4''-Ethyl-2',3,4,5-tetrafluor-1,1':4',1''-terphenyl

Endpoint summary

Description of key information

RA OECD 404: No skin irritating potential could be detected for the read-across source substance.

RA OECD 437: No skin irritating potential could be detected for the read-across source substance.

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

Study period:

March 10, 2003 - July 22, 2003

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:

April 24, 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Official Journal of the European Communities L383 A, Vol. 15, 29. December 1992.

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: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 22 weeks
- Weight at study initiation: 3.85 - 4.43 kg
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 20
- Humidity (%): 39 - 51
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light

IN-LIFE DATES: From: day 1 To: day 8

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per animal

VEHICLE
Name: Aqua pro injectione
Manufacturer: Merck KGaA, Darmstadt
Batch: 189
Released until: June 08, 2009

Duration of treatment / exposure:

4 hours

Observation period:

8 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: left side of the animal back
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Method: wiped off
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1 hour after removal, after 24, 48, 72 hours, and then daily up to experimental day 8

SCORING SYSTEM:
- Method of calculation: according OECD 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritating potential could be detected.

Other effects:

- Other adverse local effects:
none
- Other adverse systemic effects: No clinical signs and no mortality was observed. Body weight development was inconspicuous.

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritating potential could be detected.

Executive summary:

Study design

To test for primary skin irritation, 0.5 g of the test material, was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with 1 animal and followed by the confirmatory test with 2 further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days.

 

Results

Under the conditions of the present study, no signs of irritation were seen.

 

Body weight development of the treated rabbits was inconspicuous.

 

Conclusions

No skin irritating potential could be detected.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Please refer to chapter 13 for Read Across Justification.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritation potential was detected

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

GLP compliance:

yes (incl. QA statement)

Vehicle:

physiological saline

Controls:

yes

yes, concurrent vehicle

yes, concurrent positive control

Amount / concentration applied:

800 mg suspended in 4 mL saline

Duration of post- treatment incubation (in vitro):

240 min

Number of animals or in vitro replicates:

3

Details on study design:

According to guideline

Irritation parameter:

in vitro irritation score

Run / experiment:

mean

Value:

1.88

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

1

Value:

4.41

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

2

Value:

0.08

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Irritation parameter:

in vitro irritation score

Run / experiment:

3

Value:

1.16

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

With the negative control (0.9 % NaCl solution) an increase of opacity or permeability of the corneae could not be observed. The positive control (10 % (w/v) benzalconium chloride) showed clear opacity and distinctive permeability of the corneae and therefore, is classified as very severe eye irritant.

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, the test item is not considered to be an eye irritant in this study and under the experimental conditions reported.

Executive summary:

This in vitro study was performed to assess the corneal irritation and damage potential of the test material by means of the BCOP assay (OECD 437) using fresh bovine corneae. Damage is assessed by quantitative measurements of changes in corneal opacity and permeability with an opacitometer and a visible light spectrophotometer, respectively. Both measurements are used to calculate an in vitro irritation score, which is used to assign an in vitro irritancy category.

 

After a first opacity measurement of the fresh bovine corneae (t0), the test item/saline (0.9 % (w/v) NaCl in deionised water) stock, the positive, or the negative controls were applied to the epithelial surface of three corneae each and incubated for 240 minutes at 32 ± 2 °C. After the incubation phase the test item, the positive, or the negative controls were each rinsed from the corneae and opacity was measured again (t240).

 

After the opacity measurements, permeability of the corneae was determined by addition of 1 mL of a fluorescein solution to the anterior chamber of the corneal holder and subsequent incubation in a horizontal position at 32 ± 2 °C for 90 minutes. The permeability of the corneae was measured quantitatively by determination of the increase in fluorescein in the posterior chamber medium.

 

With the negative control (0.9% NaCl solution) an increase of opacity or permeability of the corneae could not be observed.

 

The positive control (10 % (w/v) Benzalconium chloride) showed clear opacity and distinctive permeability of the corneae and therefore, is classified as very severe eye irritant.

 

The test item did not cause any opacity or permeability of the corneae compared with the results of the negative control. The calculated mean in vitro irritation score was 1.88 and therefore, the test item was classified as non eye irritant.

 

In conclusion, the test item is not considered to be an eye irritant in this study and under the experimental conditions reported.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 437. A detailed read across justification is provided in chapter 13 of this dossier.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

in vitro irritation score

Run / experiment:

mean

Value:

1.88

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation parameter:

in vitro irritation score

Run / experiment:

1

Value:

4.41

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation parameter:

in vitro irritation score

Run / experiment:

2

Value:

0.08

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Irritation parameter:

in vitro irritation score

Run / experiment:

3

Value:

1.16

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

No study data with the test item is available for this endpoint. Therefore, a read-across to the read-across source substance with a very similar chemical structure and comparable physico-chemical parameters is used to evaluate the endpoint for the test item. A study was performed according to GLP and methods applied were fully compliant with OECD 404. The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin.. Afterwards the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with 1 animal and followed by the confirmatory test with 2 further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study, no signs of irritation were seen and no skin irritating potential could be detected.

 

Eye irritation

No study data with the test item is available for this endpoint. Therefore, a read-across to the read-across source substance with a very similar chemical structure and comparable physico-chemical parameters is used to evaluate the endpoint for the test item. A study was performed according to GLP and methods applied were fully compliant with OECD 405. This in vitro study was performed to assess the corneal irritation and damage potential of the test material by means of the BCOP assay (OECD 437) using fresh bovine corneae. Damage is assessed by quantitative measurements of changes in corneal opacity and permeability with an opacitometer and a visible light spectrophotometer, respectively. Both measurements are used to calculate an in vitro irritation score, which is used to assign an in vitro irritancy category. The test item did not cause any opacity or permeability of the corneae compared with the results of the negative control. The calculated mean in vitro irritation score was 1.88 and therefore, the test item was classified as non eye irritant. In conclusion, the test item is not considered to be an eye irritant in this study and under the experimental conditions reported.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation, the test item does not require classification for skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP).