Iodonium, bis[4-(1,1-dimethylethyl)phenyl]-, hexafluorophosphate(1-) (1:1)

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): corrosive

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:

21 Dec 2011 - 08 Jan 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - 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)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM

Species:

rabbit

Strain:

other: New Zealand White (Hsdlf:NZW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.56-2.80 kg
- Housing: animals were housed individually in suspended cages.
- Diet: 2930C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g (moistened with 0.5 mL distilled water to achieve a paste)

Duration of treatment / exposure:

animal 1: 3 min, 1h and 4 h; animals 2 and 3: 4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm on the back of the rabbit
- Type of wrap if used: the test substance was placed on a cotton gauze patch, which was held in contact with a strip of surgical adhesive tape. The trunk of the animal was wrapped in an elastic corset during exposure.

REMOVAL OF TEST SUBSTANCE
- Washing: residual test substance was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 min, 1 h and 4 h in animal 1; 4 h in animals 2 and 3

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean after 24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean after 24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

No effects on skin irritation were observed in animal 1 3 min and 1 h after test substance application. In the same animal very slight erythema was noted at the treated site of skin immediately and 1 h after exposure to the test substance for 4 h. Very slight erythema was also observed in animal 3 at the 24 and 48 h readiong time points after 4 h treatment. In animal 2, no skin irritation effects were noted at any of the observation time points.

Other effects:

No further local or systemic effects were observed.

The pH of the test substance at 10% (w/v) in aqueous solution was 4.5 (immediately) or 4.1 (after 10 min).

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD not classified

Executive summary:

The skin irritation potential of PF-6 was investigated in a study according to OECD guideline 404 and GLP. The test substance (0.5 g moistened with 0.5 mL distilled water) was applied to the clipped skin of 3 young adult New Zealand White (Hsdlf:NZW) rabbits under semiocclusive conditions. The first animal was exposed to the test substance for 3 min, 1 h or 4 h, whereas in the further 2 animals treatment was performed for 4 h. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after patch removal. Exposure to the test substance for 3 min or 1 h did not elicit any skin reactions at the application site of the first animal at any of the observation time points. In the same animal, very slight erythema was observed 1 h after exposure to the test substance for 4 h, which was reversible within 24 h. Very slight erythema was also observed in the third animal at the 24 and 48 h, but not at the 72 h reading time point after 4 h treatment. In the second animal, no skin irritation effects were noted at any of the observation time points. No signs of systemic toxicity were seen in any of the animals tested. The mean erythema and edema scores after 24, 48 and 72 h were 0 for the first and second animal. In the third animal, the mean erythema and edema scores after 24, 48 and 72 h were 0.67 and 0, respectively.

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:

16 - 30 Jan 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - 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)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM

Species:

rabbit

Strain:

other: New Zealand White (Hsdlf:NZW)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.1 kg
- Housing: the animal was housed in a suspended cage.
- Diet: 2930C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL (volume measured with a syringe, corresponds to 90 mg)

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48 and 72 h and 7 days

Number of animals or in vitro replicates:

1

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: the animal was killed for humane reasons immediately after the 7-day observation period

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean after 24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

Single application of the test substance to the eye of one rabbit induced scattered or diffuse corneal opacity at the 24 and 48 h readings. Translucent corneal opacity was observed 72 h and 7 days post-application. In addition, a small area of opalescent corneal opacity was observed at the 72 h reading and blood stained discharge occurred 7 days post-application. Iridial inflammation was noted in the animals at the 24, 48 and 72 h readings as well as 7 days after test substance application. Moderate to severe conjunctival redness and chemosis were observed in the animal at the 24, 48 and 72 h as well as the 7 day observation time points. All effects on the treated eye were not reversible within the 7-day observation period.

Other effects:

Due to worsening reactions and signs of pain and discomfort, the animal was killed for humane reasons immediately after the 7-day observation period.

MEASUREMENT OF pH

The pH of the test substance at 10% (w/v) in aqueous solution was 4.5 (immediately) or 4.1 (after 10 min).

RABBIT ENUCLEATED EYE TEST

In the preliminary Rabbit Enucleated Eye Test (REET), the test substance was not found to cause effects on corneal thickness, corneal opacity, corneal epithelium, and fluorescein uptake in the enucleated eyes of New Zealand white rabbits.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Eye Dam. 1, H318
DSD: Xi, R41

Executive summary:

The eye irritation potential of PF-6 was investigated according to OECD guideline 405 and in compliance with GLP. The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 1 New Zealand White (Hsdlf:NZW) rabbit. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h as well as 7 days after application. Single application of the test substance to the eye of one rabbit induced scattered or diffuse corneal opacity at the 24 and 48 h readings. Translucent corneal opacity was observed 72 h and 7 days post-application. In addition, a small area of opalescent corneal opacity was observed at the 72 h reading and blood stained discharge occurred 7 days post-application. Iridial inflammation was noted in the animals at all reading time points during the 7-day observation period. Moderate to severe conjunctival redness and chemosis were observed in the animal at the 24, 48 and 72 h as well as the 7 day observation time points. None of the observed effects on the treated eye was reversible within the 7-day observation period. Due to worsening reactions and signs of pain and discomfort, the animal was killed for humane reasons immediately after the 7-day observation period. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 1.3, 1, 2 and 2.3 in the animal, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

The skin irritation potential of PF-6 was investigated in a study according to OECD guideline 404 and GLP (Bradshaw, 2012). The test substance (0.5 g moistened with 0.5 mL distilled water) was applied to the clipped skin of 3 young adult New Zealand White (Hsdlf:NZW) rabbits under semiocclusive conditions. The first animal was exposed to the test substance for 3 min, 1 h or 4 h, whereas in the further 2 animals treatment was performed for 4 h. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after patch removal. Exposure to the test substance for 3 min or 1 h did not elicit any skin reactions at the application site of the first animal at any of the observation time points. In the same animal, very slight erythema was observed 1 h after exposure to the test substance for 4 h, which was reversible within 24 h. Very slight erythema was also observed in the third animal at the 24 and 48 h, but not at the 72 h reading time point after 4 h treatment. In the second animal, no skin irritation effects were noted at any of the observation time points. No signs of systemic toxicity were seen in any of the animals tested. The mean erythema and edema scores after 24, 48 and 72 h were 0 for the first and second animal. In the third animal, the mean erythema and edema scores after 24, 48 and 72 h were 0.67 and 0, respectively.

 

Eye Irritation

The eye irritation potential of PF-6 was investigated according to OECD guideline 405 and in compliance with GLP (Bradshaw, 2012). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 1 New Zealand White (Hsdlf:NZW) rabbit. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h as well as 7 days after application. Single application of the test substance to the eye of one rabbit induced scattered or diffuse corneal opacity at the 24 and 48 h readings. Translucent corneal opacity was observed 72 h and 7 days post-application. In addition, a small area of opalescent corneal opacity was observed at the 72 h reading and blood stained discharge occurred 7 days post-application. Iridial inflammation was noted in the animals at all reading time points during the 7-day observation period. Moderate to severe conjunctival redness and chemosis were observed in the animal at the 24, 48 and 72 h as well as the 7 day observation time points. None of the observed effects on the treated eye was reversible within the 7-day observation period. Due to worsening reactions and signs of pain and discomfort, the animal was killed for humane reasons immediately after the 7-day observation period. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 1.3, 1, 2 and 2.3 in the animal, respectively.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on eye irritation of PF-6 meet the criteria for classification as Eye Dam. 1 (H318) according to Regulation (EC) 1272/2008 and as Xi (R41) according to Directive 67/548/EEC. The available data on skin irritation of PF-6 do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.