Toxicology of Industrial Compounds

easily subjected to a process of auto-oxidation. The decrease in dopamine
levels by iron may have been caused by oxygen radicals. Circumstantial
evidence suggests that a similar mechanism of action may underly
manganese neurotoxicity. The decrease in dopamine in the basal ganglia by
manganese is also thought to occur through catalysis of dopamine
oxidation (LeBel and Bondy, 1991), possibly involving radical oxygen
species. An open question is whether manganese might participate in the
‘iron release’ hypothesis (Sloot and Gramsbergen, 1994). Current efforts
are being made to determine free radical formation by iron and manganese
and to relate this to dopamine depletion. For this purpose rats are given
salicylic acid (SA) and subsequently the SA hydroxylation products are
measured in cerebrospinal fluid and brain tissues as indices of hydroxyl
radical formation.
Developmental neurotoxins (PCBs)
K.J.VAN DEN BERG ET AL. 247
Concern has been raised about the long term consequences of low level
intake of polychlorinated biphenyls (PCBs) with respect to neurotoxicity as
it relates to nervous tissue development and intellectual performance in the
juvenile and adult stages. Several epidemiological studies with infants have
shown a negative correlation between PCB levels in cord blood and
cognitive functions and a positive correlation between PCB levels and
altered neurological parameters such as hypotonia and hyporeflexia (Rogan
et al., 1988; Jacobson et al., 1990). Experimental studies in various species
including primates have also provided arguments for neurotoxic effects in
offspring after perinatal exposure to PCBs (Tilson et al., 1990). In this
laboratory evidence has recently been obtained to indicate dramatic
reduction in sexual behaviour and reproduction in offspring that was
perinatally exposed to PCBs (Smits-van Proojie et al., 1993).
In order to investigate eventual structural alterations in the CNS,
pregnant Wistar WU rats were exposed to Aroclor 1254 on days 10–16 of
gestation. At a young age (3 weeks) and adult age (3 months) offspring
were sacrificed and various brain regions were dissected for assessment of
gliotypic and neurotypic proteins. In untreated control animals
developmental aspects of astrocytes in the central nervous system were
encountered. Both in hypothalamus and cerebellum of control animals
GFAP levels were increased by 200–300 per cent between 3 weeks and 3
months postnatally. A developmental GFAP increase was also found in
brain stem, striatum and lateral olfactory tract, although to a lesser extent.
In hippocampus and prefrontal cortex, GFAP levels remained virtually
unchanged between 3 weeks and 3 months. These results, therefore,
indicate that glial cell maturation and/or differentiation is not uniformly
distributed over the whole brain. It appeared that glial cells at birth in rats
were fully developed in brain regions dealing with cognitive functions, e.g.