reaction products of 1,4-butanediol with 1,3-chloro-2,3-epoxypropane, esters with prop-2-enoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Version / remarks:

adopted Feb. 1987

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of butane-1,4-diol and 1-chloro-2,3-epoxypropane, esters with acrylic acid

EC Number:

701-230-0

Cas Number:

52408-42-1

Molecular formula:

C16H26O8

IUPAC Name:

Reaction products of butane-1,4-diol and 1-chloro-2,3-epoxypropane, esters with acrylic acid

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ace Animals
- Age at study initiation:8-12 weeks
- Weight at study initiation: 2.3 -2.5kg
- Housing: single in suspended cages
- Diet (e.g. ad libitum): Purina rabbit chow (diet #5321) ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12h / 12h

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1ml

Duration of treatment / exposure:

substance not washed out

Observation period (in vivo):

28days
Observations after 1h, 24h, 48h, 72h, 7days, 14days, 21days, 28days

Number of animals or in vitro replicates:

3

Details on study design:

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

SCORING SYSTEM: Draize + scoring of ocular 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, and considerable area around the eye.

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 28 days

Remarks on result:

other: pannus observed on days 7 (2 animals) and 14 (1 animal). Mean individual scores = 2 - 2 - 2

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days (2 animals), 21 days (1 animal)

Remarks on result:

other: Mean individual scores = 2 - 2 - 2.7

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 28 days (1 animal)

Remarks on result:

other: Mean individual scores = 3 - 4 - 2

Irritant / corrosive response data:

Corneal opacity, noted in 3 of 3 eyes, persisted to day 28 in one eye. Iritis, noted in 3 out of 3 eyes, cleared by day 7. Conjunctival irritation, noted in 3 out of 3 eyes, persisted to day 28 in one eye.

Other effects:

There were no abnormal physical signs noted during the study.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Due to the irreversible effects in 1 animal, the test substance is considered corrosive to the eye.

Executive summary:

Three rabbits were doses with 0.1 ml of butane-1,4-diylbis(oxy-2-hydroxypropane-3,1-diyl) bisacrylate placed into the left conjunctival sac of each rabbit. The eyes remained unwashed. The eyes were examined and scored by the Draize technique at 1 hour post dose and on days 1, 2, 3, 7, 14, 21 and 28. Body weight were recorded pretest. Corneal opacity, noted in 3 of 3 eyes, persisted to day 28 in one eye. Iritis, noted in 3 out of 3 eyes, cleared by day 7. Conjunctival irritation, noted in 3 out of 3 eyes, persisted to day 28 in one eye. There were no abnormal physical signs noted during the study. Under the conditions of this study, the test article is corrosive based on persistant corneal opacity noted through day 28.