D-2-hydroxy-2-phenylacetic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vitro

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 2015-September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: see below

Version / remarks:

Ramirez T, Mehling A, Kolle SN, Wruck CJ, Teubner W, Eltze T, Aumann A, Urbisch D, Ravenzwaay BV, Landsiedel R.., LuSens: A keratinocyte based ARE reporter gene assay for use in integrated testing strategies for skin sensitization hazard identification. Toxicol In Vitro. 2014 Dec;28(8).

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: see below

Version / remarks:

OECD: Draft Proposal for a New Guideline on In Vitro Skin Sensitization: human Cell
Line Activation Test (h-CLAT), accessed on 01 Sep 2014 at http://www.oecd.org

Test guideline 5

Qualifier:

according to guideline

Guideline:

other: see below

Version / remarks:

Ashikaga T, Sakaguchi H, Sono S, Kosaka N, Ishikawa M, Nukada Y, Miyazawa , Ito Y, Nishiyama N, Itagaki H. (2010) A comparative evaluation of in vitro skin sensitisation tests: the human cell-line activation test (h-CLAT) versus the local lymph node assay (LLNA). Altern Lab Anim. 38(4):275-84.

Test guideline 6

Qualifier:

according to guideline

Guideline:

other: see below

Version / remarks:

Sakaguchi H, Ryan C, Ovigne JM, Schroeder KR, Ashikaga T. (2010) Predicting skin sensitization potential and inter-laboratory reproducibility of a human Cell Line Activation Test (h-CLAT) in the European Cosmetics Association (COLIPA) ring trials. Toxicol In Vitro. 24(6):1810-20.

Test guideline 7

Qualifier:

according to guideline

Guideline:

other: see below

Version / remarks:

Bauch C, Kolle SN, Ramirez T, Eltze T, Fabian E, Mehling A, Teubner W, van Ravenzwaay B, Landsiedel R, (2012), Putting the parts together: Combining in vitro methods to test for skin sensitizing potentials, Regul Toxicol Pharmacol, 63(3):489-504.

Test guideline 8

Qualifier:

according to guideline

Guideline:

other: see below

Version / remarks:

Urbisch D, Mehling A, Guth K, Ramirez T, Honarvar N, Kolle SN, Landsiedel R, Jaworska J, Kern P, Gerberick F, Natsch A, Emter R, Ashikaga T, Miyazawa M, Sakaguchi H. Assessing skin sensitization hazard in mice and men using non-animal test methods. Regulatory Toxicology and Pharmacology 71(2), 135-352. 2015.

GLP compliance:

yes (incl. QA statement)

Type of study:

other: In Chemico Skin Sensitisation: Direct Peptide Reactivity Assay and In Vitro Skin Sensitisation: ARE-Nrf2 Luciferase Test Method

Test material

Test material information

Constituent 1

Reference substance name:

L-2-hydroxy-2-phenylacetic acid

EC Number:

210-276-6

EC Name:

L-2-hydroxy-2-phenylacetic acid

Cas Number:

611-71-2

Molecular formula:

C8H8O3

IUPAC Name:

hydroxy(phenyl)acetic acid

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- batch No.of test material: 12-0001
- Purity test date: 99.972 area-% (HPLC, chiral)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

Results and discussion

In vitro / in chemico

Results

Parameter:

other: sensitisation

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

Acceptance criteria of the DPRA:
The acceptance criteria mentioned in section 3.9.1 were met with the exception of the vehicle control B analyzed at the end of the sample list. The average is just below the acceptance criterion 0.50 mM ± 0.05 mM. However, the deviation was minimal, and as all other acceptance criteria were met, peptide stability was considered to be acceptable.

Table 18: Historic control data of negative control / vehicle control acetonitrile.
Table 19: Historic control data of positive control EGDMA 50 mM in acetonitrile.
Historic Period
mean peptide
concentration
[mM]
SD of peptide
concentration
Jan 2012 - Aug 2015 (no. of tests performed: 82)
Cysteine-peptide 0.485 0.023
Lysine-peptide 0.502 0.015
Historic Period
mean peptide
concentration
[mM]
SD of peptide
concentration
mean peptidedepletion
[%]
SD of peptidedepletion
[%]
Feb 2012 - Aug 2015 (no. of tests performed: 60)
Cysteine-peptide 0.199 0.047 59 10
Lysine-peptide 0.434 0.028 14 5

Acceptance criteria of the LuSens
The acceptance criteria mentioned in section 3.9.2 were met in all experiments.
The positive and negative and vehicle control data is comparable to historic data as can be seen in the following table:

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the observed results and applying the evaluation criteria described in chapter 3.10, L-2-Hydroxy-2-phenylacetic acid is not peptide reactive and does not activate keratinocytes. Applying the evaluation criteria described in chapter 3.10 L-2-Hydroxy-2-phenylacetic acid is predicted not to be a skin sensitizer.