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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD protocols and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Heptan-2-one
EC Number:
203-767-1
EC Name:
Heptan-2-one
Cas Number:
110-43-0
Molecular formula:
C7H14O
IUPAC Name:
heptan-2-one
Constituent 2
Reference substance name:
Methyl n-Amyl Ketone
IUPAC Name:
Methyl n-Amyl Ketone
Details on test material:
Sponsor's identification Methyl n-Amyl Ketone
Description pale yellow liquid
Batch number TD-9024390
Purity 99.63%
Date received 01 November 2010
Expiry date 01 November 2011
Storage conditions room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:


Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories U.K. Ltd., Loughborough, UK. At the start of the study the animals weighed 2.20 to 2.53 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930 Teklad Global Rabbit diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ml of the undiluted test article was applied to each animal.
Duration of treatment / exposure:
The duration of the study was 72 hours. Eyes were not washed from the time of test article application.
Observation period (in vivo):
72 Hours
Number of animals or in vitro replicates:
Three animals were used, one as an initial screen and two more once no overt toxicity was identified in the first animal.
Details on study design:


Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used. Initially, a single rabbit was treated. A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. In order to minimise pain on application of the test item, one drop of local anaesthetic (Tetracaine hydrochloride 0.5%, Bausch & Lomb, Surrey, UK) was instilled into both eyes of these animals 1 to 2 minutes before treatment. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49). Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.Any clinical signs of toxicity, if present, were also recorded.Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.66
Reversibility:
fully reversible
Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes one hour after
treatment. Moderate conjunctival irritation persisted in one treated
eye with minimal conjunctival irritation noted in two treated eyes at
the 24-Hour observation. Minimal conjunctival irritation was noted
in two treated eyes at the 48-Hour observation.

One treated eye appeared normal at the 48-Hour observation and two treated
eyes appeared normal at the 72-Hour observation.

Other effects:

All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Individual Total Scores and Group Mean Scores for Ocular Irritation
Rabbit Number and Sex Individual Total Scores At:
1 Hour 24 Hours 48 Hours 72 Hours
69917 Male 12 4 0 0
69969 Male 12 10 4 0
69970 Male 12 4 2 0
Group Total 36 18 6 0
Group Mean Score 12.0 6.0 2.0 0.0

 Individual Scores and Individual Total Scores for Ocular Irritation
Rabbit Number and Sex 69917 Male 69969 Male 69970 Male
IPR = 3 IPR = 0+ IPR = 0+
Time After Treatment 1
Hour
24
Hours
48
Hours
72
Hours
1
Hour
24
Hours
48
Hours
72
Hours
1
Hour
24
Hours
48
Hours
72
Hours
CORNEA
E = Degree of Opacity
F =Area of Cornea Involved
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Score (E x F) x 5 0 0 0 0 0 0 0 0 0 0 0 0
IRIS
D
0 0 0 0 0 0 0 0 0 0 0 0
Score (D x 5) 0 0 0 0 0 0 0 0 0 0 0 0
CONJUNCTIVAE
A= Redness
B =Chemosis
C = Discharge
2
2
2
1
1
0
0
0
0
0
0
0
2
2
2
2
2
1
1
1
0
0
0
0
2
2
2
1
1
0
1
0
0
0
0
0
Score (A + B + C) x 2 12 4 0 0 12 10 4 0 12 4 2 0
Total Score 12 4 0 0 12 10 4 0 12 4 2 0

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following: OECD Guidelines for the Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 April 2002) and Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008. A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 48 -hour observation and two treated eyes appeared normal at the 72 -hour observation. The test item produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.