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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study with acceptable restricions.

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Cited as Directive 84/449/EEC, B.1
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Thionyl dichloride
EC Number:
EC Name:
Thionyl dichloride
Cas Number:
Molecular formula:
thionyl dichloride
Details on test material:
- Name of test material (as cited in study report): Thionylchlorid
- Physical state: clear, colourless fluid
- Analytical purity: 99.8 %
- Impurities (identity and concentrations): Sulfur dioxide 0.18 %; Sulfur dichloride 0.001 %; evaporation residue 0.0006%
- Purity test date: 12 June 1987
- Lot/batch No.: sample no. 5441, taken from batch of 11 June 1987
- Stability under test conditions: 76 % after 50 minutes (for lowest analysed concentration)
- Storage condition of test material: dry, at room temperature

Test animals

Details on test animals or test system and environmental conditions:
- Source: strain Bor: WISW (SPF Cpb), Winkelmann, Borchen
- Age at study initiation: 8 wks (males) to 10 wks (females)
- Weight at study initiation: males 183 g mean; females 173 g mean (deviations from mean < 20 %)
- Fasting period before study: 16 hours before until 4 hours after dosing
- Housing: 5/group/cage
- Diet (e.g. ad libitum): Altromin 1324 pellets (standard diet; Altromin GmbH, Lage), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

- Temperature (°C): 22 ± 2
- Humidity (%): 50 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
paraffin oil
Details on oral exposure:
- Amount of vehicle (if gavage): 5 ml/kg bw
- Justification for choice of vehicle: Test substance hydrolyses upon contact with water
- Lot/batch no. (if required): Merck-Schuchardt batch no. 706K3305274
- Purity: In order to increase stability of the test substance by elimination of water in the vehicle, the vehicle was dried at 100°C by introduction of nitrogen gas.

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw constant volume was used for application

DOSAGE PREPARATION (if unusual): preparation directly before dosing at room temperature
20, 71, 133, 260, 310, 400 (only males), 500 mg/kg bw
No. of animals per sex per dose:
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations several times on the day of dosing, twice daily on weekdays and once on weekends and bank holidays during the 14 d observation period; weighing was performed directly before dosing, after 1 week and at the end of the 14-d observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Calculation of LD50 according to Rosiello et al. (1977), J Tox Environ Health 3: 797, modified by Pauluhn (Bayer AG, report no. 11835, 1983); method based on the maximum-likelihood method according to Bliss (1938), Q J Pharm Pharmacol 11, 192.

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
270 mg/kg bw
Dose descriptor:
Effect level:
377 mg/kg bw
Dose descriptor:
Effect level:
324 mg/kg bw
95% CL:
283 - 371
male rats:
20 mg/kg: 0/5;
71 mg/kg: 0/5;
133 mg/kg: 0/5;
260 mg/kg: 0/5;
310 mg/kg: 1/5 (day 5);
400 mg/kg: 3/5 (within 2 days);
500 mg/kg: 5/5 (within 5 minutes)

female rats:
20 mg/kg: 0/5;
71 mg/kg: 0/5;
133 mg/kg: 0/5;
260 mg/kg: 2/5 (within 3 days);
310 mg/kg: 4/5 (within 2 days);
500 mg/kg: 5/5 (within 5 minutes)
Clinical signs:
Gasping, salivation, rough fur, sedation, poor condition, staggering gait, signs of aggressiveness in 2 males of the lowest dose group. Severity of symptoms demonstrated dose dependency, symptoms started 3 minutes after exposure and continued until day 7. During and immediately after application of 500 mg/kg bw the development of gases was observed from the stomach.
Body weight:
Body weight gain was retarded in male rats starting with 260 mg/kg bw and in female rats starting with 133 mg/kg bw.
Gross pathology:
Necropsy of intermittently deceased animals of the 500 mg/kg bw dose group demonstrated severe chemical burns in the gastrointestinal tract, and of the liver, kidneys and spleen. Upon necropsy a stinging odour was noted from the peritoneum. Deceased animals of the 260 mg/kg and higher dose groups showed changes of the gastrointestinal mucosa and/or discolouration of the liver.
Some of the animals sacrificed at the end of the observation period showed pale discolourations of the kidneys and/or swelling of the liver.
Other findings:
- Potential target organs: liver, kidney
- Other observations: One male of the 71 mg/kg bw dose group and one female of the 260 mg/kg bw dose group demonstrated alterations of the gastric mucosa.

Any other information on results incl. tables

During dosing and immediately thereafter development of gas was observed in the high dose group animals. Gross necropsy revealed corrosion of the gastrointestinal tract, liver, kidney and spleen in all animals that died during the study. During necropsy odor and gas development was reported.


Based on the criteria of the DSD and the CLP criteria the test substance has to be considered as harmful if swallowed (R22, GHS Cat. 4).

Applicant's summary and conclusion

Executive summary:

method: single orale application per gavage of test substance (dose 20, 71, 133, 260, 310, 400 (only males) and 500 mg/kg bw) to 5 male and 5 female rats, post-observation time 14 days

result: LD50 = 270 mg/kg bw (female rats) and LD50 = 377 mg/kg bw (male rats)

reference: Bomhard (Bayer AG), 1988