3-amino-2,4,6-triiodobenzoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Deviating from the OECD guideline 405, adopted 24 Feb. 87, the maximum administration dose of 100 mg per animals was exceeded in this study, since the planned administration volume of 0.1 ml per animal was erroneously applied without being adjusted to the maximum administration dose. This is not regarded to compromise the validity of the results since the severity of the effects observed in the individual animals was not correlated to the total dose administered.

Deviations:

yes

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3-amino-2,4,6-triiodobenzoic acid

EC Number:

221-493-0

EC Name:

3-amino-2,4,6-triiodobenzoic acid

Cas Number:

3119-15-1

Molecular formula:

C7H4I3NO2

IUPAC Name:

3-amino-2,4,6-triiodobenzoic acid

Test material form:

solid: bulk

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:Dr. Schenk, Schering AG, Germany, batch no: 37055008

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Weight at study initiation: males:.3 - 3.6 kg, females: 3.4 - 3.5 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 14 days; during this period the animals were vaccinated against rabbit hemorrhagic disease (Arvilap®)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23° c
- Humidity (%): 56 - 60%
- Photoperiod (hrs dark / hrs light): 12-hour day/12-hour night cycle

IN-LIFE DATES: From: To: not reported

Test system

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

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

Duration of treatment / exposure:

Administration frequency: single

Observation period (in vivo):

10 to 15 days

Duration of post- treatment incubation (in vitro):

72 hours after treatment

Number of animals or in vitro replicates:

2 male, 2 female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure: not reported

SCORING SYSTEM: not reported

TOOL USED TO ASSESS SCORE: not reported

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.7

Reversibility:

fully reversible within: 10 to 15 days

Remarks on result:

other: reddening

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 2.6

Reversibility:

fully reversible within: 10 to 15 days

Remarks on result:

other:

Any other information on results incl. tables

Findings
	male		female
	A	x-y	A	x-y
Conjunctivae -reddening (all conjunctivae including conjunctiva sklerae)
clear injection of a some blood vessels	18/2
diffusely carmine, individual vessels not easy to discern	7/2
diffusely flesh-red	1/1
swelling (all conjuntivae including membrana nictitans)
slight	16/2	1-14	13/2	1-10
clear with partial ectropium	1/1	1	2/1	2-3
with half eyelid closure	6/2	1-6	2/1	2-3
with more than half eyelid closure	3/1	2-4

A = summation of positive findings/number of animals concerned

x-y = first - last day of occurrence of a finding

		Animalnumber and sex
Location(finding)	Time-pointafter end of exposure	27M	33M	20F	23F
Cornea(opacity)	24hours	0	0	0	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Individualmeanvalues:		0	0	0	0
Mean value of allanimals:					0
Iris(reddening,swelling,etc.)	24hours	0	0	0	0
	48 hours	0	0	0	0
	72 hours	0	0	0	0
Individual meanvalues:		0	0	0	0
Mean value of all animals					0
Conjunctivae(reddening)	24hours	3	2	2	2
	48 hours	1	1	2	2
	72hours	2	1	1	1
Individual meanvalues:		2	1.3	1.7	1.7
Mean valueofallanimals					1.7
Conjunctivae (swelling)	24hours	4	3	3	2
	48hours	4	3	3	2
	72 hours	4	1	1	1
Individual meanvalues:		4	2.3	2.3	1.7
Mean valueofallanimals					2.6

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The substance produced clear-cut irritation of the rabbit eye which was seen for more than 24 hours, but was fully reversible until day 10 to 15 after administration.

Executive summary:

The eye of rabbits were exposed to the test substance according to OECD 405, with test concentration deviations (i.e. Deviating from the OECD guideline 405, adopted 24 Feb. 87, the maximum administration dose of 100 mg per animals was exceeded in this study, since the planned administration volume of 0.1 ml per animal was erroneously applied without being adjusted to the maximum administration dose.  This is not regarded to compromise the validity of the results since the severity of the effects observed in the individual animals was not correlated to the total dose administered.) The substance produced clear-cut irritation of the rabbit eye which was seen for more than 24 hours, but was fully reversible until day 10 to 15 after administration. According to the EU criteria for general classification and labeling requirements for dangerous substances and preparations (2), the test item has to be labeled as an eye irritant since the mean value for chemosis was larger than 2.0.