Chemistry Reference
In-Depth Information
Vertebrates can tolerate a certain degree of inhibition of brain AChE before toxic
effects are apparent. A typical dose-response curve for the inhibition of AChE by an
OP is shown in Figure 10.5. The relationship between the degree of inhibition and
the nature and severity of toxic effects is indicated in the figure. In general, effects
increase in severity with increasing dose, but the quantitative relationship between
percentage inhibition and effects is subject to considerable variation between com-
pounds and between species. A typical situation in an avian species is as follows: At
around 40-50% inhibition, mild physiological and behavioral disturbances are seen.
Above this, more serious disturbances occur; and above 70% inhibition, deaths from
anticholinesterase poisoning begin to occur (Grue et al. 1991).
There is much evidence from studies with laboratory animals that mild neuro-
physiological effects and associated behavioral disturbances are caused by levels
of OPs well below lethal doses (see, e.g., Environmental Health Criteria 63). These
include effects on EEG patterns, changes in conditioned motor reflexes, and in per-
formance in behavioral tests (e.g., maze running by rats). Many of these observations
were made after exposures too low to cause overt symptoms of intoxication. In a
study with rainbow trout (
Onchorhynchus mykiss
), diazinon and malathion caused
behavioral disturbances at quite low levels of brain AChE inhibition (Beauvais et al.
2000). With diazinon, the maximum level of inhibition (mean value) of brain ChE
was less than 50%. There was a strong negative correlation between speed and dis-
tance of swimming, and brain AChE inhibition even down to values of about 20%.
Similar results were obtained with malathion. These issues will be discussed further
in Chapter 16.
The measurement of inhibition of brain AChE is a valuable biomarker assay for
OPs and carbamates and is not just an index of exposure. Being an assay based on
Irreversible physiological
effects leading to death
Severe physiological and
behavioral effects
Reversible
Mild physiological and
behavioral effects
No observable effects
Log Dose (mg/kg)
fIgure 10.5
Stages in the progression of OP intoxication.
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