5-ethyl-2-methylpyridine

Endpoint summary

Description of key information

Several studies are available on the skin irritation / corrosion effects of the test item. In the key study according to OECD Guideline 404 (Acute dermal irritation / corrosion) similar or equivalent to EU Method B.4 the test item was moderately irritant to the skin of the rabbit, but corrosive effects were noted. 
In accordance with column 2 of REACH Annex VII section 8.2 experimental determination of eye irritation was waived. The available information on skin irritation/corrosion indicates that the criteria are met for classification as corrosive. 
There is no data available on respiratory irritation. However, there is no indication for respiratory irritation from handling and use.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study.

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Aged at least 12 weeks
- Weight at study initiation: 3.51 to 4.58 kg
- Housing: Individually housed in grid floor cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22
- Humidity (%): 40 to 70
- Air changes (per hr): Air conditioned room
- Photoperiod: daily photoperiod of 14 hours artificial light and 10 hours darkness.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours.

Observation period:

1, 48 and 72 hours and 4, 7 and 14 days after removal of the patches. No erythema or edema was noted at the day 14 observation and the study was terminated.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm2 on each animal, covered with a gauze patch.
- % coverage: 100 %
- Type of wrap if used: Patch occluded and secured using a strip of impermeable adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was wiped with a moist disposable paper towel to remove any test article still remaining.
- Time after start of exposure: 4 hours.

SCORING SYSTEM:
According to Draize, J.H. (1959) Association of the Food and Drug Officials in the U.S., Austin, Texas. The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics.

Erythema and eschar formation value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Oedema formation value
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) 4

Corrosion was considered to have occurred if the test article in contact with the skin caused destruction or irreversible alteration of the tissue. Tissue destruction was considered to have occurred if, at any of the readings, there was ulceration or necrosis. Tissue destruction did not include merely sloughing of the epidermis, or erythema, edema or fissuring.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4, 24 and 48 hours

Score:

5.2

Max. score:

8

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

At the 1 hour observation black discolouration was noted at all the test sites. On day 1 the test sites were covered by black, semi-hard or hard, indented skin. This condition persisted until day 14 in 2 animals and until day 7 in the third. Atonia occurred in all animals from day 1 until day 14.
Moderate to severe erythema was noted in all animals at the 1 hour observation. This irritation regressed and on day 14 no erythema was noted. Slight to moderate oedema was also noted in all animals at the 1 hour observation. On day 1 oedema was noted in areas surrounding the test sites in all animals. This irritation regressed and was not noted on day 14.
A primary irritation index of 4.7 was obtained. The test item was regarded as a moderate irritant to the skin of the rabbit. Corrosive effects were noted.

Interpretation of results:

Category 1 (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In this primary dermal irritation study, young adult New Zealand White rabbits (3/male) were dermally exposed to 0.5 mL of test item for 4 hours introduced to 6 cm2 (occluded gauze patch). Animals then were observed for 14 days. Irritation was scored by the method of Draize (1959).
At the 1 hour observation black discoloration was noted at all the test sites. On day 1 the test sites were covered by black, semi-hard or hard, indented skin. This condition persisted until day 14 in 2 animals and until day 7 in the third. Atonia occurred in all animals from day 1 until day 14.
Moderate to severe erythema and slight to moderate oedema was noted in all animals, all reversible within 14 days. A primary irritation index of 4.7 was obtained. The test item was regarded as a moderate irritant to the skin of the rabbit. Corrosive effects were noted.

Executive summary:

A study was carried out according to OECD Guideline 404 (Acute dermal irritation / corrosion) similar or equivalent to EU Method B.4. In this primary dermal irritation study, young adult New Zealand White rabbits (3/male) were dermally exposed to 0.5 mL of test item for 4 hours introduced to 6 cm2 (occluded gauze patch). Animals then were observed for 14 days. Irritation was scored by the method of Draize (1959).

At the 1 hour observation black discoloration was noted at all the test sites. On day 1 the test sites were covered by black, semi-hard or hard, indented skin. This condition persisted until day 14 in 2 animals and until day 7 in the third. Atonia occurred in all animals from day 1 until day 14.

Moderate to severe erythema and slight to moderate oedema was noted in all animals, all reversible within 14 days. A primary irritation index of 4.7 was obtained. The test item was regarded as a moderate irritant to the skin of the rabbit. Corrosive effects were noted.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key - Skin irritation / corrosion

A study was carried out according to OECD Guideline 404 (Acute dermal irritation / corrosion) similar or equivalent to EU Method B.4. In this primary dermal irritation study, young adult New Zealand White rabbits (3/male) were dermally exposed to 0.5 ml of test item for 4 hours introduced to 6 cm2 (occluded gauze patch). Animals then were observed for 14 days. Irritation was scored by the method of Draize, J.H. (1959). At the 1 hour observation black discoloration was noted at all the test sites. On day 1 the test sites were covered by black, semi-hard or hard, indented skin. This condition persisted until day 14 in 2 animals and until day 7 in the third. Atonia occurred in all animals from day 1 until day 14. Moderate to severe erythema and slight to moderate oedema was noted in all animals, all reversible within 14 days. A primary irritation index of 4.7 was obtained. The test item was regarded as a moderate irritant to the skin of the rabbit. Corrosive effects were noted.

Support - Skin irritation / corrosion

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Adult rabbits (6) were dermally exposed to 0.5 ml of test item for 24 hours introduced to 1x1 inches (occluded gauze patch). Following exposure animals were observed for 72 hours. Irritation was scored by the method of Draize (1959).

Very slight to severe erythema with slight to moderate edema was observed in all six animals at the 4 hours reading. Very slight to severe erythema with or without slight to severe edema was observed in all six animals throughout the remainder of the observation period. Necrosis of the skin was seen in two animals, with scab formation developing in one by the 72 hours reading. Evidence of corrosion was seen in two animals.

Support - Skin irritation / corrosion

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Adult rabbits (6) were dermally exposed to 0.5 ml of test item for 24 hours introduced to 1.5 x1.5 inches (occluded gauze patch). From initial exposure animals were observed for 48 hours. Irritation was scored by the method of Draize (1959).

Severe erythema with no to slight edema was observed in all six animals at the 4 hours reading. Severe erythema with or without slight edema was observed in all six animals throughout the remainder of the observation period. Evidence of corrosion was seen in all six animals.

Support - Skin irritation / corrosion

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Adult rabbits (6) were dermally exposed to 0.5 ml of test item for 24 hours introduced to 1.5 x 1.5 inches (occluded gauze patch). From initial exposure animals were observed for 48 hours. Irritation was scored by the method of Draize (1959).

Severe erythema with severe edema was observed in all six animals at the 4 hours reading. Severe erythema with moderate to severe edema was observed in all six animals throughout the remainder of the observation period. Evidence of corrosion was seen in all six animals.

Waiver - Eye irritation

In accordance with column 2 of REACH Annex VII, experimental determination of eye irritation was waived. The available information on skin irritation/corrosion indicates that the criteria are met for classification as corrosive. Based on EU criteria the substance is considered seriously damaging to eyes.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the data available the substance is classified and labeled according to Regulation 1272/2008/EEC (CLP) as Skin corrosive category 1B, H314 Causes severe skin burns and eye damage and according to Directive 67/548/EEC (DSD) Corrosive C, R34 Causes burns.