Mixture of reaction products of substituted copper phthalocyanine, hydrogenated resin acids, alkaline earth metal chlorides, and copper phthalocyanine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 July 2008 - 29 July 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was performed according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(2002)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2004)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

(1998)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

B508

IUPAC Name:

B508

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material: B508
- Physical state: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan France SARL, Gannat, France.
- Age at study initiation: at least 6 weeks
- Weight at study initiation: 2092 - 2324 g
- Housing: Individually in labeled cages with perforated floors
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay was provided at least three times a week.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: 20-28 days before start of treatment under laboratory conditions.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0 - 21.9
- Humidity (%): 45 - 74
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as a control

Amount / concentration applied:

TEST MATERIAL
- pH of 1% aqueous solution: 7.0-7.8
- Amount(s) applied (volume or weight with unit): 71.2 mg (range 71.0 – 71.4 mg) of the test substance (a volume of approximately 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 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 2 weeks later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Animals were treated by instillation of, on average, 71.2 mg (range 71.0 – 71.4 mg) 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 (Merck, Darmstadt, Germany) 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.

REMOVAL OF TEST SUBSTANCE
-Washing (if done): yes, with tepid water

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and at termination (animal 886) or one day after the final observation (animals 898 and 899).
- Necropsy: No data available
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 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:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2 and #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

animal #1, #2 and #3

Time point:

other: 24, 48 and 72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2 and #3

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Instillation of the test substance into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae.
The corneal injury consisted of opacity (maximum observed grade 1) and epithelial damage (10 or 25% of the corneal area). The corneal injury resolved within 72 hours in all animals.
Iridial irritation grade 1 was observed in one animal 24 hours post-treatment.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all animals.
There was no evidence of ocular corrosion.

Other effects:

Remnants of the test substance were present in the eye until 72 hours post-treatment.
Blue staining of the fur on the head and paws, caused by the test substance, was noted throughout the observation period.
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:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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

Executive summary:

B508 was instilled into one eye of three rabbits, according to OECD 405 test guideline and GLP principles. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Instillation of B508 resulted in effects on the cornea, iris and conjunctivae that resolved within 7 days and did not trigger classification according to EC regulation 1272/2008.