Trisodium bis[2-hydroxy-5-nitro-3-[[2-oxo-1-[(phenylamino)carbonyl]propyl]azo]benzenesulphonato(3-)]cobaltate(3-)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium bis[2-hydroxy-5-nitro-3-[[2-oxo-1-[(phenylamino)carbonyl]propyl]azo]benzenesulphonato(3-)]cobaltate(3-)

EC Number:

289-068-2

EC Name:

Trisodium bis[2-hydroxy-5-nitro-3-[[2-oxo-1-[(phenylamino)carbonyl]propyl]azo]benzenesulphonato(3-)]cobaltate(3-)

Cas Number:

85959-73-5

Molecular formula:

C32H22CoN8O16S2.3Na

IUPAC Name:

trisodium bis[2-hydroxy-5-nitro-3-[[2-oxo-1-[(phenylamino)carbonyl]propyl]azo]benzenesulphonato(3-)]cobaltate(3-)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH
- Age at study initiation: 9-12 weeks
- Weight at study initiation: males: 195-265 g; females: 173-218 g
- Housing: 5 animals per Makrolon cage type III
- Diet (e.g. ad libitum): pellets of Kliba 343 ad libitum
- Water (e.g. ad libitum): tap water from Itingen, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40 -70
- Air changes (per hr): 10/15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

MAXIMUM DOSE: 20 ml at 5000 mg/kg bw (group 5)

RATIONALE FOR SELECTION OF DOSES:Oral administration has been proven to be an efficacious method to assess the test article absorption.

Doses:

Group 1: 10 ml at 750 mg/kg bw
Group 2: 10 ml at 1000 mg/kg bw
Group 3: 10 ml at 2000 mg/kg bw
Group 4: 20 ml at 3000 mg/kg bw
Group 5: 20 ml at 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: 4 times in day 1; daily during days 2-15
- Frequency of weighing: before application, after 8 days and after 15 days.
- Necropsy of survivors performed: yes, all animals

Statistics:

The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence intervals for the toxicity for each sex the slope of the concentration response line were estimated.

Results and discussion

Preliminary study:

N.A.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 053 mg/kg bw

Based on:

test mat.

95% CL:

> 1 439 - < 4 878

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 336 mg/kg bw

Based on:

test mat.

95% CL:

> 934 - < 1 859

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 666 mg/kg bw

Based on:

test mat.

95% CL:

> 1 344 - < 2 147

Mortality:

Based on the values indicated in Appendix A1:
No mortality at 750 and 1000 mg/kg bw.
1 animal died at day 2 for 2000 mg/kg bw
5 animals died at day 2 for 3000 mg/kg bw
5 animals died at day 2 for 5000 mg/kg bw

Clinical signs:

The following symptoms were observed:
750 mg/kg bw: dyspnea
1000 mg/kg bw: sedation, dyspnea, curved body position, ruffled fur
2000 mg/kg bw: sedation, dyspnea, curved body position, ruffled fur, ataxis (females)
3000 mg/kg bw: sedation, dyspnea, curved body position, ruffled fur, ataxis
5000 mg/kg bw: sedation, dyspnea, curved body position, latero-abdominal position, ventral body position, ruffled fur, ataxis

Body weight:

No effects on the body weight were noted.

Gross pathology:

In killed rats, no pathologic changed were observed.
In dead animals some changes were observed (stomach and intestine descoloration, mottled lungs and discoloration, spleen and kidney discoloration.

Other findings:

N.A.

Applicant's summary and conclusion

Interpretation of results:

other: Acute Toxicity Category 4

Conclusions:

In this acute oral toxicity study, the LD50 was determined to be 1666 mg/kg bw for male/female.

Executive summary:

In this acute oral toxicity study, the LD50 was determined to be 1666 mg/kg bw for male/female.
Based on the criteria in the Regulation CE n.1272/2008, the tested substance needs to be classified as Acute Tox. Cat. 4.