2,2-bis(allyloxymethyl)butan-1-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 to 9 July 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary GLP guideline-compliant study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according 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:

2,2-bis(allyloxymethyl)butan-1-ol

EC Number:

211-661-1

EC Name:

2,2-bis(allyloxymethyl)butan-1-ol

Cas Number:

682-09-7

Molecular formula:

C12H22O3

IUPAC Name:

2,2-bis[(prop-2-en-1-yloxy)methyl]butan-1-ol

Details on test material:

TMPDE. The trade name of the substance was NEOALLYL T-20, lot no. 30341, received on 7 June 1993. The substance was a mixture of Trimethylolpropane Diallyl Ether (87.4%), Trimethylolpropane Monoallyl Ether (6.9%), and Trimethyolpropane Triallyl Ether (5.7%). The purity was given as 100%. The substance was described as a colourless liquid, and was stored in a metal canister at 4°C in the dark.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The animals were three New Zealand White rabbits supplied by David Percival Ltd., Cheshire, UK. The animals weighed 2.20 to 2.53 kg and were 12-16 weeks old at the start of the study, they were acclimatised for a minimum of 5 days. Individuals were identified by unique numbers written on the inner surface of the ear with an indelible black marker.
The rabbits were hosued individually in suspended metal cages. Free access to mains drinking water and food (RABMA Rabbit Diet, SDS Ltd., UK) was allowed throughout the study. The animal room was maintained at a temperature of 20-23°C and relative humidity of 59-65%. There were approximately 15 air changes per hour, and lighting was controlled to give 12 hours light and 12 hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 ml was instilled into the right eye

Duration of treatment / exposure:

Single administration

Observation period (in vivo):

72 hours following treatment

Number of animals or in vitro replicates:

3 females

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, 0.1 ml test substance was instilled into the conjunctival sac of the right eye. The upper and lower lids were held together for about 1 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, 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, one drop of local anaesthetic ("Ophthaine") was instilled into both eyes of these animals 1-2 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 from Draize (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics". Examination of the eye was facilitated by the use of 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 and 72 hours

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Residual test material was noted around the treated eye of all animals one hour after treatment.
Diffuse corneal opacity was noted in two treated eyes at the 24 and 48 hour observations. No other corneal effects were noted. Iridial effects were noted. Minimal conjunctival irritation was noted in all treated eyes one hour after treatment with minimal to moderate conjunctival irritation at the 24 hour observation. Minimal conjunctival redness was noted in two treated eyes at the 48 hour observation.
Treated eyes appeared normal 48 or 72 hours after treatment. Individual animal data are presented in Table 1.

Other effects:

No other effects reported.

Any other information on results incl. tables

Table 1. Individual ocular irritation scores

Rabbit Number & Sex (Bodyweight Kg)	Time After Treatment	Corneal Opacity	Iridial Inflammation	Conjunctival Redness	Conjuncitval Chemosis
95 Female (2.20)	24 hours	0	0	1	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Total		0	0	1	0
Mean		0.0	0.0	0.3	0.0
96 Female (2.53)	24 hours	1	1	2	1
	48 hours	1	0	1	0
	72 hours	0	0	0	0
Total		2	1	3	1
Mean		0.7	0.3	1.0	0.3
99 Female (2.20)	24 hours	1	1	2	2
	48 hours	1	0	1	0
	72 hours	0	0	0	0
Total		2	1	3	2
Mean		0.7	0.3	1.0	0.7

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was found to be a mild eye irritant under the conditions of this study, the severity of the effects does not trigger classification of the substance as an eye irritant under CLP Regulation (EC) No 1272/2008.

Executive summary:

The eye irritant potential of TMPDE (NEOALLYL T-20) was assessed in three New Zealand White rabbits according to OECD method 405. A single instillation of the test material to the non-irrigated eye produced diffuse corneal opacity, iridial inflammation and minimal to moderate conjunctival irritation. Treated eyes appeared normal 72 hours after treatment and the severity of the effects does not trigger classification of the substance as an eye irritant under CLP Regulation (EC) No 1272/2008.