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

Endpoint summary

Description of key information

Skin: Rabbit. No irritation. OECD 404, OPP 81-5, EU Method B.4, JMAFF 59-NohSan-4200, Reliability = 1

Skin: Rabbit. No irritation. OECD 404, OPP 81-5, EU Method B.4, JMAFF 59-NohSan-4200, Reliability = 1

Eye: Rabbit. Slight irritation resolved in 72hrs. OECD 405, OPP 81-4, EU Method B.5, JMAFF 59-NohSan-4200, Reliability = 1

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:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Substance ID: DPX-JE874 technical
Lot Number: DPX-JE874-221
Purity: 97.4%

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

deionized

Amount / concentration applied:

Approximately 0.5 g (moistened with 1 mL of deionized water)

Duration of treatment / exposure:

4 h

Observation period:

The test sites were evaluated and scored approximately 1, 24, 48, and 72 hours after the end of the 4-hour exposure period.

Number of animals:

04 Males and 02 Females

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Irritant / corrosive response data:

The test substance produced erythema (score of 1) in 4 rabbits by 1 hour after patch removal. By 24, 48 and 72 hours after patch removal, no erythema was observed in the treated rabbits. No dermal edema or corrosion was observed during this study.

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.

The test substance was evaluated for acute skin irritation potential in 6 New Zealand White rabbits. Approximately 0.5 g 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.

The test substance produced erythema (score of 1) in 4 rabbits by 1 hour after patch removal. By 24, 48 and 72 hours after patch removal, no erythema was observed in the treated rabbits. No dermal edema or corrosion was observed during this study. The mean erythema and edema score of all the animals is 0.0 and 0.0 respectively.

On the basis of the overall averages, and according to the guide to the labeling of dangerous substances published in the Official Journal of the European Communities (EEC Directive 93/21), the test substance can be classified as "NON-IRRITANT” and labeled:

Symbol – None

Risk Phrase - No Risk Sentence

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 (РII) or average of these 6 individual scores was also calculated.

The PII was 0.3, 0, 0.3, 0.3, 0.3 and 0 for the individual rabbits 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 irritant (РII less than 2) and is classified in Toxicity Category IV.

Reference 2

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

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

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

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.

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

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

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

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.61

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

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.

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.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: MAFF Japan, 59 NohSan No. 4200 (1985)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

Substance ID: DPX-JE874-221 Technical
Lot #: DPX-JE874-221
Purity: 97.4%

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hare Marland, Hewitt, New Jersey
- Weight at study initiation: 2094 to 2277 g
- Housing: The rabbits were housed singly in suspended, stainless steel, wire-mesh cages.
- Diet: Approximately 125 grams/day
- Water: ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 2°C
- Humidity: 50 ± 10%
- Photoperiod: 12-hour light/12-hour dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye of each rabbit was not treated with the test substance and served as a control.

Amount / concentration applied:

Approximately 20 mg (a weight equivalent to a 0.1 mL volume of test substance)

Duration of treatment / exposure:

The treated and control eyes of all animals remained unwashed.

Observation period (in vivo):

Approximately 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

06 Males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not done

SCORING SYSTEM: Draize Scale

TOOL USED TO ASSESS SCORE: Illumination and magnification

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The test substance produced conjunctival redness (score of 1 or 2) and chemosis (score of 1) in all treated rabbit eyes. Iritis (score of 1) was observed in 1 rabbit and discharge (score of 2) was observed in 1 rabbit only at the 1-hour evaluation. All ocular irritation resolved by 72 hours after treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is considered as non irritating to rabbit eyes

Executive summary:

The study was conducted according to OECD guideline 405 and EPA guideline 81-4.

The test substance was evaluated for acute eye irritation potential in 6 male young adult New Zealand White rabbits. Approximately 20 mg (occupying a volume of approximately 0.1 mL) was administered to 1 eye of each test animal. The eyes remained unwashed following treatment.

The conjunctiva, iris, and cornea of each treated eye were evaluated and scored according to a numerical scale approximately 1, 24, 48, and 72 hours following administration of the test substance.

The test substance produced conjunctival redness (score of 1 or 2) and chemosis (score of 1) in all treated rabbit eyes. Iritis (score of 1) was observed in 1 rabbit and discharge (score of 2) was observed in 1 rabbit only at the 1-hour evaluation. All ocular irritation resolved by 72 hours after treatment.

The over all mean irritation scores of all the animals (at 24, 48 and 72 h post application) were 0.2, 0.4, 0.0, and 0.0 for conjunctival chemosis, conjunctival redness, iritis and corneal opacity, respectively.

On the basis of the overall averages of the mean values, and according to the guide to the labeling of dangerous substances published in the Official Journal of the European Communities (EEC Directive 93/21), the test substance can be classified as "Non-irritant" and labeled:

Symbol - None

Risk Phrase – None

According to the guidance provided by the U.S. EPA for toxicity classification and label statements for eye hazards of pesticides, the test substance is classified in Toxicity Category III since all positive irritant effects resolved by 48 hours after treatment.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In two acute dermal irritation studies in rabbits conducted according to OECD guideline 404, OPP 81.5, EU Method B.4 and JMAFF 59-NohSan-4200, no dermal irritation was noted.  

An eye irritation study in rabbit was conducted according to OECD 405, OPP 81-4, EU Method B.5, and JMAFF 59-NohSan-4200. The test substance produced conjunctival redness (score of 1 or 2) and chemosis (score of 1) in all treated rabbit eyes. Iritis (score of 1) was observed in 1 rabbit and discharge (score of 2) was observed in 1 rabbit only at the 1-hour evaluation. All ocular irritation resolved by 72 hours after treatment. The over all mean irritation scores of all the animals (at 24, 48 and 72 h post application) were 0.2, 0.4, 0.0, and 0.0 for conjunctival chemosis, conjunctival redness, iritis and corneal opacity, respectively. On the basis of the overall averages of the mean values, and according to the guide to the labeling of dangerous substances published in the Official Journal of the European Communities (EEC Directive 93/21), the test substance can be classified as "Non-irritant"

Justification for classification or non-classification

The test substance produced no skin irritation and, therefore, does not need to be classified for skin irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

In the eye irritation study, conjunctival redness and chemosis was observed in all treated rabbit eyes. Iritis was observed in 1 rabbit and discharge was observed in 1 rabbit only at the 1-hour evaluation. All ocular irritation resolved by 72 hours after treatment. Therefore, the substance does not need to be classified for eye irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.