3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl acrylate

Endpoint summary

Description of key information

Skin irritation (rabbit, OECD 404): non-irritant
Eye irritation (rabbit, OECD 405): non-irritant
Respiratory irritation: not tested

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study in compliance with international guidelines

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits were supplied by an accredited supplier. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and were twelve to twenty weeks old. After an aclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to drinking water and food (Certified Rabbit Diet) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70%, respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve horns darkness.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: not applicable

Amount / concentration applied:

At each test site a quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.

Duration of treatment / exposure:

4 hours

Observation period:

One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.

Number of animals:

3 rabbits

Details on study design:

On the day before the test each rabbit was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the 1 and 4 hour exposure periods.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 ml of test material. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.

Irritation parameter:

other: erythema/eschar formation

Basis:

other: sum of 24 and 72 h readings for 3 rabbits

Time point:

other: 1 h

Score:

2

Max. score:

8

Reversibility:

fully reversible within: 72 h

Irritation parameter:

other: erythema/eschar formation

Basis:

other: sum of 24 and 72 h readings for 3 rabbits

Time point:

other: 24 h

Score:

2

Max. score:

8

Reversibility:

fully reversible within: 72 h

Irritation parameter:

other: erythema/eschar formation

Basis:

other: sum of 24 and 72 h readings for 3 rabbits

Time point:

other: 48 h

Score:

2

Max. score:

8

Reversibility:

fully reversible within: 72 h

Irritation parameter:

other: erythema/eschar formation

Basis:

other: sum of 24 and 72 h readings for 3 rabbits

Time point:

other: 72 h

Score:

0

Max. score:

8

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

other: sum of 24 and 72 h readings for 3 rabbits

Time point:

other: 1, 24, 48, 72 hours

Score:

0

Max. score:

8

Reversibility:

other: not applicable

Irritant / corrosive response data:

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) “Dermal Toxicity” In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47:
Primary Irritation Index Classification of Irritancy
0 Non-irritant
> 0 to 2 Mild irritant
> 2 to 5 Moderate irritant
> 5 to 8 Severe irritant

Interpretation of results:

not irritating

Remarks:

Migrated information mild irritant Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 0.3 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. However, the substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

October 27, 2009 / November 6, 2009

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:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Number of Animals: 3
Sex: Female, nulliparous and non-pregnant
Species/Strain: Rabbit/New Zealand albino.
Age: Young adult.
Source: Received from Robinson Services, Inc. Clemmons, NC on October 21, 2009.
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Enrichment (e.g. toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 18 - 21 °C and 35 - 63%, respectively.
Photoperiod: 12 hour light/dark cycle
Acclimation Period: 6 or 13 days
Food: Pelleted Purina Rabbit Chow #5326
Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Eurofins PSL.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

72 h

Number of animals:

3 females

Details on study design:

Approximately 24 hours prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy naive animals (not previously tested) without pre-existing skin irritation were selected for test.
Initially, only one rabbit was placed on test. Since only minimal irritation was observed in this animal, the test was completed with two additional rabbits.
Five-tenths of a milliliter of the test substance was applied to one 6-cm2 intact dose site on each animal and covered with a 1-inch x 1-inch, 4-ply gauze pad. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3-inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages. No other substances were tested on these rabbits.
After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test substance.
Individual dose sites were scored according to the Draize scoring system1 (see Table 4) immediately following patch removal and at approximately 30 - 60 minutes and 24, 48, and 72 hours after patch removal.
Individual body weights of the animals were recorded prior to test substance application (initial) and again on the last day of individual scoring.
The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

There was no edema noted at any treated site during the study. Very slight erythema was noted at two of three treated dose sites. Both animals were free from dermal irritation by 48 hours.

Other effects:

All animals appeared active and healthy and gained or maintained body weight during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

No significant irritation effects were noted during the study.
According to the Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required.

Executive summary:

A primary skin irritation test was conducted with rabbits to determine the potential of the test item to produce irritation after a single topical application. At the request of the Sponsor, the study was conducted in a stepwise manner using a single patch applied initially to one rabbit for 4-hours. Five-tenths of a milliliter of the test substance was applied to the skin of one healthy rabbit for 4-hours. The dose site was evaluated for dermal irritation by the method of Draize et al. immediately following patch removal, and at 30 - 60 minutes and 24, 48, and 72 hours after patch removal. Since only minimal irritation was observed in this animal, the test was completed on two additional animals, as described above. There was no edema noted at any treated site during the study. Very slight erythema was noted at two of three treated dose sites. Both animals were free from dermal irritation by 48 hours.

According to the Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study in compliance with international guidelines

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White rabbits were supplied by an accredited supplier. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (Certified Rabbit Diet) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and 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)

Controls:

not required

Amount / concentration applied:

A volume of 0.1 ml of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

Duration of treatment / exposure:

72 h

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J H (1977) “Dermal and Eye Toxicity Tests” In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

Initially, a single rabbit was treated. A volume of 0.1 ml of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale shown in the field "attached background material".
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

Irritation parameter:

overall irritation score

Basis:

other: animal #1, #2, #3

Time point:

other: 1 h

Score:

6

Max. score:

110

Reversibility:

fully reversible within: 48 h

Irritation parameter:

overall irritation score

Basis:

animal: #1, #2, #3

Time point:

other: 24 h

Score:

2

Max. score:

110

Reversibility:

fully reversible within: 48 h

Irritation parameter:

overall irritation score

Basis:

animal: #1, #2, #3

Time point:

other: 48 h

Score:

0

Max. score:

110

Reversibility:

other: not applicable

Irritation parameter:

overall irritation score

Basis:

animal: #1, #2, #3

Time point:

other: 72 h

Score:

0

Max. score:

110

Reversibility:

other: not applicable

Irritant / corrosive response data:

The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:
Score for conjunetivae = (A + B + C) x 2
Score for iris = D x 5
Seoreforcomea = (E x F) x 5
Using the numerical data obtained a modified version of the system described by Kay J H and Calandra 3 C (1962), 3. Soc. Cosmet. Chem. 13, 28 1-289 (see Appendix 3) was used to classify the ocular irritaney potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.

Interpretation of results:

not irritating

Remarks:

Migrated information minimal irritant Criteria used for interpretation of results: EU

Conclusions:

The test material produced a maximum group mean score of 6.0 (theoretical maximum is 110) and was classified as a minimal irritant (class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. However, according to the Official Journal of the European Union 1272/2008 (CLP) dated December 16th 2008 the test item shall not be classified as eye irritating.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

November 2, 2009 / November 15, 2009

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:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Number of Animals: 3
Sex: Male
Species/Strain: Rabbit/New Zealand albino.
Age: Young adult.
Source: Received from Robinson Services, Inc. Clemmons, NC on October 28, 2009.
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Enrichment (e.g. toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 18 - 21 °C and 39 - 64%, respectively.
Photoperiod: 12 hour light/dark cycle
Acclimation Period: 5 or 15 days
Food: Pelleted Purina Rabbit Chow #5326
Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Eurofins Product Safety Labs.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 males

Details on study design:

Prior to test initiation, both eyes of a group of animals were examined using a white light source and a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) approximately 30 seconds after instillation of the fluorescein and then evaluated for corneal damage using an ultraviolet light source. Prior to instillation, the eyes were re-examined and scored for abnormalities according to the "Scale for Scoring Ocular Lesions".
Three healthy naive animals (not previously tested) without pre-existing ocular irritation were selected for test.
Initially, only one rabbit was placed on test. In the absence of significant irritation in this animal, the remaining two animals were tested to confirm the result.
Prior to instillation, two to three drops of ocular anesthetic (Tetracaine Hydrochloride Ophthalmic Solution, 0.5%) were placed into both the treated and control eye of each animal. One-tenth of a milliliter of the test substance was then instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The other eye of each rabbit remained untreated with the test substance and served as a control. The rabbits were then returned to their designated cages.
Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with Draize et al. at 1, 24, 48, and 72 hours post-instillation. The fluorescein dye evaluation procedure was used in the treated eye at 24 hours to verify the absence of corneal damage. Individual scores were recorded for each animal. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted.
Individual body weights of the animals were recorded prior to test substance instillation (initial) and again on the last day of individual scoring.
The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of eye and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

There was no corneal opacity noted for any treated eye during the study. Iritis was evident in two treated eyes and all three treated eyes exhibited conjunctivitis. All animals were free of ocular irritation by 72 hours.

Other effects:

All animals appeared active and healthy. No biologically significant weight loss occurred in any of the rabbits. Apart from eye irritation, there were no other clinical findings.

Interpretation of results:

GHS criteria not met

Conclusions:

No significant eye irritation effects were noted in the study.
According to the Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required.

Executive summary:

A primary eye irritation test was conducted with rabbits to determine the potential for test item to produce irritation from a single instillation via the ocular route. A skin irritation study was previously conducted. Minimal irritation was observed in this study. At the request of the Sponsor, the study was conducted in a stepwise fashion. Initially, one-tenth of a milliliter of the test substance was instilled into the conjunctival sac of the right eye of one healthy rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize et al. Since irritation cleared by 48 hours and there was no significant irritation observed in this animal, the test was completed on two additional animals, as described above. There was no corneal opacity noted for any treated eye during the study. Iritis was evident in two treated eyes and all three treated eyes exhibited conjunctivitis. All animals were free of ocular irritation by 72 hours.

According to the Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin Irritation/Corrosion

Two valid in vivo studies according to OECD TG 404 are available. No significant effects were noted in both studies on rabbits. All mean values (24/48/72h) for irritation scores were less than 1. Slightly irritant effects seen were fully reversible within the 72 hours of observation period.

Therefore, according to criteria set out in Regulation (EC) No. 1272/2008, the substance shall not be classified as skin irritant.

Eye Irritation:

Two valid in vivo studies according to OECD TG 405 are available. No significant effects were noted in both studies on rabbits. All mean values (24/48/72h) for irritation scores were less than 1. Slight irritant effects shown were fully reversible within the 72 hours of observation period.

Therefore, according to criteria set out in Regulation (EC) No. 1272/2008, the substance shall not be classified as eye irritant.

Respiratory irritation:

No data available.