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Description of key information

Lowest LD50 is obtained in female rabbits is 143 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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
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
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.
Species:
rat
Strain:
Wistar
Remarks:
Porton
Sex:
male/female
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
Preliminary study:
Yes, but not detailed
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.
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

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
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
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.
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
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 : 100-250 mg/kg
Female : 75-400 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
Preliminary study:
Yes, but not detailed
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 143 mg/kg bw
Based on:
test mat.
95% CL:
>= 61 - <= 236
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 231 mg/kg bw
Based on:
test mat.
95% CL:
>= 186 - <= 493
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.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
In an acute oral study in rats, Ballantyne and Swanston (1978):
- the LD50 for male rabbits is : 231 mg/kg bw
- the LD50 for female rabbits is : 143 mg/kg bw

Executive summary:

In an acute oral study in rats, Ballantyne and Swanston (1978):

- the LD50 for male rabbits is : 231 mg/kg bw

- the LD50 for female rabbits is : 143 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
143 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
NTP reference value
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
no guideline specified, but result considered by NTP as reliable
Deviations:
not specified
GLP compliance:
not specified
Key result
Sex:
male
Dose descriptor:
LC50
Remarks:
rats
Effect level:
ca. 88 480 other: mg.min/m3
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LC50
Remarks:
mouse
Effect level:
ca. 50 010 other: mg.min/m3
Based on:
test mat.
Interpretation of results:
GHS criteria not met
Conclusions:
In rats, NTP (1990) reported LC50 by inhalation in male rats of 88 480 mg x min/m3 and in male mice of 50 010 mg x min/m3
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
50 010 mg/m³

Additional information

Justification for classification or non-classification