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Neurotoxicity

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Description of key information

In a guideline 90-day subchronic dietary study conducted in Wistar rats, effects occurred at the high dose of 750 ppm (equivalent to 49.7 mg/kg bw/day in males and 53.6 mg/kg bw/day in females), which consisted of changes in neurobehavioral parameters and associated brain histopathology. The NOAEL was the next lower dose of 150 ppm (equivalent to 9.8 mg/kg bw/day in males and 10.2 mgkg bw/day in females).

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
9.8 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

In a guideline 90-day subchronic dietary study conducted in Wistar rats, effects occurred at the high dose of 750 ppm (equivalent to 49.7 mg/kg bw/day in males and 53.6 mg/kg bw/day in females), which consisted of changes in neurobehavioral parameters and associated brain histopathology, and changes in hematology, clinical chemistry, urinalysis, organ weights, and pathology of the thymus. The NOAEL was the next lower dose of 150 ppm (equivalent to 9.8 mg/kg bw/day in males and 10.2 mgkg bw/day in females).

In a Developmental Neurotoxicity study, the NOAEL of 94.3 mg/kg/day is based on treatment-related brain vacuolisation at all doses. No functional effects were seen.

There was no NOAEL in a behavioral screening study in drinking water.  Runway learning and swim escape effects were observed.

Justification for classification or non-classification