2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.03,19.05,17.06,14.07,12.023,25.024,32.025,30]hexatriaconta-1(36),2,5,7,9,11,14,16,18,20,23,25,27,29,32,34-hexadecaene

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:

guideline study

Remarks:

Study meets the requirements of OECD Guideline 405 and EU Method B.5 (84/449/EEC)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

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)

Version / remarks:

84/449/EEC

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.0³,¹⁹.0⁵,¹⁷.0⁶,¹⁴.0⁷,¹².0²³,³⁵.0²⁴,³².0²⁵,³⁰]hexatriaconta-1(36),2,5,7(12),8,10,14,16,18,20,23(35),24(32),25,27,29,33-hexadecaene

EC Number:

606-790-9

Cas Number:

215247-95-3

Molecular formula:

C34H22Cl2N4O2

IUPAC Name:

2,20-dichloro-13,31-diethyl-4,22-dioxa-13,18,31,36-tetraazanonacyclo[19.15.0.0³,¹⁹.0⁵,¹⁷.0⁶,¹⁴.0⁷,¹².0²³,³⁵.0²⁴,³².0²⁵,³⁰]hexatriaconta-1(36),2,5,7(12),8,10,14,16,18,20,23(35),24(32),25,27,29,33-hexadecaene

Test material form:

solid: nanoform

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Animal specifics: Hoechst AG, conventional breed
- Source: Hoechst AG, Kastengrund
- Age at study initiation: 3 months to 5 months
- Weight at study initiation: 2.2 kg to 3.9 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls
- Diet (e.g. ad libitum): standard laboratory diet (Albtromin 2123) ad libitum, appr. 15 g hay daily
- Water (e.g. ad libitum): deionized chlorinated water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

One administration 24 hours

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

Application of the substance to the conjunctival sac of the left eye of each animal, the right eyes served as control respectively

REMOVAL OF TEST SUBSTANCE
- Washing: Washing with physiological saline at approx. 37 °C 24 h after administration and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution (24, 48 and 72 h after administration) took place
- Time after start of exposure: see above

TOOL USED TO ASSESS SCORE: 0.01 % solution of fluorescein sodium, under UV light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since on effects occured

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effects occured

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: grade 1 chemosis was observed in all animals at 1 hour and was fully reversible within 24 hours

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of three animals

Time point:

other: after 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

The score refers to redness of conjunctiva, which was evident in all animals 1 h after treatment (score 2 in all 3 animals). The value of 0.3 is the mean (of the three assessments at 24, 48 and 72 h) for all animals combined as well as for each individual animal. At 48 and 72 h, this score was 0 in all animals. Other parameters examined (opacity of cornea, iris, chemosis of conjunctiva) showed scores of 0 at all time points.

Other effects:

Blue staining of eye discharge was observed at 1 hour after application.

Any other information on results incl. tables

Results table:

Animal	Evaluation interval(after application)	Opacity ofcornea	Redness ofconjunctiva	Chemosis ofconjunctiva	Iris	Violet eyedischarge	Fluoresceinestaining
# 1	1 hour	0	2	1	0	x
# 2		0	2	1	0	x
# 3		0	2	1	0	x
# 1	24 hours	0	1	0	0		0
# 2		0	1	0	0		0
# 3		0	1	0	0		0
# 1	48 hours	0	0	0	0
# 2		0	0	0	0
# 3		0	0	0	0
# 1	72 hours	0	0	0	0		0
# 2		0	0	0	0		0
# 3		0	0	0	0		0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

67/548/EEC: Eye irritation: no classification warranted
1272/2008/EC: Eye irritation: no classification warranted

In a OECD guideline and GLP compliant primary eye irritation test in rabbits, Hostaperm-Violett RL spez. (Pigment Violet 23) caused grade 1 chemosis after one hour and conjunctival reddening grade 2 after 1 hours and grade 1 after 24 hours. No effects were observed for these and other parameters at the other reading times up to 72 hours. Therefore, Hostaperm-Violett RL spez. (Pigment Violet 23) can be regarded as not eye irritating.

Executive summary:

A study with the test item according to OECD Guideline 405 and EU Method B.5 was performed to investigate the irritation potential to the rabbit eye.

One and 24 hours after treatment the conjunctivae of the animals showed definitely injected blood vessels up to a diffuse crimson red colour. Additionally, a very slight swelling and slight from substance coloured eye discharge were observed in the animals one hour after treatment. 48 hours after treatment all signs of irritation were reversible.

Testing of Pigment Violet for primary eye irritation in the rabbit showed that the substance is not irritating to the eye.