Sodium (3-hydroxy-2-pentylcyclopentyl)acetate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

Remarks:

skin irritation : in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-11-25 to 2009-05-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

as at 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

as at 2004

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (3-hydroxy-2-pentylcyclopentyl)acetic acid and sodium (3-hydroxy-2-pentylcyclopentyl)acetate

EC Number:

932-898-3

IUPAC Name:

Reaction mass of (3-hydroxy-2-pentylcyclopentyl)acetic acid and sodium (3-hydroxy-2-pentylcyclopentyl)acetate

Details on test material:

- Name of test material (as cited in study report): R0034833C
- Physical state: slightly yellow liquid
- Analytical purity: 30.26%
- Composition of test material, percentage of components:
R0034833A (sodium salt form) content, expressed as acid form: 25.76%
R00348338 (acid form) content: 4.5%
NaCl content: 1.6%
Water content: 45.6%
Dipropylene glycol content: 19.0%
Dried extract: 34.0%
Active content: 30.26%
pH: 7.0
Majority diastereoisomers ratio: 57/43
Other diastereoisnmers and isomers content: 9.3%
ER2423 content Not Detected < 0.02%
ER2425 content Not Detected < 0.02%
Inter-molecular esters content Not Detected < 0,01%
intro-molecular esters content 0.08%
ER2410 content 0.8%
Methanol content Not Detected < 1000 ppm

Results consistent with ID LIMB 2% 12631

- Purity test date: 2008-08-01
- Lot/batch No.: R0034833C 027 P 001
- Expiration date of the lot/batch: June 2009
- Stability under test conditions: not reported
- Storage condition of test material: at +4°C and protected from light

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Grimaud Frères Sélection S.A.S., La Corbière, Roussay, France- Age at study initiation: 2 to 4 months- Weight at study initiation: 2.5 ± 0.2 kg- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm)- Diet (e.g. ad libitum): ad libitum, Control Ref.: 110 pelleted diet (SAFE, Augy, France)- Water (e.g. ad libitum): ad libitum, drinking water filtered by a FG Millipore membrane (0.22 micron)- Acclimation period: at least 5 dENVIRONMENTAL CONDITIONS- Temperature (°C): 18 ± 3- Humidity (%): 30 to 70- Air changes (per hr): ca. 12- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 mL- Concentration (if solution): 100 % of the mixture defined under "Details on test material" VEHICLE- Amount(s) applied (volume or weight with unit):- Concentration (if solution):- Lot/batch no. (if required):- Purity:

Duration of treatment / exposure:

- anterior left flank: application for 3 min- anterior right flank: application for 1 h- posterior right flank: application for 4 h

Observation period:

3 min, 1 hour, 24, 48 and 72 hours, study ended on day 4 in the absence of persistent irritation reactions.

Number of animals:

3

Details on study design:

TEST SITE- Area of exposure: - anterior left flank: application for 3 min (sentinel animal) - anterior right flank: application for 1 h (sentinel animal) - posterior right flank: application for 4 h (sentinel animal + 2 animals for confirmatory testing)- % coverage: 6 cm²- Type of wrap if used: dry gauze pad, held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandageREMOVAL OF TEST SUBSTANCE- Washing (if done): wiped off by means of a dry cotton pad- Time after start of exposure: - anterior left flank: after the application for 3 min (sentinel animal) - anterior right flank: after the application for 1 h (sentinel animal) - posterior right flank: after the application for 4 h (sentinel animal + 2 animals for confirmatory testing)SCORING SYSTEM:Draize scoring systemErythema and eschar formation:. no erythema........................................................................................................... 0. very slight erythema (barely perceptible) ............................................................. 1. well-defined erythema........................................................................................... 2. moderate to severe erythema................................................................................. 3. severe erythema (beet redness) to slight eschar formation (injuries in depth)...... 4Edema formation. no edema ............................................................................................................... 0. very slight edema (barely perceptible).................................................................. 1. slight edema (edges of area well-defined by definite raising) .............................. 2. moderate edema (raised approximately 1 millimeter) .......................................... 3. severe edema (raised more than 1 millimeter and extending beyond areaof exposure)........................................................................................................... 4Any other lesions were noted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 3 min

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: 3 min exposure

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: 1 h exposure

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: 4 h exposure

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48

Remarks on result:

other: 4 h exposure

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48

Score:

0

Max. score:

4

Remarks on result:

other: 4 h exposure

Results 6

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

4

Remarks on result:

other: 4 h exposure

Results 7

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 3 min, 1 h, 4h, 24 h, 48 h, 72 h

Score:

0

Max. score:

4

Remarks on result:

other: No edema seen in any animal at any time point.

Irritant / corrosive response data:

After a 3-minute or 1-hour exposure (one animal):- a very slight erythema on day 1After a 4-hour exposure (three animals):- a very slight erythema in all animals on day 1, persisting in one of them on day 2- mean scores over 24, 48 and 72 hours for each animal - erythema: 0.0, 0.0 and 0.3 - edema: 0.0, 0.0 and 0.0

Other effects:

No other effects noted.

Any other information on results incl. tables

- Table 1:  Individual cutaneous examinations and mean values of the scores recorded for each animal

Rabbit number	Dermal Irritation			Scores		Mean irritation	Interpretation (+) (-)
		1h D1	24h, D2	48h, D3	72h, D4	score (1)
3-minute exposure - Cutaneous examinations and mean values of the scores recorded for the first animal (24, 48 and 72 hours)
750	Erythema	1	0	0	0	0.0
	Edema	0	0	0	0	0.0
	Other	*	*	*	*
1-hour exposure - Cutaneous examinations and mean values of the scores recorded for the first animal (24, 48 and 72 hours)
750	Erythema	1	0	0	0	0.0
	Edema	0	0	0	0	0.0
	Other	*	*	*	*
4-hour exposure - Individual cutaneous examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)
750	Erythema	1	0	0	0	0.0	(-)
	Edema	0	0	0	0	0.0	(-)
	Other	*	*	*	*
711	Erythema	1	0	0	0	0.0	(-)
	Edema	0	0	0	0	0.0	(-)
	Other	*	*	*	*
712	Erythema	1	1	0	0	0.3	(-)
	Edema	0	0	0	0	0.0	(-)
	Other	*	*	*	*

(1) mean of scores on days 2, 3 and 4 h = hour

D = day

(+) = irritant according to E.E.C. criteria

(-) = non-irritant according to E.E.C. criteria

* = none

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The potential of the test item R0034833C (batch No. R0034833C 027 P 001) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 24th April 2002) and EC (2004/73/EC, B.4, 29th April 2004) guidelines and GLP.Under the experimental conditions of this study, the test item R0034833C (batch No. R0034833C 027 P 001) was well-tolerated when applied topically to rabbits.

Executive summary:

The potential of the test item Mexoryl SBO (termed R0034833C in the study report, batch No. R0034833C 027 P 001) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 24th April 2002) and EC (2004/73/EC, B.4, 29th April 2004) guidelines . The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied simultaneously for 4 hours to two other animals. A single dose of 0.5 mL of the undiluted test item was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.

The mean values of the scores for erythema and edema were calculated for each animal. The interpretation of results was carried out according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

After a 3-minute or 1-hour exposure (one animal) a very slight erythema was noted on day 1. After a 4-hour exposure (three animals) a very slight erythema was noted in all animals on day 1, persisting in one of them on day 2. Mean scores over 24, 48 and 72 hours for each animal were 0.0, 0.0 and 0.3 for erythema and 0.0,

0.0 and 0.0 for edema.

Under the experimental conditions of this study, the test item R0034833C (batch No. R0034833C 027 P 001) was well-tolerated when applied topically to rabbits.

According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) and CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL, the test item should not be classified as irritating to the skin.