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

Eye irritation

Administrative data

Endpoint:

eye 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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

of 1981

Deviations:

no

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 / tissue source

Species:

rabbit

Strain:

other: Tattooed New Zealands (albino rabbit)

Details on test animals or tissues and environmental conditions:

- Number: 6 animals,
- Bodyweight: 2.5 to 3.0 kg
- Housing: Individual housing in cages.
- Diet: Commercially available standard laboratory diet for rabbits ( Altromin, Lage, Germany).
Prior to dosing the animals were starved for 16 hours.
- 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

Vehicle:

other: CMC (carboxymethyl cellulose "Tylose") containing 40% test substance

Controls:

not required

Amount / concentration applied:

Undiluted test substance could not be administered. Therefore, a dose formulation was prepared containing 40.5% WS400130.
After warming this test substance dilution to 40°C, 0.1 ml of it was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.

Duration of treatment / exposure:

There was no mentioning in the report that eyes were rinsed after treatment. Consequently the treatment/exposure period was equivalent to the entire observation period following administration, which was 7 days, or lasted until removal of the test material by physiological mechanisms, whichever happened sooner.

Observation period (in vivo):

7 days (i.e. the final observation time point was 7 days post instillation)

Number of animals or in vitro replicates:

6 adult rabbits

Details on study design:

Eyes were evaluated for occular lesions using ultraviolet light. Before and after the test the eyes of all animals were examained after staining with 2% fluorescein thus supporting the recognition of corneal lesions.

The numerical scoring system listed in Table 1 in the field below was adopted. Time points of evaluation were: Pretest (prior to treatment), 1, 2, 4, 8, 24, 48, 72 and 96 hours after administration and daily thereafter until 7 days after administration. Grades attained at 24, 48 and 72 hours after administration were included in the mean gradings of ocular lesions used for eye irritation/corrosion classification.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: Corneal irritation or opacity was not evident during the study

Remarks on result:

other: Treated with a dose formulation containing 40.5% WS400130

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: Iridal changes were not evident during the study

Remarks on result:

other: Treated with a dose formulation containing 40.5% WS400130

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 4 hours

Remarks on result:

other: Treated with a dose formulation containing 40.5% WS400130

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: Chemosis was not evident during the study

Remarks on result:

other: Treated with a dose formulation containing 40.5% WS400130

Results 5

Irritation parameter:

other: lacrimation score

Basis:

mean

Remarks:

over 6 animals and 3 time points

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 4 hours

Remarks on result:

other: Treated with a dose formulation containing 40.5% WS400130

Irritant / corrosive response data:

Corneal and iridic lesions and chemosis were not evident throughout the study. Conjunctival redness and lacrimation, both findings grade 1, were seen in all treated eyes at 1 and 2 hours post instillation having completely disappeared in all animals by 4 hours post instillation. Examination of the eyes at 4 and 8 hours post instillation and daily afterwards until 7 days post instillation did not reveal any findings.

Other effects:

There was no mentioning of any other effects in the report.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating according to EU regulation

Conclusions:

WS400130 could not be administered undiluted. Therefore, a dilution in CMC (Tylose) containing 40.5% WS400130 was tested. The outcome of the present study does not necessitate any labelling regarding eye irritation according to EU classification rules [REGULATION (EC) 1272/2008]. The findings noted were very minor in degree, restricted to the 1 and 2 hour post instillation time points and fully reversible within 4 hours. Therefore, they fell within the category “not irritating to eyes”.