4,4’-Bis[sec-alkyl(C10-C13)phenyl]iodonium tetrakis(pentafluorophenyl)borate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 March -24 April 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

temperature and relative humidity in the animal room was sometimes outside the range

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4,4’-Bis[sec-alkyl(C10-C13)phenyl]iodonium tetrakis(pentafluorophenyl)borate

EC Number:

810-260-4

Cas Number:

1115251-57-4

IUPAC Name:

4,4’-Bis[sec-alkyl(C10-C13)phenyl]iodonium tetrakis(pentafluorophenyl)borate

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): PI2080
- Physical state: Limpid amber highly viscous liquid
- Analytical purity: 97 ± 3 %
- Lot/batch No.: 11GP0077
- Date of receipt: 10 February 2012
- Expiration date of the lot/batch: January 2014
- Storage condition of test material: Stored at room temperature and protected from light
- pH of the test item: 6-7 (measured at 25 °C diluted at 1.15 % in isopropanol; for injectable formulations)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Argenvilliers, France.
- Age at study initiation: 3-4 months
- Weight at study initiation: Mean body weight - 3210 g (3075-3295 g)
- Housing: Animals were individually housed in noryl cages (Tecniplast, 65.3 cm x 65.3 cm x 45 cm).
- Diet: Pelleted breeding diet "type 110C" (SAFE, Augy, France), ad libitum
- Water: Tap water (filtered using a 0.22 μm filter), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 50 ± 20 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h 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(s) applied (weight with unit): 0.5 g

Duration of treatment / exposure:

- First animal: 3 minutes, 1 and 4 h
- Other two animals: 4 h

Observation period:

15 days for first two animals and 11 days for third animal

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Anterior right flank (1 h exposure), anterior left flank (3 minutes exposure) and posterior right flank (4 h exposure) in first animal; posterior right flank (4 h exposure) in remaining two animals.
- Type of wrap if used: Test item was placed on a gauze pad, moistened with drinking water treated by reverse osmosis and applied to an area of approximately 6 cm2 . The gauze pad was held in place by a non-irritating semi-occlusive dressing and a restraining bandage.
- Untreated flank served as control.

REMOVAL OF TEST SUBSTANCE
- After removal of the dressing, any residual test item was wiped off by means of moistened cotton pad with acetone, then with drinking water.
- Time after start of exposure: 4 h

SCORING SYSTEM: According to OECD Guideline 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 15 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 11 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 11 days

Irritant / corrosive response data:

First animal (animal no.: Y30151):
- After a 3-minute exposure, a very slight erythema (grade 1) was only noted on Day 1.
- After a 1 h exposure, a well-defined erythema (grade 2) was observed from Days 1 to 4 then very-slight erythema (grade 1) persisted until Day 8. A slight edema (grade 2) was noted from Days 1 to 3. In addition, dryness of the skin was recorded from Days 6 to 15 (until the end of the observation period).

Three animals:
- After a 4 h exposure, a well-defined or moderate erythema (grade 2 or 3) was noted in all animals from Days 1 to 4 then very slight to moderate erythema (grades 1 to 3) persisted until Day 7 in animal Y30153, Day 12 in animal Y30151 and until the end of the observation period (Day 15) in animal Y30152.

Edema was observed in all animals during the observation period as follows:
- Animal no. Y30151: Severe edema (grade 4) was noted on Day 1 followed by slight edema (grade 2) from Days 2 to 4 then very slight edema (grade 1) persisted until Day 7.
- Animal no. Y30152: Very slight edema (grade 1) was recorded on Days 1 and 2. Then, severe edema (grade 4) was noted from Days 3 to 6, followed by a decrease of severity (moderate to very slight edema; grades 3 to 1) until Day 13.
- Animal no. Y30153: Slight edema (grade 2) was observed on Days 1 and 2.
- In addition, dryness of the skin was recorded in all animals from Day 5 (animals Y30152 and Y30153) or 6 (animal Y30151) until Day 10 (animal Y30153) or 15 (animals Y30151 and 30152). Crusts were also observed in animal Y30152 on Days 14 and 15.
- Cutaneous reactions were observed until the end of the observation period (Day 15) in 2/3 animals (Y30151 and Y30152).

Other effects:

- No clinical signs and no mortality were observed.
- Body weight of the animals was unaffected by the test item treatment.

Any other information on results incl. tables

Table 7.3.1/1: Individual Skin Reactions

Rabbit Number	Dermal Irritation	Scores
		D1 (1 h)	D2 (24 h)	D3 (48 h)	D4 (72 h)	Mean (24, 48 and 72 h)	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14	D15
Y30151	Erythema	2	2	2	2	2.0	2	2	2	2	2	2	1	1	0	0	0
	Edema	4	2	2	2	2.0	1	1	1	0	0	0	0	0	0	0	0
	Other	*	*	*	*		*	S	S	S	S	S	S	S	S	S	S
Y30152	Erythema	2	2	3	3	2.7	3	3	3	2	2	2	2	2	2	1	1
	Edema	1	1	4	4	3.0	4	4	3	2	2	1	1	1	1	0	0
	Other	*	*	*	*		S	S	S	S	S	S	S	S	S	S/A	S/A
Y30153	Erythema	2	2	2	2	2.0	1	1	1	0	0	0	0	-	-	-	-
	Edema	2	2	0	0	0.7	0	0	0	0	0	0	0	-	-	-	-
	Other	*	*	*	*		S	S	S	S	S	S	*	-	-	-	-

 

h = hour; D = day; * = none; S = dryness of the skin; A = crust; - = cutaneous examination not performed

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, test item, PI2080 is classified as "R38 Irritating to skin" according to the criteria of Annex VI to the Directive 67/548/EEC and classified as category 2 with the hazard statement "H315: Causes skin irritation" according to the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, three male New Zealand White rabbits were dermally exposed to 0.5 g of test item, PI2080 under a semi-occlusive dressing. The test item was first evaluated on a single animal and the duration of exposure was 3 minutes on the anterior left flank, 1 h on the anterior right flank and 4 h on the posterior right flank. Then, test item was applied for 4 h to two other animals. After removal of the residual test item with moistened cotton pad, irritation was scored as outlined in the OECD Guideline 404 at 1, 24, 48 and 72 h and Days 5 to 15 after exposure.

No clinical signs and no mortality were observed. Body weight of the animals was unaffected by the test item treatment. In the first animal, after a 3-minute exposure, a very slight erythema was only noted on Day 1. After a 1 h exposure, a well-defined erythema was observed from Days 1 to 4 then very-slight erythema persisted until Day 8. A slight edema was noted from Days 1 to 3. Dryness of the skin was recorded from Days 6 to 15. After a 4 h exposure, a well-defined or moderate erythema was noted in all animals from Day 1 to Day 4 then very slight to moderate erythema persisted until Days 7, 12 and 15. In the first animal, severe edema was noted on Day 1 followed by slight edema from Days 2 to 4 then very slight edema persisted until Day 7. In the second animal, very slight edema was recorded on Days 1 and 2. Then, severe edema was noted from Days 3 to 6, followed by a decrease of severity (moderate to very slight edema) until Day 13. In the third animal, slight edema was observed on Days 1 and 2. In addition, dryness of the skin was recorded in all animals from Day 5 (2/3 animals) or 6 (1/3 animals) until Day 10 (1/3 animals) or 15 (2/3 animals). Crusts were also observed in 1/3 animals on Days 14 and 15. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 2.7, 2.0 for erythema and 2.0, 3.0, 0.7 for edema score, respectively. In this study, test item, PI2080 is a skin irritant for male rabbits.

 

Under the test conditions, test item, PI2080 is classified as "R38 Irritating to skin" according to the criteria of Annex VI to the Directive 67/548/EEC and classified as category 2 with the hazard statement "H315: Causes skin irritation" according to the CLP Regulation (EC) N° (1272-2008).