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to brain cholinesterase levels. The most sensitive parameter was posture, which was
found to change when brain cholinesterase activity fell below 88% of the control
value. Reductions in flying and singing, and increased resting were associated with
inhibition to below 61% of the normal level. Within 5 hours, behavior returned to
normal, reflecting the relatively rapid metabolic detoxication of this insecticide, as
with most other OP insecticides.
Linkages between cholinesterase inhibition and behavior have also been studied
in terrestrial arthropods that are exposed to OP and carbamate insecticides on agri-
cultural land (Engenheiro et al. 2005). In a study with the isopod Porcellio dilatatus
exposed to soil contaminated with dimethoate, measurements were made of locomo-
tor activity. A relationship was found between several locomotor parameters and the
degree of cholinesterase inhibition. Locomotor behavior is crucial in this species for
burrowing, avoiding predation, seeking food, migration, and reproduction.
16.6.2
e f f e c T s of f c of m b i n a T i of n s of f c h e m i c a l s
w i T h d i f f e r i n g m o d e s of f a c T i of n
As has already been discussed, in heavily polluted areas, disturbances of the nervous
system of free-living animals may be caused by chemicals with contrasting modes of
action interacting with more than one site of action at the same time. For examples
of sites of action, see Table 16.1. It should be emphasized that some of these sites of
action can be responsive to naturally occurring as well as human-made neurotoxins.
Thus, when measuring responses of animals at the whole-organism level to complex
mixtures of chemicals (e.g., in fish deployed into polluted waters), the effects of
chemicals acting through different pathways are difficult if not impossible to distin-
guish using assay systems that operate at higher organizational levels. For example,
in a study of the effects of neurotoxic compounds on primates, dieldrin and the OP
sarin produced similar effects on EEG patterns even though one chemical was acting
through the GABA receptor, whereas the other was causing cholinesterase inhibition
(Burchfield et al. 1976).
This complication aside, assays at the whole-organism level do have the advan-
tage of presenting an integrated measurement of the effects of one or more com-
pounds. It should be added that a better in-depth picture can be obtained by using
such assays in combination with others that operate at lower organizational levels. In
the aforementioned example given, inclusion in the study of assays for brain acetyl-
cholinesterase inhibition and binding to critical sites on the GABA receptor should
give a more complete picture of the toxic effects caused by the chemicals, thereby
allowing some distinction to be made between the respective contributions of sarin
and dieldrin to disturbances of the EEG pattern.
Because of their wide-ranging and “holistic” character, assays of behavioral
effects have been used as screening procedures when testing for neurotoxicity (see,
for example, Iversen 1991, Tilson 1993). They can provide sensitive indications of
neurotoxic disturbances, which can then be traced back to their ultimate cause by
using mechanistic biomarker assays.
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