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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:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The negative response observed in the animal treated with undiluted substance was not confirmed by testing 2 additional animals.
Principles of method if other than guideline:
The method used to assess eye irritancy is a modification of that prescribed for purposes of the United States Federal Hazardous Substances Labelling Act. In addition corneal damage is also assessed objectively by measurement of corneal swelling.
3 rabbits were treated with 100 µL of a 10 % dilution, 1 rabbit was treated with 100 µL of a 50 % dilution and 1 rabbit was treated with 100 µL undiluted substance. No additional rabbits were tested to confirm the negative results observed for the undiluted substance.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: commercial supplier
- Age at study initiation: >= 7 weeks
- Weight at study initiation: >= 1 kg
- Housing: singly in cages from which all hay, straw or similar potentially irritant material is excluded
- Water: ad libitum
- Acclimation period: yes, duration not reported

Test system

Vehicle:
other: Tween 80
Controls:
other: Left eye served as untreated control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 µL
- Concentration: 10 % (3 rabbits), 50 % (1 rabbit), 100 % (1 rabbit)
Observation period (in vivo):
Conjunctival damage: 15 minutes after treatment
Corneal, conjuntival and iridial reaction: 1, 2, 3, 4, 7, 9, 11, 16, 18 and 21 days after treatment. The assessment is stopped earlier if the eye returned to normal.
Number of animals or in vitro replicates:
Unchanged substance: 1 rabbit
50 % in Tween 80: 1 rabbit
10 % in Tween 80: 3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM:
CORNEA
0: Normal
0.5: Any change form normal, including slight dulling of corneal lustre
1: Scattered or diffuse areas of opacity, or loss of corneal epithelium. Iris clearly visible
2: Easily discernible, greyish, translucent areas, details of iris slightly obscured
3: Grey-white areas, no details of iris visible, size of pupil barely discernible
4: Complete corneal opacity, iris not discernible

IRIS
0: Normal
+: Any divergence from normal, congestion of iridial vessels, deepening of folds
++: Severe congestion of iridial vessels or deepening of folds. Loss of iridial reflex to light

AREA OF CORNEA OR IRIS AFFECTED
1: Less than 1/4 of area affected
2: Between 1/4 and 1/2 of area affected
3: Between 1/2 and 3/4 of area affected
4: Between 3/4 and whole area affected

CONJUNCTIVAE
Redness (palpebral and bulbar conjunctivae and nictitating membrane)
0: Vessels normal
1: Some vessels definitely injected
2: Diffuse, crimson red, individual vessels not easily discernible
3: Diffuse, beefy red

Chemosis
0: No swelling
1: Any swelling above normal
2: Obvious swelling with partial eversion of eyelids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

Discharge
0: No discharge
1: Any discharge different from normal
2: Discharge with moistening of lids and hairs just adjacent to the lids
3: Discharge with moistening of lids and considerable area round eye

TOOL USED TO ASSESS SCORE: hand torch

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 100 µL undiluted test substance
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 100 µL undiluted test substance
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Remarks on result:
other: 100 µL undiluted test substance
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Remarks:
5 days
Remarks on result:
other: 100 µL undiluted test substance
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: 100 µL 50 % in Tween 80
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 100 µL 50 % in Tween 80
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: 100 µL 50 % in Tween 80
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: 100 µL 50 % in Tween 80
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: 100 µL 10 % Tween 80
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
other: 100 µL 10 % Tween 80
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: 100 µL 10 % Tween 80
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: 100 µL 10 % Tween 80

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to the scores obtained for the undiluted substance, the substance has a low potential to be irritating to the eyes. However, it has to be considered that only one animal was dosed with undiluted substances instead of three as instructed in OECD TG 405.
Executive summary:

The potential of 3,5,5 -trimethylhexyl acetate to induce eye irritation was tested in a screening test performed according to the modified Federal Hazardous Substances Labelling Act method. Three rabbits were treated with 100 µL of a 10% dilution of the substance in Tween 80, one rabbit was treated with 100 µL of a 50% dilution in Tween 80 and one rabbit with 100 µL undiluted substance. In the eyes treated with 10% dilution, only slight superficial corneal imperfections were caused that persisted for three to five days. Conjunctivitis was also slight and persisted for two to four days. In the eye treated with 50% dilution, a loss of 1/4 or corneal epithelium was seen, with slight corneal swelling. Corneal repair was complete after 5 days and the moderate conjuntivitis with oedema also healed after 5 days. In the eye treated with undiluted substance, the cornea remained unaffected. Only slight conjunctivitis was seen which persisted for four days.

The numerical grading of the ocular lesions was equivalent to the grading suggested in OECD TG 405. The mean of the cornea, iris and chemosis scores at 24, 48 and 72 h was below 1 in all animals and the mean of the conjunctivae scores at 24, 48 and 72 h was below or equal to 1.