Poly(polyalkylammonium) poly(µ-alkoxy)-µ6-oxido-polyhedropoly(chloridometal)ate polyalkanol solvate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-09-19 to 2012-11-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study; GLP study without deviation

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:

2002

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Indate (2-), hexachlorododeca-µ-methoxy-µ6-oxohexa-, hydrogen, compd. with N-methylmethanamine (1:2:2)

Cas Number:

1381802-10-3

Molecular formula:

[In6O(OMe)12Cl6]2–[NH2Me2]+2 · 2MeOH

IUPAC Name:

Indate (2-), hexachlorododeca-µ-methoxy-µ6-oxohexa-, hydrogen, compd. with N-methylmethanamine (1:2:2)

Test material form:

solid: crystalline

Details on test material:

Purity: >99%

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: 
- Source: LPT, Laboratory of Pharmacology and Toxicology, Löhndorf (Germany)
- Sex: male
- Age: approx. 7 to 9 months
- Weight at study initiation: 2.4 kg up to 3.1 kg
- Housing: single
- Diet: ad libitum, ssniff K-H (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimatisation period: at least 20 days
- Controls: identical animal, second eye
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30% - 70%
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: identical animal, left eye

Amount / concentration applied:

Amount: 100 mg of the fine mortared test item were administered per eye and tested in three animals.

Duration of treatment / exposure:

Single instillation into the conjunctival sac of the right eye. One hour after administration the eyes were rinsed with 20 mL 0.9% aqueous
NaCl solution.

Observation period (in vivo):

1, 24, 48, 72 hours and 4 to 15 days after the administration

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

ADMINISTRATION: The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further
animals were employed 24 hours after start of the initial test.
100 mg of the fine mortared test item were administered per eye and tested in three animals.
The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.

REMOVAL OF TEST SUBSTANCE
- Washing: One hour after administration the eyes were rinsed with 20 mL 0.9% aqueous NaCl solution.
TOOL USED TO ASSESS SCORE: The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, 72 hours and 4 to 15 days after the administration. The eye reactions were observed and registered.
24 hours, 7 and 14 days after administration the eyes were treated additionally with fluorescein3 and examined. The eye reactions were observed
and registered.

SCORING SYSTEM: Draize scale

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 15 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 11 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

AVERAGE SCORE
- Cornea: 0.67
- Iris: 0
- Conjunctivae (Redness): 1.0
- Conjunctivae (Chemosis): 2.0

Other effects:

There were no systemic intolerance reactions.

Any other information on results incl. tables

Acute eye irritation/corrosion test of the test item

 

Examination of the treated eye

Time after administration	C O R N E A	I R I S	C O N J U N C T I V A E
	Opacity		Redness^#	Chemosis^##
	A n i m a l n o. : 1 / 2 / 3
right eye: 100 ml test item
before dosing	0/0/0	0/0/0	0/0/0	0/0/0
1 hour	0/0/0	0/0/0	1/1/1	2/1/1
24 hours	1/1/0	0/0/0	1/1/1	4/2/2
48 hours	1/1/0	0/0/0	1/1/1	3/2/1
72 hours	1/1/0	0/0/0	1/1/1	2/1/1

# refers to palpebral and bulbar conjunctivae; excluding cornea and iris

## Swelling: refers to lids and/or nictitating membrane

24 hours fluorescein test: all animals: corneal staining (up to 1/4 of the surface)

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information

Conclusions:

According to the EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures,
the test item is i r r i t a t i n g to eyes (labelling requirement: H319).

Executive summary:

The purpose of this study was to obtain information on the influence of the test item on rabbit eyes (irritation/corrosion test), according to OECD guideline 405, EC method B.5. and OCSPP guideline 870.2400.

 

Under the present test conditions a single administration of 100 mg test item per animal into the conjunctival sac of the right eye of three rabbits caused following effect:

Corneal opacity (grade 1) was observed in animal no. one 24 hours to 10 days and in animal no. two 24 hours to 14 days after instillation.

The fluorescein tests performed 24 hours and 7 days after instillation revealed corneal staining in all animals (up to 1/4 of the surface).

Conjunctival redness (grade 1) was observed in all animals 1 hour to 7 days, in animal no. 1 until 9 days and in animal no. 3 until 10 days after instillation.

Chemosis was observed in all animals:

- animal no. 1: 24 hours (grade 4), 48 hours (grade 3), 1 hour and 72 hours to 5 days (grade 2) and 6 days (grade 1) after instillation;

- animal no. 2: 24 and 48 hours (grade 2), 1 hour and 72 hours to 5 days (grade 1) after instillation;

- animal no. 3: 24 hours (grade 2), 1 hour, 48 and 72 hours (grade 1) after instillation.

The irises were not affected by instillation of the test item.

There were no systemic intolerance reactions.

According to the EC Regulation 1272/2008 and subsequent regulations on classification, labelling and packaging of substances and mixtures, the test item is i r r i t a t i n g to eyes..