Reaction mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate

Endpoint summary

Description of key information

Based on the results of the avaible studies, the Reaction mass of TFAK/TFSK is not considered as irritating to the skin or eyes.

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:

20 Jun 2018 to 10 Sep 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP Guideline study

Justification for type of information:

The in vivo data have been generated as part of a new substance notification in China for which this test is a standard requirement.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2017

Deviations:

yes

Remarks:

See below

Principles of method if other than guideline:

Deviations:
- Six times points of humidity deviated with the highest value measured being 73%. Deviations were very short time periods. This does not affect the quality and integrity of the study.
- At 24 and 48h, the observation of one of the animals deviated by about 4h. Because no dermal irritant symptoms were seen, this deviation was considered not to affect the quality and integrity of the study.

GLP compliance:

yes (incl. QA statement)

Remarks:

2016-05-30

Species:

rabbit

Strain:

other: Japanese white

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Qinqdao Kangda Biological Technology Limited Company
- Age at study initiation: 92-95 days
- Weight at study initiation: 2018-2293 g
- Housing: Individually in stainless wire cages
- Diet (e.g. ad libitum): rabbit maintenance feed, ad libitum
- Water (e.g. ad libitum): purified drinking water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2 - 20.9
- Humidity (%): 47-73
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 Jun 2018 To: 28 Jun 2018

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4h

Observation period:

72h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5x2.5cm
- Type of wrap if used: elastic bandage and medical paper tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substances wiped off with cotton moisted with tepid water
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
Immediately, 1, 24, 48 and 72h after patch removal

SCORING SYSTEM:
- Method of calculation: according to the guideline

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

There were no observable abnormalities for the three control sites and for the three test sites.

Other effects:

No abnormal signs or symptoms were observed.
All animals showed expected gains in body weights.

		Individual scores - Observation time (hour)				Mean scores 24-48-72h
		1	24	48	72
Animal 1	Edema	0	0	0	0	0
	Erythema	0	0	0	0	0
Animal 2	Edema	0	0	0	0	0
	Erythema	0	0	0	0	0
Animal 3	Edema	0	0	0	0	0
	Erythema	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The Reaction mass of TFSK/TFAK is not iritating to the skin.

Executive summary:

In an in vivo skin irritancy study following OECD TG 404 and under GLP conditions, three rabbits were dosed with 0.5 mL of the test substance. No mortality or systemic toxicity was observed. All erythema and edema scores were equal to 0. Based on the outcome of this study, it can be concluded that the test substance is not classified as corrosive or irritant to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Jun 2018 to 10 Sep 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP Guideline study

Justification for type of information:

The in vivo data have been generated as part of a new substance notification in China for which this test is required to confirm negative in vitro data.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017

Deviations:

yes

Remarks:

Six times points of humidity deviated with the highest value measured being 73%. Deviations were very short time periods. This does not affect the quality and integrity of the study.

GLP compliance:

yes (incl. QA statement)

Remarks:

2016-05-30

Species:

rabbit

Strain:

other: Japanese white

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Qinqdao Kangda Biological Technology Limited Company
- Age at study initiation: ca. 95 days
- Weight at study initiation: 2076 - 2592 g
- Housing: Individually in suspended stainless wire cages
- Diet (e.g. ad libitum): Rabbit maintenant feed, ad libitum
- Water (e.g. ad libitum): Purified drinking water, ad libitum
- Acclimation period: at least 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2 - 20.9
- Humidity (%): 47 -73
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 June 2018 To: 29 June 2018

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Observation period (in vivo):

72h

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM:
According to the OECD guideline

TOOL USED TO ASSESS SCORE: fluorescein (at 24h), binocular loupe for all time points.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

There were no observable abnormalities for the three control eyes at all observations after dosing.
There was no retention of fluorescein for the three control and treated eyes 24h after dosing.

Other effects:

- Lesions and clinical observations: No significant adverse systemic effect was observed.

		Individual scores - Observation time (hour)				Mean scores 24-48-72h
		1	24	48	72
Animal 1	Cornea	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctivae redness	1	0	0	0	0
	Conjunctivae chemosis	1	0	0	0	0
Animal 2	Cornea	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctivae redness	1	0	0	0	0
	Conjunctivae chemosis	0	0	0	0	0
Animal 3	Cornea	0	0	0	0	0
	Iris	0	0	0	0	0
	Conjunctivae redness	1	0	0	0	0
	Conjunctivae chemosis	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The Reaction mass of TFSK/TFAK is not iritating to eyes.

Executive summary:

An eye irritation study was performed according to OECD TG 405 and under GLP conditions. An instillation of 0.1 ml of the test item in one eye of 3 rabbits was performed. One eye remained untreated and served as a control. No irreversible effects were noted. Based on the results above, the test material is not classified for eye irritation.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-04-23 (Study plan signature) to 2013-05-27 (final report)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study

Qualifier:

no guideline available

Principles of method if other than guideline:

The principle of the assay is based on the fact that irritant chemicals are cytotoxic to the HCE reconstructed human corneal epithelium after a short term exposure. Irritant chemicals are sufficiently cytotoxic to cause cell death in the different cell layers.
Viability of HCE is measured by the MTT method after one hour of exposition to 30 µL of the substance.
If viability > 50% the substance is considered as non irritant.

GLP compliance:

yes (incl. QA statement)

Vehicle:

unchanged (no vehicle)

Controls:

other:

Amount / concentration applied:

- Amount applied : 30 µL per tissue
- Concentration : Test item as such

Duration of treatment / exposure:

- 1 hour per tissue

Number of animals or in vitro replicates:

- 3 tissues tested

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing : D-PBS
- Time after start of exposure: 1 hour

SCORING SYSTEM: MTT viability assay

TOOL USED TO ASSESS SCORE: Optical density measurement at 570 nm using a multiskan Ascent plate reader

Irritation parameter:

other: Cell viability

Remarks:

The cell viability is determinated by the measurement of the reduction of the dye MTT.

Value:

ca. 94

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

Viability =94 % (+/- 4%)
40% Reaction mass of TFAK/TFSK in water solution is non Irritant for the eye.

Individual and mean corrected Optical Density (OD) values and tissue viabilities for the test item, thenegative and positive controls :

Group	Tissue n°	OD measurements		Mean ODblanck	cOD		Mean cOD	Viability (%)
		1st	2nd		1st	2nd
Negative control	1	0.718	0.736	0.038	0.680	0.698	0.689	101
	2	0.746	0.741		0.708	0.703	0.706	104
	3	0.690	0.684		0.652	0.646	0.649	95
Positive control	1	0.073	0.054	0.038	0.035	0.016	0.026	4
	2	0.051	0.051		0.013	0.013	0.013	2
	3	0.053	0.051		0.015	0.013	0.014	2
Test item	1	0.701	0.694	0.038	0.664	0.657	0.660	97
	2	0.677	0.687		0.640	0.650	0.645	95
	3	0.647	0.687		0.610	0.610	0.610	89

cOD = blanck corrected optical density

SD = Standard deviation

Mean tissue viability and standard deviations for the test item, the negative and positive controls :

Group	cOD		Viability (%)
	Mean	SD	Mean	SD
Negative control	0.681	0.029	100	4
Positive control	0.018	0.007	3	1
Test item	0.638	0.026	94	4

cOD = blanck corrected optical density

SD = Standard deviation

Qualitative assessment of tissue viability

 

Treatment	Tissue 1	Tissue 2	Tissue 3
Negative control	B	B	B
Positive control	W	W	W
Test item	B	B	B

B : blue discoloration of the tissue (viable)

W : white discoloration of the tissue (dead)

Interpretation of results:

GHS criteria not met

Remarks:

Viability > 50%

Conclusions:

Under the experimental conditions of this study, a 40% solution of Reaction Mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate in water is considered to be non irritant to the eye.

Executive summary:

The objective of this study was to evaluate the ocular irritation potential of a 40% solution of the test item (Reaction Mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate) in water, using the HCE reconstructed human corneal epithelial model and according to GLP.

Preliminary tests were performed to detect the ability of the test item (a 40% solution of Reaction Mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate in water) to directly reduce MTT as well as its coloring potential.

Following the preliminary tests, the ocular irritation potential of the test item was tested in the main test. The test item, the negative and positive controls were topically applied on three tissues and incubated at room temperature during 1 hour (± 3 minutes). At the end of the treatment period, each tissue was rinsed with D-PBS and incubated for 16 (± 1) hours at, 5% CO₂in a humidified incubator. The cell viability was then assessed by means of the colorimetric MTT reduction assay.

Relative viability values were calculated for each tissue and expressed as a percentage of the mean viability of negative control tissues viability which was set at 100% (reference viability).

In the preliminary test, the test item was found not to have direct MTT reducing properties. The test item was also found not to have a coloring potential. All acceptance criteria for the negative and positive controls were fulfilled. The study was therefore considered to be valid. Following a 1 hour exposure and a 16-hour recovery period, the relative mean viability of the test item‑treated tissues was 94% with a standard deviation of 4%.

Under the experimental conditions of this study, the test item, a 40% solution of Reaction Mass of potassium trifluoroacetate and potassium trifluoromethanesulphinate in water (batch No.13GM015B), tested in its original form, is considered to be non irritant to the eye.

According to these results, the classification of the test item for eye irritation potential should be the following: Not classified / No category (Regulation (EC) No. 1272/2008 and GHS criteria).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritating properties of the Reaction mass of TFSK/TFAK were studied in a GLP-compliant OECD Guideline 404 study with rabbits. 0.5 mL of the undiluted test substance (30% reaction mass of TFSK/TFAK in water) were applied under semi-occlusive conditions to the skin of 3 rabbits for 4 hours. After the removal of the patches animals were observed for 72 hours. No evidence of skin irritation was noted (erythema and edema scores were 0 at all time points (24, 48 and 72 hours) in all animals). Based on the results of the study, the Reaction mass of TFSK/TFAK is considered to be not irritating to skin.

Eye irritation

A GLP compliant in vitro eye irritation test has been performed on human reconstructed corneal epithelium tissues with a solution of 40% Reaction mass of TFSK/TFAK in water. Following a 1 hour exposure and a 16-hour recovery period, the relative mean viability of the test item-treated tissues was 94% with a standard deviation of 4%. Based on this result, the Reaction mass of TFSK/TFAK is considered to be non-irritant to the eye.

Eye irritating properties of the Reaction mass of TFSK/TFAK were also studied in a GLP-compliant OECD Guideline 405 study with rabbits. 0.1 mL of the undiluted test material (30% reaction mass of TFSK/TFAK in water) was instilled in one eye of three rabbits and the eyes were observed after 1, 24, 48 and 72 hours. Untreated eyes served as negative control. At approximately one hour after dosing, the treated eyes only showed slight eye irritant symptoms such as some blood vessels hyperaemic and/or some swelling above normal at conjunctivae. No abnormalities were observed at 24, 48 and 72 hours after treatment. Based on the results of the study, the Reaction mass of TFSK/TFAK was concluded to be not irritating to eyes.

Justification for classification or non-classification

Based on the results of the skin and eye irritation study, the Reaction mass of TFSK/TFAK does not need to be classified for skin and eye irritation according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.