dimethyl 5-methylpyridine-2,3-dicarboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl 5-methylpyridine-2,3-dicarboxylate

EC Number:

601-161-5

Cas Number:

112110-16-4

Molecular formula:

C10 H11 N O4

IUPAC Name:

Dimethyl 5-methylpyridine-2,3-dicarboxylate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Skippack Farms, Skippack, Pennsylvania
- Age at study initiation: 10-13 weeks of age
- Housing: individually, in stainless-steel cages with slatted floors over dry bedding
- Diet (e.g. ad libitum): PMI Certified Rabbit Diet (#5322), ad libitum
- Water (e.g. ad libitum): filtered tap water, ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 4 °C
- Humidity (%): 50% ± 20%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

Corneal irritation was examined using an ultraviolet light and 2% Fluorescein Sodium Ophthalmic Solution at 24 hours, day 4, day 7 and day 10.
The eyes were examined at the following intervals: pretreatment (approximately -5 hrs), 1 hr., 24 hrs., 48 hrs., 72 hrs., day 4, day 7 and day 10.

Number of animals or in vitro replicates:

6 male animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
At the end of the 24 hour exposure period, the treated eyes were rinsed with tap water

SCORING SYSTEM: Draize scale

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72h

Score:

1.9

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72h

Score:

0.6

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72h

Score:

0.4

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

other: discharge

Basis:

mean

Remarks:

(all animals)

Time point:

other: 24, 48 and 72h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: 4 days

Irritant / corrosive response data:

At 1 hour postdosing, slight to moderate conjunctival redness, moderate to severe (one animal) chemosis and a slight to moderate ocular discharge were observed. At the 24 hour observation, translucent areas of corneal opacity, slight iris effects, moderate conjunctival redness, slight to moderate chemosis and a slight to moderate (one animal) ocular discharge were observed. At 48 hours, corneal opacities and iris effects generally remained unchanged from the 24 hour observation. Conjunctival irritation was characterized as a slight (one animal) to moderate conjunctiva redness and a slight ocular discharge (two animals). At 72 hours, diffuse (one animal) to translucent areas of corneal opacity and slight iris effects with a slight to moderate conjunctival redness and a slight conjunctival discharge (one animal) were observed. At the day 4 observation, diffuse to translucent (one animal) areas of corneal opacity, slight iris effects (one animal) and a slight conjunctival redness were observed with all signs of irritation resolving in one animal. By day 7, all signs of irritation had resolved in all but one animal. The remaining animal exhibited a diffuse area of corneal opacity which had resolved by the day 10 observation.

Other effects:

No signs of systemic toxicity or mortality were observed during the study.

Any other information on results incl. tables

Table 1: Individual eye irritation data

Animal number	Area examined	Pre treatment	1 hour	24 hours	48 hours	72 hours	4 days	7 days	10 days
1	Cornea Density	0	0	2	2	1	0	NE	NE
	Iris	0	0	1	1	0	0	NE	NE
	Conjunctivae Redness Chemosis Discharge	0 0 0	2 2 2	2 2 2	2 0 1	1 0 0	0 0 0	NE NE NE	NE NE NE
2	Cornea Density	0	0	2	2	2	1	0	NE
	Iris	0	0	0	0	1	0	0	NE
	Conjunctivae Redness Chemosis Discharge	0 0 0	2 3 1	2 1 1	2 0 1	2 0 0	1 0 0	0 0 0	NE NE NE
3	Cornea Density	0	0	2	2	2	1	0	NE
	Iris	0	0	1	1	0	0	0	NE
	Conjunctivae Redness Chemosis Discharge	0 0 0	2 2 2	2 1 1	2 0 0	1 0 1	0 0 0	0 0 0	NE NE NE
4	Cornea Density	0	0	2	2	2	1	0	NE
	Iris	0	0	1	0	0	0	0	NE
	Conjunctivae Redness Chemosis Discharge	0 0 0	1 2 2	2 1 1	2 0 0	1 0 0	0 0 0	0 0 0	NE NE NE
5	Cornea Density	0	0	2	2	2	2	1	0
	Iris	0	0	1	1	1	1	0	0
	Conjunctivae Redness Chemosis Discharge	0 0 0	1 2 2	2 1 1	1 0 0	2 0 0	1 0 0	0 0 0	0 0 0
6	Cornea Density	0	0	2	2	2	1	0	NE
	Iris	0	0	0	1	0	0	0	NE
	Conjunctivae Redness Chemosis Discharge	0 0 0	2 2 2	2 1 0	2 0 0	1 0 0	0 0 0	0 0 0	NE NE NE
NE = Not Evaluated

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of this study, the test substance needs to be classified for eye irritation (Cat.2, H319) according to Regulation (EC) No. 1272/2008. According to Directive 67/548/EEC the test substance needs to be classified for eye irritation with Xi; R36.

Executive summary:

Six male albino rabbits (New Zealand White strain) were used for the study. The rabbits were dosed with 100 mg of the test substance by instillation into the conjunctival sac of the left eye. The right eye served as the untreated control. At the end of the 24-hour exposure period, the treated eyes were rinsed with tap water. The eyes were examined at the following intervals: pretreatment (approximately -5 hrs), 1 hr., 24 hrs., 48 hrs., 72 hrs, day 4, day 7 and day 10. The eyes were scored using the Draize scale for the evaluation of eye irritation.

At 1 hour postdosing, slight to moderate conjunctival redness, moderate to severe (one animal) chemosis and a slight to moderate ocular discharge were observed. At the 24 hour observation, translucent areas of corneal opacity, slight iris effects, moderate conjunctival redness, slight to moderate chemosis and a slight to moderate (one animal) ocular discharge were observed. At 48 hours, corneal opacities and iris effects generally remained unchanged from the 24 hour observation. Conjunctival irritation was characterized as a slight (one animal) to moderate conjunctival redness and a slight ocular discharge (two animals). At 72 hours, diffuse (one animal) to translucent areas of corneal opacity and slight iris effects with a slight to moderate conjunctival redness and a slight conjunctival discharge (one animal) were observed. At the day 4 observation, diffuse to translucent (one animal) areas of corneal opacity, slight iris effects (one animal) and a slight conjunctival redness were observed with all signs of irritation resolving in one animal. By day 7, all signs of irritation had resolved in all but one animal. The remaining animal exhibited a diffuse area of corneal opacity which had resolved by the day 10 observation.

No signs of systemic toxicity or mortality were observed during the study period.