Toxicokinetics and metabolism of linuron in rabbit:in vivoandin vitrostudies

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Abstract
1. Linuron (N′-(3,4-dichlorophenyl)-N-methoxy-N-methylurea) metabolism and kinetic behaviour were investigated after oral and i.v. administration to six New Zealand White female rabbits. 2. After i.v. dosage, linuron distributes quickly and widely to peripheral tissues and its is rapidly eliminated; rapid absorption was also observed after oral administration of the herbicide which undergoes extensive first pass metabolism in the liver. 3. The major metabolites obtained from both in vivo (serum samples) and in vitro (microsomal fractions incubated with linuron) experiments were identified by h.p.l.c.-mass spectrometry as N′-(3,4-dichlorophenyl)-N-methoxyurea, N′-(3,4-dichlorophenyl) urea, and N′-(6-hydroxy-3,4-dichlorophenyl) urea. 4. Given the common metabolites reported in rat and rabbit, and the fact that linuron is a liver enzyme inducer in rat, it may be possible that linuron also induces the P450 system in rabbit. Hence, despite the low acute toxicity of linuron in rabbit, the intake of hay and feed contaminated by the herbicide could be a health risk for these breeding animals since it could modify the effectiveness of many drugs commonly used in veterinary practice and metabolized by the same liver enzymes.