Sodium 5-oxo-DL-prolinate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 March 2012 to 30 March 2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A valid study is available on the read across substance, sodium 5-oxo-L-prolinate, which is a structural analogue of the registered substance. Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.. Read-across is considered to be suitable based on the structural similarities between the read across substance (sodium 5-oxo-L-prolinate) and the substance to be registered (sodium 5-oxo-DL-prolinate).

Justification for type of information:

A valid study is available on the read across substance, sodium 5-oxo-L-prolinate, which is a structural analogue of the registered substance. Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.. Read-across is considered to be suitable based on the structural similarities between the read across substance (sodium 5-oxo-L-prolinate) and the substance to be registered (sodium 5-oxo-DL-prolinate).

Cross-reference

Reason / purpose for cross-reference:

other: Target substance

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted on read across material

Justification for type of information:

A valid study is available on the read across substance, sodium 5-oxo-L-prolinate, which is a structural analogue of the registered substance. Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.. Read-across is considered to be suitable based on the structural similarities between the read across substance (sodium 5-oxo-L-prolinate) and the substance to be registered (sodium 5-oxo-DL-prolinate).

Reason / purpose for cross-reference:

read-across source

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Mean

Value:

95

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

no indication of irritation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Propan-2-ol

EC Number:

200-661-7

EC Name:

Propan-2-ol

Molecular formula:

C3H8O

IUPAC Name:

Propan-2-ol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Physical state: White to pale yellow powder.
- Storage condition of test material: Controlled Room temperature (15-25°C, below 70 RH %), Protected from humidity.

Test animals

Details on test animals or test system and environmental conditions:

EPISKIN-SM
Supplier: SkinEthic, France

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 20 mg

Duration of treatment / exposure:

15 ± 0.5 minutes

Number of animals:

Not applicable

Results and discussion

In vitro

Results

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

Mean

Value:

95

Vehicle controls validity:

valid

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

no indication of irritation

In vivo

Other effects:

CELL VIABILITY
- Cell viability of treated disks was 95 %, see Table 1 for results.

VALIDITY OF THE TEST
The mean OD value of the three negative control tissues was 0.641. The positive control result showed 26 % viability. Each standard deviation value (SD) of the % viability was below 18. All validity criteria were within acceptable limits and therefore the study can be considered as valid.

INDICATOR FOR POTENTIAL FALSE VIABILITY
> Possible direct MTT reduction with the test material: No colour change was observed after three hours of incubation of the test item in MTT solution. The test material did not interact with the MTT, therefore additional controls and data calculations were not necessary. A false estimation of viability can be precluded.
> Colouring potential of the test material: As the test material has an intrinsic colour, one additional chemical-treated tissue was used for the non specific OD evaluation. Mean OD (measured at 540 nm) of this tissue was determined as 0.025, Non Specific Colour % was calculated as 4 %. Therefore additional data calculation was not necessary.

Any other information on results incl. tables

Table 1: Optical Density (OD) and the Calculated % Viability

Substance	Optical Density (OD)		Viability (%)
Negative Control	1	0.639	100
	2	0.607	95
	3	0.676	105
	Mean	0.641	100
	Standard Deviation (SD)		5.00
Positive Control	1	0.150	23
	2	0.191	30
	3	0.155	24
	Mean	0.165	26
	Standard Deviation (SD)		3.79
Test Material	1	0.555	87
	2	0.627	98
	3	0.633	99
	Mean	0.605	95
	Standard Deviation (SD)		6.66

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, exposure to the test material resulted in a mean relative cell viability of 95 %. Since the cell viability was determined to be > 50 % of the negative control the test material was considered to be non-irritating.

Executive summary:

The potential for the test material to cause skin irritation was predicted in an in vitro study using the EPISKIN Model. The study was conducted under GLP conditions and in line with OECD 439 and EU Method B.46. The test material was applied topically to the surface of the skin for 15 minutes, which was terminated by rinsing with PBS 1 x solution (0.9 %). Epidermis units were then incubated at 37°C for 42 hours in an incubator with 5 % CO2. The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37 °C in 5 % CO2 protected from light. The formazan extract in acidified isopropanol was then spectrophotometrically evaluated for optical density (OD) and quantified. Positive and negative controls were run concurrently and tissue viability was expressed as a % relative to the negative control.

Under the conditions of the test, exposure to the test material resulted in a mean relative cell viability of 95 %. Since the cell viability was determined to be > 50% of the negative control the test material was considered to be non-irritating.

This study was conducted on the the read across substance, sodium 5-oxo-L-prolinate.