methylethylketone peroxide trimer

Eye irritation

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

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

Results

Results 1

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

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: see above

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal: 14

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 13

Irritation parameter:

conjunctivae score

Basis:

animal: 14

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 14

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

Results 15

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

Results 16

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.