Reaction mass of Phosphorous(1+), (N-ethylethanaminato) diphenyl(phenylmethyl)-(T-4)-salt with 4, 4' - [2,2,2-trifluoro-1-(trifluoromethyl) ethylidene bis[phenol] (1:1) and (4,4'-[2,2,2-Trifluoro-1-(trifluoromethyl)ethylidene]diphenol

Endpoint summary

Description of key information

Based on in vivo studies in rabbits (OECD 404 and 405, respectively), the Reaction mass of AminoPhosphonium salt and Bisphenol AF is considered as non-irritating to the skin and irritating to the eyes. As a precaution, the registered substance is also considered as a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 2014 - August 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3706OB
- Expiration date of the lot/batch: 01 March 2019
- Purity test date: >99%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: by Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: At the start of the study the animals weighed 2.65 or 2.80 kg
- Housing: suspended cages
- Diet / water: Free access to mains drinking water and food was allowed throughout the study
- Acclimation period: at least five

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g of the test item

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL of distilled water

resulting to a 10% w/w aqueous preparation of the test item

Duration of treatment / exposure:

Duration of treatment: 3 minutes, 1 hour and 4 hours after application.

Observation period:

72 hours after exposure

Number of animals:

2 animals
The number of animals used was the minimum required to achieve the objectives of the study. Testing was conducted on two animals and the response in these animals was such that exposure of a third animal would not affect classification of the test item, therefore no further testing was needed.

Details on study design:

TEST SITE
- Area of exposure: 3

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:

OBSERVATION TIME POINTS
Immediately following removal of the patches (3 minutes, 1 hour and 4 hours) and approximately 1, 24, 48 and 72 hours later

SCORING SYSTEM:
- Method of calculation: Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Skin irritation:
- 3-Minute Exposure Period: No evidence of skin irritation was noted during the study. (See table 1 in "Any other information on results incl. tables)
- 1-hour Exposure Period: No evidence of skin irritation was noted during the study.(See table 1 in "Any other information on results incl. tables)
- 4-hour Exposure Period: No evidence of skin irritation was noted during the study.(See table 2 in "Any other information on results incl. tables)

Body Weight: Both animals showed expected gain in body weight during the study. (See table 3 in "Any other information on results incl. tables)

Other effects:

Measurement of pH:
10% w/w aqueous preparation of the test item immediately after preparation = 7.33
10% w/w aqueous preparation of the test item ten minutes after preparation = 7.33

Table 1 :   Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction	Observation Time (following patch removal)	Individual Scores Rabbit Number and Sex 74487 Female
		3-Minute Exposure	1-Hour Exposure
Erythema/Eschar Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0
Edema Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0

Table 2 :   Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Scores		Total
		Rabbit Number and Sex
		74487 Female	74520 Female
Erythema/Eschar Formation	Immediately	0	0	(0)
	1 Hour	0	0	(0)
	24 Hours	0	0	0
	48 Hours	0	0	(0)
	72 Hours	0	0	0
Edema Formation	Immediately	0	0	(0)
	1 Hour	0	0	(0)
	24 Hours	0	0	0
	48 Hours	0	0	(0)
	72 Hours	0	0	0
Sum of 24 and 72-Hour Readings (S) = 0
Primary Irritation Index (S/4) : 0/4 = 0.0
Classification:         NON-IRRITANT

( ) =   Total values not used for calculation of primary irritation index

Table 3:    Individual Body Weights and Body Weight Change

Rabbit Number and Sex	Individual Body Weight (kg)		Body Weight Change (kg)
	Day 0	Day 3
74487 Male	2.80	2.95	0.15
74520 Male	2.65	2.74	0.09

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals.

Executive summary:

The dermal irritancy potential of the test item following single, 3-Minute, 1 and 4-Hour, semi-occluded applications to the intact rabbit skin was assessed according to the OECD Guidelines for  the Testing of Chemicals No.404  "Acute  Dermal Irritation/Corrosion" (adopted 24 April 2002). The study was conducted in compliance with the principles of Good Laboratory Practice.

At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 mL of distilled water to achieve a paste, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch on three suitable sites selected on the back of the rabbit.

3-Minute and 1-Hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation. A single 4-Hour, semi occluded application of the test item to the intact skin of two rabbits produced no evidence of skin irritation.

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item, Reaction mass of AminoPhosphonium salt and BisphenolAF, does not meet the criteria laid down in CLP; Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures and the Globally Harmonized System of Classification and Labelling of Chemicals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 2014 - September 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3706OB
- Expiration date of the lot/batch: 01 March 2019
- Purity test date: >99%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.42 to 2.79 kg
- Housing: suspended cages
- Diet / Water: Free access to mains drinking water and food was allowed throughout the study
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of test item

VEHICLE
no vehicule

Duration of treatment / exposure:

A single application of the test item

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment; Additional observations were made on Days 7 and 14 to assess the reversibility of the ocular effects.

Duration of post- treatment incubation (in vitro):

14 days

Number of animals or in vitro replicates:

Three animals : 2 females and 1 male

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritant / corrosive response data:

No corneal effects were noted during the study.
Iridial inflammation was noted in all treated eyes 1 hour after treatment, in two treated eyes at the 24-Hour observation and persisted in one treated eye at the 48 and 72-Hour observations.
Moderate conjunctival irritation was noted in all treated eyes 1 hour after treatment. Moderate conjunctival irritation was noted in two treated eyes and minimal conjunctival irritation was noted in one treated eye at the 24, 48 and 72-Hour observations. Moderate conjunctival irritation persisted in one treated eye at the 7-Day observation.
Two treated eyes appeared normal at the 7-Day observation and one treated eye appeared normal at the 14-Day observation.

Other effects:

Body Weight : All animals showed expected gain in body weight during the study.


Measurement of pH:
10% w/w aqueous preparation of the test item immediately after preparation = 7.33
10% w/w aqueous preparation of the test item ten minutes after preparation = 7.33

Table 1:    Individual Scores for Ocular Irritation

Rabbit Number and Sex	74530 Female									74607 Female					74667 Male
	IPR = 0									IPR = 0					IPR = 0
Time After Treatment	1 Hr	24 Hr		48 Hr		72 Hr		7 Dy		1 Hr	24 Hr	48 Hr	72 Hr	7 Dy	1 Hr		24 Hr		48 Hr		72 Hr		7 Dy		14 Dy
CORNEA
Degree of Opacity	0	0		0		0		0		0	0	0	0	0	0		0		0		0		0		0
Area of Cornea Involved	0	0		0		0		0		0	0	0	0	0	0		0		0		0		0		0
IRIS	1	0		0		0		0		1	1	0	0	0	1		1		1		1		0		0
CONJUNCTIVAE
1 Redness	2	2		1		1		0		2	2	2	2	0	2		2		2		2		2		0
1 Chemosis	2	1		0		0		0		2	2	2	1	0	2		2		2		2		1		0
1 Discharge	1	0		0		0		0		2	3	2	2	0	2		2		2		2		1		0

IPR= Initial Pain Reaction

Hr = Hours

Dy = Day

Table 2:     Individual and Mean Scores for Cornea, Iris and Conjunctivae

Rabbit number and Sex	Time After Treatment	Corneal Opacity	Iridial Inflammation	Conjunctival Redness	Conjunctival Chemosis
74530 Female	24 Hours	0	0	2	1
	48 Hours	0	0	1	0
	72 Hours	0	0	1	0
Total		0	0	4	1
Mean		0.0	0.0	1.3	0.3
74607 Female	24 Hours	0	1	2	2
	48 Hours	0	0	2	2
	72 Hours	0	0	2	1
Total		0	1	6	5
Mean		0.0	0.3	2.0+	1.7
74667 Male	24 Hours	0	1	2	2
	48 Hours	0	1	2	2
	72 Hours	0	1	2	2
Total		0	3	6	6
Mean		0.0	1.0+	2.0+	2.0+

+ = Positive criterion according to CLP/GHS criteria.

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the experimental conditions of this study and according to the criteria laid down in GHS, the test item is considered as as Irritating to eyes (Category 2A), due to the absence of complete reversibility 7 days following instillation.

Executive summary:

The potential of the test item to induce eye irritation was assessed in New Zealand White rabbit according to the OECD Guidelines for the Testing of Chemicals No.405  "Acute  Eye Irritation/Corrosion".The study was conducted in compliance with the principles of Good Laboratory Practice.

A single application of the test item to the non-irrigated eye of three rabbits produced iridial inflammation between 1 and 72 hours following dosing and moderate conjunctival irritation between 1 hour and 7 days following dosing. Two treated eyes appeared normal at the 7-Day observation and one treated eye appeared normal at the 14-Day observation.

The test item was classified as Irritating to eyes (Category 2A) according to the Globally Harmonized Classification System.

The Signal Word "Warning" and the Hazard Statement "H319: Causes serious eye irritation" are therefore required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the absence of specific data on respiratory irritation, and based on eye irritation potential, the test item Reaction mass of AminoPhosphonium salt and Bisphenol AF is considered as a respiratory irritant in a precautionary approach.

Justification for classification or non-classification

Based on GLP- and OECD TG-compliant studies, the Reaction mass of AminoPhosphonium salt and Bisphenol AF is classified as Eye Irrit. 2A, H319, according to the GHS criteria. A STOT SE 3, H335 classification is also applied.