Pyridine, alkyl derivs.

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. No 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 irritating. Based on EU criteria the substance is considered irritating to eyes. 
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 / corrosion, other

Remarks:

skin irritation: in vivo - none in vitro test were performed because several in vivo studys are aveailable.

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)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data.

Type of coverage:

occlusive

Preparation of test site:

other: site 1: shaved; site 2: abraded

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

24 hours.

Observation period:

24, 48 and 72 hours after initial application.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 1 x 1 inch
- % coverage: 100 %
- Type of wrap if used: Animals were immobilized with patches secured in place by adhesive tape. The entire trunk of the animal was then wrapped with an impervious material such as rubberized cloth for the 24-hour period of exposure.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 24 hours exposure the patches were removed.
- Time after start of exposure: 24 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
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

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4, 24 and 48 hours

Score:

4.6

Max. score:

8

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

2.2

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

4

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours

Score:

2.7

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

2.6

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours

Score:

2.7

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours

Score:

2.7

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

4

Reversibility:

no data

Irritant / corrosive response data:

The primary irritation index was 4.6 (4, 24 and 48 hours after treatment). There was no evidence of corrosion. Well-defined erythema with slight to moderate oedema was observed in both sites of all six animals at the 4 hours reading. Well-defined to moderate erythema with slight to moderate oedema was seen in all six animals at the 24 hours reading. Similar observations were mode in all six animals at the 48 and 72 hours reading.

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is not considered to be corrosive to rabbit skin, although there was evidence of moderate irritation.

Executive summary:

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 x 1 inches (occluded gauze patch). Following exposure animals were observed for 72 hours. Irritation was scored by the method of Draize (1959).

There was no evidence of corrosion. Well-defined erythema with slight to moderate oedema was observed in both sites of all six animals at the 4 hours reading. Well-defined to moderate erythema with slight to moderate oedema was seen in all six animals at the 24 hours reading. Similar observations were mode in all six animals at the 48 and 72 hours reading.

The test item is not considered to be corrosive to rabbit skin, although there was evidence of moderate irritation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Several studies on skin irritation / corrosion revealed slight to moderate irritation effects. No corrosive effects were noted. A study on eye irritation was waived. There is no data available on respiratory irritation.

Key – Skin irritation

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Six adult rabbits were dermally exposed to 0.5 mL of test item for 24 hours introduced to 1 x 1 inch2 (occluded gauze patch). Following exposure animals were observed for 72 hours. Irritation was scored by the method of Draize (1959).

There was no evidence of corrosion. Well-defined erythema with slight to moderate oedema was observed in both sites of all six animals at the 4 hours reading. Well-defined to moderate erythema with slight to moderate oedema was seen in all six animals at the 24 hours reading. Similar observations were mode in all six animals at the 48 and 72 hours reading.

The test item is not considered to be corrosive to rabbit skin, although there was evidence of moderate irritation.

Support 1 – Skin irritation

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Six adult rabbits were dermally exposed to 0.5 mL of test item for 4 hours introduced to 1 x 1 inch2 (occluded gauze patch). Following exposure animals were observed for 72 hours. Irritation was scored by the method of Draize (1959).

The primary irritation index of was 1.9 (4, 24 and 48 hours after treatment). There was no evidence of corrosion. Very slight erythema with or without very slight oedema was observed in both sites of one animal and in one site of one other animal at the 4 hours reading. Moderate oedema only was seen in both sites of two other animals. Very slight to slight oedema was seen in both sites of five animals and was accompanied in two animals by very slight erythema at the 24 hours reading. Assessment of erythema was prevented in one animal by light brown staining of the skin by the sample. Very slight to well-defined erythema with very slight to slight oedema was seen in both sites of all six animals at the 48 hours reading. Very slight erythema with or without very slight to slight oedema was seen in five animals at the 72 hours reading. Slight oedema only was seen in the sixth animal.

The test item is not considered to be corrosive to rabbit skin, although there was evidence of distinct irritation.

Support 2 – Skin irritation

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Six adult rabbits were dermally exposed to 0.5 mL of test item for 4 hours introduced to 1 x 1 inch2 (occluded gauze patch). Following exposure animals were observed for 72 hours. Irritation was scored by the method of Draize (1959).

The primary irritation index of was 0.4 (4, 24 and 48 hours after treatment). There was no evidence of corrosion. Very slight oedema was seen in one animal at the 4 hours reading. Very slight to slight oedema was seen in both sites of one animal and in one site of one other animal at the 24 hours reading. Very slight to moderate oedema was seen in both sites of two animals and in one site of one other animal at the 48 hours reading. Very slight to slight oedema was seen in both sites of four animals at the 72 hours reading and was accompanied by very slight erythema in two animals.

The test item is not considered to be corrosive to rabbit skin, although there was evidence of slight irritation.

Support 3 – Skin irritation

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Six adult rabbits were dermally exposed to 0.5 mL of test item for 4 hours introduced to 2.5 x 2.5 cm2 (occluded gauze patch). Following exposure animals were observed for 48 hours. Irritation was scored by the method of Draize (1959).

The primary irritation index of was 4.5 (4, 24 and 48 hours after treatment). The test item is therefore regarded as a moderate irritant. The structure of the tissue at the contact site was not destroyed within 24 hours of application and is therefore considered non-corrosive.

The test item is regarded as a moderate irritant and did not produce a corrosive response.

Support 4 – Skin irritation

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Six adult rabbits were dermally exposed to 0.5 mL of test item for 4 hours introduced to 2.5 x 2.5 cm2 (occluded gauze patch). Following exposure animals were observed for 48 hours. Irritation was scored by the method of Draize (1959).

The primary irritation index of was 1.4 (4, 24 and 48 hours after treatment). The test item is therefore regarded as a mild irritant. The structure of the tissue at the contact site was not destroyed within 24 hours of application and is therefore considered non-corrosive.

The test item is regarded as a slight irritant and did not produce a corrosive response.

Support 5 – Skin irritation

A study was carried out similar or equivalent to EU Method B.4 and OECD Guideline 404 (Acute dermal irritation / corrosion). Six adult rabbits were dermally exposed to 0.5 mL of test item for 4 hours introduced to 2.5 x 2.5 cm2 (occluded gauze patch). Following exposure animals were observed for 48 hours. Irritation was scored by the method of Draize (1959).

The primary irritation index of was 0.9 (4, 24 and 48 hours after treatment). The test item is therefore regarded as a mild irritant. The structure of the tissue at the contact site was not destroyed within 24 hours of application and is therefore considered non-corrosive.

The test item is regarded as a slight irritant and did not produce a corrosive response.

Support 6 – Skin irritation

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 4 hours introduced to 2.5 x 2.5 cm2 (occluded gauze patch). Following exposure animals were observed for 48 hours. Irritation was scored by the method of Draize (1959).

The primary irritation index of was 4.1 (4, 24 and 48 hours after treatment). The test item is therefore regarded as a moderate irritant. The structure of the tissue at the contact site was not destroyed within 24 hours of application and is therefore considered non-corrosive.

The test item is regarded as a moderate irritant and did not produce a corrosive response.

Waiver - Eye irritation

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 irritating. Based on EU criteria the substance is considered irritating to eyes.

Waiver - Respiratory irritation

There is no data available on respiratory irritation.

Justification for selection of eye irritation endpoint:
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 irritating. Based on EU criteria the substance is considered irritating to eyes.

Effects on skin irritation/corrosion: moderately irritating

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 and eye irritating category 2, H315 and H319: Causes skin and eye irritation and according to Directive 67/548/EEC (DSD) as Irritating Xi; R36/38 Irritating to eyes and skin.