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

Endpoint summary

Description of key information

Oral (Rat-Wistar, GLP, non-audited report, OECD TG 423): LD50 > 2000 mg/kg [Schering AG, 1993-05-17]
Dermal (Rat-Wistar, GLP, non-audited report, OECD TG 402 and 404): LD50 > 2000 mg/kg [Schering AG, 1994-05-25]

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992-03-24 to 1993-05-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

other: "New approaches to acute toxicity testing of chemicals" (Bundesgesundheitsblatt 32, pp. 336-340, 1989).

Version / remarks:

1989

GLP compliance:

yes

Test type:

standard acute method

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- Age at study initiation:
- Weight at study initiation: 85-92 g males; 87-104 g females
- Housing: individually under conventional conditions
- Fasting period before study: 18-19 h
- Diet (e.g. ad libitum): adlibitum: pel. Atromin R®
- Water (e.g. ad libitum): ad libitum: demineralized, acidified water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23

IN-LIFE DATES: From: 24.03.1992 To: 19.04.1992

Route of administration:

oral: gavage

Vehicle:

other: 0.9 g NaCl + 0.085 g Mrj ad 100 mL demin. water

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 1, 7 or 8 and 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- 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 i.g. application of 2000 mg test item/kg was tolerated by all treated animals without any clinical findings. The body weight gain observed on day 7 (male) or 8 (female) and at the end of the test on day 14 was within the normal range for rats (M+F) of the age and strain which are routinely used in our laboratory. Autopsy revealed no compound-related or suspected compound-related findings.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

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

Executive summary:

In an acute oral toxicity study according to "New approaches to acute toxicity testing of chemicals" (Bundesgesundheitsblatt 32, pp. 336-340, 1989)., groups of fasted, young adult Wistar rats (3/sex) were given a single oral dose of TIP-Diamidchlorid (100% a.i.) in 0.9 g NaCl + 0.085 g Mrj ad 100 mL demin. water at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 Combined > 2000 mg/kg bw

No mortality occurred during this limit test.

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

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Quality is high, guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Quality high, guideline study

Additional information

The single oral administration of ZK91445 to male and female Wistar rats was well tolerated without any treatment-related findings. Acute oral toxicity of ZK 91445 in Wistar rats is above 2000 mg/kg body weight.

The single dermal administration of ZK 91445 to male and female Wistar rats was well tolerated without any treatment-related findings. Acute dermal toxicity of ZK91445 is above 2000 mg/kg body weight.

Justification for classification or non-classification

Based on the available data the substance does not need to be classified according to Regulation (EC) No. 1272/2008 (CLP) with regard to acute oral or dermal toxicity.