2,6-dibromo-4-cyanophenyl heptanoate

Endpoint summary

Description of key information

Key, M-283361-01-1; skin irritation (rabbit, EPA OPP 81-5, GLP): not irritating

Key, M-280111-01-1; eye irritation (rabbit, EPA OPP 81-4, GLP): not irritating

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:

11 - 21 Jul 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2015

Deviations:

yes

Remarks:

Age and weight of animals not reported, environmental and general conditions of animals not reported, no data on untreated skin

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ray Nichols Rabbitry, Lumberton, Texas, USA
- Age at study initiation: Young adults
- Weight at study initiation: not specified
- Housing: individually in suspended, wire bottom, stainless steel cages
- Diet: Purina Rabbit Chow, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: From: 11 To: 21 Jul 1989

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 100% actual test material as received
- The test item has been liquified by heating to 45 °C prior to treatment.

Duration of treatment / exposure:

4 h

Observation period:

10 days

Number of animals:

3 per sex

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: a surgical gauze patch, held in place by non-irritating adhesive tape covered by semi-permeable dressing (orthopedic stockinette) loosely wrapped around the trunk of the animal

REMOVAL OF TEST SUBSTANCE
- Washing: test sites were gently washed with tap water and gauze
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h; 7 and 10 days after washing

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

female

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

female

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

male

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

female

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

female

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

female

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

All rabbits had erythema and edema that persisted through Day 7. The majority of edemas observed were very slight, scored with grade 1 in 5/6 animals. Well-defined erythemas were noted in all rabbits. 1 h after washing 3/6 animals revealed erythema of very mild degree (score 1). The remaining 3 animals showed erythema of grade 2. Ath the 24 h reading time point, 5/6 rabbits showed erythema of mild degree scored with grade 2. No skin reactions were noted latest on Day 10.

Other effects:

In individual cases sloughing of the skin of various thicknesses was observed at the 7 and 10 days reading time point.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

The study is in accordance with EPA guideline no. 81-5 and was conducted under GLP conditions. Although the study possesses deviations from the current OECD guideline no. 404 (skin irritation), such as missing information on age and weight of animals, environmental and general conditions of animals, and no data on untreated skin, it is considered valid and reliable. Under the conditions chosen the test substance did not induce skin irritation to rabbits. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for skin irritation is required.

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:

10 - 17 Jul 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2021

Deviations:

yes

Remarks:

Age and weight of animals not reported, environmental and general conditions of animals not reported, no data on untreated eye, no anesthetics and systemic analgesics were applied

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ray Nichols Rabbitry, Lumberton, Texas, USA
- Age at study initiation: young adults
- Weight at study initiation: not reported
- Housing: individually in suspended, wire bottom, stainless steel cages
- Diet: Purina Rabbit Chow, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

IN-LIFE DATES: From: 10 Jul 1989 To: 17 Jul 1989

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: 100% actual test material as received
- The test item has been liquified by heating to 45 °C prior to treatment.

Duration of treatment / exposure:

30 seconds (wash group)
continuous treatment (non-wash group)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

non-wash group: 3 per sex
wash group: 3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: either no washing was performed (non-wash group) or the treated eye was rinsed with deionized water for one minute (wash group)
- Time after start of exposure: 30 seconds (wash group only)

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: 0.2% fluorescein sodium ophthalmic solution

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of two animals scored (wash group)

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: one male was found dead on Day 1

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

male (non-wash group)

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

male (non-wash group)

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

male (non-wash group)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

female (non-wash group)

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #5

Remarks:

female (non-wash group)

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #6

Remarks:

female (non-wash group)

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of two animals scored (wash group)

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: one male was found dead on Day 1

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all six animals (non-wash group)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 to 7 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

of two animals scored (wash group)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: one male was found dead on Day 1

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all six animals (non-wash group)

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of two animals scored (wash group)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: one male was found dead on Day 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all six animals (non-wash group)

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

No effects on iris and cornea opacity were noted in any animal (wash and non-wash group). The test item induced conjunctivae redness in all animals of the non-wash group at the 1 h reading time point (6/6 animals scored grade 1). Full reversibility was observed after 4 (3/6 animals) to 7 days (3/6 animals). Chemosis was also observed at the 1 h reading time point for the non-wash group; 6/6 animals were scored grade 1 for this endpoint. In one animal the effect was already reversed after 24 h, in 3/6 animals after 48 h and in the remaining 2 animals after 72 h. In the wash group, conjunctivae redness was observed in all animals at the 1 h reading time point (grade 1) and full reversibility was observed after 72 h. In the same group, chemosis of grade 1 was noted in all three animals 1 h after exposure lasting until the 48 h reading time point.

Other effects:

One male of the wash group was found dead on Day 1 of the study (24 h after exposure). Positive fluorescein staining did not occur in any of the non-washed or washed eyes.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

The study is in accordance with EPA guideline no. 81-4 and was conducted under GLP conditions. Although the study possesses deviations from the current OECD guideline no. 405 (eye irritation), such as missing information on age and weight of animals, environmental and general conditions of anima, no anesthetics and systemic analgesics were applied; in some animals washing occured 30 sec after substance instillation, it is considered valid and reliable. Under the conditions chosen the test substance did not induce eye irritation to rabbits. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for eye irritation is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

The irritancy potential of the test substance to skin was evaluated according to EPA OPP 81-5 and in compliance with GLP (M-283361-01-1). The study is also in accordance with OECD guideline 404 with some deviations such as missing information on age, weight, housing conditions and general condition of animals and on untreated skin. In this study, the test item was liquified by heating to 45 °C prior to topical application of 0.5 mL test substance (purity 94.4%) to the clipped flank of 3 male and 3 female New Zealand White rabbits under a semi-occlusive dressing for 4 h. After patch removal, the skin was washed with water and scored for erythema and edema at reading time points 1, 24, 48, 72 h and 7 and 10 days after washing. All rabbits had erythema and edema that persisted through Day 7. The majority of edemas observed were very slight, scored with grade 1 in 5/6 animals. Well-defined erythemas were noted in all rabbits. 1 h after washing 3/6 animals revealed erythema of very mild degree (score 1). The remaining 3 animals showed erythema of grade 2. Ath the 24 h reading time point, 5/6 rabbits showed erythema of mild degree scored with grade 2. No skin reactions were noted latest on Day 10. The mean erythema score (24/48/72 h) was 2, 1.7, 1, 2, 2 and 2 for the six rabbits, respectively. The mean edema score over 24, 48 and 72 h was 1 in 5/6 rabbits and 1.3 in 1/6 rabbits. Sloughing of the skin of various thicknesses was observed in individual cases at the 7 and 10 days reading time point. In conclusion, the test substance did not exhibit skin-irritating properties in the conducted study.

 

 

Eye irritation

A GLP-conform eye irritation/corrosion study was performed according to EPA OPP 81-4 to evaluate the eye irritancy potential of the test substance (M-280111-01-1). The study is also in accordance with OECD guideline 405 with some deviations such as missing information on age, weight, housing conditions and general condition of animals. The test material (94.4% purity) was liquified by heating to 45 °C prior to instillation of 0.1 mL into the eye of each of nine New Zealand White rabbits (6 males and 3 females). In three of the six male rabbits, the eyes were rinsed with deionized water for 1 minute 30 seconds after start of exposure (wash group). In the remaining animals, the eyes were not rinsed (non-wash group). One of the rabbits in the wash group was found dead on Day 1 of the study (24 h after washing). No effects on iris and cornea opacity were noted in any animal (wash and non-wash group). The test item induced conjunctivae redness in all animals of the non-wash group at the 1 h reading time point (6/6 animals scored grade 1). Full reversibility was observed after 4 (3/6 animals) to 7 days (3/6 animals). Chemosis was also observed at the 1 h reading time point for the non-wash group; 6/6 animals were scored grade 1 for this endpoint. In one animal the effect was already reversed after 24 h, in 3/6 animals after 48 h and in the remaining 2 animals after 72 h. In the wash group, conjunctivae redness was observed in all animals at the 1 h reading time point (grade 1) and full reversibility was observed after 72 h. In the same group, chemosis of grade 1 was noted in all three animals 1 h after exposure lasting until the 48 h reading time point. In the non-wash group the mean scores evaluated over 24, 48 and 72 h were 0.0 (iris, all six animals), 0.0 (opacity, all six animals), 1.0 (conjunctivae redness, all six animals) and 0.7, 0.7, 0, 0.3, 0.3 and 0.3 for the six animals exposed (chemosis). In the wash group, mean scores evaluated over 24, 48 and 72 h were 0.0 (iris), 0.0 (opacity), 0.7 (conjunctivae score) and 0.3 (chemosis) for both animals scored at these reading time points. In conclusion, the test substance did not exhibit eye-irritating properties in the conducted study.

Justification for classification or non-classification

The available data on skin and eye irritation/corrosion do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.