Complementary to the human clinical data, several animal
studies have verified that toluene targets the central,
not peripheral, nervous system. Beyond this generalization,
however, animal studies have not been particularly
helpful in elucidating the specific mechanisms of myelin
damage noted in humans. Two different studies in rats
exposed to toluene by inhalation or by oral dosing
showed that toluene concentrations were highest in brainstem
areas (medulla, pons) with high lipid content (42,
51), and lowest in the cerebral cortex and hippocampus,
where less myelin is found (42), underscoring the lipophilic
distribution of toluene (1). Other animal studies
have raised the possibility that the hippocampus may be
damaged by toluene, although the data are inconclusive
and this area has not yet been shown to be preferentially
affected in humans. Mattia et al reported that, following
gavage treatment of rats with toluene, the highest level
of induced reactive oxygen species was in the hippocampus;
however, they confined their studies to investigating crude synaptosomal fractions from only three sites: the
cerebellum, hippocampus, and striatum (52). Similarly,
using rats with inhalation exposure to toluene, Korbo et
al found neuronal loss in the hippocampus but only studied
this single neuroanatomic site (54). More recent studies
have also reported Purkinje cell loss and hippocampal
neuronal loss in rats with inhalation exposure (55). In
contrast, Ikeuchi and Hirai investigated the effects of toluene
on guinea pig hippocampal slices and found inhibition
of synaptic transmission but no morphological abnormalities
(56)