[(2-chlorophenyl)methylene]malononitrile

Endpoint summary

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

Reference

Reference 1

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

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

Reference 2

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

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

Value:

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

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

Value:

50 010 mg/m³ air