5,7-Di-t-butyl-3-[3,5-dimethyl-4-[(1,3,7,9-tetra-t-butyl-5-methyl-5H-benzo[d][1,3,2]benzodioxaphosphocin-11-yl)oxy]phenyl]-3H-benzofuran-2-one

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-06-08 to 2016-09-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, as this is in line with OECD 404

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

5,7-Di-t-butyl-3-[3,5-dimethyl-4-[(1,3,7,9-tetra-t-butyl-5-methyl-5H-benzo[d][1,3,2]benzodioxaphosphocin-11-yl)oxy]phenyl]-3H-benzofuran-2-one

EC Number:

817-187-7

Cas Number:

1803088-15-4

Molecular formula:

C54 H73 O5 P

IUPAC Name:

5,7-Di-t-butyl-3-[3,5-dimethyl-4-[(1,3,7,9-tetra-t-butyl-5-methyl-5H-benzo[d][1,3,2]benzodioxaphosphocin-11-yl)oxy]phenyl]-3H-benzofuran-2-one

Details on test material:

- State of aggregation: Solid / white
- Storage Condition: room temperature under light exclusion

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature; under light exclusion ; no direct sunlight

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo CRS (Switzerland) Limited
- Age at study initiation: approx. 7-9 months
- Weight at study initiation: 3.70 - 4.51 kg
- Housing: individual housing
- Diet: STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

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

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g was loaded on the test patch (2.5 x 2.5 cm)

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsolateral part of the trunk
- Type of wrap if used: The item was covered with a test patch and adhesive fleece

REMOVAL OF TEST SUBSTANCE
- Washing: The test item was removed at the end of the exposure period with polyethylenglycol
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
Immediately after removal of the patch, approx. 1, 24, 48, 72 h after removal of the patch

SCORING SYSTEM: Evaluation of skin reactions was performed according to the quoted guidelines.
- Method of calculation: For evaluation mean values of erythema and edema were calculated based on readings at 24, 48, 72 h. Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Very slight erythema (grade 1) was observed in two animals immediately after removal of the patch and persisted until hour 1 or hour 24. The third animal was free of any findings. The cutaneous reactions were reversible in two animals within 24 or 48 hours after removal of the patch.

Other effects:

- Other adverse local effects: none
- Other adverse systemic effects: none

Any other information on results incl. tables

Table 1. Tabulation of irritant response data for each individual animal at each observation time as well as calculation of the means

Readings	Animal No.	Erythema	Edema
0 h	1	1	0
	2	0	0
	3	1	0
1 h	1	1	0
	2	0	0
	3	1	0
24 h	1	1	0
	2	0	0
	3	0	0
48 h	1	0	0
	2	0	0
	3	0	0
72 h*	1	0	0
	2	0	0
	3	0	0
Mean 24 h – 72 h	1	0.3	0.0
	2	0.0	0.0
	3	0.0	0.0
Mean	-	0.1	0.0

*Study discontinued because the animals were free of findings

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described cutaneous reactions as well as the average score for irritation, the test item does not show a skin irritating potential under the test conditions chosen.

Executive summary:

The potential of the test item to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 g of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch. The following test item-related clinical observations were recorded during the course of the study: Very slight erythema (grade 1). The cutaneous reactions were reversible in two animals within 24 or 48 hours after removal of the patch. The third animal did not show any findings. Mean scores over 24, 48 and 72 hours for each animal were 0.3, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema. Considering the described cutaneous reactions as well as the average score for irritation, the test article does not show a skin irritating potential under the test conditions chosen.