N-chlorosuccinimide

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 19 October 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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-chlorosuccinimide

EC Number:

204-878-8

EC Name:

N-chlorosuccinimide

Cas Number:

128-09-6

Molecular formula:

C4H4ClNO2

IUPAC Name:

1-chloropyrrolidine-2,5-dione

Constituent 2

Reference substance name:

N-CHLORSUCCINIMID

IUPAC Name:

N-CHLORSUCCINIMID

Details on test material:

- Identification: BN-Chlorsuccinimid
- Description: White solid
- Batch no.: SHEN 219
- Purity/Formulation: 99.7%
- 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: Stabvle in water fioir 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: 200.9 - 221.6 g; females: 179.8 - 196.6 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 maintainance diet, ad libitum
- Water: Tap water from Füllingsdorf, ad libitum
- Acclimation period: One week under laboratory condtions, after health examination. Only animals without any visible signs of illnes 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

Remarks:

(bi-distilled)

Details on oral exposure:

The test article was placed into a glas 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). Homogeneity of the test article was maintained during treatment using a magnetic stirrer (Janke & Kinkel, 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:

500 mg/kg bw (Group 1)
1000 mg/kg bw (Group 2)
2000 mg/kg bw (Group 3)

No. of animals per sex per dose:

5 males and 5 females: 500 mg/kg bw (Group 1)
5 males and 5 females: 1000 mg/kg bw (Group 2)
5 males and 5 females: 2000 mg/kg bw (Group 3)

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 apperance and behaviour four to five 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:

The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was used to calculate the mean lethal dose. The 90%, 95% and 99% confidence limits for the toxicity value and the slope of the dos response line were calculated.

Results and discussion

Preliminary study:

not applicable

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 212 mg/kg bw

Based on:

test mat.

95% CL:

927 - 1 704

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 529 mg/kg bw

Based on:

test mat.

95% CL:

959 - 6 036

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

952 mg/kg bw

Based on:

test mat.

95% CL:

574 - 1 451

Mortality:

The following mortality was observed:
500 mg/kg bw (Group 1): males: 0%, females: 0%
1000 mg/kg bw (Group 2): males: 0%, females: 60%
2000 mg/kg bw (Group 3): males: 80%, females: 100%

For further details please see also the attached background material: Pfister.1995.Acute oral toxicity study with N-chlorosuccinimide in rats_ tabels and appendices.pdf

Clinical signs:

other: The following clinical signs were observed during the observation period: 500 mg/kg bw (Group 1): sedation (5/5)*, ruffled fur (3/5) 1000 mg/kg bw (Group 2): sedation (5/5), ruffled fur (3/5), emaciation (1/3), lacrimation (0/2) 2000 mg/kg bw (Group 3):

Gross pathology:

The following macroscopic organ findings were observed at necropsy:

500 mg/kg bw (Group 1): scheduled necropsy - no findings

1000 mg/kg bw (Group 2): scheduled necropsy - one male presented stomache distended with gas; spontaneous deaths - one female presented stomache distended with gas and black-brown contents in jejunum

2000 mg/kg bw (Group 3): scheduled necropsy - one male presented distended stomache; spontaneous deaths - one male and two females contained reddish fluid in body cavities, one male presented distended stomache

For further details please see also the attached background material: Pfister.1995.Acute oral toxicity study with N-chlorosuccinimide in rats_ tabels and appendices.pdf

Other findings:

For further details please see also the attached background material: Pfister.1995.Acute oral toxicity study with N-chlorosuccinimide in rats_ tabels and appendices.pdf

Any other information on results incl. tables

For further details please see also the attached background material: Pfister.1995.Acute oral toxicity study with N-chlorosuccinimide in rats_ tabels and appendices.pdf

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 of N-chlorosuccinide is 1212 mg/kg bw in rats.

Executive summary:

N-chlorosuccinimide was administered to three groups of 5 male and f 5 male and 5 female rats by oral gavage at single doses of 500, 1000 and 2000 mg/kg bw.

The following mortality was observed:
500 mg/kg bw (Group 1): males: 0%, females: 0%
1000 mg/kg bw (Group 2): males: 0%, females: 60%
2000 mg/kg bw (Group 3): males: 80%, females: 100%

Based on these observations, the LD50 estimation for acute oral toxicity in rats of both sexes, observed over a period of 14 days is 1212 mg/kg bw.