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Neurotoxicity

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Description of key information

Female Fischer 344 rats treated with a single oral dose (up to 5000 mg/kg bw) or with repeated doses (up to 1500 mg/kg bw per day for 14 days) of di(2-ethylhexyl) phthalate showed no neurobehavioural effects, as evaluated by functional observational battery and motor activity testing.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
1 500 mg/kg bw/day

Additional information

The neurobehavioural effects were tested in rats by a functional observational battery (FOB) and motor activity measurements before exposure, at specified times after a single dose exposure, and during and after a 14-day repeated dose exposure (Moser et al., 1995). Female Fischer 344 rats (number not given) were administered 150, 500, 1,500 or 5,000 mg/kg/d of DEHP (> 99% pure) (single dose study), or 50, 150, 500 or 1,500 mg/kg/d of DEHP (repeated exposure, 14 days) in corn oil by gavage. The FOB included following measures: autonomic, activity, excitability, neuromuscular, sensorimotor, and physiological measures. Motor activity was measured in a maze. The FOB was performed on each rat just prior to the first dose.

Thereafter, the FOB followed by motor activity assessments was conducted at 4 and 24 hours after exposure (single dose study), and on day 4 and 9 (before the daily dose) and 24 hours after the last dose. No lethality occurred. A single administration of the highest dose produced pronounced signs of general debilitation in two rats 24 hours after dosing. No changes in body weight were observed in either study.

No functional domain was overall affected in either study.

In a BASF study (2001) realized according to the EPA OPPTS 870.6200 guideline and in compliance with Good Laboratory Practices, F2 pups from a 2-generation study were tested for neurotoxicity in a Neurotoxicity Screening Battery, a Functional observation battery, a FOB Motor activity assessment and a Water maze test.

No sign of neurofunction impairment was noted in any of the various parameters of the Water Maze Test, the Functional Observation Battery, and the Motor Activity Assessment.

Justification for classification or non-classification