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

Endpoint summary

Description of key information

SKIN
Not irritating (rabbit); OECD 404 and EU Method B.4
EYE
Irritating (rabbit); OECD 405 and EU Method B.5

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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

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

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 days

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 March to 15 March 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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 5 months
- Weight at study initiation: 3.44 to 3.78 kg
- Housing: individually, in suspended stainless steel cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 to 2 months

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22
- Humidity (%): 32 to 57
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
- Rabbit No.1: From 6 March 1995 to 13 March 1995
- Rabbits Nos. 2 and 3: From 8 March 1995 to 15 March 1995

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single application, not washed out of the eye

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

Three. One animal was initially treated with the test material. As a severe irritation response was not observed, two more rabbits were treated.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: scored according to OECD guideline. Also scored for pain reaction to instillation of the test material and for area of the cornea affected by the lesion and discharge from the conjunctivae.

TOOL USED TO ASSESS SCORE: ophthalmoscope or pencil beam torch. From 24 h fluorescein was used for examination of the cornea, viewed under uv-light.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

4

Reversibility:

other: reversible in 2/3 rabbits within 48 or 72 h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

other: fully reversible in 2/3 rabbits within 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other: fully reversible in 2/3 rabbits in 48 or 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no reaction

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritant / corrosive response data:

The sentinel rabbit (No.1) showed a diffuse beefy-red conjunctiva during the first 24 h, which gradually reduced but injection of the blood vessels persisted to study termination on day 8. Iritis, very slight chemosis and slight to moderate discharge with mucus were evident during the first 24 h but had reversed by 48 h, 48 h and 8 days, respectively. No effects on the cornea were apparent.

Animal No.2 showed pink to crimson conjunctiva and very slight or slight discharge (with mucus) during the first 72 h but had mainly reversed by day 8. An area of very slight corneal opacity, very slight or slight chemosis and iritis were seen at 24 and 48 h.

Animal No.3 showed crimson or beefy-red conjunctiva, very slight or slight chemosis, very slight or slight discharge, iritis and opacity of the cornea all of which were still present on day 8. Pannus formation (which is irreversible) affecting both the upper and lower edges of the cornea was evident on day 8, which resulted in the decision to terminate the study at this point.

Other effects:

The pain response for animal No. 1 upon instillation of the test substance was moderate (grade 3; on a scale of 0 to 5).

Interpretation of results:

Category I

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was irritating when 0.1 mL was instilled into the eyes of three New Zealand White rabbits.

Executive summary:

In a GLP study conducted according to OECD Guideline 405 and to EU Method B.5, the test material (approximately 65 % active substance, 35 % xylene) was assessed for its irritant potential when instilled into the eyes of three New Zealand White rabbits.

Each animal was treated with 0.1 mL of the undiluted test material in the right eye and the eyelids gently held together for 1 second before releasing. The left eye was untreated and served as a concurrent control.The rabbits were observed at 1, 24, 48 and 72 h and at 8 days after instillation for signs of occular irritation. Initially only one animal was treated which experienced a moderate pain response; to prevent this in the other two animals they were treated with an anesthetic before instillation of the test material (including the control eye).

Moderate to severe conjunctivitis was evident in all three rabbits during the first 72 h after exposure which was not fully reversible by 8 days. Moderate iritis was seen in one animal at 1 and 24 h, at 24 and 48 h in another, and throughout the study in the third. No corneal opacity was evident in one animal, was present at 24 and 48 h in a second and in the third was present from 1 h through to day 8. In this latter animal the irreversible lesion, pannus, was evident on day 8, affecting both the upper and lower edges of the cornea.

In conclusion, the test material was irritating when 0.1 mL was instilled into the eyes of three New Zealand White rabbits, causing pannus in one animal.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

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. The study was awarded a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997).

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.

Eye irritation

In a GLP study conducted according to OECD Guideline 405 and to EU Method B.5, the test material (approximately 65 % active substance, 35 % xylene) was assessed for its irritant potential when instilled into the eyes of three New Zealand White rabbits. The study was awarded a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997).

Each animal was treated with 0.1 mL of the undiluted test material in the right eye and the eyelids gently held together for 1 second before releasing. The left eye was untreated and served as a concurrent control.The rabbits were observed at 1, 24, 48 and 72 h and at 8 days after instillation for signs of occular irritation. Initially only one animal was treated which experienced a moderate pain response; to prevent this in the other two animals they were treated with an anesthetic before instillation of the test material (including the control eye).

Moderate to severe conjunctivitis was evident in all three rabbits during the first 72 h after exposure which was not fully reversible by 8 days. Moderate iritis was seen in one animal at 1 and 24 h, at 24 and 48 h in another, and throughout the study in the third. No corneal opacity was evident in one animal, was present at 24 and 48 h in a second and in the third was present from 1 h through to day 8. In this latter animal the irreversible lesion, pannus, was evident on day 8, affecting both the upper and lower edges of the cornea.

In conclusion, the test material was irritating when 0.1 mL was instilled into the eyes of three New Zealand White rabbits, causing pannus in one animal.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on eye irritation: irritating

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to skin irritation.

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance requires classification with respect to eye irritation as Category 1 (H18; Causes serious eye damage).