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

Skin irritation / corrosion

Administrative data

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: dermal

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

As described in Schlede, E. et al.: A national validation study of the acute-toxic-class method - an alternative to the LD59 test Arch. Toxicol. 66, 455-470, 1992

GLP compliance:

yes

Test type:

other: similar to Acute toxic class

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

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:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
I 194 mg test item + 0.16 mL vehicle-1)
ll 169 mg test item + 0.17 mL vehicle-1)
lll 180 mg test item + 0.18 mL vehicle-1)
IV 204 mg test item + 0.24 mL vehicle-1)
1 v 19a mg test item + 0.21 mL vehicle-1)
1 Vl 200 mg test item + 0.23 mL vehicle-1)

1) Vehicle: 0.9% (w/v) NaCl-solution

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 1, 7 and 14
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

The single dermal application of 2000 mg/kg of the test item was tolerated without compound-related clinical findings. The slight to moderate swelling of both forelimbs in one female animal on days 2 and 3 is not considered to be compound-related. It was probably caused by the bandage used for dermal exposure. A higher dosage than 2000 mg/kg was not tested in the present study since this dose level is established as the upper limit dose for classification and labelling requirements concerning dangerous substances in accordance with the EEC Commission Directive no. 79/831 EEC of 18. Sep. 1979 (equivalent to the corresponding German regulations). The body weight gain observed on day 7 and at the end (day 14) of the test was within the normal range for rats (M+F) of the age and strain which are routinely used in the laboratory. On day 14 of the test all surviving animals were sacrificed without showing any compound-related clinical findings.  

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 of TIP-Diamidchlorid in male and female rats after a single dermal application is > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study according to Schlede, E. et al.: A national validation study of the acute-toxic-class method - an alternative to the LD59 test Arch. Toxicol. 66, 455-470, 1992 and EEC Commission Directive no. 79/831 EEC of 18. Sep. 1979 (equivalent to the corresponding German regulations), groups of young adult Wistar rats (3/sex) were dermally exposed to TIP-Diamidchlorid (100% a.i) in 0.9% NaCl for 24 hours at a dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Combined > 2000 mg/kg bw

No mortality occurred in this limit test.

There were no treatment related clinical signs, necropsy findings or changes in body weight.

TIP-Dichlorid is of LOW Toxicity based on the LD50 in male and female Wistar rats.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

rac-3-(2,3-Diacetoxypropylcarbamoyl)-2,4,6-triiodo-5-methoxyacetylaminobenzoyl chloride

EC Number:

604-759-4

Cas Number:

150928-21-5

Molecular formula:

C18 H18 Cl I3 N2 O8

IUPAC Name:

rac-3-(2,3-Diacetoxypropylcarbamoyl)-2,4,6-triiodo-5-methoxyacetylaminobenzoyl chloride

Test animals

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.