Benzoic acid, 3-[[(2,3-dihydroxypropyl)amino]carbonyl]-5-nitro-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

rac-N-(2,3-Dihydroxypropyl)-5-nitroisophthalamic acid

EC Number:

602-890-1

Cas Number:

122731-58-2

Molecular formula:

C11 H12 N2 O7

IUPAC Name:

rac-N-(2,3-Dihydroxypropyl)-5-nitroisophthalamic acid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Controls:

other: left eye served as control

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

test substance remained in eye and was not flushed out

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2 males and 2 females

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.42

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Other effects:

Single application of ZK 39116 led to slight to severe reddening, swelling and vascular injection as well as secretion and eye lid closure mainly on the application day. On days 2 and 3, the findings gradually subsided and only slight findings were observed until days 5 to 6.

Any other information on results incl. tables

Results of the study

		Irritant Effects (Score)
Animal		24 h	48 h	72 h	Mean scores
1 (male)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	2	2	1	1.67
	Conjunctivae (swelling)	2	1	0	1.0
2 (male)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	2	2	1	1.67
	Conjunctivae (swelling)	1	0	0	0.33
3 (female)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	1	1	1	1.0
	Conjunctivae (swelling)	1	0	0	0.33
4 (female)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddining)	2	1	1	1.33
	Conjunctivae (swelling)	1	1	1	1.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single conjunctival application of ZK 39166 provoked on the whole transient slight to moderate intolerance reactions. Since the rabbit eye reacts more sensitively than the human eye due to anatomical and physiological differences, no significant effects are to be expected after inadvertent contact between the human eye and this substance.

Executive summary:

The local tolerance of ZK 39166 was tested after a single application of solid substance measured as 0.1 ml/eye into the conjunctival' sac of the right eye in 2 male and 2 female New Zealand White rabbits. The volume of 0.1 ml corresponded to 52 - 59 mg.
The respective left eye remained untreated and served as control.
Observations were performed before application, 0.5; 1 and 2 hours thereafter and then every 24 hours until day 7 of the test.
A single application of 0.1 ml ZK 39166 into the conjunctival sac of the rabbit eye led to slight to severe reddening, swelling and vascular injection as weil as secretion and eye lid closure mainly on the application day. On days 2 and 3, the findings gradually subsided and only slight findings were observed until days 5 to 6.
According to the system of evaluation recommended for the EU, the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters comea and iris, 1.4 for conjunctival reddening and 0.7 for conjunctival swelling.