Benzoic acid, 4-hydroxy-, docosyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline- and GLP-Study with no deficiencies.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

docosyl 4-hydroxybenzoate

EC Number:

920-338-0

Cas Number:

109236-76-2

Molecular formula:

C29 H50 O3

IUPAC Name:

docosyl 4-hydroxybenzoate

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test Animals: Healthy New Zealand White Rabbits Hsdlf: NZW.
Source: Harlan Winkelmann GmbH, D-33178 Borchen.

Three female animals were used. Body weight at the commencement of the study was >2.0 kg. The animals were derived from a controlled full bamer maintained breeding system (SPF).

According to Art. 9.2, No.7 of the German Act on Animal Welfare the animals are bred for experimental puiposes.

Animal Husbandry: Semi-barrier in an air conditioned room.
- Temperature: 18 ± 3°C (recommendations of TVT, GV-SOLAS; see References)
- Relative, humidity; 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark Air change: at least 10 x / hour
- Free access to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
Certificates of food, water and bedding are filed at BSL Bioservice
- Housed in ABS - plastic rabbit cages, floor 4200 cm
- Adequate acclimatization period (at least 5 days)

Preparation of the Animals:
Approximately 24 hours before the test and immediately prior to application both eyes of the test animals were examined. A health inspection was performed to ensure the good state of health of the animals.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated contralateral eye served as control.

Amount / concentration applied:

A dose of 0.1 g of the undiluted test item was applied to the test site.

Observation period (in vivo):

All animals were observed for 72 hours after dosing.

Number of animals or in vitro replicates:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Redness and discharge

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

6

Results 8

Irritation parameter:

conjunctivae score

Remarks:

Redness and discharge

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

6

Results 9

Irritation parameter:

conjunctivae score

Remarks:

Redness and discharge

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

6

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0.33

Max. score:

4

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

4

Any other information on results incl. tables

In this eye irritation study the test item was applied to the lower conjunctival sac of one eye of 3 female NZW - rabbits (HsdIf:NZW) at a dose of 0.1 g per application site. The untreated other eye served as control.

Observations were calculated and compared to the control eyes, 24 h, 48 h, 72 h post-dose.

Animal no. 1 showed redness, chemosis and discharge grade 1 of the conjunctiva 1 h after the instillation. Further, it showed redness grade 1 and discharge as well as chemosis grade 2 of the conjunctiva 24 h after the instillation. 48 hours post instillation, chemosis grade 1 of the conjunctiva was observed. No further signs of irritation were observed 72 hours post instillation.

Animal no. 2 showed redness as well as chemosis grade 1 and discharge grade 2 of the conjunctiva 1 h after the instillation. 24 hours post instillation, discharge grade 1 of the conjunctiva was recorded. No further signs of irritation were observed 48 hours as well as 72 hours post instillation.

Animal no. 3 showed redness, chemosis and discharge grade 1 of the conjunctiva 1 h as well as 24 hours post instillation. No further signs of irritation were observed 48 hours as well as 72 hours post instillation.

No other toxic effects were observed.

The eye of animal no. 1 was rinsed with isotonic saline, NaCl 0,9% (lot no. 8221A121, Braun Melsungen AG); the eyes of animal no. 2 and animal no. 3 were not rinsed.

At the end of the observation period (72 hours) the treated eyes of all animals were examined with the aid of a fluorescein solution (Fluorescein SE Thilo®, lot no. H 702, Alcon Pharma GmbH). No corneal lesions were found in any animal at any time.

Throughout the observation period no significant weight loss was recorded in the test animals.

The calculated mean scores did not exceed the limit values according to the Directive 2001/59/EC in any case.

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information not sufficient for classification Criteria used for interpretation of results: EU

Conclusions:

Considering the reported data of this irritation study it can be stated that the test item 4-Hydroxybenzoic acid behenylester produced slightly to moderately irritating effects, which were fully reversible in all animals.
According to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 2001/59/EC) the test item does not have to be classified and has no obligatory labelling requirement for eye irritation (for details see Evaluation of Results)