2-Butenedioic acid (2Z)-, reaction products with ammonium di-.mu.3-hydroxyhexacosa-.mu.-oxododecaoxododecatungstate(6-) (6:1), ammonium octa-.mu.-oxodi-.mu.3-oxodi-.mu.4-oxododecaoxoheptamolybdate(6-) (6:1), nickel(2+) nitrate (1:2) and nickel(2+) sulfate (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 Jul - 24 Jul 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study (according to OECD Guideline 405 adopted 24th April 2002 (no anesthetics or analgesics were used)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 405 (Acute Eye Irritation / Corrosion) (adopted 24 April 2002)

Deviations:

yes

Remarks:

no information on clinical signs or pain/distress are given in the test report

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

no information on clinical signs or pain/distress are given in the test report

GLP compliance:

yes (incl. QA statement)

Remarks:

GROUPE INTERMINISTERIEL DES PRODUITS CHIMIQUES

Test material

Test material information

Constituent 1

Reference substance name:

dioxomolybdenum; oxonickel; trioxotungsten

EC Number:

800-777-3

Cas Number:

1351378-24-9

Molecular formula:

(Ni)z(Mo)x(W)yO(13 – 20)x

IUPAC Name:

dioxomolybdenum; oxonickel; trioxotungsten

Test material form:

other: grained solid

Details on test material:

- Name of test material (as cited in study report): 2-Butenedioic acid (2Z)-, reaction products with ammonium di-µ3-hydroxyhexacosa-µ-oxododecaoxododecatungstate(6-) (6:1), ammonium octa-µ-oxodi-µ3-oxo-µ4-oxododecaoxoheptamolybdate(6-) (6:1), nickel(2+) nitrate (1:2) and nickel(2+) sulfate (1:1)
- Physical state: green, grained solid
- Analytical purity: > 99%
- Lot/batch No.: 19266-184-1
- Expiration date of the lot/batch: May 2018
- Storage condition of test material: at room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste, Linxe, France
- Age at study initiation: 12 - 13 weeks
- Weight during study period: 2.66 - 3.78 kg
- Housing: individual
- Diet: SDS - C15, ad libitum
- Water: tap-water from public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

1 h (remaining test item was rinsed with physiological saline 1 h after instillation in all animals)

Observation period (in vivo):

14 days
Reading time points: 1, 24, 48, 72 h and on Day 7 and 14

Number of animals or in vitro replicates:

1 female (initial test)
2 females (confirmatory test)

Details on study design:

SCORING SYSTEM: similar to Draize scoring system, supplemented with scoring for discharge and extent of opacity

Discharge:
No discharge - 0
Slight discharge (normal slight secretions in the inner corner to be taken into account) -2
Discharge with moistening of the eyelids and neighbouring hairs - 2
Discharge with moistening of the eyelids and large areas around the eye -3

Cornea: Extent of opacity:
Opaque area present but covering 1/4 or less - 1
Between 1/4 or 1/2 - 2
Between 1/2 and 3/4 - 3
Between 3/4 and the entire surface - 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 2 days

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritant / corrosive response data:

The test item induced slight to severe eye reactions:
- slight to moderate corneal opacity in 3/3 animals noted 24 h after instillation which was fully reversible within 2 days.
- congestion of the iris in 1/3 animals noted 24 h after instillation which was fully reversible within 2 days.
- moderate to severe redness of the conjunctivae in 3/3 animals noted after 24 h instillation which was fully reversible latest within 14 days.
- slight to severe chemosis in 3/3 animals noted 24 h after instillation which was fully reversible latest within 14 days.
Further, white coloration of the inferior conjunctiva was noted in animal#1 between Day 2 and Day 7.

Other effects:

No information on clinical signs or pain/distress are reported.

Any other information on results incl. tables

Table 1. Eye reactions after instillation.

 

Rabbit #   1           2           3	Time [h]	conjunctivae		iris	cornea		conjunctivae		iris	cornea
		redness	swelling				redness	swelling
	24	2	3	0	1
	48	2	1	0	0
	72	2	1	0	0
	average	2	1.7	0.0	0.3	Time to reversion	14 days	7 days	0	2 days
	24	3	4	1	2
	48	3	3	0	0
	72	3	2	0	0
	average	3	3	0.3	0.7	Time to reversion	14 days	14 days	2 days	2 days
	24	2	1	0	1
	48	1	0	0	0
	72	1	0	0	0
	average	1.3	0.3	0.0	0.3	Time to reversion	2 days	7 days	0	2 days

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Eye irrit 2, H319
DSD: not classified