2,6-dibromo-4-cyanophenyl octanoate

Endpoint summary

Description of key information

Key, M-185075-01-2; skin irritation (rabbit, OECD 404, GLP): not irritating

Key, M-185080-01-1; eye irritation (rabbit, OECD 405, 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:

15 Jun - 22 Jun 1999

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:

adopted 1992

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 2015

Deviations:

yes

Remarks:

housing temperature slightly different, age of animals not provided

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, Prouzel, France
- Age at study initiation: not specified
- Weight at study initiation: 2.5 ± 0.1 kg
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm)
- Diet: 112 C pelleted diet (UAR, Villemoissonsur-Orge, France), ad libitum
- Water: drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
No contaminants were known to have been present in the diet or drinking water at levels which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 Jun To: 22 Jun 1999

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g
A single dose of 0.5 g test item was grounded to a fine powder, which was applied to a moistened gauze pad. This was held in place on the clipped skin site of the right flank by means of an adhesive hypoallergenic aerated semi-occlusive dressing and restraining bandage.

VEHICLE
No vehicle was used.

NEGATIVE CONTROL
The untreated skin on the left flank served as a control.

POSITIVE CONTROL
No positive control was used.

Duration of treatment / exposure:

4 h

Observation period:

6 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure:
clipped skin on the right flank
- Type of wrap if used:
adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing:
After removal of the dressing, any residual test substance was wiped off by means of a dry gauze pad.
- Time after start of exposure:
4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and on Day 5 and 6

SCORING SYSTEM:
- Method of calculation: Draize scoring system

OTHER:
As possible irritant effects were anticipated, the test substance was evaluated on a single animal in the first instance. The duration of exposure was 3 min on one flank and 4 h on the other flank. Since the test substance was not irritant on this first animal, it was then applied for 4 h to two other animals.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Remarks:

on Day 6

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks:

on Day 5

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

3 min-exposure (one animal)
No cutaneous reactions were observed.

4 h-exposure (three animals)
No cutaneous reactions were observed in one animal at any time point. In the other two animals, very slight or well-defined erythema (grade 1 or 2) were noted from Day 1 up to Day 5 at the latest. No oedema were observed. The mean scores over 24, 48 and 72 h for each animal were 0.0, 2.0 and 1.0 for erythema and 0, 0 and 0 for oedema. For details, please refer to the attachment 1.

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 OECD TG 404, was conducted under GLP and is considered valid and reliable. Under the conditions chosen the test substance caused slight reversible irritation when applied topically 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:

23 Jun - 26 Jun 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 1987

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2021

Deviations:

yes

Remarks:

housing temperature slightly different, no anesthetics and analgesics used, age of rabbits not provided

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, Prouzel, France
- Age at study initiation: not specified
- Weight at study initiation: 2.6 ± 0.2 kg
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm)
- Diet: 112 C pelleted diet (UAR, Villemoissonsur-Orge, France), ad libitum
- Water: drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
No contaminants were known to have been present in the diet or drinking water at levels, which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Jun To: 26 Jun 1999

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg
A single dose of 100 mg of the test substance, first ground to a fine powder, was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test substance.

VEHICLE
No vehicle was used.

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

Observation period: 21 days
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: DRAIZE criteria as stated in OECD TG 405

TOOL USED TO ASSESS SCORE: Where required one or two drops of 0.5% sodium fluorescein solution were instilled into the eye to determine the presence or absence of corneal opacity and to evaluate the affected area.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of two animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of three animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

of two animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight conjunctival reactions were observed in all animals 1 h after treatment. This included a very slight chemosis (grade 1, 2/3 animals), a very slight redness of the conjunctiva (grade 1, 2/3 animals) and/or clear discharge (3/3 animals). A slight iritis (grade 1) was recorded in two animals at the 1 h reading time point only. The signs of minimal eye irritation had completely resolved latest by 48 h after ocular instillation of the test substance. No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 h were 0.0, 0.0 and 0.3 for chemosis, 0.0, 0.0 and 0.3 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. For details, please refer to attachment 1.

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 OECD TG 405, was conducted under GLP and is considered valid and reliable. Under the conditions chosen the test substance caused minimal ocular irritation in 1/3 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

The irritancy potential of the test substance to skin was evaluated according to OECD guideline 404 and in compliance with GLP (M-185075-01-2). 0.5 g of the test substance was ground to a fine powder, which was applied via a moistened gauze pad to the skin of 3 rabbits. The pad was held in place on the clipped skin of the right flank by means of an adhesive hypoallergenic aerated semi-occlusive dressing and restraining bandage. As possible irritant effects were anticipated, the test substance was evaluated on a single animal in the first instance. The duration of exposure was 3 min on one flank and 4 h on the other flank. Since the test substance was not irritant on this first animal, it was then applied for 4 h to two further animals. The untreated skin on the other flank served as a control in the remaining 2 rabbits. The pads and excess material were removed after 4 h. Skin irritation responses were assessed at 1, 24, 48, and 72 h after patch removal. The irritation responses were scored according to the Draize scale. No cutaneous reactions were observed during the study in the first animal. Slight irritation (erythema grade 1 or 2) was observed in 2 rabbits following the 4-hour exposure but had resolved latest by day 5. . No oedema was observed. Mean scores over 24, 48 and 72 h for each animal were 0.0, 2.0 and 1.0 for erythema and 0.0, 0.0 and 0.0 for oedema. Under the conditions of the assay, the test substance caused slight reversible irritation when applied topically to rabbits. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for skin irritation is required.

Similar results were obtained in a previously conducted study, which is briefly mentioned here for purposes of data completeness (M-253375-01-1). The study was performed 1978  according to FIFRA: Federal Register, Vol. 43, No. 163. The entire trunk of 3 male and 3 females New Zealand White rabbits was closely clipped a few days before dosing. Just before application of the test material, the trunk was trimmed carefully as necessary. 0.5 g of the test item were applied to each of 4 sites per rabbit. On 2 sites, abrasions were made, which penetrated only the stratum corneum. Plastic sheeting was placed loosely around the trunk and secured. Each animal was placed in a restraining device for a 24 h contact period. Afterwards, the covering and excess sample were removed. Readings were made 24 and 72 h after the end of the contact period and scoring was performed according to the system of Draize. All rabbits had erythema, in varying degrees of severity, persisting through 72 h. No edema was noted. No death occurred during the study. Similar to the key study, the present study revealed that the test substance caused slight irritation when applied topically to rabbits. However, it has to be noted that skin responses were not scored 48 h after patch removal and the duration of the observation period was insufficient to establish the reversibility of the dermal lesions at Day 14 (animals sacrificed 3 days after the end of the contact period). Furthermore, the study was not conducted according to GLP as it was not mandatory at that time. No information on the test material used in the present study is available. Therefore, the study is considered of highly limited reliability in regard to current standards and is not considered for hazard assessment and  classification according to CLP criteria.

 

 

Eye irritation

A GLP-conform eye irritation/corrosion study was performed according to OECD Guideline 405 to evaluate the eye irritancy potential of the test substance (M-185080-01-1). Three male New Zealand White rabbits were treated with 0.1 g of the test substance. The test substance was ground to a fine powder prior to instillation into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The eyelids were held together for 1 sec to avoid any loss of test item. The untreated eye served as a control. The eyes were not washed after administration of the test item. The irritation response, was assessed at 1, 24, 48, and 72 h after ocular instillation and the responses were scored according to the system described in the OECD guideline 405. Very slight conjunctival reactions were observed in all animals 1 h after treatment. This included a very slight chemosis (grade 1, 2/3 animals), a very slight redness of the conjunctiva (grade 1, 2/3 animals) and/or clear discharge (grade 1, 3 animals). A slight iritis (grade 1) was recorded in two animals at the first reading time point 1 h after substance instillation. All signs of minimal eye irritation had completely resolved latest by 48 h after ocular instillation of the test substance. No other ocular reactions were observed during the study. Mean scores calculated for each animal over 24, 48 and 72 h were 0.0, 0.0 and 0.3 for chemosis, 0.0, 0.0 and 0.3 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. Under the conditions of the study, the test substance caused minimal ocular irritation in rabbits. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for eye irritation is required.

A further study on the eye irritation potential is available which was performed 1978 according to FIFRA: Federal Register, Vol. 43, No. 163 (M-253375-01-1). 0.1 g of the test substance was placed on the everted lower lid of the eye of 5 male and 4 female New Zealand White rabbits and the lids were held together for 1 sec. A total of 9 eyes were dosed using one eye per rabbit. Six eyes were left unwashed and 3 were rinsed 20 to 50 sec after application of the sample. Readings were made 1, 2, 3, 4 and 7 d later according to the system of Draize.. Three of the 6 unwashed eyes had conjunctival redness and corneal opacity at 24 h. In most cases the reactions were the least severe that could be scored and disappeared within 72 h. None of the 3 washed eyes had any irritation of the cornea, iris or conjunctivae. Under the test conditions and considering the findings, the test substance was mildly irritating to unwashed eyes. It has to be noted that the study was not conducted according to GLP as it was not mandatory at that time. No information on the test material used in the present study is available. Therefore, the study is considered of highly limited reliability in regard to current standards and is not considered for hazard assessment and classification according to CLP criteria.

References not included in IUC:

Detailed information on references not included in IUC are available in the CSR and in chapter 13.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.