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Diss Factsheets

Administrative data

Description of key information

Based on in vivo eye and skin irritation studies the substance is not considered to be irritating to the eye or the skin

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:
22nd November 1988 to 25th November 1988
Reliability:
1 (reliable without restriction)
Justification for type of information:
The testing using the guinea pig maximisation test protocol was completed on 25 November 1988. The LLNA 429 was not formally adopted by the OECD until 22 July 2010.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
Composition:
99.2% L-654,969, 0.2% lovastatin ammonium salt, 0.2% triol
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system 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
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Test substance was applied under a gauze pad moistened with 0.5ml distilled water
Controls:
no
Amount / concentration applied:
0.5g moistened with 0.5ml water
Duration of treatment / exposure:
4 hours
Observation period:
4 days
Number of animals:
3
Details on study design:
0.5g of the test item moistened with 0.5ml water was applied to a gauze patch (2.5cm). The treated patch was occluded with elastic adhesive dressing. Patches were removed after 4 hours. The residual test item was gently wiped off with water.
The skin sites were examined 1, 2, 3 and 4 days after removal of patches for signs of skin reaction and symptoms. Dermal reactions for erythema /eschar or oedema of test sites of each animal were scored and recorded.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: Max. duration: d; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: other: Max. duration: d; Max. value at end of observation period: 0 (related to all animals)
Interpretation of results:
GHS criteria not met
Conclusions:
A single, semi-occlusive application of L-654,969 to intact rabbit skin for four hours elicited no dermal irritation.
The test substance does not require labelling with risk phrase R38 "Irritating to skin".
Executive summary:

The study was performed to assess the acute dermal irritation/corrosion of L-654 969 in New Zealand rabbits. The method was designed to be in accordance with OECD Guidelines 'Acute Dermal Irritation/Corrosion' (404). 

Three male rabbits were used for the study. A quantity of 0.5g of the test item was applied to the skin of each animal for an exposure period of 4 hours.  Dermal reactions (erythema/eschar and oedema) of test sites were scored at approximately 1, 2, 3 and 4 days after patch removal. 

No abnormal signs or symptoms were observed in any animal throuhout the course of the test. The scores of erythema/eschar and oedema for all animals at 1, 2, 3 and 4 days were all 0 after patch removal.  

A single, semi-occlusive application of L-654,969 to intact rabbit skin for four hours elicited no dermal irritation. The test substance does not require labelling with risk phrase R38 "Irritating to skin".

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:
29th November 1988 to 13th December 1988
Reliability:
1 (reliable without restriction)
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
Specific details on test material used for the study:
Composition:
99.2% L-654,969, 0.2% lovastatin ammonium salt, 0.2% triol
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
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.
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)
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".

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification