Benzoic acid, 3-amino-5-[[[2,3-bis(acetyloxy)propyl]amino]carbonyl]-2,4,6-triiodo-

Endpoint summary

Description of key information

Skin irritation (Rat, GLP): non-skin irritant [Schering AG, Report No. -draft-, 1994-07-06]

Eye irritation (Rabbit, GLP): non-eye irritant [Schering AG, Report No. -draft-, 1994-11-23]

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February to April 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Principles of method if other than guideline:

A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion (comparable to OECD TG 402 and 404). The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint. As described in ATP 96/54/EC ANNEX IV A, PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS, a strategy of testing for irritancy allows the non-performance of a test if an acute toxicity study by the dermal route has been conducted at the limit test dose with the substance (method B.3), and no skin irritation was observed, further testing for skin irritation (method B.4) may be unnecessary.

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Type of coverage:

occlusive

Vehicle:

physiological saline

Controls:

yes, concurrent vehicle

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3/sex/dose

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

At 2000 mg/kg (3 male rats exposed) clinical signs such as apathy, lateral position, retarded respiration and eyelid closure were observed. Two male rats died. Only one male rat survived and therefore mean irritation score could not be determined.

No compound-related findings were observed in hematology.

 

Interpretation of results:

GHS criteria not met

Conclusions:

Since the test substance was tolerated without any local skin irritation, classification is not required

Executive summary:

The single dermal administration of Tamip diacetate to male and female rats in the doses of 200 mg/kg and male rats of 2000 mg/kg results at high dose in clinical signs in all male rats. Two male rat died. The female animals were without any clinical signs. The test substance was tolerated without any local skin irritations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Weight at study initiation: 3.5 -4.1 kg
- Housing: individually under conventional conditions in metal cages
- Diet (e.g. ad libitum): ad libitum: pell. AItromin® K
- Water (e.g. ad libitum): ad libitum: demineralized water
- Acclimation period: > 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 70-74
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

test substance remained in eye and was not flushed out

Observation period (in vivo):

72h

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: According to the score system in the "|llustrated Guide for Grading Eye Irritation by Hazardous Substances", U.S. Department of Health, Education and Welfare, Food and Drug Administration, Washington D.C. 20204, USA. The score system can also be found in the Annex to EEC Directive 92/69/EWG, dated 31. Jul. 1992, for the 17th adaption of the EEC Directive 67/548/EWG.

TOOL USED TO ASSESS SCORE: not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

Slight to moderate transient irritation on the rabbit conjuctiva mainly on application day. All animals were without any symptoms from day 2 or 3 onwards

 

Animal No. and sex	Location	Finding	Right eye 100 mg test item, hours after application			results	left eye control untreated, hours after application			results
			24	48	72		24	48	72
	Cornea		0	0	0	negative	0	0	0	negative
	Iris		0	0	0		0	0	0
	Conjunctiva	Reddening	1	0	0		0	0	0
		swelling	0	0	0		0	0	0
	Cornea		0	0	0	negative	0	0	0	negative
	Iris		0	0	0		0	0	0
	Conjunctiva	Reddening	1	0	0		0	0	0
		swelling	0	0	0		0	0	0
	Cornea		0	0	0	negative	0	0	0	negative
	Iris		0	0	0		0	0	0
	Conjunctiva	Reddening	1	0	0		0	0	0
		swelling	0	0	0		0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is non-eye irritant, classification is not required

Executive summary:

The single administration of Tamip diacetate to the right eye of female rabbits in the doses of 100 mg/kg results in slight to moderate transient irritation on the rabbit conjuctiva mainly on application day. All animals were without any symptoms from day 2 or 3 onwards. The test substance is non-eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The single dermal administration of Tamip diacetate to male and female rats in the doses of 200 mg/kg and male rats of 2000 mg/kg results at high dose in clinical signs in all male rats. Two male rat died. The female animals were without any clinical signs. The test substance was tolerated without any local skin irritations. (Schering AG, Report No. -draft-, 1994-07-06)

The single administration of Tamip diacetate to the right eye of female rabbits in the doses of 100 mg/kg results in slight to moderate transient irritation on the rabbit conjunctiva mainly on application day. All animals were without any symptoms from day 2 or 3 onwards. The test substance is non-eye irritant. (Schering AG, Report No. -draft-, 1994-11-23)

Justification for classification or non-classification

Tamip diacetate was tested in one skin and one eye irritation test and did not show any irritation potential.

Classification according to Directive 67/548/EEC and Regulation (EC) 1272/2008 (CLP) is not required.