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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:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Animals where housed with 2 in a cage during acclimatisation. The animals showed normal during the acclimatization period, it was considered not to affect the animals and study results.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 97%
- Source: Aldrich Chemical Company, Milwaukee, WI, USA
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: DSM Engineering Plastics B.V. lotnumber SN0620140520
- Expiration date of the lot/batch: 2016.07.01
- Purity test date: 99.93%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Store in a cool area (IO-20°C). Containers that have been opened must be filled with dry nitrogen for at least 1min and then sealed. Be careful not to import any water or impurities during the filling and sealing course.
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Easily soluble in cold water


FORM AS APPLIED IN THE TEST white waxy solid

Test animals

Species:
rat
Strain:
other: Sprague Dawley (SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Supplier: Beijing Vital River Laboratory Animal Technology Co., Ltd.
License No.: SCXK (Jing) 2012—0001, Qualification: 11400700112907.

- Age at study initiation: 51-60 days on arrival, in the range of 8-12 weeks at the commencement of each
animal’s dosing.
- Weight at study initiation: 182-222g
- Housing:Animals were raised
in suspended, stainless steel cages (L32.0cm >(L167.0cmXW70.0cm>Animals were housed individually during the test.
- Diet : diet with complete nutrition supplied by Beijing keaoxieli Feed Co., Ltd. Product License No: SCXKUing) 2012-0001, Batch NO. 15063223).
- Water (e.g. ad libitum): purified water (by HT-R01000 purity system.)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5-24.5 °C
- Humidity (%): 45%-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): lighting sequence was 12 hours light, 12 hours dark.

Administration / exposure

Route of administration:
oral: gavage
Doses:
300 mg/kg BW and 2000 mg/kg BW
No. of animals per sex per dose:
3
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 min and at l, 2 and 4 hours after dosing and then once each day for up to 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention had been directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Preliminary study:
LD50 is 488.7 mg/kg b.w. for rats was available. Based on that value the test doses were selected.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality
Dose Level-The first dosing (300mg/kg): One animal was dead on Day 2 after dosing. Dose Level-The second dosing (300mg/kg): There were no deaths or moribund during the test. Dose Level-The third dosing (2000mg/kg): All animals were dead in 4h after dosing. Mortality summary results were given in appendix Table 1.
Clinical signs:
Dose Level-The first dosing (300mg/kg): Animals showed decrease in locomotor activity, emaciation, and soiled perinea region after dosing.
Dose Level-The second dosing (3 00mg/kg): There were no abnormal findings after dosing from the first day until the end of the test.
Dose Level-The third dosing (2000mg/kg): Animals showed decrease in locomotor activity, emaciation, secretion around mouth and nose, semi-closed eyes, weak breath, soiled fur around the mouth and nose after dosing. Individual clinical observations were given in appendix Table 2.
Body weight:
All surviving animals showed a increase in body weight during the first week, but most of the surviving animals showed a decrease during the second week.
Individual and mean body weights see appendix table 3.
Gross pathology:
Necropsy
No abnormalities were found at necropsy.
Necropsy results see appendix table 4.

Any other information on results incl. tables

Table 1. Mortality summary results
Dosing
sequence
Dose
(mg/kg)
sex Animal
amounth
Time (d) Mortality
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
1 300 Female 3 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1/3
2 300 Female 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0/3
3 2000 Female 3 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3/3

Table 2. Individual Clinical observations
Dose
(mg/kg)
Animal ID Symptons After Dosing
(Hours)
Symptoms During Period After Dosing
(Days)
0.5 1 2 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14
300 2100 N N N N S E1D - - - - - - - - - - - -
2101 N N N N N N N N N N N N N N N N N N
2102 N N N N H N N N N N N N N N N N N N
300 2200 N N N N N E1D - - - - - - - - - - - -
2201 N N N N N N N N N N N N N N N N N N
2202 N N N N N N N N N N N N N N N N N N
300 2300 N SE SE Se FD - - - - - - - - - - - - - -
2301 N SE SE SeW FD - - - - - - - - - - - - - -
2302 N N SE FD - - - - - - - - - - - - - -
Note: N=no sign; S=decrease in locomotor activity; E1=emaciation, E=secretion around mouth and nouse, Se-semi closed eyes, W=weak breath, D=death, F=soiled fur around the mouth and nouse, H=soiled perinea region.

Table 3. Individual and Mean Body Weights
Dose
(mg/kg)
Dose
(mg/kg)
Animal ID Body Weight (g) at Day Body Weight Gain (g) During Week
Grouping Day0 Day7 Day14 At Death 1 2
300 Female 2100 204 191 - - 149 - -
2101 233 212 246 268 - 34 22
2102 226 209 255 263 - 46 8
Mean +/- SD 221 +/- 15 204 +/- 11 251 +/- 6 266 +/- 4 - 40 +/- 8 15 +/- 10
N 3 3 2 2 1 2 2
300 Female 2200 201 183 - - 149 - -
2201 219 212 246 268 - 34 22
2202 225 209 255 263 - 46 8
Mean +/- SD 215+/- 12 199 +/- 15 245 +/- 16 226 +/- 11 - 46 +/- 9 -20+/-6
N 3 3 3 3 - 3 3
2000 Female 2300 196 191 - - 184.53 - -
2301 216 212 - - 199.86 - -
2302 222 209 - - 203.18 - -
Mean +/- SD 211 +/- 14 198 +/- 7 - - - - -
N 3 3 0 0 3 2 2
Note: body weight(g), N=Number of animals per group, SD= Standard deviation

Table 4. Indivudual Negroscopy Findings
Animal ID sex Dose
(mg/kg)
Death time Findings
2100 Female 300 Day2 No abnormalities
2101 Female 300 Sheduled Negroscopy No abnormalities
2102 Female 300 Sheduled Negroscopy No abnormalities
2200 Female 300 Sheduled Negroscopy No abnormalities
2201 Female 300 Sheduled Negroscopy No abnormalities
2202 Female 300 Sheduled Negroscopy No abnormalities
2300 Female 2000 Day 0 No abnormalities
2301 Female 2000 Day 0 No abnormalities
2302 Female 2000 Day 0 No abnormalities

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results, the acute oral LDso in the rats for Succinonitrile was estimated to be among 300 mg/kg b.w. - 2000 mg/kg b.w..
According to the GHS’s classification criteria for acute oral toxicity, the test item was classified as Category 4.
Executive summary:

Introduction: The study was performed to assess the acute oral toxicity of Succinonitrile in Sprague Dawley rats. The method was designed to meet the OECD Guideline for Testing of Chemicals: Acute Oral Toxicity-Acute Toxic Class Method (TG423, 2001).

Method: The test item was tested using a stepwise procedure, each group using three female animals. The first step dosing and second step dosing were 300 mg/kg and the third step dosing was ZOOOmg/kg. Clinical observations and bodyweight were monitored during the study. All animals were subjected to a gross necropsy.

Results:

Mortality

Dose Level-The first dosing (300mg/kg): One animal was dead on Day 2 after dosing.

Dose Level-The second dosing (300mg/kg): There were no deaths or moribund during

the test.

Dose Level-The third dosing (2000mg/kg): All animals were dead in 4h after dosing.

Clinical observations

Dose Level-The first dosing (300mg/kg): Animals showed decrease in locomotor

activity, emaciation, and soiled perinea region after dosing.

Dose Level-The second dosing (3 00mg/kg): There were no abnormal findings after

dosing from the first day until the end of the test.

Dose Level-The third dosing (2000mg/kg): Animals showed decrease in locomotor

activity, emaciation, secretion around mouth and nose, semi-closed eyes, weak breath,

soiled fur around the mouth and nose after dosing.

Body Weight

All surviving animals showed a increase in body weight during the first week, but most of the surviving animals showed a decrease during the second week.

Necropsy

No abnormalities were found at necropsy.

Conclusion:

Based on the results, the acute oral LDso in the rats for Succinonitrile was estimated to be among 300 mg/kg b.w. - 2000 mg/kg b.w.. According to the GHS’s classification criteria for acute oral toxicity, the test item was classified as, Category 4.