Most of the major classes of pesticides have
been in use for a long time, and the more obvious hazards that they present to
humans are now well understood. Hence much of the work that is needed to protect
the health of pesticide users from poisoning relates to practical matters such
as safe packaging and use of protective clothing. These things are important, as
readily avoidable poisonings are still far too common world-wide. So what need
is there for new research?
Unlike acute poisoning the more subtle forms of toxicity
which might be produced by pesticides are difficult to identify in humans.
Epidemiological surveys are an important way of looking for these effects, and
such surveys have indicated that, for example, sheep farmers with larger flocks
perform less well in some neurobehavioural tests. This may or may not have been
caused by the farmers' greater OP pesticide usage. Most surveys present
similar difficulties in assigning cause to effect, since other possible causal
factors often co-vary with pesticide exposure. One way round this almost
unsolvable problem is to focus on mechanism of action, to identify possible
toxic effects, and then look for these specific effects in exposed populations.
This is the approach of the MRC Toxicology Unit at Leicester University.
Two of the Unit's recent advances
provide positive news from the research front. The first comes from the search
for new targets of OP pesticides. We already know about several of these
targets, most importantly acetylcholineserase, but have always suspected that
there were other, unidentified targets. Researchers at the Unit have now found
two new brain proteins that are at least as sensitive as these known targets to
a range of pesticides. A crucial point to be discovered is what these new
proteins do in the brain. However, if there are new unexplained forms of OP
pesticide toxicity out there, it is likely that our new proteins will be
involved. We are currently working hard to identify their function, and to find
out what effect (if any) their inhibition might have on brain function, in order
to identify more sensitive tests.
The second advance is the first ever demonstration of the
protein target for OP pesticide induced polyneuropathy (NTE). In a major
breakthrough researchers have purified and sequenced the NTE protein, and used
antibodies to picture its distribution in the brain. It has long been known that
the interaction of some OPs with this protein causes a highly specific
neuropathy in humans and in animals. This has enabled scientists to predict
which agents would cause neuropathy and which would be safe, with considerable
degree of success, but without knowing exactly how or why. With this
breakthrough it is possible to see the NTE protein and study it by molecular
biological methods which should lead to rapid progress to understanding this
rare but individually devastating form of toxicity.
Dr. David Ray is a researcher at the MRC Toxicology Unit, University of Leicester.
[This
article first appeared in Pesticides News No. 37,
September 1997, page 19]