3-iodo-2-propynyl butylcarbamate

Endpoint summary

Description of key information

Following a 4 h semi-occlusive exposure to the test item it is concluded that this material is not considered to be irritant to rabbit skin.

Based on experimental study data, the test item is considered to be a severe irritant to the ocular tissue of the rabbit.

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:

1989-09-05 to 1989-09-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: P-8907-4914-P100

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark under ambient conditions

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Cheshire Rabbit Farms Limited
- Age at study initiation: young adult
- Housing: individually in aluminium cages with grid floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 d

ENVIRONMENTAL CONDITIONS
- Temperature: mean 18 °C
- Humidity: mean 65 %
- Photoperiod: 12 h (07:00 - 19:00) light; 12 h dark

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g moistened with water

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3 males, 3 females

Details on study design:

TEST SITE
- Area of exposure: dorsal area of trunk
- coverage: 2.5 cm x 2.5 cm gauze patch
- Type of wrap if used: micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing: skin was wiped with damp tissues
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
Skin reactions were assessed 1, 24, 48 and 72 h after patch removal

SCORING SYSTEM:
According to EPA recommended scoring system

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:

1.33

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: no further observations performed after 72 h post exposure

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 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:

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:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 h

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

Irritant / corrosive response data:

Slight - moderate erythema (score 1 and 2) and slight oedema (score 1) were noted in 2 of the 6 rabbits 24 h after patch removal with slight erythema persisting in one rabbit until the 72 h assessment. Latter showed a decreasing trend in erythrema score.

Interpretation of results:

GHS criteria not met

Conclusions:

Following a 4 h semi-occlusive exposure to the test item it is concluded that this material is not considered to be irritant to rabbit skin.

Executive summary:

The primary skin irritation potential of the test material was investigated in New Zealand White rabbits.

Following a 4 h semi-occlusive exposure of the test item slight-moderate erythema and slight oedema were noted in 2 rabbits 24 h after patch removal, with slight erythema persisting in one rabbit until the 72 h assessment. Latter showed a decreasing trend in erythrema score. It remains unclear if longer observation period could have revealed full reversibilty. 

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:

1990-03-27 to 1990-06-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 89115175

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Mohican Valley Rabbitry, Loudonville, Ohio
- Age at study initiation: adult
- Weight at study initiation: 2.0 - 2.4 kg
- Housing: individually; in suspended stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16.1 - 21.1 °C (61 - 70 °F)
- Humidity: 40 - 60 %
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 1990-03-27 to 1990-04-17

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.055 mg; equivalent to 0.1 mL

Duration of treatment / exposure:

30 seconds

Observation period (in vivo):

Both eyes of each animal were examined for signs of irritation at 1, 24, 48 and 72 hours and up to 21 days after dosing using the ocular irritation grading system.

Number of animals or in vitro replicates:

3 rinsing group, 6 non rinsing group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing with 50 mL of physiological saline (three of nine animals)
- Time after start of exposure: 30 sec

SCORING SYSTEM: according to EPA guideline

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #4

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #5

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal #6

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal: #7

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritation parameter:

cornea opacity score

Basis:

animal: #8

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: #9

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

animal #4

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

animal #5

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 d

Irritation parameter:

iris score

Basis:

animal #6

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

iris score

Basis:

animal: #7

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

iris score

Basis:

animal: #8

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

animal: #9

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

animal #4

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

animal #5

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

conjunctivae score

Basis:

animal #6

Remarks:

No rinse group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal: #7

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 d

Irritation parameter:

conjunctivae score

Basis:

animal: #8

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal: #9

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

No rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21d

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

No rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

No rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

No rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

animal #5

Remarks:

No rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

animal #6

Remarks:

No rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

animal: #7

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 d

Irritation parameter:

chemosis score

Basis:

animal: #8

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritation parameter:

chemosis score

Basis:

animal: #9

Remarks:

Rinsed group

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

No irritation was observed in the control eyes. Normal background fluorescein dye retention (stippling/mechanical abrasions) was noted in 4/9 control eyes but was not considered significant.
In the no rinse test group, exposure to the test article produced substantial injury to the ocular tissue of the rabbit. Corneal opacity was observed in 6/6 test eyes by the 24 hour scoring interval. The corneal injury was associated with corneal epithelial sloughing and further confirmed by positive fluorescein dye retention. Normal background fluorescein dye retention (stippling) was also observed in 3/6 test eyes but was not considered significant. The corneal opacity persisted in all no rinse test eyes to test termination (day 21) and was accompanied by corneal vascularization. Iritis was observed in 6/6 test eyes at 1 hour postdose and resolved in all no rinse animals by day 21. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation diminished over the test period but persisted to study day 21.
In the rinsed test group, exposure to the test article followed by a saline rinse resulted in a decrease in the severity and duration of the ocular response. In 2/3 rinsed test eyes, iritis was observed at the 1 hour postdose and resolved by 48 hours. Conjunctival irritation was also noted in these two test eyes at 1 hour postdose and resolved by day 7. In the remaining rinsed test animal, ocular responses generally resembled those noted in the rinsed test group. However, all reactions in this latter animal resolved by 21 days postdose.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the no rinse test data, the test item is considered to be a severe irritant to the ocular tissue of the rabbit. Ocular reactions in rinsed test eyes were less severe and completely reversible by 21 days postdose.

Executive summary:

The potential eye irritant and/or corrosive effects of the test item were evaluated in New Zealand White rabbits. Each of nine animals received a 0.055 g dose (0.1 mL equivalent) of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. At 30 seconds postinstillation, both eyes of three rabbits were rinsed with 50 mL of physiological saline (rinsed group); no rinsing procedure was utilized on the six remaining rabbits (no rinse group). Test and control eyes were examined for signs of irritation for up to 21 days following dosing.

In the no rinse test group, exposure to the test article produced substantial injury to the ocular tissue of the rabbit. Corneal opacity was observed in 6/6 test eyes by the 24 hour scoring interval. The corneal injury was associated with corneal epithelial sloughing and further confirmed by positive fluorescein dye retention. Normal background fluorescein dye retention (stippling) was also observed in 3/6 test eyes but was not considered significant. The corneal opacity persisted in all no rinse test eyes to test termination (day 21) and was accompanied by corneal vascularization. Iritis was observed in 6/6 test eyes at 1 hour postdose and resolved in all no rinse animals by day 21.Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation diminished over the test period but persisted to study day 21.

In the rinsed test group, exposure to the test article followed by a saline rinse resulted in a decrease in the severity and duration of the ocular response. In 2/3 rinsed test eyes, iritis was observed at the 1 hour postdose and resolved by 48 hours. Conjunctival irritation was also noted in these two test eyes at 1 hour postdose and resolved by day 7. In the remaining rinsed test animal, ocular responses generally resembled those noted in the rinsed test group. However, all reactions in this latter animal resolved by 21 days postdose.

Based on the no rinse test data, the test item is considered to be a severe irritant to the ocular tissue of the rabbit.As noted above, ocular reactions in rinsed test eyes were less severe and completely reversible by 21 days postdose.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation in vivo

The primary skin irritation potential of the test material was investigated in New Zealand White rabbits.

Following a 4 h semi-occlusive exposure of the test item slight-moderate erythema and slight oedema were noted in 2 rabbits 24 h after patch removal, with slight erythema persisting in one rabbit until the 72 h assessment. Latter showed a decreasing trend in erythrema score. It remains unclear if longer observation period could have revealed full reversibilty. 

Eye irritation in vivo

The potential eye irritant and/or corrosive effects of the test item were evaluated in New Zealand White rabbits. Each of nine animals received a 0.055 g dose (0.1 mL equivalent) of the test article in the conjunctival sac of the right eye. The contralateral eye of each animal remained untreated and served as a control. At 30 seconds postinstillation, both eyes of three rabbits were rinsed with 50 mL of physiological saline (rinsed group); no rinsing procedure was utilized on the six remaining rabbits (no rinse group). Test and control eyes were examined for signs of irritation for up to 21 days following dosing.

In the no rinse test group, exposure to the test article produced substantial injury to the ocular tissue of the rabbit. Corneal opacity was observed in 6/6 test eyes by the 24 hour scoring interval. The corneal injury was associated with corneal epithelial sloughing and further confirmed by positive fluorescein dye retention. Normal background fluorescein dye retention (stippling) was also observed in 3/6 test eyes but was not considered significant. The corneal opacity persisted in all no rinse test eyes to test termination (day 21) and was accompanied by corneal vascularization. Iritis was observed in 6/6 test eyes at 1 hour postdose and resolved in all no rinse animals by day 21. Conjunctivitis (redness, swelling and discharge) was noted in 6/6 test eyes at the 1 hour scoring interval. The conjunctival irritation diminished over the test period but persisted to study day 21.

In the rinsed test group, exposure to the test article followed by a saline rinse resulted in a decrease in the severity and duration of the ocular response. In 2/3 rinsed test eyes, iritis was observed at the 1 hour postdose and resolved by 48 hours. Conjunctival irritation was also noted in these two test eyes at 1 hour postdose and resolved by day 7. In the remaining rinsed test animal, ocular responses generally resembled those noted in the rinsed test group. However, all reactions in this latter animal resolved by 21 days postdose.

Based on the no rinse test data, the test item is considered to be a severe irritant to the ocular tissue of the rabbit. As noted above, ocular reactions in rinsed test eyes were less severe and completely reversible by 21 days postdose.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on eye irritation, the test item is classified and labelled as severe eye damaging (H318: "Causes serious eye damage") according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.

Classification on skin irritation is not warranted.