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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
Study period:
from 2006-03-29 to 2006-06-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
April 24, 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
2004/73/EC
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sokalan PG B62;

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Age at day 0: 2 – 3 months.
Body weight range at day 0: 2.38 kg – 2.57 kg.
The animals were housed (single housing) in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 – 24°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Day / night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Stainless steel wire mesh cages with grating, floor area: 3000 cm²
Feeding: Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day).
Drinking water: ad libitum.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: left untreated eye used as negative control
Amount / concentration applied:
Undiluted (the solid test substance was comminuted immediately before application with mortar and pestle).
Amount applied: 0.1 ml (about 26 mg of the comminuted test substance)
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Comment: rinsed after 1 h.
The test substance was applied in a single dose to the conjunctival sac of the right eyelid. About 1 hour after application the treated eye of the animals was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
OBSERVATIONS and EVALUATION:
Just before application of the test substance and after the last reading the body weight was determined. Approx. 1, 24, 48 and 72 hours after application individual ocular examinations were made. Daylight tubes were used as illumination for reading. Necropsies were not performed at the end of the study. The evaluation is based on the criteria of the Commission Directive 67/548/EEC and theOECD Harmonized Integrated Classification System.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-72h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-72h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-72h
Score:
0
Max. score:
3
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.4
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-72h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24-72h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.1
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Moderate conjunctival redness (grade 2) was observed in all animals 1 h after application and persisted in one animal up to 24 h. Moderate conjunctival redness decreased to slight (grade 1) after 24 h or 48 h in one animal, each. Slight conjunctival chemosis (grade 1) was noted in a single animal at the 1 h reading and persisted up to 24 h. Slight discharge (grade 1) was observed in all animals 1 hour after application. In addition, injected scleral vessels in a circumscribed area were noted in a single animal at the 1 h reading only. The occular reactions were reversible within 24 h, 48 h and 72 h after application in one animal, each. Mean scores calculated for each animal over 24, 48 and 72 h were 0.0 for corneal opacity and for iris lesions,1.0/0.3/0.0 for redness of the conjunctiva and 0.3/0.0/0.0 for chemosis.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an in vivo eye irritation study in rabbits 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate was shown to be not irritation to the eye.
Executive summary:

In an in vivo eye irritation test according to OECD 405 (GLP), an amount of 0.1 mL bulk volume (about 26 mg) of the test substance (purity: 93.0 weight-%) was applied to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About 1 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application.

Slight or moderate conjunctival redness, slight conjunctival chemosis and slight discharge were observed in the animals during the observation period. In addition, injected scleral vessels in a circumscribed area were noted in a single animal after 1 hour, only. The ocular reactions were reversible. One animal had recovered by 24 hours (all scores "0" for cornea, iris and conjunctiva). A second animal had recovered by 48 hours, and the third by 72 hours. Mean scores calculated for each animal over 24, 48 and 72 h were 0.0 for corneal opacity and for iris lesions,1.0/0.3/0.0 for redness of the conjunctiva and 0.3/0.0/0.0 for chemosis.

Considering the described ocular reactions as well as the average score for irritation, 1-((2-Butyloctyloxymethyl)-2-(3,4-dihydro-isoquinolinium-2-yl)ethyl)sulfate does not show an eye irritation potential under the test conditions chosen.