Toxicology of Industrial Compounds

induced delayed neuropathy (OPIDN) (Cherniack, 1988). This has led to
investigations into structure-activity relationships of OPs with NTE in vitro
that have proved to be valuable in predicting OPIDN (Davis et al. 1985).
Furthermore, certain tissue culture systems, such as neuroblastoma cell
lines, contain NTE and AChE activity that may be suited for identification
of OPs causing OPIDN (Veronesi, 1992). Biochemical assays for NTE and
AChE, in conjunction with neurobehavioural observations and
neuropathology, are currently incorporated into US and Japanese
neurotoxicity testing guidelines.
A second group of industrial chemicals for which indications exist on
their mechanism of action include certain compounds causing peripheral
neuro-pathy such as acrylamide, carbon disulphide and n-hexane. It is
generally assumed that the primary action of these chemicals is the
crosslinking of axonal proteins (Graham et al., 1982), a process that blocks
axonal transport (Sickles, 1991) and may lead to degeneration of distal
axons (Spencer and Schaumberg, 1980). The basic information thus
collected is yet to be developed into a useful biomarker.
The pyrethroid insecticides represent a third group of chemicals for
which the neurotoxic mechanism of action has been elucidated. The major
symptoms of pyrethroid intoxication, e.g. convulsions, tremors, paralysis,
are primarily the result of interaction of the pyrethroids with sodiumchannels
on nerve membranes (Lund and Narahashi, 1982). Whereas
under normal circumstances a sodium channel is only opened during a
depolarization event, pyrethroids prolong opening of these channels
thereby causing repetitive excitation of nerve and nerve terminals. In tissue
culture systems, e.g. neuroblastoma cell lines, direct electrophysiological
studies on cells have been done to investigate the effectiveness of different
pyrethroids for opening of sodium channels (Oortgiesen et al., 1989).
Biomarkers of neurotoxicity
It is clear that a mechanistic understanding of the neurotoxicity of
suspected chemicals is and will be proceeding at a slow pace. Eventual
utilization of this knowledge in the form of biological markers for
neurotoxicity risk assessment procedures is, necessarily, a long-term
objective. In the mean time alternative approaches have been proposed
recently that (a) may provide biomarkers that could aid to further define
underlying mechanisms and (b) are directly linked to neurotoxic
mechanisms of actions.
Gliotypic and neurotypic proteins
K.J.VAN DEN BERG ET AL. 239
Insults to the brain by a large variety of agents or conditions, e.g. viral
infection, auto-immune encephalitis, trauma and chemicals, evoke a fairly