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Neurotoxicity

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Neurobehavioral testing was performed in groups of male mice or rats to detect short-term effects occurring within up to 60 min after intraperitoneal or oral exposure. In mice, intraperitoneal doses ranged from 5-200 mg/kg bw and oral doses were 50 or 100 mg/kg bw. Rats were exposed to a single dose of 100 mg/kg bw, either by intraperitoneal or oral application. The tests included observation of behaviour in the open field test, rota rod performance, spontaneous motor activity, and pentobarbital sleeping time, covering endpoints as locomotor activity, muscle relaxation, anxiolytic activity, and barbiturate induced sleeping behaviour.

In mice, a central nervous depressant effect of citral was indicated after intraperitoneal application starting at 50 mg/kg bw for spontaneous motor activity and in the elevated plus maze test (Carlini 1986; Do Vale 2002), but no effects were found after oral application up to the high dose of 100 mg/kg bw (Carlini 1986).

Furthermore, intraperitioneal application of 100 mg/kg citral in rats resulted in central nervous depressant effects but no effects were found after oral application of this dose to rats (Carlini 1986).

In summary, after oral application no neurological effects were found up to the highest tested dose (100 mg/kg bw) , both in mice and in rats.

Intraperitoneal application represents a mode of exposure which is not relevant for human exposure. The dose is delivered into the body independent of absorption from the gastrointestinal tract and circumventing first-pass metabolism in the liver. Consequently, the intraperitoneal effects observed are not relevant for human risk assessment.

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