Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate

Endpoint summary

Description of key information

Skin: OECD 404; no skin irritation was observed in rabbits. Reliability = 1
Eye: OECD 405; eye damage was observed in rabbits. Reliability = 1
Respiratory:  No signs of respiratory tract irritation were observed in a rat acute inhalation study up to 5200 mg/m3. 

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:

'From 23 AUG 2007 to 21 NOV 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at the time of study conduct.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect dated 2002.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Remarks:

The study was conducted according to the guideline in effect at the time of study conduct.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Not reported
- Weight at study initiation: 3033, 3167, 3044 g
- Housing: singly in stainless steel, wire-mesh cages suspended above cage boards
- Diet (e.g. ad libitum): 125 grams of rabbit food daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22ºC
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: The adjacent areas of untreated skin were used for comparison.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 m/L

Duration of treatment / exposure:

4 hours

Observation period:

up to 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm2
- % coverage: 100
- Type of wrap if used: 2-ply gauze pad which was held in place with non-irritating tape and the trunk of each rabbit was wrapped with porous tape and further secured with waterproof tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): gently washed with warm water to remove excess test substance and gently patted dry
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize Scale

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Erythema (score of 1 or 2) but no edema was observed in the 3 rabbits on the day of dosing. No dermal irritation was observed at 24, 48/50, or 72 hours after removal of the test substance. No clinical signs were observed, and no body weight loss occurred. See Table 1 below.

Table 1: Dermal Responses Observed in Individual Rabbits
ERYTHEMA
Rabbit Number	Evaluation after Removal of Test Substance
	0 Minutes	60 Minutes	24 Hours	48 Hours	72 Hours
264	2	2	0	0	0
275	--	2	0	0	0
276	--	1	0	0	0
EDEMA
Rabbit Number	Evaluation after Removal of Test Substance
	0 Minutes	60 Minutes	24 Hours	48 Hours	72 Hours
264	0	0	0	0	0
275	--	0	0	0	0
276	--	0	0	0	0

Interpretation of results:

other: no classification is required

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test substance produced erythema, which cleared by 24 hours, when applied to the skin of rabbits. This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).

Executive summary:

The test substance was applied as a single 0.5-mL dermal dose to the shaved intact skin of a single New Zealand White rabbit. Since no corrosion occurred, 2 additional rabbits were treated. The test substance was applied to a 6 cm² area of skin. The application area was covered with a 2-ply gauze square which was held in place with non-irritating tape and covered with porous tape for a semi-occlusive dressing. The rabbits were exposed to the test substance for 4 hours after which the test substance was removed. Test sites were evaluated and scored by the method of Draize for signs of dermal irritation approximately 60 minutes, and 24, 48/50, and 72 hours after test substance removal. The rabbit that was initially treated was also examined immediately after test substance removal. Erythema (score of 1 or 2) but no edema was observed in the 3 rabbits on the day of dosing. No dermal irritation was observed at 24, 48/50, or 72 hours after removal of the test substance. No clinical signs were observed, and no body weight loss occurred. Under the conditions of this study, the test substance produced erythema, which cleared by 24 hours, when applied to the skin of rabbits.

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:

From 20 SEP 2007 to 14 Dec 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

2002

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Remarks:

The study was conducted according to guideline in effect at time of study conduct.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Remarks:

The study was conducted according to guideline in effect at time of study conduct.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

The study was conducted according to guideline in effect at time of study conduct.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 2846 g
- Housing: singly in a stainless steel, wire-mesh cage suspended above a cage board.
- Diet: 125 grams of PMI® Nutrition International, LLC Certified Rabbit LabDiet® 5322 daily
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22°C
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: control was untreated eye of test animal

Amount / concentration applied:

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

Duration of treatment / exposure:

28 hours

Observation period (in vivo):

at dosing, 1, 24 and 28 hours

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: unwashed



SCORING SYSTEM: Draize Scale


TOOL USED TO ASSESS SCORE: illumination and magnification, fluorescein stain examinations were conducted on the day after instillation.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 28 hours

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 28 hours

Remarks on result:

other: 1-28 h

Remarks:

positive indication of irritation. because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 28 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 28 hours

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Score:

0

Max. score:

2

Reversibility:

not fully reversible within: 28 h

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 28 hours

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 28 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 28 h

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1h

Score:

0

Max. score:

3

Reversibility:

not fully reversible within: 28 h

Remarks on result:

other: Brown and white discoloration of the conjunctiva

Remarks:

1-28 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

not fully reversible within: 28 hours

Remarks on result:

other: Brown and white discoloration of the conjunctival membrane of the treated rabbit eye was observed at 1, 24, and 28 hours after instillation of the test substance.

Remarks:

1-28h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 28 h

Score:

0

Max. score:

3

Reversibility:

not fully reversible within: 28 h

Remarks on result:

other: Brown and white discoloration of the conjunctiva

Remarks:

1-28h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 28h

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 28 hours

Remarks on result:

other: 1-18 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 28 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 28 h

Remarks on result:

other: 1-28 h

Remarks:

because significant scores were noted 1 hour after instillation of the test material, only one animal was treated. This rabbit was sacrificed for humane reasons 28 hours following instillation of the test material

Irritation parameter:

other: Discharge

Basis:

animal #1

Time point:

24 h

Score:

>= 2

Max. score:

3

Reversibility:

not fully reversible within: 28 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1

Score:

0

Max. score:

2

Irritant / corrosive response data:

Brown and white discoloration of the conjunctival membrane of the treated rabbit eye was observed at 1, 24, and 28 hours after instillation of the test substance. Corneal opacity (score of 2), iritis (score of 1), conjunctival chemosis (score of 2 or 4), and discharge (score of 2 or 3) were also observed. Fluorescein stain examinations were positive for corneal injury in the treated eye. The rabbit was euthanized the day after treatment for humane reasons.
The ocular scores from the animal with respect to observation time are presented in Table 1.

Table 1: Individual Animal Ocular Effects
	Rabbit No.	Cornea		Iritis	Conjunctiva			Fluorescein Stain	Other
		Opacity	Area		Redness	Chemosis	Discharge
1 Hour	279	2	4	0	0	2	3	NA	-
24 Hours	279	2	2	1	0	4	2	POS	*
28 Hours	279	2	4	1	0	4	2	POS	*

POS= positive for corneal injury

NA = not applicable

- = No other effects

* = Brown and white discoloration of the conjunctiva

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the conditions of this study, the test substance produced ocular effects in a rabbit.
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).

Executive summary:

An aliquot of 0.1 mL of test substance was administered to 1 eye of the animal. The treated and control eye remained unwashed following treatment. The conjunctiva, iris, and cornea of the treated eye were evaluated and scored according to a numerical scale approximately 1, 24, and 28 hours following administration of the test substance. Brown and white discoloration of the conjunctival membrane of the treated rabbit eye was observed at 1, 24, and 28 hours after instillation of the test substance. Corneal opacity (score of 2), iritis (score of 1), conjunctival chemosis (score of 2 or 4), and discharge (score of 2 or 3) were also observed. Fluorescein stain examinations of the treated eye were positive for corneal injury. The rabbit was euthanized the day after treatment for humane reasons. Under the conditions of this study, the test substance produced ocular effects in a rabbit.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

After application of a single 0.5-mL dermal dose to the shaved intact skin of rabbits for 4 hours, erythema (score of 1 or 2) but no edema was observed on the day of dosing. No dermal irritation was observed at 24, 48/50, or 72 hours after removal of the test substance.

After instillation of 0.1 mL of test substance into the lower conjunctival sac of the eye of 2 rabbits, brown and white discoloration of the conjunctival membrane was observed at 1, 24, and 28 hours. Corneal opacity (score of 2), iritis (score of 1), conjunctival chemosis (score of 2 or 4), and discharge (score of 2 or 3) were also observed. Fluorescein stain examinations of the treated eye were positive for corneal injury. The rabbit was euthanized the day after treatment for humane reasons. Under the conditions of this study, the test substance produced ocular effects in a rabbit.

No signs of respiratory tract irritation were observed in an acute inhalation study in rats at a concentration of 5200 mg/m³.

Justification for selection of skin irritation / corrosion endpoint:
OECD Guideline, GLP study

Justification for selection of eye irritation endpoint:
OECD Guideline, GLP study

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the observations following eye exposure, the substance is classified as Irritation Category 1 (Causes serious eye damage) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

There was no evidence of irritation in skin irritation studies or respiratory irritation during inhalation exposures. Therefore, the substance does not need to be classified for skin or respiratory tract irritation according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.