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Toxicological information

Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Directive 92/69/EEC, B.1. "Acute Toxicity-Oral", July 31, 1992.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 212 mg/kg bw
Based on:
test mat.
95% CL:
927 - 1 704
Sex:
male
Dose descriptor:
LD50
Effect level:
1 529 mg/kg bw
Based on:
test mat.
95% CL:
959 - 6 036
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:
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): sedation (5/5), hunched posture (3/2), ventral recumbency (1/0), dyspnea (5/5), ruffled fur (5/5), red urine (1/1), emaciation (3/2)

* ( / ) = number of male/female animals.
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
Body weight:
The rate of body weight gain of the animals of group 1 (500 mg/kg bw) during the observation period was within the normal range for rats of this strain and age. Animals treated with test article at 1000 mg/kg bw lost weight during the first eight days of the study period and one male continiued to loose weight until the end of the study period. In the highest dose group (2000 mg/kg bw) all animals lost weight until their deaths.

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
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.