4'-Butyl-4-ethoxy-2,3-difluoro-1,1'-biphenyl

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

30 Sep 2019 - 14 Jan 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The study was performed for a registration in a non-EU country.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

EC No 440/2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4'-butyl-4-ethoxy-2,3-difluoro-1,1'-biphenyl

EC Number:

695-755-1

Cas Number:

1229661-51-1

Molecular formula:

C18H2F2O

IUPAC Name:

4'-butyl-4-ethoxy-2,3-difluoro-1,1'-biphenyl

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Species: Rabbit
Strain: New Zealand White
Condition: SPF-Quality
Source: Charles River France, L’Arbresle, France
Number of Animals: 3 Males
Age at the Initiation of Dosing: young adult animals (approximately 12-15 weeks old) were selected.
Weight at the Initiation of Dosing: 2571 to 3184 g
Acclimatisation: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C
- Humidity (%): 48 to 76%.
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12/12 hours

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of skin irritation observed in the first animal.

Details on study design:

TEST SITE
Approximately 24 hours before dosing, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring,
the treated skin area was re-clipped at least 3 hours before the observations.
The animal was treated by dermal application of 0.5 grams of the test item. The test item was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. Four hours after the application, the dressing was removed and the skin cleaned of residual test item using tap water.

SCORING SYSTEM:
- Method of calculation:

The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 and 14 days after the removal of the dressings and test item. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of the animal served as control.
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

Erythema and eschar formation:
No erythema .............................................................................................................................................................. 0
Very slight erythema (barely perceptible) ................................................................................................................. 1
Well-defined erythema ............................................................................................................................................... 2
Moderate to severe erythema..................................................................................................................................... 3
Severe erythema (beef redness) * ............................................................................................................................ 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema.................................................................................................................................................................. 0
Very slight oedema (barely perceptible)..................................................................................................................... 1
Slight oedema (edges of area well-defined by definite raising)................................................................................. 2
Moderate oedema (raised approximately 1 millimeter)................................................................................................ 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) ................................. 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of mild irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

Four hours exposure to 0.5 g of the test material resulted in very slight, well defined or moderate to severe (scattered) erythema and very slight to well-defined oedema in the treated skin areas of all three rabbits. Scaliness of the skin was noted in one animal after 7 days. The skin irritation resolved completely within 7 days in two animals and within 14 days after exposure in the remaining animal.

Other effects:

No staining of the treated skin by the test item was observed and no test item remnants were seen.
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), the test material should be classified as: mild skin irritant (Category 3).
According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), the test material does not have to be classified and has no obligatory labelling requirement for skin irritation.

Executive summary:

The objective of this primary skin irritation study was to assess the possible irritation or corrosion potential of a single dose of the test material when administered to the intact skin of rabbits.

Three rabbits were exposed to 0.5 grams of the test material, moistened with 0.3 mL water by application onto clipped skin for 4 hours using a semi-occlusive

dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 and 14 days after exposure.

The exposure resulted in very slight, well defined or moderate to severe (scattered) erythema and very slight to well-defined oedema in the treated skin areas of all three rabbits. Scaliness of the skin was noted in one animal after 7 days. The skin irritation resolved completely within 7 days in two animals and within 14 days after exposure in the remaining animal.

Based on these results:

• According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), the test material should be classified as: mild skin irritant (Category 3).

• According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), the test material does not have to be classified and has no obligatory labelling requirement for skin irritation.