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Diss Factsheets

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
Study period:
29th November 1988 to 13th December 1988
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium 7-(2,6-dimethyl-8-(2,2-dimethylbutyryloxy)-1,2,6,7,8,8a-hexahydro-1-naphthyl)-3,5-dihydroxyheptanoate
EC Number:
404-520-2
EC Name:
Ammonium 7-(2,6-dimethyl-8-(2,2-dimethylbutyryloxy)-1,2,6,7,8,8a-hexahydro-1-naphthyl)-3,5-dihydroxyheptanoate
Cas Number:
139893-43-9
Molecular formula:
C25 H43 O6 N
IUPAC Name:
ammonium 7-{8-[(2,2-dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl}-3,5-dihydroxyheptanoate
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Composition:
99.2% L-654,969, 0.2% lovastatin ammonium salt, 0.2% triol

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source: A. Smith, Warlingham, Surrey, England
Animals were acclimatised to laboratory conditions. The rabbits were housed in metal cages with perforated floors. Each animal was identified by a numbered aluminium tag placed through the edge of one ear.
Temperature: 19oC
Humidity: 30-70%
Light sequence: 12 hour light / 12 hour dark
Food: SDS Standard Rabbit Diet
Water: ad libitum

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
45mg
Duration of treatment / exposure:
7 days
Observation period (in vivo):
1 hour, 1, 2, 3, 4 and 7 days
Number of animals or in vitro replicates:
3
Details on study design:
Eye Examination before Testing
The eyes of each animal were examined to ensure that there was no pre-exisitng corneal damage or conjunctival inflammation.

Administration Method
0.45mg of test item was placed into the everted lid of one eye of each animal. after gently pulling the lower lid away from the eyeball. The lids were gently held together for approximately one second in order to prevent loss of the material. The other eye remained untreated and served as a control.

Observation
Examination of the eye was made 1 hour after administration of the test item. All treated eyes were examined at approximately 1, 2, 3, 4, and 7 days after administration.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.7
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: other: Max. duration: 7 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.7
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: other: Max. duration: 3 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: other: Max. duration: 4 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: other: Max. duration: 0 h; Max. value at end of observation period: 0 (related to all animals)

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
A corneal opacity was observed in one animal 3 and 4 days after instillation only. A diffuse crimson-red colouration of the conjunctivae was observed in two animals. Mild conjunctival reactions were observed in the remaining animal.
All eyes had returned to normal by day 7. The substance does not require labelling with risk phrase R36 "Irritating to eyes".
Executive summary:

The study was performed to assess the acute eye irritation/corrosion of L654 969 in New Zealand rabbits. The method was designed to be in accordance with the OECD Guidelines 'Acute Eye Irritation/Corrosion' (405).


Three male rabbits were used for the study. Each animal was administered 0.45mg of the test item in one eye. The untreated eye served as the control. The rabbits were observed and recorded for initial reaction after 1 hour, then 1, 2, 3, 4, and 7 days after administration. Ocular lesions were scored for treated eyes. 


A corneal opacity was observed in one animal 3 and 4 days after instillation only. A diffuse crimson-red colouration of the conjunctivae was observed in two animals. Mild conjunctival reactions were observed in the remaining animal.
All eyes had returned to normal by day 7.


Based on the above results in New Zealand rabbits, installation of L654 969 into the rabbit eye elicted a positive response in two or the three animals according to OECD test criteria. The substance does not require labelling with risk phrase R36 "Irritating to eyes".