The lack of effects of pretreatment with phenobarbital and chlorpromazine on the acute toxicity of benzene in rats

Female CD rats were injected ip daily for 3 days with either phenobarbital (75 mg/kg) or chlorpromazine (15 mg/kg). On the fourth morning the animals were either subjected to a 4-hr inhalation exposure of benzene or given an ip injection of 50% ($\text{v}\text{v}$) of benzene and mineral oil. Animals were injected with doses of 1, 2, 3 and 4 g benzene/kg body weight. In the inhalation studies, animals were exposed to 6 levels of benzene ranging from 11,500 to 15,500 ppm. The LD50 for animals injected with benzene and the LC50 for animals inhaling benzene were calculated for control groups and those pretreated with either phenobarbital or chlorpromazine. Neither the LD50 or the LC50 were affected by any of the treatment protocols. In order to determine that the pretreatment was stimulating benzene metabolism, a method for measuring benzene metabolism has been developed using ¹⁴C]benzene. These studies have shown that phenobarbital and 3-MC do induce benzene metabolism in the liver, that chlorpromazine slightly induces benzene metabolism in the lung, and that pretreatment by these compounds does not affect the acute inhalation toxicity or the ip toxicity of benzene.