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

Endpoint summary

Description of key information

OECD 401: LD50 (oral, rat) 300 - 2000 mg/kg bw

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:

October 31, 1996 - November 27, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

02-1987

Deviations:

no

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

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

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.

Preliminary study:

A range finding was performed.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 250 mg/kg bw

Quality of whole database:

Guideline study under GLP conditions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the provided information there is need for classification for Acute Tox Class 4 according to the EU Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures, as amended for the 10th time in Regulation (EU) No 2017/776.