Benzoyl chloride, 3-[[[2,3-bis(acetyloxy)propyl]amino]carbonyl]-2,4,6-triiodo-5-[(2-methoxyacetyl)amino]-

Endpoint summary

Description of key information

Skin irritation (Rat-Wistar, GLP, non-audited report, OECD TG 404 & 423): not irritating or corrosive to skin [Schering AG, 1994-05-25]
Eye irritation (Rabbit-NZW, GLP, non-audited report, OECD TG 405): not irritating [Schering AG, 1994-11-20]

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:

1994-02-23 to 1994-03-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

According to EEC Commission Directive no. 79/831 EEC of 18. Sep. 1979 (equivalent to the
corresponding German regulations)

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

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Schering AG
- Weight at study initiation: Males: 84-92 g; Females: 99-102 g
- Fasting period before study: 18-19.5 h
- Housing: individually under conventional conditions
- Diet (e.g. ad libitum): ad libitum: Pell. Altromin® R
- Water (e.g. ad libitum): ad libitum: Demineralized acidified water, pH 2-3
- Acclimation period: 7 days males; 9 days females

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 56-62

- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23.02./25.02.1994 To: 08.03./10.03.1994

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

168 - 184 mg test item/male animal and 198 - 204 mg test item/female animal
Paste was applied.

Duration of treatment / exposure:

24 h

Observation period:

3 days

Number of animals:

3 males and 3 females

Details on study design:

OBSERVATION TIME POINTS
30-60 min; 24h, 48h, 72h
SCORING SYSTEM:
- Method of calculation: According to Draize et al.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Local tolerance test with the test item on the intact skin of rats. Calculation of the irritation index according to Draize

Test substance		Animal number and sex						Ø	X1
		26M	27M	28M	30F	31F	32F
Findings	Time-point after application
Reddening and scar formation	30-60 min	0	0	0	0	0	0
	24 h	0	0	0	0	0	0
	48 h	0	0	0	0	0	0
	72 h	0	0	0	0	0	0
								0
swelling	30-60 min	0	0	0	0	0	0
	24 h	0	0	0	0	0	0
	48 h	0	0	0	0	0	0
	72 h	0	0	0	0	0	0
								0	0
			Irritation Index for males and females					0

Interpretation of results:

GHS criteria not met

Conclusions:

TIP-Diamidchlorid in male and female rats after a single dermal application: No local intolerance reactions at the application sites were observed.

Executive summary:

In a primary dermal irritation study according to EEC Commission Directive no. 79/831 EEC of 18. Sep. 1979 (equivalent to the corresponding German regulations), young adult Wistar rats (3/sex) were dermally exposed to 168-184 mg (males) and 198-204 mg (females) of TIP-Diamidchlorid (100 % a.i.) in 0.9% NaCl for 24 hours. Animals then were observed for 3 days. Irritation was scored by the method of Draize et al..

In this study, TIP-Diamidchlorid is not a dermal irritant.

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:

1994-04-22 to 1994-11-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

other: EEC Directive 92/69/EWG, dated 31. Jul. 1992, for the 17th adaption of the EEC Directive 67/548/EWG.

Version / remarks:

1992

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: 3.8 -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:

Amount / concentration applied:

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

Duration of treatment / exposure:

single application, observation for at least 72h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

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:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Findings	Right eye 100 mg TIP-Dimidchlorid/eye
	A	x-y
Outer eyelids
- Slight secretion with wetting of surrounding fur	9/3	1-2
- slight swelling of the margin eyelids	2/1	1-1
- Incomplete eyelid closure	1/1	1-1
Conjunctiva palpebrae
- slight reddening	1/1	1-1
- slight injection of blood vessels	3/1	1-1
Membrana nicitans
- slight reddening	3/1	1-1
- slight injection of blood vessels	6/3	1-1
Conjunctiva sclerae
- slight reddening	3/1	1-1
- slight injection of blood vessels	7/3	1-1
A = summation of positive findings/number of animals concerned x-y = first – last days of occurrence of a finding

 

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	0	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	0	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	0	0	0		0	0	0
		swelling	0	0	0		0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

According to the score system in the "lllustrated Guide for Grading Eye Irritation by hazardous Substances" animals reacted negatively. The substance is not considered to be irritating to the eyes.

Executive summary:

In a primary eye irritation study according to  EEC Directive 92/69/EWG, dated 31. Jul. 1992, for the 17th adaption of the EEC Directive 67/548/EWG., 100 mg of TIP-Diamidchlorid (100 % a.i.) was instilled into the conjunctival sac of the right eye of young adult New Zealand rabbits (3 females). Animals then were observed for 3 days.  Irritation was scored by the method of 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.

In this study, TIP-Diamidchlorid is not an eye irritant based on the absence of any severe damages, i.e. reddening/swelling of conjunctivae, chemosis or corneal opacity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

TIP-Diamidchlorid did not show a skin irriating or corrosive potential in rats when administered semi-occlusively to the shorn back for 24 hours.

TIP-Diamidchlorid provoked very slight to slight transient irritations on the rabbit conjunctiva after single conjunctival application on the day of administration. TIP-Diamidchlorid is not regarded as an eye irritant.

Justification for classification or non-classification

Based on the available data TIP-Diamidchlorid does not need to be classified according to Regulation (EC)No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS).