Fatty acids, C18, unsatd., dimers, reaction products with N,N-dimethyl-1,3-propanediamine and 1,3-propanediamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

of 1981

Deviations:

yes

Remarks:

24 h instead of 4 h exposure to a 50% emulsion of test substance in vehicle. Skin examination 0 h, 48 h and 6 days after patch removal.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA

Deviations:

not specified

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Number: 5 animals,
- Average bodyweight: 3 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS

Room temperature kept constant at 18±2°C, the relative humidity at 50-60%. 12 hours illumination per day.

Test system

Type of coverage:

occlusive

Preparation of test site:

other: abraded versus only shaved

Vehicle:

other: Mixture of CMC (carboxymethyl cellulose) and Tween 20 containing 50% test substance

Controls:

not required

Amount / concentration applied:

Dose formulation: Emulsion in mixture of CMC (carboxymethyl cellulose) and Tween 20 containing 50% of the test substance

0.5 g of a 50% test substance emulsion (after warming it up to 37°C) was administered to the skin by means of a "2.5 cm2" cellulose patch.*

* Comment by the data submitter:
There is no indication in the report, whether the size of treated skin patches was inadvertently stated as only "2.5 cm2" in reality having been sized 2.5 cm x 2.5 cm (i.e. ca. 6 cm2) or whether, contrarily to the cited OECD 404 test guideline, the size of the treated skin patches was really confined to only 2.5 cm2. Regardless whether the treated skin patch was ca. 6 cm2 or only 2.5 cm2, the study results are considered to be valid for assessment.

Duration of treatment / exposure:

24 hours

Observation period:

7 days (i.e. the final observation time point was 6 days post patch removal)

Number of animals:

5

Details on study design:

TEST SITE PREPARATION

Samples of 0.5 g of the test emulsion (containing 50% test substance) were applied to the shaved intact and to shaved and then abraded skin of albino rabbits by means of cellulose patches. Patches were fixed with Leukoplast(R) and the whole trunk of each animal was enwrapped by a rubber cloth during the 24 hour treatment period, in order to delay evaporation of substances. From the coverage of the whole animal trunk (patches inclusive) with rubber cloth occlusive treatment was concluded by the data submitter, although the report did not specify whether this coverage was considered to be occlusive or semi-occlusive.

Two untreated skin sites (one of shaved intact skin and one of shaved and then abraded skin) served as controls. Only skin reactions different to controls were graded as positive skin reactions.


TREATMENT PERIOD AND REMOVAL OF TEST SUBSTANCE

Occlusive treatment lasted 24 hours. Then the dressings were removed. There was no mentioning in the report that exposed skin patches were cleaned from residual test substance after treatment.

TIME POINTS OF SKIN EVALUATION:

The treated skin patches were evaluated 24 and 72 hours and 7 days post application (i.e. immediately and 48 hours and 6 days post patch removal). The scoring system for the grading of skin reactions is listed in Table 1 (next field below).

Reporting of irritation results in the present robust study summary has been focused to those attained on intact skin, as currently valid test guidelines do not require treatment of abraded skin.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: erythema formation was not evident

Remarks on result:

other: 50% test substance emulsion administered to intact skin for 24 hours

Results 2

Irritation parameter:

edema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: edema formation was not evident

Remarks on result:

other: 50% test substance emulsion administered to intact skin for 24 hours

Results 3

Irritation parameter:

erythema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 72 hours post treatment start, i.e. within 48 hours post patch removal

Remarks on result:

other: 50% test substance emulsion administered to abraded skin for 24 hours

Results 4

Irritation parameter:

edema score

Remarks:

as defined in Table 1

Basis:

mean

Remarks:

over 5 animals and 2 time points

Time point:

other: 24 and 72 h post treatment start

Score:

0

Max. score:

4

Reversibility:

other: edema formation was not evident

Remarks on result:

other: 50% test substance emulsion administered to abraded skin for 24 hours

Irritant / corrosive response data:

In each animal, shaved intact skin patches treated with a 50% test substance emulsion were free from erythema, scab or edema formation at any observation time point of the study.

On abraded skin patches treated with a 50% test substance emulsion, the only findings were erythema grade 1 at 24 hours post treatment start in 4 of 5 animals which had reversed to normal by 72 hours post treatment start in all affected animals. The fifth animal was free from skin reactions at all observation time points and the 4 affected animals at 72 hours and 7 days post treatment start. Edema were not evident.

Other effects:

None

Applicant's summary and conclusion

Interpretation of results:

other: not irritating according to EU regulation

Conclusions:

Occlusive administration of a 50% test substance emulsion (i.e. containing 50% WS400130) to shaved, intact skin of five rabbits for 24 hours did not induce any skin reactions during the present study. The same treatment to abraded skin induced only grade 1 erythema in 4 of 5 animals which were fully reversible within 72 hours post treatment start. In view of the absence of any irritating effects of the 50% emulsion on intact skin and the very mild and fully reversible erythema reaction of abraded skin during the present study, the submitter proposes that only 4 h exposure of intact skin to undiluted WS400130 would not induce skin reactions necessitating any labelling regarding skin irritation according to EU classification rules [REGULATION (EC) 1272/2008].