Reaction mass of 29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32 copper and hydrogen [29H,31H-phthalocyaninesulphonato(3-)-N29,N30,N31,N32]cuprate(1-), compound with dodecylamine (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 January 2015 - 16 January 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The test is described in OECD 438 and is approved by international regulatory agencies as a replacement for the identification of nonirritant, corrosives/severe irritants in the in vivo Rabbit Eye Assay (OECD 405).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

bis((9Z,26Z,35Z)-9,18,27,36,37,39,40,41-octaaza-38-cupradecacyclo[17.17.3.1¹⁰,¹⁷.1²⁸,³⁵.0²,⁷.0⁸,³⁷.0¹¹,¹⁶.0²⁰,²⁵.0²⁶,³⁹.0²⁹,³⁴]hentetraconta-1,3,5,7,9,11,13,15,17(41),18,20,22,24,26,28(40),29,31,33,35-nonadecaene); dodecan-1-amine; sulfonylideneoxidane

EC Number:

908-084-9

IUPAC Name:

bis((9Z,26Z,35Z)-9,18,27,36,37,39,40,41-octaaza-38-cupradecacyclo[17.17.3.1¹⁰,¹⁷.1²⁸,³⁵.0²,⁷.0⁸,³⁷.0¹¹,¹⁶.0²⁰,²⁵.0²⁶,³⁹.0²⁹,³⁴]hentetraconta-1,3,5,7,9,11,13,15,17(41),18,20,22,24,26,28(40),29,31,33,35-nonadecaene); dodecan-1-amine; sulfonylideneoxidane

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch number: 141016
- Appearance: Blue powder
- Purity: ≥85.5%
- Expiry date: 19 Nov 2018
- Storage conditions: Controlled Room Temperature (15-25oC, below 70 RH%)

Test animals / tissue source

Species:

chicken

Strain:

other: ROSS 308

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: TARAVIS KFT. (Address: 9600 Sárvár, Rábasömjéni út. 129., Hungary)

- Number of animals: 7 treatements (3 test item, 3 positive and 1 negative control)

- Characteristics of donor animals: age - : approx. 7 weeks old

- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): heads transported to the lab at ambient temperature at the earliest convenience. The heads were inspected for appropriate quality and wrapped with tissue paper moistened with saline, then placed in a plastic box which was closed. The heads were received at the lab. and processed within approximately 2 hours of collection.

- Time interval prior to initiating testing: acclimatization for approximately 45 to 60 minutes

- indication of any existing defects or lesions in ocular tissue samples: If the cornea was in good condition, the eyeball was carefully removed from the orbit for testing. Eyes with a high baseline fluorescein staining (i.e., > 0.5) or corneal opacity score (i.e., > 0.5) were rejected. any eye with cornea thickness deviating more than 10 % from the mean value for all eyes, or eyes that showed any other signs of damage, were rejected and replaced.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30mg

Duration of treatment / exposure:

10s

Observation period (in vivo):

Test eyes were evaluated at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse

Number of animals or in vitro replicates:

7 (3 test item treated, 3 positive control and 1 negative control)

Details on study design:

SELECTION AND PREPARATION OF ISOLATED EYES

NUMBER OF REPLICATES

NEGATIVE CONTROL USED
30 μL of physiological saline (Salsol solution, 0.9% (w/v) NaCl solution)

POSITIVE CONTROL USED
30 mg Imidazole

APPLICATION DOSE AND EXPOSURE TIME
10s

OBSERVATION PERIOD
evaluated at approximately 30, 75, 120, 180 and 240 minutes

REMOVAL OF TEST SUBSTANCE
- Volume and washing procedure after exposure period: 20 mL physiological saline at ambient temperature
- Indicate any deviation from test procedure in the Guideline

METHODS FOR MEASURED ENDPOINTS:
Corneal thickness and corneal opacity were measured at all time points. Fluorescein retention was measured on two occasions, at base line (t=0) and approximately 30 minutes after the post-treatment rinse. Haag-Streit Bern 900 slit-lamp microscope was used for the measurements.

Results and discussion

In vitro

Results

Results 1

Irritation parameter:

percent corneal swelling

Run / experiment:

mean at up to 75 min

Value:

14.1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 2

Irritation parameter:

percent corneal swelling

Run / experiment:

mean at up to 240min

Value:

27.2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 3

Irritation parameter:

cornea opacity score

Run / experiment:

mean

Value:

2.33

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Results 4

Irritation parameter:

fluorescein retention score

Run / experiment:

mean

Value:

2.33

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Interpretation of results:

other:

Conclusions:

Based on this in vitro eye irritation in the isolated chicken eyes test with test item, the test item is not classified as a severe irritant and not classified as nonirritant. It is concluded that an in vivo study is required for proper classification.