Furan-2,5-dicarboxylic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 January, 2013 - 12 February, 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Version / remarks:

(2012)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

(1998)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Furan-2,5-dicarboxylic acid

EC Number:

221-800-8

EC Name:

Furan-2,5-dicarboxylic acid

Cas Number:

3238-40-2

Molecular formula:

C6H4O5

IUPAC Name:

furan-2,5-dicarboxylic acid

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): FDCA
- Physical state: White to off-white crystalline powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: Animals used withihn the study were at least 6 weeks old (actual 9 weeks old)
- Weight at study initiation: Body weights were at least 1.0 kg (actual 2806 - 2808 g)
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amounts applied: average 51.4 mg (range: 50.8 mg – 51.7 mg, approx. 0.1 mL)

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 and 14 days after instillation of the test substance.

Number of animals or in vitro replicates:

3 males

Details on study design:

STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 15 Days later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Both eyes were topically anaesthetized using a local anaesthetic. Approximately 10 minutes prior to treatment, 1 drop was applied to the eyes. No routine pretreatment with a systemic analgesic was done. The subcutaneous injection was
considered to cause unwanted additional distress, since in the majority of cases instillation of test materials does not cause much distress in the topically anesthetized eye. No post-treatment with systemic analgesics were needed.
Animals were treated by instillation of the test substance (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently
pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. This procedure was repeated to assess recovery. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20%.

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

OBSERVATIONS (beschrijf beperkt)
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 and 14 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded. The irritation was assessed according to OECD 405.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Slight dulling of the normal luster of the cornea, reversible within 72 hours.

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Slight dulling of the normal luster of the cornea, reversible within 48 hours.

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Slight dulling of the normal luster of the cornea, reversible within 48 hours.

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Instillation of approximately 51 mg into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae.
The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 25, 10 or 10 % of the corneal area). Slight dulling of the normal luster of the cornea was noted up to 48 hours after exposure in all animals. The corneal injury resolved within 72 hours in all animals. Iridial irritation grade 1 was observed after 24 hours and had resolved therafter. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days in all animals.
There was no evidence of ocular corrosion.

Other effects:

No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

According to Regulation (EC) No 1272/2008

Conclusions:

In an eye irritation study with rabbits, performed according to OECD 405 test guidelines and GLP principles, irritation was observed.

Executive summary:

FDCA was tested in an acute eye irritation/corrosion study in 3 male rabbits, performed according to OECD 405 test guidelines and GLP principles.

Instillation of the test substance resulted in effects on the cornea, iris and conjunctivae.

The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 25, 10 or 10 % of the corneal area). Slight dulling of the normal luster of the cornea was noted up to 48 hours after exposure in all animals. The corneal injury resolved within 72 hours in all animals. Iridial irritation grade 1 was observed after 24 hours and had resolved thereafter. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 14 days in all animals.

There was no evidence of ocular corrosion. No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality

occurred.

Based on these results, the test substance should be classified as Irritating to eyes (Category 2) and labeled as H319: Causes serious eye irritation, according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.