Sodium long chain alkyl salicylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1985-07-22 to 1985-08-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., sodium salts

Molecular formula:

Na(C21-25H33-41O3)

IUPAC Name:

Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., sodium salts

Details on test material:

- Physical state: Dark brown liquid
- Stability under test conditions: Stable for the duration of the study
- Expiry date: Assigned as one calendar month from the date of issue (18 July 1985)
- Storage conditions of test material: In the dark at ambient temperature
- Date received: 08 July 1985
- Density/Specific gravity: 0.985 kg/L at 20 °C

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age on receipt from supplier: 3-6 months
- Age at study initiation: 4-9 months
- Weight at study initiation: 4790-4862 g (female); 4008-4106 g (male)
- Housing: Singly housed in hanging, stainless-steel cages with all-mesh floors and tops and half-mesh fronts; each cage measured 67 x 43 x 45 cm. The cages were mounted in three rows of two on a single-sided rack (a total of six cages).
- Diet: ad libitum by means of a top-loading food hopper
- Water: Filtered but untreated from water from the public supply by means of an automatic valve-regulated drinking line
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 16-19 °C
- Humidity (%): Monitored but values not stated
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): Light 06:00 to 18:00 GMT; Dark 18:00 to 06:00 GMT via fluorescent tubes

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

21 days

Number of animals:

Three males and three females

Details on study design:

A semi-occlusive patch test was used to assess the primary skin irritation induced by the undiluted test material. Each animal was identified by means of a number metal ear tag and/or a number written on the pinna.

Dorsal hair between the shoulders and hindquarters was closely shorn with fine electric clippers. A test site was selected and a 2 x 2 cm lint patch dosed with 0.5 mL of the test material applied to it. The patch and surrounding skin were covered by a single layer of gauze held in place by means of an elastic adhesive bandage.

After 4 hours the wrapping and patch were removed. The site was examined and scored for erythema and oedema on a graded scale of 0 to 4 using the criteria given in the applicable tables (attached). Observations were made at 30 minutes after removal of the patch (i.e. approximately 4 hours after application) and at 24, 48 and 72 hours plus 7, 14, and 21 days after application.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 804M

Time point:

24 h

Score:

2

Reversibility:

not reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal: 804M

Time point:

48 h

Score:

2.5

Reversibility:

not reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal: 804M

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 4

Irritation parameter:

erythema score

Basis:

animal: 800M

Time point:

24 h

Score:

2

Reversibility:

not reversible

Results 5

Irritation parameter:

erythema score

Basis:

animal: 800M

Time point:

48 h

Score:

2.5

Reversibility:

not reversible

Results 6

Irritation parameter:

erythema score

Basis:

animal: 800M

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 7

Irritation parameter:

erythema score

Basis:

animal: 805M

Time point:

24 h

Score:

2

Reversibility:

not reversible

Results 8

Irritation parameter:

erythema score

Basis:

animal: 805M

Time point:

48 h

Score:

2.5

Reversibility:

not reversible

Results 9

Irritation parameter:

erythema score

Basis:

animal: 805M

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 10

Irritation parameter:

erythema score

Basis:

animal: 833F

Time point:

24 h

Score:

2

Reversibility:

not reversible

Results 11

Irritation parameter:

erythema score

Basis:

animal: 833F

Time point:

48 h

Score:

2.5

Reversibility:

not reversible

Results 12

Irritation parameter:

erythema score

Basis:

animal: 833F

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 13

Irritation parameter:

erythema score

Basis:

animal: 801F

Time point:

24 h

Score:

2

Reversibility:

not reversible

Results 14

Irritation parameter:

erythema score

Basis:

animal: 801F

Time point:

48 h

Score:

2

Reversibility:

not reversible

Results 15

Irritation parameter:

erythema score

Basis:

animal: 801F

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 16

Irritation parameter:

erythema score

Basis:

animal: 836F

Time point:

24 h

Score:

2

Reversibility:

not reversible

Results 17

Irritation parameter:

erythema score

Basis:

animal: 836F

Time point:

48 h

Score:

2

Reversibility:

not reversible

Results 18

Irritation parameter:

erythema score

Basis:

animal: 836F

Time point:

72 h

Score:

2

Reversibility:

not reversible

Results 19

Irritation parameter:

edema score

Basis:

animal: 804M

Time point:

24 h

Score:

1

Reversibility:

not reversible

Results 20

Irritation parameter:

edema score

Basis:

animal: 804M

Time point:

48 h

Score:

1

Reversibility:

not reversible

Results 21

Irritation parameter:

edema score

Basis:

animal: 804M

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 22

Irritation parameter:

edema score

Basis:

animal: 800M

Time point:

24 h

Score:

1

Reversibility:

not reversible

Results 23

Irritation parameter:

edema score

Basis:

animal: 800M

Time point:

48 h

Score:

2

Reversibility:

not reversible

Results 24

Irritation parameter:

edema score

Basis:

animal: 800M

Time point:

72 h

Score:

4

Reversibility:

not reversible

Results 25

Irritation parameter:

edema score

Basis:

animal: 805M

Time point:

24 h

Score:

1

Results 26

Irritation parameter:

edema score

Basis:

animal: 805M

Time point:

48 h

Score:

1

Results 27

Irritation parameter:

edema score

Basis:

animal: 805M

Time point:

72 h

Score:

4

Results 28

Irritation parameter:

edema score

Basis:

animal: 833F

Time point:

24 h

Score:

1

Results 29

Irritation parameter:

edema score

Basis:

animal: 833F

Time point:

48 h

Score:

1

Results 30

Irritation parameter:

edema score

Basis:

animal: 833F

Time point:

72 h

Score:

4

Results 31

Irritation parameter:

edema score

Basis:

animal: 801F

Time point:

24 h

Score:

1

Results 32

Irritation parameter:

edema score

Basis:

animal: 801F

Time point:

48 h

Score:

2

Results 33

Irritation parameter:

edema score

Basis:

animal: 801F

Time point:

72 h

Score:

4

Results 34

Irritation parameter:

edema score

Basis:

animal: 836F

Time point:

24 h

Score:

1

Results 35

Irritation parameter:

edema score

Basis:

animal: 836F

Time point:

48 h

Score:

1

Results 36

Irritation parameter:

edema score

Basis:

animal: 836F

Time point:

72 h

Score:

1

Max. score:

4

Irritant / corrosive response data:

All rabbits had slight inflammation of the treated site by 24 hours post-dosing which progressively increased until, by 72 hours, five rabbits had necrosis; by 7 days all six rabbits were thus affected. By 14 days the treated skins were either lifting or had lifted to reveal slightly discoloured new skin with small, semi-raw areas in three animals (see Table 2, attached). There are additional time points included in the study which have not been included in the Results table above as this is an older study conducted out to 21 days. the maximum results were however obtained after around 72hrs and did not reverse so only timepoints to 72hrs are relevant. All data has been provided in the attachment for reference.

By 21 days the skin reaction had cleared completely in two rabbits but three animals still had a light brown discolouration of the skin; it was anticipated that this would clear in time. However, the skin of 805 M was discoloured (purple) and thickened, which was taken as a permanent alteration to the skin of this animal.

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test material caused irreversible damage to the skin of one rabbit and is therefore considered to be corrosive.

Executive summary:

The potential of the test material to cause skin irritation was assessed in a study conducted using methodology equivalent to that outlined in the standardised guideline OECD 404 under GLP conditions.

Three males and three female New Zealand White rabbits were exposed to the test material in a semi-occlusive fashion for 4 hours. A lint patch dosed with 0.5 mL of the undiluted test material was applied to the shaved skin of the rabbits. Following the exposure, rabbits were observed 30 minutes after removal of the patch (i.e. approximately 4 hours after application) and at 24, 48 and 72 hours plus 7, 14, and 21 days after application. The site was examined and scored for erythema and oedema on a graded scale of 0 to 4.

There was so little inflammation (erythema) half an hour after removal of the patch that a score between 0 and 1 was assigned for each animal. Although not a standard procedure, if the response was considered to be between the scores usually used (i.e., 0 to 4 for both erythema and oedema) an intermediate score was allocated. Inflammation progressed afterwards, reaching a maximal point on day 7 when all animals were assigned 4 for both erythema and oedema and a note was added in the report to state “All treated skins thickened with light brown, necrotic appearance so maximum scores given.“ At 14 days there was some recovery, but 3 out of the 6 rabbits still had erythema values > 2. At 21 days 2 animals appeared to have completely recovered, 3 animals presented “Light brown discolouration of skin; probably not permanent effect” but the remaining one presented “treated skin thickened and discoloured (purple); probably permanent effect”. Although on the basis of the group mean 24, 48 and 72 hour scores for erythema and oedema (2.7 and 1.9, respectively) the test material would be classified as a moderate irritant, this scheme is clearly inappropriate in this case where the skin responses increased with time up to and including 7 days post-dosing and one animal developed irreversible skin effects.

Under the conditions of this study the test material caused irreversible damage to the skin of one rabbit and is therefore considered to be corrosive.