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Toxicological information

Eye irritation

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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).
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
of 1981
Deviations:
no
Qualifier:
according to
Guideline:
other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Remarks:
Certified by BAM according to DIN EN 45001.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: The test material contained 50% WS400517 in organic solvent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Number: 3 animals,
- Average bodyweight: 3.2 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: The test material contained 50% WS400517 in organic solvent and was used after warming to 37°C
Controls:
not required
Amount / concentration applied:
After warming undiluted test material (no vehicle) to 37°C, 0.1 ml of it was instilled 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 post instillation
Number of animals or in vitro replicates:
3 adult rabbits
Details on study design:
Eyes were evaluated for occular lesions using ultraviolet light. 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 for each animal.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 7 days post instillation
Remarks on result:
other: Only 1 animal with corneal lesions, i.e. opacity
Irritation parameter:
iris score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Iridal changes were not evident during the study
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
24/48/72 h
Score:
1.9
Max. score:
3
Reversibility:
not fully reversible within: 7 days post instillation
Remarks on result:
other: fully reversible in 2 animals, whereas in the other animal still grade 1 at 7 days post instillation
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
24/48/72 h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible within: 6 days post instillation
Irritation parameter:
other: lacrimation score
Basis:
mean
Remarks:
over 3 animals and 3 time points
Time point:
24/48/72 h
Score:
0.9
Max. score:
3
Reversibility:
fully reversible within: 5 days post instillation
Irritant / corrosive response data:
Adverse effects on the iris were not evident during the 7-day observation period. Corneal findings (opacity and area affected, grade 1 to 2) were confined to one animal (No. 2) and occurred rather late during the observation period (from 3 to 6 days post test material instillation). By 7 days post instillation, the corneal finding was no longer evident. Conjunctival redness, chemosis and lacrimation, grade 1 to 2, were seen in all animals and had completely resolved in two animals (Nos. 1 and 3) within 5 days after instillation. In the other animal (No. 2) a trend to reversibility was evident during the observation period with chemosis and lacrimation having completely resolved and conjunctival redness, grade 1, still present by 7 days post instillation. The ocular findings in treated eyes are detailed in Table 2.
Other effects:
Daily determination of bodyweight did not reveal any test related changes. Bodyweight gain was normal.

Any other information on results incl. tables

Table 2: Ocular Lesions of each Animal

 

 

Cornea

 

Iris

 

Conjunctivae

Animal 

Time after dosing

 

Opacity

(0-4)

Area

(0-4)

 

 

(0-2)

 

Redness

(0-3)

Chemosis

(0-4)

Lacrimation

(0-3)

 

 

 

 

 

 

 

 

 

 

 

 

 

1

 1 hour

 

0

0

 

0

 

2

2

1

 

 2 hours

 

0

0

 

0

 

2

2

2

 

 4 hours

 

0

0

 

0

 

2

2

2

 

 8 hours

 

0

0

 

0

 

2

2

2

 

24 hours

 

0

0

 

0

 

2

2

1

 

48 hours

 

0

0

 

0

 

2

1

1

 

72 hours

 

0

0

 

0

 

1

1

0

 

96 hours

 

0

0

 

0

 

1

0

0

 

 5 days

 

0

0

 

0

 

0

0

0

 

 6 days

 

0

0

 

0

 

0

0

0

 

 7 days

 

0

0

 

0

 

0

0

0

 

 

 

 

 

 

 

 

 

 

2

 1 hour

 

0

0

 

0

 

1

1

1

 

 2 hours

 

0

0

 

0

 

2

2

2

 

 4 hours

 

0

0

 

0

 

2

2

2

 

 8 hours

 

0

0

 

0

 

2

2

2

 

24 hours

 

0

0

 

0

 

2

2

2

 

48 hours

 

0

0

 

0

 

2

2

1

 

72 hours

 

2

2

 

0

 

2

2

1

 

96 hours

 

2

2

 

0

 

2

2

1

 

 5 days

 

2

2

 

0

 

1

1

0

 

 6 days

 

1

1

 

0

 

1

0

0

 

 7 days

 

0

0

 

0

 

1

0

0

 

 

 

 

 

 

 

 

 

 

 

3

 1 hour

 

0

0

 

0

 

1

1

1

 

 2 hours

 

0

0

 

0

 

2

2

1

 

 4 hours

 

0

0

 

0

 

2

2

1

 

 8 hours

 

0

0

 

0

 

2

2

2

 

24 hours

 

0

0

 

0

 

2

2

1

 

48 hours

 

0

0

 

0

 

2

1

1

 

72 hours

 

0

0

 

0

 

2

1

0

 

96 hours

 

0

0

 

0

 

1

0

0

 

 5 days

 

0

0

 

0

 

0

0

0

 

 6 days

 

0

0

 

0

 

0

0

0

 

 7 days

 

0

0

 

0

 

0

0

0

 

 

 

 

 

 

 

 

 

 

Applicant's summary and conclusion

Interpretation of results:
other: not irritating, see explanation in conclusion
Remarks:
expert judgment
Conclusions:
According to European classification rules [REGULATION (EC) 1272/2008] the degree and incidence of conjunctival redness seen in the present study could lead to classification as an eye irritant Category 2. However, the material tested in the present study contained a substantial amount of at least one formulation constituent classified as skin and eye irritant Category 2 [REGULATION (EC) 1272/2008]. Therefore and because of the absence of any relevant toxicity or indication of an irritating potential in all other toxicity studies performed with neat WS400517 or with any of its formulations, the eye irritation seen in the present study is attributed to the irritating formulation constituent and not to WS400517. Consequently, it is proposed not to classify WS400517 as an eye irritant according to EU classification rules [REGULATION (EC) 1272/2008].