Benzoic acid, 2-hydroxy-, C14-18-alkyl derivs.

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 February to 24 February 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study to GLP conducted using material that consisted of 65 % active ingredient and 35 % xylene.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Benzoic acid, 2-hydroxy-,C14-18 alkyl derivs.

EC Number:

931-472-4

Cas Number:

182700-89-6

IUPAC Name:

Benzoic acid, 2-hydroxy-,C14-18 alkyl derivs.

Constituent 2

Reference substance name:

605-976-7

EC Number:

605-976-7

IUPAC Name:

605-976-7

Test material form:

liquid: viscous

Details on test material:

- Physical state: pale brown viscous liquid
- Stability under test conditions: no data
- Storage condition of test material: under nitrogen at ambient temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Weight at study initiation: 3.01 to 3.29 kg
- Housing: individually in stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 3 to 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22
- Humidity (%): 32 to 57
- Air changes (per hr): 10; no recirculation
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
- Animal No.1: From 6 February 1995 to 21 February 1995
- Animals Nos. 2 and 3: From 9 February 1995 to 24 February 1995

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h and 7, 10, 13 and 16 days after removal of the patch

Number of animals:

Three. Initially one animal was tested. As there was no severe irritation, the other two animals were tested.

Details on study design:

TEST SITE
- Area of exposure: two sites on each side of the dorsum, one site was treated and the other received an untreated patch.
- % coverage: 3 x 2 cm
- Type of wrap if used: gauze patch, covered in cotton wool and secured with an elasticated bandage held in place with waterproof plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed in warm water and dried with paper tissues
- Time after start of exposure: 4 hr

SCORING SYSTEM: Draize grading system as described in OECD guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 13 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 days

Results 7

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Very slight erythema in two animals and well-defined erythema in the third animal was seen at 1 to 72 h after removal of the patch which had disappeared in the former animals by 7 days and in the latter by 10 days. Very slight oedema was observed in one rabbit at 24 and 48 h and in another at 48 and 72 h. Very slight or slight oedema was evident in the third rabbit 1 h after removal of the patch and persisted for 10 days. Loss of elasticity and/or flexibility beginning at 48 h in all animals persisted for up to 13 days. Exfoliation was seen in two rabbits beginning on day 10 (which was still present in one animal on day 13) and in the third rabbit on day 13 (which was still present on day 16) after patch removal.

The control sites showed no responses.

Other effects:

No data

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material induced slight (reversible) irritation when 0.5 mL was applied for 4 h to the shaved skin of three rabbits under a semi-occlusive dressing.

Executive summary:

In a GLP study conducted according to OECD guideline 404/EU Method B.4, the test material (approximately 65 % active substance, 35 % xylene) was assessed for irritant potential when applied to the skin of three New Zealand White rabbits under a semi-occlusive patch for 4 h.

On the day before exposure, the dorsal region between the shoulders was clipped free of hair and examined for irregularities and irritation. The test material (0.5 mL) was applied directly to the skin and covered with a gauze patch held in place with a semi-occluded dressing. After 4 h the patch was removed and the area washed to remove excess test material. The skin was examined for signs of skin irritation at 1, 24, 48 and 72 h and 7, 10, 13 and 16 days after removal of the patch.

Very slight erythema in two animals and well-defined erythema in the third animal was seen 1 to 72 h after removal of the patch, which had disappeared in the former animals by 7 days and in the latter by 10 days. Very slight oedema was observed in one rabbit at 24 and 48 h and in another at 48 and 72 h. Very slight or slight oedema was evident in the third rabbit from 1 h after removal of the patch and persisted for 10 days. Loss of elasticity and flexibility beginning at 48 h in all animals persisted for up to 13 days. Exfoliation was seen in two rabbits beginning on day 10 (which was still present in one animal on day 13) and in the third rabbit on day 13 (which was still present on day 16) after patch removal.

In conclusion, the test material, which contained 35 % xylene (a known irritant) caused slight irritation to the skin of rabbits, though this was not severe enough to warrant classification in accordance with EU criteria.