Malononitrile

Endpoint summary

Description of key information

Study was conducted in compliance with the GLP-standards as set forth in title 40, of U.S. Code of Federal Regulation, part 160, with EPA, TOSCA GLP Regulation 40 CFR part 792.
25 male and 25 female rats (28-day study) and 75 male and 75 female rats  (90-day study) of the Crl: CD (SD) BR strain were used.
Test article was formulated in water and administered orally by gavage, once daily. A constant dose volume of 10mg/kg/day  (group 5) was used for 14 days.
90-day study, treatment at 0.4 mg/kg/day was not associated with any toxicologically significant changes and can therefore be considered as the no-effect level for  this compound in the rat.
NOEL 0.4 mg/kg/bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

0.4 mg/kg bw/day

Additional information

The objective of the study was to determine the oral toxicity of Malononitrile in the rat following administration for 28 days and to select dose levels for a subsequent 90 day toxicity study.

The majority of high dose (4 mg/kg/day and 8 mg/kg/day from beginning of week 3) males had AST (GOT) levels above those of the controls, and the high dose females had urea levels outside the control range. The mean absolute and relative liver weights of the high dose males were greater than those of the controls. Microscopically, the high dose males had centrilobular hypertrophy in the liver and hyaline droplets in the kidney. No effects at dose level 0.04 mg/kg/day and 0.4 mg/kg/day after 28 days treatment.

To demonstrate a clear toxic effect, 10 mg/kg/bw/day is considered to be a suitable high dose level for the subsequent 90 -day study.

90 -day study, treatment at a dose level of 10 mg/kg/day brought a increase in liver weight which was associated with hepatocyte hypertrophy and vacuolation on histopathological examination. Clinical pathology changes in alkaline phospatase and cholesterol levels my be related to these findings. The clinical pathology and histopathology changes were completely reversible after a four week period without treatment, although there remained a small difference in the weight of the liver. The increased plasma urea levels in animals treated at 10 mg/kg/day and females treated at 2 mg/kg/day are therefore of unknown origin and do not, in isolation, indicate a clear effect on the kidney.

Treatment at 0.4 mg/kg/day was not associated with any toxicologically significant changes and can therefore be considered as the no-effect level for this compound in the rat.

Justification for classification or non-classification

According to the results of the 90 -day study there is no reason for classification.