Oxirane, 2-ethyl-, homopolymer, ether with 1,2-ethanediol (2:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12/07/2013-19/07/2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Conducted at a GLP accredited laboratory

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oxirane, 2-ethyl-, homopolymer, ether with 1,2-ethanediol (2:1)

IUPAC Name:

Oxirane, 2-ethyl-, homopolymer, ether with 1,2-ethanediol (2:1)

Constituent 2

Reference substance name:

1-[2-(2-hydroxybutoxy)ethoxy]butan-2-ol

EC Number:

695-757-2

Cas Number:

897381-19-0

Molecular formula:

UVCB

IUPAC Name:

1-[2-(2-hydroxybutoxy)ethoxy]butan-2-ol

Test material form:

other: liquid

Details on test material:

Clear light yellow liquid. It stored at room temprature in dark.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The animals were randomly assigned to the study based upon sex, body weight and apparent good health. 3 Female rabbit were used.
Age Range: 12 weeks at start of dosing; records of dates of birth for animals used in this study are retained in the Calvert archives.
Body Weight Range: 2.8 to 3.0 kilograms at the outset (Day 1) of the study.
Animal Source: Millbrook
Experimental History: Purpose-bred and experimentally naive at the outset of the study.
Housing: Animals were individually housed in compliance with USDA Guidelines. The room in which the animals were kept was documented in the study records. No other species were kept in the same room.
Lighting: 12 hours light/12 hours dark
Room Temperature: 17-21 C degrees
Relative Humidity: 44 to 81%
Food: All animals had access to PMI Certified Hi-Fiber Rabbit Ojet #5325 as per Calvert SOP. The lot number(s) and specifications of each lot used are archived at Calvert. No contaminants were known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer records of which are maintained in the Calvert archives.
Water: Water was available ad libitum to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP's. No contaminants were known to be present in the water at levels that would be expected to interfere with the results of this study.
Acclimation: Study animals were acclimated to their housing for a minimum of 7 days prior to dosing.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eyes without treatment

Amount / concentration applied:

0.1 mL was placed in the conjuctival sac of the right eye via ocular instillation.

Duration of treatment / exposure:

Once

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 0679

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 48h

Results 2

Irritation parameter:

iris score

Basis:

animal: 0679

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: 0679

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 8 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal: 0679

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal: 0680

Time point:

24/48/72 h

Score:

0

Results 6

Irritation parameter:

iris score

Basis:

animal: 0680

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 48h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: 0680

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 0680

Time point:

24/48/72 h

Score:

1.33

Reversibility:

fully reversible within: Day6 at late hours

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal: 0681

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 48h

Results 10

Irritation parameter:

iris score

Basis:

animal: 0681

Time point:

24/48/72 h

Score:

0

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal: 0681

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal: 0681

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

No corneal, iris or conjunctival irritation was observed in the untreated eyes of the rabbits at any time point. Due to the irritation seen in the first animal (0679) at 1 hour post dose, the next two animals (0680 and 0681) were not dosed until the 24 hour scores of the first animal dosed were observed/recorded for animal welfare reasons.
Corneal irritation (opacity scores of 1-2, involving approximately one quarter to greater than three quarters of the cornea, scores of 1 and 4) was observed in the treated eyes of the animals at 1 and 24 hours post dose but resolved by 48 hours post dose. Scores of 1 for iritis were observed in two animals at one hour post dose with resolution by 24 hours post dose. One animal showed scores of 1 for iritis at 24 hours post dose with resolution by 48 hours post dose.
Conjunctival redness (scores of 1) was observed beginning at 1 hour post dose through Day 7 for the first animal dosed (0679) and through Day 6 for the last two animals dosed (0680 and 0681).
A score of 4 for chemosis was observed at one hour post dose for the first animal (0679) dosed with the chemosis decreasing to a score of one 24 hours post dose and persisting through Day 5. Chemosis (scores of 3-4) were observed beginning at 1 hour post dose with full resolution by Day 7 in the last two animals dosed (0680 and 0681). A score of 3 for discharge was observed at 1 hour for the first animal dosed (0679} with the discharge decreasing to a score of one 24 hours post dose and persisting through Day 5. Scores of 3 for discharge were observed at 1 hour post dose for the last two animals (0680 and 0681) dosed with a decrease in discharge seen by 24 hours and full resolution of discharge in both animals by Day 7. Since the first animal dosed (0679) was observed to be normal on Day 8 and the next two animals dosed (0680 and 0681) were observed to be normal on Day 7, the study was terminated.

Other effects:

No mortality was observed in the animals during the study. There were no treatment-related clinical signs noted.

Any other information on results incl. tables

Scoring: An animal exhibited a positive reaction if the test article produced at any observation one or more of the following signs: opacity of the cornea (other than a slight dulling of the normal luster), inflammation of the iris (other than a slight deepening of the rugae or a light hyperemia of the circumcorneal blood vessels) or an obvious swelling in the conjunctivae (excluding the cornea and iris) with partial eversion of the eyelids or a diffuse crimson color with individual vessels not easily discernible.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Precursor PO 206 was not an irritant to eyes, according to EEC criteria, whilst the subtance was found to fall into the GHS Category 2A-Reversible Eye Effects.

Executive summary:

The purpose of this study was to determine the potential irritant and/or corrosive effects of the test article on the eyes of rabbits.

The test article Precursor PD 206, was initially instilled into the anesthetized right eye of one male New Zealand White rabbit at a dose of 0.1 mL. Upon instillation of the test article, the eyelids were held closed app.1 second to limit loss of material. The anesthetized left eye was untreated. Following the twenty-four hour scores of the first animal, two additional animals were dosed. Both eyes of all three animals were examined and scored for ocular irritation according to the method of Draize (4) prior to dosing. 1 hour after dosing (+/-15min), at 24, 48, 72 hours (+/-1 hour) through Day 7 (0680 and 0681) and Day 8 (0679) post dose.

No corneal, iris or conjunctival irritation was observed in the untreated eyes of the rabbits at any time point. The ocular irritation detected in the treated eyes were fully reversible in Day 8. Precursor PO 206 was not an irritant to eyes, according to DSD criteria, whilst the subtance was found to fall into the CLP Category 2 - Reversible Eye Effects.