Hexafluoropropene, oxidized, oligomers, reduced, fluorinated

Endpoint summary

Description of key information

An in vivo skin irritation study, conducted according to OECD guideline No. 404 and in vivo eye irritation study conducted according to OECD guideline No. 405 are reported. Both of the studies were conducted under GLP. The reliability of the studies according to Klimish score is K1. Basing on experimental results, according to REGULATION (EC) No 1272/2008, GALDEN LMW does not meet the classification criteria for human health both for skin and eye irritation.

The potential of GALDEN LMW to be irritating to the respiratory tract was assessed basing on the results of the acute toxicity study conducted by inhalation on rats. Basing on the results GALDEN LMW is not irritant to the respiratory tract following single exposure.

Signs of irritant effects were noted in the respiratory tract following repeated exposures by inhalation at high concentrations (ca. 20000 ppm) in a 14-day inhalation study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Remarks:

Skin irritation/corrosion

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 May 1992 to 22 May 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline-conform study conducted under GLP.

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)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: livestock farming
- Age at study initiation: about 2-3 months
- Weight at study initiation: about 2.5 - 3 kg
- Housing: individual caging in air-conditioned rooms. Metal cages measuring 62 x 47.5 x 38 cm.
- Diet (e.g. ad libitum): Certificated pelleted diet, supplied with vitamins and trace elements. Available ad libitum
- Water (e.g. ad libitum): from municipal water main system, filtered and disrtibuted ad libitum.
- Acclimation period: about 2 months. Animals were observed daily to ascertain their fitness for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +-2
- Humidity (%): 50 % +- 15
- Air changes (per hr): about 15/ hour
- Photoperiod (hrs dark / hrs light): 12 hour cicle (7 a.m.-7 p.m.)

IN-LIFE DATES: From: To: not reported

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml /animal
- Concentration (if solution): not applicable

VEHICLE
Test material was applied as supplied by the sponsor.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 females

Details on study design:

Firstly one rabbit was used and three treatment sites were prepared. On the first site the test article was applied for an exposure period of 3 minutes. No serious gross skin reactions are noted and the test article was applied for an exposure period of 1 hour on the second site. The application area was covered with a gauze patch loosely held in contact with the skin by an impermeable, non.irritant, hypoallergenic tape. No serious gross reactions are observed after the one-hour exposure period and the test article was appliedfor an exposure period of 4 hours on the third skin site. This area was covered with a gauze patch as above. The test was completed using two additional animals with a 4 hour exposure period.

TEST SITE
- Area of exposure: about 6 cm2
- % coverage: occlusive
- Type of wrap if used: gauze patch loosely held in contact with the skin by an impermeable, non.irritant, hypoallergenic tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 hours

SCORING SYSTEM: the skin reaction was scored according to the following scale:

VALUE ERYTHEMA AND ESCHAR FORMATION
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well-defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to slight eschar formatioon (injuries in deoth)


VALUE EDEMA FORMATION
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well defined by definite raising)
3 Moderate edema (raised approximately 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 60 min

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

same result in all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 60 min

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

same result in all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No dermal modifications were observed in any animal.

Other effects:

No animals died.
No clinical signs or behavioral alterations were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions adopted, GALDEN LMW is to be considered "NON IRRITANT" for the skin when administered by dermal route to rabbits.

Executive summary:

The purpose of the study was to evaluate the acute dermal irritation and/or corrosive effects on skin following the application of the test article GALDEN LMW.

The test method was in accordance with the EEC Guidelines B.4 and with OECD guidelines 404 (Paris 1981, and subsequent revisions).

Three New Zeland White female rabbits were treated with a single application of 0.5 ml of the test article.

Approximately 24 hours before the test, fur was clipped from the trunk of the animals. Care was taken not to abrade the skin. Only animals with intact skin were used.

The test article was applied to a small area (approximately 6 cm2) of skin. Firstly one rabbit was used and three treatment sites of the skin were prepared. On the first site the test article was applied for an exposure period of 3 minutes. No serious gross skin reactions were noted and the test article was applied for an exposure period of 1 hour on the second site. The application area was covered with a gauze patch loosely held in contact with the skin by an impermeable, non-irritant, hypoallergenic tape. No serious gross reaction were observed after the one-hour exposure period and the test article was applied for an exposure period of 4 hours on the third skin site. This area was covered with a gauze patch as above. The test was completed using two additional animals with a 4 hour exposure period. At the end of the exposure period, residual test substance was removed, without altering the existing response of the integrity of the epidermis.

Neither deaths occurred as a result of treatment, nor clinical signs or behavioral alterations were observed untoward.

At the application site, no dermal reactions were detected in any rabbit.

The test article GALDEN LMW when administered by dermal route to rabbits under the experimental conditions adopted, is to be considered "NON IRRITANT" for the skin.

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:

9 June 1992 to 12 June 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline-conform study conducted under GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(1981 and subsequest revisions)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: livestock farming
- Age at study initiation: about 2-3 months
- Weight at study initiation: about 2.5 - 3 kg
- Housing: individual caging in air-conditioned rooms. Metal cages measuring 62 x 47.5 x 38 cm.
- Diet (e.g. ad libitum): Certificated pelleted diet, supplied with vitamins and trace elements. Available ad libitum
- Water (e.g. ad libitum): from municipal water main system, filtered and disrtibuted ad libitum.
- Acclimation period: about 3 weeks. Animals were observed daily to ascertain their fitness for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +-2
- Humidity (%): 50 % +- 15
- Air changes (per hr): about 15/ hour
- Photoperiod (hrs dark / hrs light): 12 hour cicle (7 a.m.-7 p.m.)

IN-LIFE DATES: From: To: not reported

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml /animal
- Concentration (if solution): not applicable

VEHICLE
Test material was applied as supplied by the sponsor.

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

at 1, 24, 48 and 72 hours after the test article application.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with sterile saline.
- Time after start of exposure: 24h

SCORING SYSTEM:
The ocular reaction was scored according to the following scale (guide issued by U.S. Consumer Product Safety Commission (CPSC)).
The ocular irritation score was evaluated in conjuction with the nature and the reversibility or otherwise of the responses observed.

VALUE "CORNEA
Opacity: degree of density (most dense area taken for reading)"
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible
2 Easily discernible translicent area, details of iris slightly obscured
3 Nacreous area, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity.


VALUE IRIS
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combinations of any theof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, hemorrhage, gross destruction (any or all of these)


VALUE "CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)"
0 Blood vessels normal
1 Some blood vessels definitely hyperemic (injected)
2 Diffuse, crimson colour, indivicual vessels not easily discernible
3 Diffuse beefy red

VALUE "CONJUNCTIVAE
Chemosis:lids and /or nictating membranes"
0 No swelling
1 Any swelling above normal (includes nictating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half closed
4 Swelling with lids more that half closed


TOOL USED TO ASSESS SCORE: visual inspection.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

other: 60 min

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

other: 60 min

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

other: 60 min

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

other: 60 min

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

same results in all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Cornea and iris: no modification of this tissues was observed in any animals.
Conjunctivae: no changes were seen at all the observations performed in any treated rabbit.

Other effects:

No animals died.
No clinical signs or behavioral alterations were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

The test article GALDEN LMW when administred by ocular route to rabbit under the experimental conditions adopted, is to be considered "NON IRRITANT" for the eye.

Executive summary:

The purpose of the study was to evaluate the acute eye irritation and/or corrosive effects on the eye following the application of the test article GALDEN LMW.

The test method was in accordance with the EEC Guidelines B.5 and with OECD guidelines 405 (Paris 1981, and subsequent revisions).

Three New Zealand White rabbit were treated with a single administration of 0.1 ml of the test article GALDEN LMW.

Both eyes of each experimental animal selected for the testing were examined within 24 hours before testing started.

The test article was placed in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about 3 -4 seconds in order loss of material. The other eye (the left), remaining untreated, served as control. The eyes of the animals were washed out at 24 hours following the test article administration.

The U.S. Consumer Product Safety Commission (CPSC) guide was used as reference source for evaluating and scoring the reaction.

No clinical signs or behavioural alterations were observed.

No sign of ocular irritancy were seen in all treated animals at all the observations.

The test article GALDEN LMW when administred by ocular route to rabbit under the experimental conditions adopted, is to be considered "NON IRRITANT" for the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Under the in vivo dermal irritation study, three females New Zeland White rabbits were treated with a single application of 0.5 ml of undiluted GALDEN LMW. The duration of exposure was 4 hours and the exposure area was covered by an occlusive patch. The observation period was 72 hours.

Neither deaths occurred as a result of treatment, nor were observed untoward clinical signs or behavioral alterations. At the application site, no dermal reactions were detected in any rabbit. In conclusion, GALDEN LMW when administered by dermal route to rabbits is to be considered "NON IRRITANT" for the skin.

 

Under the in vivo eye irritation study, three males New Zeland White rabbits were treated with a single application of 0.1 ml of undiluted GALDEN LMW. 

The test article was placed in the conjunctival sac of the right eye of each animal, then the eyes of the animals were washed out at 24 hours following the test article administration. The observation period was 72 hours.

The U.S. Consumer Product Safety Commission (CPSC) guide was used as reference source for evaluating and scoring the reaction.

No clinical signs or behavioural alterations were observed during exposure or observation period. No signs of ocular irritancy were seen in all treated animals at all the observations.

In conclusion, GALDEN LMW when administred by ocular route to rabbit is to be considered "NON IRRITANT" for the eye.

GALDEN LMW was tested on rats in one acute toxicity study by inhalation. No human exposure data by inhalation are available.

In the acute toxicity study, no clinical signs of respiratory tract irritation and no macroscopic findings on the respiratory system were observed in rat during and/or following exposure to the vapours at the concentration of 1627 mg/L. Basing on the results, GALDEN LMW is concluded to be not irritant for the respiratory system. However, signs of irritation on the respiratory tract were observed following repearted exposures to high concentrations.

Justification for classification or non-classification

No signs of irritation have been observed under the in vivo studies of eye and dermal irritation.

GALDEN LMW does not meet the classification criteria according to GHS and Regulation (EC) No 1272/2008 for the hazard classes “Serious eye damage / irritation” and “Skin irritation/corrosion”.

Moreover, no signs of respiratory irritation were observed after single exposure by inhalation in the acute toxicity study conducted at the high concentration, therefore GALDEN LMW does not fulfill the classification criteria for respiratory tract irritation - STOT SE 3 according to GHS and the Regulation (EC) No. 1272/2008 (CLP).