Pyridine-2-carbaldehyde

Endpoint summary

Description of key information

The available data include two in vivo studies for skin irritation/corrosion and one in vivo study for eye irritation. In all three studies, irreversible corrosive/severe irritation effects were observed.

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:

1997-11-11 to 1997-12-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.60 - 2.69kg
- Housing: individual
- Diet (e.g. ad libitum): STANRAB SQC Rabbit diet, ad libitum
- Water (e.g. ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21°C
- Humidity (%): 46 - 66%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12h/12h

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

three exposure durations: 3 min; 1 h; 4 h

Observation period:

1, 24, 48 and 72h and 7 and 14 days after removal of the patch

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5cm
- Type of wrap if used: surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 3 min; 1 h; 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72h and 7 and 14 days after removal of the patch

SCORING SYSTEM:
- Method of calculation: Draize

Irritation parameter:

erythema score

Remarks:

exposure: 4h

Basis:

mean

Time point:

24/48/72 h

Score:

1.22

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: observation after 72h on two animals not possible because of adverse skin reaction

Irritation parameter:

edema score

Remarks:

exposure: 4h

Basis:

mean

Time point:

24/48/72 h

Score:

0.89

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: observation after 72h on two animals not possible because of adverse skin reaction

Irritation parameter:

edema score

Remarks:

exposure: 1h

Basis:

mean

Time point:

24/48/72 h

Score:

0.94

Max. score:

4

Reversibility:

other: observation after 7 and 14 days on two animals not possible because of adverse skin reaction

Irritation parameter:

erythema score

Remarks:

exposure: 3min

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Remarks:

exposure: 3min

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Other effects:

Other adverse local effects:
Green coloured dermal necrosis over whole treatment site occured
- in 2 of 3 animals after 4h-exposure for at least 48h. Afterwards observation was not possible because of adverse skin reaction.
- in 2 of 3 animals after 1-h-exposure for at least 72h. Afterwards observation was not possible because of adverse skin reaction.
- in 0 of 3 animals after 3-min-exposure.

4h exposure
		observation time
animal nr		24h	48h	72h
I	erythema	2	2	2
	edema	2	2	2
II	erythema	4	4	*
	edema	3	2	*
III	erythema	4	4	*
	edema	3	2	*

* = observation not possible because of adverse skin reaction

1h exposure
		observation time
animal nr		24h	48h	72h
I	erythema	2	2	2
	edema	1	1	1
II	erythema	4	4	4
	edema	3	2	2
III	erythema	4	4	4
	edema	3	2	2

3min exposure
	observation time
animal nr		24h	48h	72h
I	erythema	1	1	0
	edema	0	0	0
II	erythema	1	1	0
	edema	0	0	0
III	erythema	1	1	0
	edema	0	0	0

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

The test material caused necrosis after 4-h-exposure and after 1-h-exposure. The effects were not reversible. The test item caused no skin reaction after 3-min-exposure.
Therefore the test item is classified as Skin corrosiv category 1B based on GHS data.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

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:

1983-05-31 to 1983-06-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.5 - 2.9 kg
- Housing: The animals were caged individually in stainless steel cages , with automatic drinking water supply and cleaning system
- Diet (e.g. ad libitum): rabbit maintenance diet (standard Kliba 341 (Klingentalmühle AG , 4303 Kaiseraugst , Switzerland) , ad libitum
- Water (e.g. ad libitum): tap water , ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-2
- Humidity (%): 55 +-10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml/rabbit

Duration of treatment / exposure:

single application into the conjunctival sac of the left rabbit eye, without rinsing out

Observation period (in vivo):

1/ 24/ 48/ 72 hours after treatment

Number of animals or in vitro replicates:

3

Details on study design:

Route of administration :
Single , into the conjunctival sac of the rabbit eye

Dose application :
The test substance was placed into the conjunctival sac of the left eye of each animal after retracting the lower lids from the eye ball . The eyelids were then gently held closed for about one second in order to prevent loss of the test substance . The right eye was untreated and served as control .
The eyes were examined and the grade of ocular reactions recorded at 1 , 24 , 48 and 72 hours after treatment .
In addition , the coloration of the cornea was recorded in connection with the colour of the test substance . Mortality and toxic symptoms were recorded daily.

Sacrifice and Necropsy :
The study was terminated 72 hours after administration of the test article.
All rabbits were killed at the end of the opbservation period by an intraveneous injection of T61 into the ear vein.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye was not washed after treatment

SCORING SYSTEM: Draize scoring system
GRADES FOR OCULAR LESIONS
CORNEA
Opacity: degree of density (area most dense taken far reading).
No ulceration or opacity ..........0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible ..........1*
Easily discernible translucent area, details of iris slightly obscured ..........2*
Nacrous areas-, no details of iris visible, size of pupil barely discernible ..........3*
Opaque cornea, iris not discernible through the aacity ..........4*

IRIS
Normal ..........0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) ..........1*
No reaction to light, haemorrhage, gross destruction (any or all of these) ..........2*

CONJUNCTIVAE
Redness (refers to palpebral and bulbar canjunctivae, cornea and iris).
Blood vessels normal ..........0
Some blood vessels definitely hyperaemic (injected) ..........1
Diffuse, crimson colour, individual vessels not easily discernible ..........2*
Diffuse, beefy red ..........3*

Chemosis: lids and/or nictating membranes
No swelling ..........0
Any swelling above normal (includes nictating membranes) ..........1
Obvious swelling with partial aversion of lids ..........2*
Swelling with lids about half closed ..........3*
Swelling with lids more than half closed ..........4*

* Starred figures indicate positive effect

TOOL USED TO ASSESS SCORE: slit lamp 30 SL (C. Zeiss AG , Zuerich/Switzerland) and Varta Cliptrix diagnostic-lamp (A. Riegger , Basel/Switzerland)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean over 1,24,48 and 72h

Score:

2.75

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean over 1,24,48 and 72h

Score:

3.25

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean over 1,24,48 and 72h

Score:

3.25

Max. score:

4

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean over 1,24,48 and 72h

Score:

1.25

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean over 1,24,48 and 72h

Score:

0.75

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean over 1,24,48 and 72h

Score:

0.75

Max. score:

2

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean over 1,24,48 and 72h

Score:

2.5

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean over 1,24,48 and 72h

Score:

2.5

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean over 1,24,48 and 72h

Score:

2.5

Max. score:

3

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean over 1,24,48 and 72h

Score:

4

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean over 1,24,48 and 72h

Score:

3.75

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean over 1,24,48 and 72h

Score:

3.5

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

The test substance showed a severe irritation when applied on the rabbit eye mucosa.
A corrosion effect of the cornea was observed at each of the measuring intervals, in all rabbits.

Interpretation of results:

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

Conclusions:

The study was performed according to the OECD TG405 without deviations and according to the good laboratory practice principles, it is considered to be of highest quality (reliability Klimisch 1). The criteria of validity of the test system are fulfilled. The test material was found to cause a severe irritation when applied to the rabbit eye mucosa. A corrosion effect of the cornea was observed at each of the measuring intervals, in all rabbits.
A substance has to be classified in Category 1 (irreversible effects on the eye), if, when applied to the eye of an animal, a substance produces:
– at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days;
and/or
– at least in 2 of 3 tested animals, a positive response of:
– corneal opacity = 3 and/or
– iritis > 1.5
calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

No statement has been made regarding reversibilty, but the 2nd criterion is fulfilled (mean scores corneal opacity = 3 in at least 2 of 3 animals) and hence, the substance has to be classified in Eye damage Category 1.

Executive summary:

The test substance Pyridine-2-aldehyde was investigated for its potential to cause irritation in the rabbit eye according to OECD TG405. 0.1 ml of pure substance was instilled into the conjunctival sac, the untreated eye served as control. Under the conditions of this experiment Pyridine-2-aldehyde was found to cause a severe irritation when applied to the rabbit eye mucosa. A corrosion was observed at each of the measuring intervals in all rabbits. No discoloration of the cornea and conjunctivae which could be related to effects of the test material was observed. The primary irritation index was found to be for the unrinsed eye : 10.2 . No statement has been made regarding reversibilty, but the mean scores of corneal opacity = 3 in at least 2 of 3 animals and hence, the substance has to be classified in Eye damage Category 1.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In the key study for skin irritation, a dermal necrotic effect was observed following exposure to the test item for 1 and 4 hours. No effect was observed following a 3 minute exposure period. This falls into the criteria for a Cateogory 1B Skin corrosive/irritant (H314) according to CLP criteria (Regulation EC No 1272/2008). This classification is re-inforced by the supporting study, whereby necrosis was observed in all animals following a 4 hour exposure period.

For eye irritation, a corrosion effect of the cornea was observed at each of the measuring intervals, in all rabbits and on a mean corneal opacity score >3 in two of the three rabbits tested was noted. Therefore the test item can be classified as a Category 1 Eye Irritant (H318) according to CLP criteria (Regulation EC No 1272/2008).