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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:
May 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
429-320-2
EC Name:
-
Cas Number:
24748-23-0
Molecular formula:
C12H24O6
IUPAC Name:
3,6,9-triethyl-3,6,9-trimethyl-1,2,4,5,7,8-hexaoxonane
Constituent 2
Reference substance name:
Initiator D-129
IUPAC Name:
Initiator D-129
Details on test material:
Nature of substance: liquid
Batch no.: 1400-005
Storage: at ca. 4 degr C.
42 percent peroxide in mineral spirits

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White rabbits, supplied by David Percival Ltd, Moston,
Sandbach, Cheshire, UK, were used. At the start of the study the animals
weighed 2.64 to 2.97 kg and were twelve to sixteen weeks old. After a
minimum acclimatisation period of 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 metal cages. Free access
to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets
Services Ltd, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 17 to 20' C and relative
humidity of 46 to 65%. The rate of air exchange was approximately fifteen
changes per hour and the lighting was controlled by a time switch to give
twelve hours continuous light and twelve hours darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL
Duration of treatment / exposure:
single application into the conjunctival sac of one eye
Observation period (in vivo):
1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3
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. Animals shOWing
evidence of ocular lesions were rejected and replaced.
One rabbit was initially treated. A volume of 0.1 ml of the test material was
instilled 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 instillation, to prevent loss of
the test material, and then released. The left eye remained untreated and was
used for control purposes. Immediately after administration of the test material,
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 instillation
of the test material, one drop of local anaesthetic ("Ophthaine", 0.5%
proxymetacaine hydrochloride, E R Squibb & Sons Limited, Hounslow,
Middlesex, 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 I, (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.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable as no corneal effects were seen
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
other: see above
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0.22
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable as no chemosis was seen
Irritation parameter:
cornea opacity score
Basis:
animal: 129
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable as score is 0
Remarks on result:
other: Score 0 after 1 hr
Irritation parameter:
cornea opacity score
Basis:
animal: 14
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable as score is 0
Remarks on result:
other: Score - after 1 hr
Irritation parameter:
cornea opacity score
Basis:
animal: 20
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable as score is 0
Remarks on result:
other: Score 0 after 1 hr
Irritation parameter:
iris score
Basis:
animal: 129
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable as score is 0
Remarks on result:
other: Score 0 after 1 hr
Irritation parameter:
iris score
Basis:
animal: 14
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable as score is 0
Remarks on result:
other: Score 0 after 1 hr
Irritation parameter:
conjunctivae score
Basis:
animal: 129
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Score 1 after 1 hr
Irritation parameter:
conjunctivae score
Basis:
animal: 14
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Score 2 after 1 hr
Irritation parameter:
conjunctivae score
Basis:
animal: 14
Time point:
48 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal: 14
Time point:
72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: 129
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable as score is 0
Remarks on result:
other: Score 0 after 1 hr
Irritation parameter:
chemosis score
Basis:
animal: 14
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: Score 1 after 1 hr
Irritation parameter:
chemosis score
Basis:
animal: 20
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hr
Remarks on result:
other: Score 1 after 1 hr
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 2 days
Other effects:
None

Any other information on results incl. tables

Summary of ocular lesions

 

Anim.

No.

Effect

Hours

Days after application

Mean

score cornea

Days

1/2/3

Mean score iritis

Days 1/2/3

 

Mean score redness Days 1/2/3

Mean score chemosis Days 1/2/3

1

1

2

3

7

21

129

Cornea*

Iris

Redness

Chemosis

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

-

-

-

-

-

-

-

-

0

 

0

 

 

0

 

 

 

0

14

Cornea*

Iris

Redness

Chemosis

0

0

2

1

0

0

1

0

0

0

0

0

0

0

0

0

-

-

-

-

-

-

-

-

0

 

0

 

 

0.33

 

 

 

0

20

Cornea*

Iris

Redness

Chemosis

0

0

2

1

0

0

1

0

0

0

0

0

0

0

0

0

-

-

-

-

-

-

-

-

0

 

0

 

 

0.33

 

 

 

0

Mean all anim.

 

 

 

 

 

 

 

 

0

 

0

 

0.22

 

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Because very slight eye irritation was seen which fully disappeared within 2 days, no classification is needed.

The test substance would not be classified as an eye irritant in accordance with the criteria for classification in accordance with Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures Version 3.0 November 2012.

Executive summary:

The study was performed to assess the irritancy potential of the test material following a single instillation to the rabbit eye (Safepharm Standard Method Number 560.01). The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method 85 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

No corneal or iridial effects were noted during the study. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation in two treated eyes one hour after treatment. Minimal conjunctival redness was noted in two treated eyes at the 24-hour observation. Treated eyes appeared normal at the 24 or 48-hour observations.

The test substance would not be classified as an eye irritant in accordance with the criteria for classification in accordance with Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures Version 3.0 November 2012.