3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione;famoxadone (ISO)

Skin irritation / corrosion

Administrative data

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:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: MAFF Japan, 59 NohSan No. 4200 Testing Guidelines for Toxicity Studies (1985)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5-methyl-5-(4-phenoxyphenyl)-3-(phenylamino)-1,3-oxazolidine-2,4-dione

EC Number:

603-520-1

Cas Number:

131807-57-3

Molecular formula:

C22H18N2O4

IUPAC Name:

5-methyl-5-(4-phenoxyphenyl)-3-(phenylamino)-1,3-oxazolidine-2,4-dione

Test material form:

solid

Specific details on test material used for the study:

Substance ID: DPX-JE874
Lot Number: DPX-JE874-221
Purity: 97.28%

Test animals

Species:

rabbit

Strain:

other: HM:(NZW)fBR New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hare Marland, Hewitt, New Jersey
- Weight at study initiation: 2166 to 3117 g
- Housing: Housed singly in suspended, stainless steel, wire-mesh cages
- Diet: Approximately 125 g/day
- Water: ad libitum
- Acclimation period: 7 or 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1°C
- Humidity: 50 ± 10%
- Photoperiod 12-hour light/12-hour dark cycle

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

deionozed

Amount / concentration applied:

Approximately 0.5 g (moistened with 1 mL of deionized water to form a thick paste)

Duration of treatment / exposure:

4 h

Observation period:

The test sites were evaluated and scored according to a numerical scale, approximately 1, 24, 48, and 72 hours after the end of the 4-hour exposure period. One rabbit was further examined at 4
and 7 days after test substance removal.

Number of animals:

06 Females

Details on study design:

TEST SITE
- Area of exposure: Approximately 6 cm2
- Type of wrap if used: Test site is covered with a 2-ply, 1-inch gauze square. The patch was held in place with non-irritating tape. The rubber sheeting was then wrapped around the animal and secured with clips to retard evaporation and to keep the test substance in contact with the skin without undue pressure

REMOVAL OF TEST SUBSTANCE
- Washing: Gently washed with warm water to remove excess test substance and gently patted dry.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
Approximately 1 hour after removal of the test patches, the test sites were evaluated for erythema, edema, and other evidence of dermal effects and were scored according to the Draize Scale. Additional evaluations were made at approximately 24, 48, and 72 hours after removal of the patches. One rabbit was further examined at 4 and 7 days.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.61

Max. score:

4

Reversibility:

fully reversible within: 7 d

Results 8

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 13

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 14

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 15

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Irritant / corrosive response data:

Two rabbits exhibited no dermal irritation throughout the study. The remaining 4 rabbits
exhibited erythema (score of 1 or 2) at 1 and 24 hours after test substance removal. At 48 hours,
dermal irritation had cleared in 2 rabbits; erythema (score of 1 or 2) was observed in the
remaining 2 rabbits. At 72 hours, dermal irritation had cleared in one rabbit; erythema (score of
2) and desquamation were observed in one rabbit. This rabbit exhibited erythema (score of 1)
and desquamation at 4 days. All dermal irritation cleared in this rabbit by 7 days. No edema,
was observed during the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is classified as Non-Irritant

Executive summary:

The test substance was evaluated for acute skin irritation potential in 6 female New Zealand White rabbits according to the guidelines OECD 404 and US EPA 81-5. Approximately 0.5 g of the test substance was administered to a localized test site on the back of each animal. The test sites were covered with a semi-occlusive dressing to ensure contact between the skin and test substance. The animals were exposed to the test substance for approximately 4 hours.

The test sites were evaluated and scored according to a numerical scale, approximately 1, 24, 48, and 72 hours after the end of the 4-hour exposure period. One rabbit was further examined at 4 and 7 days after test substance removal.

Two rabbits exhibited no dermal irritation throughout the study. The remaining 4 rabbits exhibited erythema (score of 1 or 2) at 1 and 24 hours after test substance removal. At 48 hours, dermal irritation had cleared in 2 rabbits; erythema (score of 1 or 2) was observed in the remaining 2 rabbits. At 72 hours, dermal irritation had cleared in one rabbit; erythema (score of 2) and desquamation were observed in one rabbit. This rabbit exhibited erythema (score of 1) and desquamation at 4 days. All dermal irritation cleared in this rabbit by 7 days. No edema, significant weight loss, or clinical signs of toxicity were observed during the study.

Mean values erythema scores observed at 24, 48, and 72 hours following exposure are 1.0, 0.5 and 0.33 respectively and the mean edema scores are 0.0, 0.0 and 0.0 respectively.

Based on the overall averages of the mean values calculated for erythema and edema, according to the guide to the labeling of dangerous substances published in the Official Journal of the European Communities (EEC Directive 93/21), Famoxadone can be classified as "NON-IRRITANT" and labeled:

Symbol - None

Risk Phrase - No Risk Phrase

For each of 6 rabbits, the values for both erythema and edema derived at 1, 24, 48, and 72 hours were summed and divided by 4 to obtain a primary dermal irritation score. A Primary Irritation Index (P.I.I.) or average of these 6 individual scores was also calculated. These values are 0.5, 2.0, 1.0. 0.5, 0 and 0 for the individual animals respectively.

According to the guidance provided by the U.S. EPA on data reporting and for toxicity classification and label statements for skin hazards of pesticides, the test substance is considered to be a mild or slight skin irritant (P.I.I. less than 2) and is classified in Toxicity Category IV. This classification is based on the calculated P.I.I. of 0.67 and the presence of erythema (score of 2) at 72 hours.