5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, polymer with 1,2-propanediol

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:

other: Guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1,2-propanediol

EC Number:

613-407-9

Cas Number:

63948-88-9

Molecular formula:

not applicable

IUPAC Name:

5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1,2-propanediol

Test material form:

solid: particulate/powder

Details on test material:

Product name: ZAN 573, 100% purity (UVCB)
Chemical name: 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-,
polymer with 1,2-propanediol (85%) and Trimellitic anhydride (15%)
CAS numbers : 63948-88-9: 85% and 552-30-7: 15%
Batch number: 130072591
Appearance: Yellow to brown solid, coarse powder
Purity: treated as 100% (for more details see above)
Manufacturing date: 24 January 2014
Expiry date: 24 January 2016
Storage conditions: Controlled room temperature (15-25°C, below 70 RH%)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS, New Zealand White rabbits, male
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: 14-15 weeks
- Weight at study initiation: 3556 g and 3939 g
- Housing: metal wire rabbit cages
- Diet (e.g. ad libitum): Cargill Takarmány Zrt., H-5300 Karcag, Madarasi út, Hungary, ad libitum.
- Water (e.g. ad libitum): municipal tap water, ad libitum.
- Acclimation period: 34 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.4 – 21.2
- Humidity (%): 30-75
- Air changes (per hr):15/20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Test system

Controls:

no

Amount / concentration applied:

0.1 g of the powdered test item

Observation period (in vivo):

1, 24, 48, 72 hours and 1 week

Number of animals or in vitro replicates:

3

Details on study design:

The test substance was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for at least one second in order to prevent loss of the material. The untreated contralateral eye was served as the control. The treated eye was rinsed with physiological saline solution at the first observation time point in all animals at one hour after the application of test item as the irritation scores were greater than 1 and residual test item was noted on the eye.

The eyes were examined at 1, 24, 48 and 72 hours after treatment in all animals and 1 week after the treatment in one animal. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill-health during the study were recorded. At the end of the observation period, the animal was sacrificed. All rabbits were examined for distress at least twice daily, with observations at least 6 hours apart. Clinical observations or signs of ill-health were recorded.

The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (02 October 2012).

Sixty minutes (60 ±10 min) prior to test substance application, a systemic opiate analgesic was administered subcutaneous injection. Repeat injections were given on the first day as appropriate to maintain an adequate level of analgesia. Five minutes (5 ±1.5 min) prior to test substance application, a topical ocular anaesthetic was applied to each eye (including the control eye to ensure direct comparison of any ocular observations). Eight hours after test substance application, a systemic opiate analgesic and a nonsteroidal anti-inflammatory drug were administered by subcutaneous injection. The systemic opiate analgesic was again injected ~12 hours after the post-treatment analgesic and then every 12 hours, and NSAID injected every ~24 hours, until eye scores were zero. Systemic opiate analgesic: Buprenorphine 0.01 mg/kg. Topical ocular anaesthetic: Humacain (oxybuprocaine) one-two drops per eye. Nonsteroidal anti-inflammatory drug: Meloxicam 0.5 mg/kg.

Results were presented and interpreted according to Regulation (EC) No 1272/2008, and UN Globally Harmonised System of Classification and Labelling of Chemicals (Rev. 5) (2013), as follows:

Irreversible effects on the eye/serious damage to eyes (Category 1):
These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight.

Category for irreversible eye effects
If, when applied to the eye of an animal, a substance produces:
— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/or
— at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 3 and/or iritis > 1.5, calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

Reversible effects on the eye/irritating to eyes (Category 2):

Category for reversible eye effects
If, when applied to the eye of an animal, a substance produces:
— at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 1 and/or, iritis ≥ 1, and/or, conjunctival redness ≥ 2 and/or, conjunctival oedema (chemosis) ≥ 2.
— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

According to the UN GHS (Rev. 5) (2013), within this category an eye irritant is considered mildly irritating to eyes (Category 2B) when the effects listed above are fully reversible within 7 days of observation.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The body weights of the animal were considered to be within the normal range of variability.
The animal individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:
chemosis : 0.00, 0.00, 1.00
discharge : 0.33, 0.67, 2.67
redness : 1.00, 1.00, 2.00
cornea opacity : 0.00, 0.33, 0.33
iris : 0.00, 0.00, 0.00
One of 3 animals displayed irritation effects of a score of 2 in any of the above criteria.

Other effects:

During the study, the control eye of each animal was symptom-free.
There were no clinical sign of systemic toxicity observed in the animals during the study and no mortality occurred.
Initial Pain Reaction (IPR) or any Pain Reaction (PR) was not observed during the experimental period.
Two animals were euthanized after the 72 hours observation and one animal after the 1 week observation.

Any other information on results incl. tables

TABLE 2: MEAN VALUES OF EYEIRRITATION

                                           (24, 48, 72 hours reading)

Animal Number	Sex	Cornea Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
01820	male	0.00	0.00	1.00	0.00	0.33
01823	male	0.33	0.00	1.00	0.00	0.67
01814	male	0.33	0.00	2.00	1.00	2.67

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

One of 3 animals met one criterion of eye irritation Criteria used for interpretation of results: EU

Conclusions:

The test item ZAN 573, applied to rabbit eye mucosa, caused conjunctival and corneal irritant effects in all three animals at one hour after application. The effects were fully reversible within 1 week.