N,N-dimethylpyridin-4-amine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically valid study in a reputable industry laboratory, predating GLP and OECD method development

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Preceeds establishment of guideline. A single rabbit is initially tested with 2 drops of liquid into the right eye (washed) and the left eye (unwashed). Observations are made immediately, and at 1, 24 and 48 hours, and 6 to 8 days (and longer). A grading scale is used to describe the severity of eye irritation, with and without fluorescein treatment.

GLP compliance:

no

Remarks:

Predates establishment of GLP

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylpyridin-4-amine

EC Number:

214-353-5

EC Name:

N,N-dimethylpyridin-4-amine

Cas Number:

1122-58-3

Molecular formula:

C7H10N2

IUPAC Name:

N,N-dimethylpyridin-4-amine

Constituent 2

Reference substance name:

2,6-dichloropyridine

EC Number:

219-282-3

EC Name:

2,6-dichloropyridine

Cas Number:

2402-78-0

IUPAC Name:

2,6-dichloropyridine

Constituent 3

Reference substance name:

N,N-dimethyl pyridin-4-amine

IUPAC Name:

N,N-dimethyl pyridin-4-amine

Test material form:

not specified

Details on test material:

reported as a 50% aqueous solution; yellow liquid. Molecular weight: 122

Test animals / tissue source

Species:

rabbit

Test system

Vehicle:

water

Controls:

no

Amount / concentration applied:

2 drops of a liquid material or solution

Observation period (in vivo):

immediately, and at 1, 24 and 48 hours, and 6, 8 and 14 days

Number of animals or in vitro replicates:

1

Details on study design:

Method:
Stain both eyes with fluorescein (5% in H2O), was promptly and examine for any evidence of injury. Allow rest period of 24 hours before introducing the test material. Introduce 2 drops of a liquid material or a solution in the concentration called for (i.e, 100, 10, 1% etc.), onto the right eyeball. If a solid, use a small amount on a spatula. This eye is washed (within 30 sec.) for 2 minutes in a flowing stream of tepid water. The left eye is then treated with 2 drops as described above, but the eye is unwashed.
Both eyes are observed immediately for pain. Within 2-3 minutes after the unwashed eye is treated, each is observed for conjunctival and corneal response. Similar observations are made of both eyes at 1 hour, 24 hours, 48 hours, and 6-8 days. Note that both eyes are stained with fluorescein (5% water solution) at 1 hour, 24 hours, 48 hours, and 6-8 days. This necessitates the washing of both eyes to remove the excess stain.
Observation may include unusual types or severity of responses not fully covered by the descriptions under Grading of Responses. Particular remarks may be made concerning the lids, nictitating membranes, iris and eye chambers.

Results and discussion

In vivo

Results

Irritation parameter:

other: Overall irritation score

Basis:

animal #1

Time point:

other: 0, 1, 24 and 48 hours, and 6 and 12 days

Score:

5

Max. score:

6

Reversibility:

not reversible

Remarks on result:

other: nonstandard scoring criteria

Irritant / corrosive response data:

Severe to very severe eye irritation was observed in the one animal tested, in either washed or unwashed eyes, after instillation of a 50% aqueous solution of DMAP. Conjunctival and corneal effects were scored as 5 or 6 (of a maximum of 6) at 1 hour after instillation, and throughout 12 days following testing. There was little evidence of healing/reversibility after 12 days, with heavy necrosis and loss of function.

Any other information on results incl. tables

Results of Eye Irritation Study

Observation Time	Response	Left eye (not washed)	Right eye (washed)
Immediate	Pain	3	3
	Conjunctiva	5	5
	Cornea	3+	4
1 hour	Conjunctiva	5+	5
	Cornea-before fluorescein stain	5	5
	Cornea-after fluorescein stain	5	5
	Internal effects	Can’t see
24 hours	Conjunctiva	6	5+
	Cornea-before fluorescein stain	6	5
	Cornea-after fluorescein stain	5	5
	Internal effects	Can’t see
48 hours	Conjunctiva	6	6
	Cornea-before fluorescein stain	6	5+
	Cornea-after fluorescein stain	5	5
	Internal effects	Can’t see
6 days	Conjunctiva	6	6
	Cornea-before fluorescein stain	6	6
	Cornea-after fluorescein stain	6	6
	Internal effects	Can’t see
12 days	Conjunctiva. Note: Blood vessels injecting into both corneas	5	4
	Cornea-before fluorescein stain	6	5
	Cornea-after fluorescein stain	6	5
	Internal effects	Can’t see	1

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Very severe damage which is likely irreversible Criteria used for interpretation of results: EU

Conclusions:

Instillation of 50% aqueous solution of DMAP into the eye of a rabbit resulted in severe to very severe eye damage, regardless of washing. There was little evidence of healing/reversibility after 12 days, with heavy necrosis and loss of function. The is consistent with the damage estimated from a skin corrosive substance.