2-Pyridinecarboxamide, 4-(4-aminophenoxy)-N-methyl-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September to November 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide

EC Number:

608-211-5

Cas Number:

284462-37-9

Molecular formula:

C13 H13 N3 O2

IUPAC Name:

4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: female
- Source: Charles River, 88353 Kißlegg, Germany
- Age at study initiation: not specified
- Weight at study initiation: 3.0-3.8 kg
- Housing: individually in cage units Metall/Noryl by EBECO. Excrement trays below the cages contained low dust wood granulate bedding (J. Rettemnaier & Söhne, 73479 Ellwangen-Holzmühle, Germany). The wood granulate was changed at least twice weekly. The animals were regularly transferred to clean cages.
- Diet: ad libitum, standard diet “Ssniff K-Z” 4mm (manufacturer: Ssniff Spezialdiäten GmbH, 59494 Soest, Germany), approximately 100 g per animal per day.
- Water: ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 55 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the eye, which remained untreated, served as control

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

test substance remained in the eye (eye was not rinsed) until 1 h after instillation, the eyes were rinsed with saline 1 h following instillation.

Observation period (in vivo):

1, 24, 48 and 72 hours after instillation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 1h after instillation with physiological saline
- Time after start of exposure: 1 h

SCORING SYSTEM: according to Draize et al.

TOOL USED TO ASSESS SCORE: fluorescein, 24 h after application, the eyes were treated with fluorescein and examined. If changes were observed additional fluorescein tests were performed on day 7, 14 and 21 until the changes observed had completely subsided, however for not more than 21 days after application.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1,2,3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: mean score after 72 hours: 0.0

Results 2

Irritation parameter:

iris score

Basis:

animal: #1,2,3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: mean score after 72 hours: 0.0

Results 3

Irritation parameter:

chemosis score

Basis:

animal: #1,2,3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: mean score after 72 hours: 0.0

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: #1,3

Time point:

24/48/72 h

Score:

0 - 1

Max. score:

3

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: mean score after 72 hours: 0.3

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

other: mean score after 72 hours: 0.0

Irritant / corrosive response data:

Redness of conjunctivae (grade 1) was observed in all animals 1 hour after instillation. The fluorescein test performed after 24 hours revealed no corneal effects.

Other effects:

No systemic intolerance reactions were observed.

Any other information on results incl. tables

Irritant effects on the eye
Animal 1, Body Weight 3715 g
Observation		1h		24h	48h		72h	day 7	day 14	day 21
Degree of cornea opacity		0		0	0		0	-	-	-
Area of cornea opacity		0		0	0		0	-	-	-
Fluorescein-degree		#		0	#		#	-	-	-
Coloration area		#		0	#		#	-	-	-
Iris		0		0	0		0	-	-	-
Redness conjunctivae		1		1	0		0	-	-	-
Chemosis conjunctivae		0		0	0		0	-	-	-
Animal 2, Body Weight 3792 g
Observation		1h		24h	48h		72h	day 7	day 14	day 21
Degree of cornea opacity		0		0	0		0	-	-	-
Area of cornea opacity		0		0	0		0	-	-	-
Fluorescein-degree		#		0	#		#	-	-	-
Coloration area		#		0	#		#	-	-	-
Iris		0		0	0		0	-	-	-
Redness conjunctivae		1		0	0		0	-	-	-
Chemosis conjunctivae		0		0	0		0	-	-	-
Animal 3, Body Weight 2999 g
Observation		1h		24h	48h		72h	day 7	day 14	day 21
Degree of cornea opacity		0		0	0		0	-	-	-
Area of cornea opacity		0		0	0		0	-	-	-
Fluorescein-degree		#		0	#		#	-	-	-
Coloration area		#		0	#		#	-	-	-
Iris		0		0	0		0	-	-	-
Redness conjunctivae		1		1	0		0	-	-	-
Chemosis conjunctivae		0		0	0		0	-	-	-
-: no further examination
#: no examination
Animal 1	day 1-3:		Soft feces
Animal 2	day 2 and 3:		soft feces
	day 1 and 2		reduced food intake
	day 1		reduced water intake
Animal 3	day 2 and 3		redcued food intake

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an eye irritation study according to OECD TG 405 the test substance was instilled into the conjunctival sac of one eye of 3 female rabbits. Eye irritation was assessed after 1, 24, 48 and 72 hours using the Draize scale. In this study Picolinamid-Phenylether shows very slight irritant effects (mean irritation index for conjunctivae score = 0.3 of max. 3) which were fully reversible within 2 days. No irritation effects were registered for cornea, iris and conjunctival chemosis up to 72 hours after instillation. The weight of these evidences indicates that the test substance may be considered as "slightly irritating to the eyes". No systemic intolerance reactions were observed.

Executive summary:

In a primary eye irritation study similar to OECD TG 405, 0.1 mg of Picolinamid-phenylether was instilled into the conjunctival sac of one eye of 3 young adult female New Zealand White rabbits (3/sex) and the animals were observed for 21 days. The eyes were not washed until 1h after instillation, thereafter washing was performed with physiological saline. Irritation was scored by the method of Draize.

 

A single application of the test substance into the conjunctival sac provoked slight irritation of the conjunctiva in one animal which lasted up to 2 h after application. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters corneal opacity, iris score, chemosis score and conjunctivae score. In this study, the test item is not an eye irritant.