N-bromosuccinimide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 June 1995 to 18 September 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according to GLP .

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Directive 92/69/EEC, B.1. "Acute Toxicity-Oral", July 31, 1992.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-bromosuccinimide

EC Number:

204-877-2

EC Name:

N-bromosuccinimide

Cas Number:

128-08-5

Molecular formula:

C4H4BrNO2

IUPAC Name:

1-bromopyrrolidine-2,5-dione

Constituent 2

Reference substance name:

N-BROMSUCCINIMID

IUPAC Name:

N-BROMSUCCINIMID

Details on test material:

- Identification: N-Bromsuccinimid
- Description: White solid
- Batch no.: SHEN 009
- Purity/Formulation: 100%
- Stability of Test Article: Stable under storage conditions; for 1 year as from sponsor' s signature date on data sheet.
- Stability of test Article in Vehicle: Stable in water for 2 hours.
- Storage conditions: In the original container at room temperature away from direct sunlight.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd.; Wölferstrasse 4, 4414 Füllingsdorf/Switzerland
- Age at study initiation: male: 8 weeks, females: 10 weeks
- Weight at study initiation: males: 195.9 - 218.5 g; females: 175.0 - 187.1 g
- Fasting period before study: approximately 16h
- Housing: Makrolon type 4 with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
- Diet: Pellet standard Kliba 343, Batch no. 86/95 rat maintenance diet, ad libitum
- Water: Tap water from Füllingsdorf, ad libitum
- Acclimation period: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24°C
- Humidity (%): 48 to 90 %
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 artificial fluorescent light (approx. 100 Lux)
:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test article was placed into a glass beaker on a tared Mettler PM 480 balance, and the vehicle (bi-distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra Turax, Janke & Kunkel, D-79219 Staufen). The preparation was made shortly before dosing. The animals received a single dose of the test article on a mg/kg bw basis by oral gavage following fasting for approx. 16 hours, but with free access to water. Food was provided again approx. 3 hours after dosing.
Application Volume: 10 ml/kg

Doses:

1000 mg/kg bw (Group 1)
2000 mg/kg bw (Group 2)

No. of animals per sex per dose:

5 males and 5 females: 1000 mg/kg bw (Group 1)
5 males and 5 females: 2000 mg/kg bw (Group 2)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: each animal was examined for changes in appearance and behaviour four times during day 1 and once daily for surviving animals during days 2-15. weighing: day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights

Statistics:

not applicable

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In group one (1000 mg/kg bw) no deaths occurred . In group 2 (2000 mg/kg bw) one male died one hour after treatment with the test article, two males died on test day 2 and 3 respectively, and one female died on test day 12.
For further details please see also the attached background material: '1995.Pfister.acute oral toxicity study with N-Bromosuccinimide in rats_ tables and appendices.pdf'.

Clinical signs:

other: Group 1 (1000 mg/kg bw): sedation (5/5)* ruffled fur (5/5) Group 2 (2000 mg/kg bw) sedation (4/5), ruffled fur (4/5), hunched posture (2/5), ventral and lateral recumbency (1/0), dyspnoea (5/5), diarrhea (0/1), emaciation (3/5). * ( / ) = number of male

Gross pathology:

Group 1 (1000 mg/kg bw): no findings.
Group 2 (2000 mg/kg bw): scheduled necropsy: no findings; spontaneous death: ileum distended with gas (1/0)*, reddish discoloration of stomach (1/0), hemorrhagic-water fluid in body cavities (1/0), yellowish liquid in stomach (0/1)

* ( / ) = number of male/female animals.
For further details please see also the attached background material: '1995.Pfister.acute oral toxicity study with N-Bromosuccinimide in rats_ tables and appendices.pdf'.

Other findings:

For further details please see also the attached background material: '1995.Pfister.acute oral toxicity study with N-Bromosuccinimide in rats_ tables and appendices.pdf'.

Any other information on results incl. tables

For further details please see also the attached background material: '1995.Pfister.acute oral toxicity study with N-Bromosuccinimide in rats_ tables and appendices.pdf'.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 of N-bromosuccinimide is > 2000 mg/kg bw in rats.

Executive summary:

N- bromosuccinimide was administered to two groups of 5 male and female by oral gavage at single doses of 1000 and 2000 mg/kg bw.

In group one (1000 mg/kg bw) no deaths occurred in group two (2000mg/kg bw) one male died one hour after treatment with the test substance, two males died on test day 2 and 3 respectively, and one female died on test day 12.

Based on these observations, the LD50 estimation for acute oral toxicity in rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg bw.

Therefore no classification is required according to DSD and CLP.