Dibenzo[d,f][1,3,2]dioxaphosphepin, 6,6'-[[3,3',5,5'-tetrakis(1,1-dimethylethyl)[1,1'-biphenyl]-2,2'-diyl]bis(oxy)]bis-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 April - 18 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD).

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:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May, 2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

august 1998

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No8147, Nov 24, 2000

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay, Labor fuer biologische Analytik GmbH, Heidelberg, Germany

Test material

Test material information

Constituent 1

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): L4-Ligand
- Physical state: white solid
- Analytical purity: 97.0g/100g ± 0.3g/100g
- Lot/batch No.: 0005473663
- Expiration date of the lot/batch: 01 February, 2013
- Storage condition of test material: room temperature, under N2; protected agianst humidity
- Other: homogeneous by visual inspection

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approximately 3 months
- Weight at study initiation: 2.28 - 2.39 kg
- Housing: single housing in stainless steel wire mesh cages with grating shallow cage floor enriched with wooden gnawing blocks
- Diet: STANRAB (P) SQC, SDS Special Diets Services, Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

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

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL bulk volume (about 36 mg)

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

72 hours
reading time points: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3 (sequential testing)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: 3 to 6 mL of hand warm tap water
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize Scoring System

TOOL USED TO ASSESS SCORE: hand-slit lamp, fluorescein and otoscope lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal#1 - animal#3

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal#1 - animal#3

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 hours

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal#2 + animal#3

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal#1 - animal#3

Time point:

other: mean over 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Slight conjunctival redness was noted in all animals at the 1 hours reading time point and persisted in one animal up to 24 hours. Additional findings like injected scleral vessels in a circumscribed area were noted in one animal up to 24 hours after application. All occular reactions were reversible within 48 hours.

Other effects:

No other effects were observed during the study.

Any other information on results incl. tables

Table1: Individual Occular Observations

	animal #1				animal #2				animal #3
hours	cornea	Iris	Redness	Chemosis	Cornea	Iris	Redness	Chemosis	Cornea	Iris	Redness	Chemosis
1	0	0	1	0	0	0	1	0	0	0	1	0
24	0	0	1	0	0	0	0	0	0	0	0	0
48	0	0	0	0	0	0	0	0	0	0	0	0
72	0	0	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

DSD: not classified
CLP: not classified