Toxicology of Industrial Compounds

K.J.VAN DEN BERG ET AL. 245
hyperactive behaviour. In adults neurotoxicity is more often encountered
as peripheral neuropathy after chronic occupational exposure to lead
(Marsh, 1985). A number of mechanisms have been implicated in lead
neurotoxicity (Bressler and Goldstein, 1991), but as yet no central
hypothesis has emerged.
In order to investigate the effect of lead on CNS structural proteins, a
subchronic dosing experiment with adult rats was performed in which
animals received daily doses of lead acetate (4, 8, 12.5 mg kg −1 i.p.) for 28
days. GFAP concentrations were subsequently determined in different brain
regions. Already at the lowest dose level GFAP levels were found to be
significantly increased in several brain regions, notably in different parts of
the cortex, hippocampus and striatum, while cerebellum and brain stem
remained unaffected. Neurobehavioural assessment of animals, preceding
the neurochemical analysis, also revealed significant alterations of
neuromuscular function, excitability and spontaneous activity.
Methylmercury has caused a number of poisonings in man (Marsh, 1985)
where it appears to affect in particular both the central and peripheral
nervous system. In an animal experiment, adult rats were subchronically
dosed with methylmercury (0.75 or 2 mg kg −1 ) for 28 days.
Neurobehavioural assessment indicated that grip strength was significantly
impaired. Neurochemical analysis of GFAP in the central nervous system
was performed in selected brain regions and, in addition, in various
segments of the spinal cord. Increased GFAP levels were observed in the
cerebrum only in the frontal cortex, also in brain stem and in spinal cord. A
further detailed analysis of brain stem sub-structures showed significantly
enhanced GFAP levels in pons and medulla oblongata but not in midbrain.
In spinal cord GFAP concentration was increased in specific
sections, e.g. in the cervical and lumbar segments but not in the thoracic
segment.
The results with these particular examples of heavy metals have indicated
the unsuspected presence of regions in the central nervous system with
astrogliosis, as determined in a biochemical GFAP assay. The neuronal
damage involved has not yet been confirmed independently, e.g. by
assessment of synaptophysin. The possibilities remain, therefore, that
reactive astrocytosis by these heavy metals may be indirectly a result of
breaching the integrity of the blood-brain barrier (Bressler and Goldstein,
1991) or of a direct toxic action on astroglial cells (Selvin Testa et al.,
1990; Stark et al., 1992).
Manganese is a well recognized industrial neurotoxin associated with
neurologic effects after prolonged exposure in occupational settings (Katz,
1985). The clinical manifestations of manganism bear a large similarity to
those of Parkinson’s disease (PD). The neurodegenerative disease PD is
characterized by a selective loss of neurons in the basal ganglia.