-2-olate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

A dataset on 145 chemicals tested in alternative assays for skin sensitization undergoing prevalidation

Author:

Andreas Natsch, Cindy A. Ryan, Leslie Foertsch, Roger Emter,
Joanna Jaworska, Frank Gerberick and Petra Kern

Year:

2013

Bibliographic source:

J. Appl. Toxicol. 2013; 33: 1337–1352

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 442C (In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay (DPRA))

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Test guideline 3

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 442E (In Vitro Skin Sensitisation assays addressing the Key Event on activation of dendritic cells on the Adverse Outcome pathway for Skin Sensitisation)

GLP compliance:

not specified

Type of study:

other: direct peptide binding assay, activation of keratinocytes, and activation of dendritic cells

Test material

Test material information

Constituent 1

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Cas Number:

67-63-0

Molecular formula:

C3H8O

IUPAC Name:

propan-2-ol

Details on test material:

- Name of test material (as cited in study report): Propanol-(2) (2-propanol, isopropyl alcohol )
- Substance type: organic
- Physical state: liquid

In vitro test system

Details on the study design:

This study was carried out at the time that the current OECD guideline in vitro tests for sensitization were in ECVAM prevalidation. It compares the results of a standard 3 tests in vitro testing battery against quality LLNA in vivo data, which had all been obtained according
to the OECD 429 protocol and had shown a clear dose–response curve or negative result. Considering chemical availability, compatibility with assay conditions (e.g. suitable solubility in testing medium), no interference with read out in assay (e.g. no co-elution in HPLC for the DPRA), and a good coverage of non-sensitizer and sensitizers of different sensitization potencies, chemicals were chosen and tested. A complete set of in vivo and alternative in vitro data was compiled for 145 different chemicals, with only three data gaps for the U937-CD86 test (OECD Guideline 442E: In Vitro Skin Sensitisation assays addressing the Key Event on activation of dendritic cells on the Adverse Outcome pathway for Skin Sensitisation).

Results and discussion

In vitro / in chemico

Results

Results 1

Run / experiment:

other: DPRA

Parameter:

other: Cysteine [% pept. remain.]

Value:

100

Results 2

Run / experiment:

other: DPRA

Parameter:

other: Lysine [% pept. remain.]

Value:

99.5

Remarks on result:

no indication of skin sensitisation

Results 3

Run / experiment:

other: KeratinoSens assay

Parameter:

other: EC1.5, EC3, and IC50 (mM)

Value:

2

Remarks on result:

no indication of skin sensitisation

Results 4

Run / experiment:

other: U937-CD86 test.

Parameter:

other: EC150 (mM)

Value:

7

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

In this study, 145 different chemicals were tested in vitro and compared against good quality in vivo LLNA data. In vitro test results for isopropanol are in accordance with the in vivo LLNA. The study documented a good sensitivity, specificity and accuracy for the in vitro approach when validated against the LLNA (82, 77, and 81%, n=145).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Isopropanol was reported negative in both a guideline local lymph node assay and a, guideline comparable, in vitro battery of 3 tests, which comprised a DPRA, KeratinoSens assay and U937-CD86 assay. The test battery was carried out on 145 chemicals and the study documented a good sensitivity, specificity and accuracy for this approach when validated against good quality in vivo LLNA data.