6-diazo-5,6-dihydro-5-oxonaphthalene-2-sulphonyl chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 31, 1996 - November 27, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

02-1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

07-1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

6-diazo-5,6-dihydro-5-oxonaphthalene-2-sulphonyl chloride

EC Number:

223-211-1

EC Name:

6-diazo-5,6-dihydro-5-oxonaphthalene-2-sulphonyl chloride

Cas Number:

3770-97-6

Molecular formula:

C10H5ClN2O3S

IUPAC Name:

6-(-lambda5-diazynylidene)-5-oxo-5,6-dihydronaphthalene-2-sulfonyl chloride

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Hoe:WISKf(SPF71)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Kastengrund, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 151 - 187 g
- Fasting period before study: From about 16 hours before dosing to 3-4 hours after treatment
- Housing: groups of 5 in type 4 macrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From days 1 to 15

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

Doses were based on a range finding study.
Dosing volume: 10 mL/kg.

Doses:

1250, 1600 and 2000 mg/kg bw

No. of animals per sex per dose:

1250 mg/kg: 5 m / 5 f
1600 mg/kg: 5 f
2000 mg/kg: 5 m / 5 f

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: once or twice daily
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes (gross pathology)

Statistics:

Standard statistical methods have been applied for data processing.

Results and discussion

Preliminary study:

A range finding was performed.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 250 - < 1 600 mg/kg bw

Based on:

test mat.

Mortality:

1250 mg/kg: 1/5 m, 1/5 f
1600 mg/kg: 5/5 f
2000 mg/kg: 5/5 m, 5/5 f

Clinical signs:

Decreased spontaneous activity, squatting posture, sunken flanks, bristled coat, irregular respiration, panting, stupor, prone position, narrowed palpebral fissures, increased salivation and diarrhoea.
All clinical signs had reversed in the surviving animals at day 4 of the study. Additionally the bedding of the cages was discoloured yellow up to day two of the study.

Body weight:

Surviving animals showed expected gain in bodyweight during the study.

Gross pathology:

Animals found dead:
Stomach: full of test compound, full of a reddish-black mass, Haemoccult test positive, mucosa discoloured black.
Intestinal tract: full of a reddish-black mass, Haemoccult test positive, mucosa of the small intestine diffuse reddened, small intestine full of a yellowish mucous.
Abdominal cavity: full of a clear, colourless fluid.
Connective and supportive tissue: discoloured by the test compound.

The animals killed at the end of the observation period showed no macroscopically visible changes.

Any other information on results incl. tables

Study design

The test item diluted in DMSO was tested for acute toxicity in rats after single oral administration of 1250 - 2000 mg/kg body weight. This GLP study was performed according to the OECD GL 401. The surviving animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

Results

At dose levels of 1250, 1600 and 2000 mg/kg the mortality was 1/5 m and 1/5 f, 5/5 f or 5/5 m and 5/5 f, respectively. Clinical signs of intoxication included decreased spontaneous activity, squatting posture, sunken flanks, bristled coat, irregular respiration, panting, stupor, prone position, narrowed palpebral fissures, increased salivation and diarrhoea. All clinical signs had reversed in the surviving animals at day 4 of the study. Additionally the bedding of the cages was discoloured yellow up to day two of the study. Surviving animals showed expected gain in bodyweight during the study.

Abnormalities noted at necropsy of rats that died during the study were effects on the stomach (full of test compound, full of a reddish-black mass, Haemoccult test positive, mucosa discoloured black), intestinal tract (full of a reddish-black mass, Haemoccult test positive, mucosa of the small intestine diffuse reddened, small intestine full of a yellowish mucous), abdominal cavity (full of a clear, colourless fluid), and connective and supportive tissue (discoloured by the test compound). No abnormalities were noted at necropsy of animals killed at the end of the study.

Conclusion

For regulatory purposes, the median lethal dose (LD50) can be declared in the range of 1250 to 1600 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

For regulatory purposes, the median lethal dose (LD50) can be declared in the range of 1250 to 1600 mg/kg.

Executive summary:

This study was performed according to GLP and is fully compliant with OECD GL 401. Based on the result of this study, the median lethal dose (LD50) can be declared in the range of 1250 to 1600 mg/kg.