1,1,4,4-tetramethylbutane-1,4-diyl bis(2-ethylperoxyhexanoate)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 October 1992 - 6 November 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is performed according to OECD guidelines and GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,1,4,4-tetramethylbutane-1,4-diyl bis(2-ethylperoxyhexanoate)

EC Number:

235-935-5

EC Name:

1,1,4,4-tetramethylbutane-1,4-diyl bis(2-ethylperoxyhexanoate)

Cas Number:

13052-09-0

Molecular formula:

C24H46O6

IUPAC Name:

5-[(2-ethylhexanoyl)peroxy]-2,5-dimethylhexan-2-yl 2-ethylhexaneperoxoate

Details on test material:

Name: Trigonox 141
CAS No.: 13052-09-0

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England.
- Age at study initiation: The rabbits were approximately three and a half to four months old.
- Weight at study initiation: 3.12 - 3.35 kg
- Housing:individually in suspended stainless steel cages mounted in mobile batteries (Modular Systems and Development Company Limited, London, England).
- Diet (e.g. ad libitum): ad libitum, standard pelleted rabbit diet, (S.Q.C. Rabbit Diet - Special Diets Services Limited, Witham, Essex, England).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20
- Humidity (%): 49-58
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 5 October 1992 - 6 November 1992

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): as such

Duration of treatment / exposure:

single instillation in one eye

Observation period (in vivo):

The behaviour of each rabbit was observed for several minutes immediately following instillation of the test material to allow assessment of the initial pain response. The animals were returned to their cages and checked at least twice during the first hour after dosing, at regular intervals throughout the day and daily to ensure that the treated eye was not subject to infection or causing distress. Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours after treatment.

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM:
Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of Cornea Involved
1 One quarter (or less) but not zero
2 Greater than one quarter but less than half
3 Greater than half but less than three quarters
4 Greater than three quarters, up to whole area

Iris
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

Discharge
0 No discharge
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs just adjacent to lids
3 Discharge with moistening of the lids and hairs a considerable area around the eye


TOOL USED TO ASSESS SCORE: ophthalmoscope

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Conjunctival effects were observed after 1 hour.

Irritant / corrosive response data:

Injection of the conjunctival blood vessels was observed in all rabbits during the first hour following instillation Trigonox 141. Very slight discharge and very slight chemosis were also observed in two of these rabbits at this time. The test eyes of all rabbits were overtly normal at the 24 hour examination.
Instillation of the test material caused practically no initial pain response.

Any other information on results incl. tables

Rabbit No and sex	Region of the eye		Hours after instillation				Average 24-48-72 hours
			1	24	48	72
1-m	Cornea	Degree of opacity	0	0	0	0	0
		Area	0	0	0	0	0
	Iris		0	0	0	0	0
	Conjunctivae	Redness	1	0	0	0	0
		Chemosis	0	0	0	0	0
		Discharge	0	0	0	0	0
2-m	Cornea	Degree of opacity	0	0	0	0	0
		Area	0	0	0	0	0
	Iris		0	0	0	0	0
	Conjunctivae	Redness	1	0	0	0	0
		Chemosis	1	0	0	0	0
		Discharge	1	0	0	0	0
3-m	Cornea	Degree of opacity	0	0	0	0	0
		Area	0	0	0	0	0
	Iris		0	0	0	0	0
	Conjunctivae	Redness	1	0	0	0	0
		Chemosis	1	0	0	0	0
		Discharge	1	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The mean values for ocular lesions recorded 24, 48 and 72 hours after treatment did not equal or exceed the CLP C&L limits.

Executive summary:

The potential to cause damage to the conjunctiva, iris or cornea was assessed in three New Zealand White rabbits, each subjected to a single ocular instillation of 0.1 ml of the test material. Ocular reactions were assessed 1, 24, 48 and 72 hours after treatment. Injection of the conjunctival blood vessels was observed in all rabbits during the first hour following instillation. Very slight discharge and very slight chemosis were also observed in two of these rabbits at this time. The test eyes of all rabbits were overtly normal at the 24 hour examination. Instillation of the test material caused practically no initial pain response.