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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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The Comparative Acute Mammalian Toxicity of l-Chloroacetophenone (CN) and 2-Chlorobenzylidene Malononitrile (CS)
Author:
B. Ballantyne and D. W. Swanston
Year:
1978
Bibliographic source:
Archhees of TOXICOLOGY 40, 75-95 (1978)
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
For the acute oral toxicity studies with CN and CS in PEG 300, the solutions were introduced into the stomach through gum elastic catheters with the aid of a syringe attached to one end of the catheter. All animals that died and 3-week survivors from the acute oral and parenteral studies were submitted to post mortem examination and the following tissues removed for histological examination: lung, liver, kidney, adrenal, stomach, small intestine, gonad, thymus, and spleen.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Specific details on test material used for the study:
CS was purified by differential crystalization from ethanol, and its purity checked by determination of melting point. For oral toxicity, polyethylene glycol 300 (PEG 300) was used as solvent.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Porton
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
the solutions were introduced into the stomach through gum elastic catheters with the aid of a syringe attached to one end of the catheter.
Doses:
Male : 500-1590 mg/kg
Female : 629-1588 mg/kg
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Statistics:
L(ct)50 and LDs0 values together with 95% confidence limits and slopes of regression lines were computed from the dosage-mortality data by probit analysis using a Fortran computer programme. The programme allows calculation of the weighted linear regression of probit-response on log-dose using the maximum likelihood procedure

Results and discussion

Preliminary study:
Yes, but not detailed
Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 1 284 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 184 - <= 1 779
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 366 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 184 - <= 1 531
Mortality:
Animals that died had multiple extensive haemorrhagic erosions of the gastric mucosa, particularly in the body of the stomach, with perforation of the wall in a few animals. In the latter cases there was increased peritoneal fluid present and, in those surviving for several days, intra-abdominal adhesions. The gastric mucosa and submucosawas congested and oedematous over fairly wide areas. Congestion of spleen,thymus, small intestine and lung was frequently observed. In a few instances thesmall intestinal villi were congested and there was necrosis of their tips. The kidneysfrom a few animals showed small foci of acute cortical tubular necrosis. Survivors sacrificed 3 weeks after dosing showed areas of regeneration of the gastric mucosaand occasional adhesions between small intestine and liver or parietal peritoneum
Other findings:
Toxic signs, in the form of pilo-erection, increased salivation and tremor, appeared within 2-4 h of dosing. These signs were followed by rapid shallow breathing and reduced locomotion. Abdominal tension and scouring were frequently observed. Depending on the dosage, survivors recovered within 2--10 days. Animals that died showed a continual deterioration in their general state of health and death occurred between 4 h and 7 days after dosing, the majority of deaths occurring within the first 24 h. Death was preceeded by increasing difficulty with breathing, convulsions and collapse; a few animals had a diarrhoea-like condition.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In an acute oral study in rats, Ballantyne and Swanston (1978) reported the LD50 of 1366 mg/kg in males and 1284 mg/kg in females
Executive summary:

In an acute oral study in rats, Ballantyne and Swanston (1978) reported the LD50 of 1366 mg/kg in males and 1284 mg/kg in females