Reaction mass of 2-(2-(2-butoxyethoxy)ethoxy)ethanol and 3,6,9,12-tetraoxahexadecan-1-ol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study to GLP for which original study report is available.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-(2-butoxyethoxy)ethoxy)ethanol

EC Number:

205-592-6

EC Name:

2-(2-(2-butoxyethoxy)ethoxy)ethanol

Cas Number:

143-22-6

Molecular formula:

C10H22O4

IUPAC Name:

2-(2-(2-Butoxyethoxy)ethoxy)ethanol

Constituent 2

Reference substance name:

3,6,9,12-tetraoxahexadecan-1-ol

EC Number:

216-322-1

EC Name:

3,6,9,12-tetraoxahexadecan-1-ol

Cas Number:

1559-34-8

Molecular formula:

C12H26O5

IUPAC Name:

3,6,9,12-tetraoxahexadecan-1-ol

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Solvent 14
- Physical state: pale straw-colored liquid
- Lot/batch No.: S14/TK E120 AN 108278

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

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 a cage label.

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 -16 weeks old.
- Weight at study initiation: 2.46 – 2.62 kg
- Housing: Animals were individually housed in suspended metal cages.
- Diet: STANRAB SQC Rabbit Diet, Special Diets Services Ltd., Witham, Essex, U.K. ad libitum.
- Water: Ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-20°C
- Humidity: 49 – 59%
- Air changes: 15 changes per hour
- Photoperiod: 12 hour light/12 hour dark cycle.

IN-LIFE DATES: From: 13 December 1993 To: 6 January 1994

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- For the purpose of this study the test material was used as supplied.
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

One rabbit was initially treated.  A volume of 0.1 ml of the test material was instilled into the conjucntival 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 instillations, 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.

Observation period (in vivo):

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. 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”).
Additional observations were made on days 7, 14 and 21 to assess the reversibility of the ocular effects.

Number of animals or in vitro replicates:

Three.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Time point:

other: 48 hours

Score:

41

Max. score:

110

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.2

Max. score:

4

Reversibility:

not fully reversible within: 21 days.

Remarks on result:

other: No corneal opacity remaining but one animal still showing vascularisation.

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

2.1

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1.9

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

Dulling of the normal luster of the cornea was noted in all treated eyes one hour after treatment.  Areas of diffuse corneal opacity were noted in all treated eyes at the 24 hour observation with areas of diffuse to translucent corneal opacity at the 48 and 72-hour observations.  Areas of diffuse corneal opacity were noted in two treated eyes at the 7-day observation.  Vascularisation of the cornea was noted in all treated eyes at the 7-day observation and in one treated eye at the 14 and 21-day observations.

Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24, 48 and 72-hour observations.  No other iridial effects were noted.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment and at the 24 and 48-hour observations with minimal to moderate conjunctival irritation at the 72 hour and 7 day observations.  Minimal conjunctival redness was noted in one treated eye at the 14-day observation. Two treated eyes appeared normal fourteen days after treatment.

Any other information on results incl. tables

Individual total scores and group mean scores for ocular irritation.

Rabbit # and Sex	1 hour	24 hour	48 hour	72 hour	7 days
45 male	19	37	49	39	4
44 male	19	37	37	37	25
200 male	19	37	37	26	7
Group Total	57	111	123	102	36
Group Mean Score	19.0	37.0	41.0	34.0	12.0

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The test material produced a maximum group mean score of 41.0 and was classified as a MODERATE IRRITANT (CLASS 5 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified Kay and Calandra classification system. However, because of the irreversible nature of some effects, the test material was also classified as an irreversible eye irritant according to EEC labelling regulations.

Executive summary:

In a guideline (OECD 405) and GLP eye irritancy study, the substance was found to be an irreversible eye irritant. Whilst the immediate acute irritancy response was sufficient to trigger classification as a reversible eye irritant, the lesions seen were particularly persistent and vascularisation in one animal did not fully reverse during the observation period.