7765

• UCREFRP Catalog Number: 7765
• Author: Beyers, D. W. and P. J. Sikoski
• Title: Acetylcholinesterase Inhibition in Federally Endangered Colorado Squawfish Exposed to Carbaryl and Malathion
• USFW Year: 1993
• USFW - Doc Type: Environmental Toxicology and Chesistry
• Copyright Material: YES

938

D.W. BEYERS AND P.l. SIKOSKI

adverse effect over the entire range of toxicant concentrations
and to estimate an effect threshold.
Justification for the linear-plateau regression model is
based on the threshold concept [19,20]. A basic tenet of this
concept is that toxic effects appear only when toxicant-
induced changes in an organism exceed its ability to compen-
sate by homeostatic mechanisms. Protective mechanisms that
may influence toxicity of carbaryl and malathion as estimated
by brain AChE inhibition include MFO system [21], perme-
ability of the blood-brain barrier, and affinity of plasma and
hepatic esterases for AChE inhibitors [22,23]. These mech-
anisms decrease toxic effects by sequestering, eliminating, or
reducing absorption of toxicants but may be overwhelmed
by high concentrations or long-term exposure.

Utility of A ChE-inhibition studies

Results of this study demonstrate that AChE inhibition
is a more sensitive indicator of exposure to carbaryl or mal-
athion than growth or survival in standardized toxicity tests.
NOECs for AChE inhibition by carbaryl or malathion were
15 and five times lower, respectively, than NOECs (445 p.g/L
carbaryl and 1,680 p.g/L malathion) for survival and growth
of Colorado squawfish in 32-d ELS tests [7]. Several expla-
nations can be offered to account for this disparity.
First, development of tolerance in ELS tests may have re-
duced sensitivity of study fish. Tolerance to organophospho-
rus and carbamate insecticides is common, and explanations
for the phenomenon have been suggested [24,25]. In stan-
dardized toxicity tests, fish may initially suffer sublethal
effects that diminish during the exposure period due to de-
velopment of tolerance. For example, in 32-d ELS tests,
Beyers [13] observed that incidence of sublethal effects (loss
of equilibrium or failure to feed) was initially high but de-
creased early in the exposure period. Mortality accounted for
a portion of the observed decrease, but many fish appeared
to recover from toxic effects even though exposure concen-
trations were unchanged. The relatively long duration of ex-
posure in 32-d ELS tests probably facilitated development of
tolerance to carbaryl and malathion, and allowed study fish
to recover from the observed sublethal effects, Thus, effect-
concentration estimates from ELS tests were inflated because
transient whole-organism sublethal effects were not reflected
by growth or survival measured at end of the exposure pe-
riod, and development of tolerance permitted fish to physi-
ologically adapt to the toxicants, In contrast, short duration
of chemical exposure in AChE-inhibition studies (24 h) pre-
cluded physiological adaptation to toxicants, and a sublethal
effect (AChE inhibition) was detected at a temporal scale
consistent with its appearance.
A second explanation for the observed disparity between
end points is that sublethal and within-organism effects like
AChE inhibition occur at lower concentrations than whole-
organism responses like reduced survival or growth [26,27].
This relation has been observed in birds, mammals, and fishes
exposed to AChE inhibitors [28,29]. With few exceptions,
2:70070 inhibition by carbamate and organophosphate insec-
ticides results in death in fish [29]. As AChE inhibition de-
clines from 70 to 20%, adverse effects become more subtle
and may include reduced or suspended reproduction, paral-

ysis, reduced stamina, and behavioral deficit. Further reduc-
tion of AChE inhibition results in diminution of adverse
effects until only a measurable depression of AChE activity,
of uncertain biological significance, is detectable. However,
there is an energetic cost of compensating toxic effects even
at low levels of AChE inhibition. Energy expended to com-
pensate adverse effects is not available for growth, reproduc-
tion, or maintenance of other physiological systems. If
additional resources are available to offset the energetic cost
of compensation, whole-organism responses like survival and
growth may not reflect the within-organism effects of the tox-
icant. However, if additional resources cannot be obtained,
an energy deficit may occur and be evidenced in standard tox-
icological end points (e.g., reduced growth). ELS toxicity
tests are replete with additional resources because food is
generally superabundant and easily captured, and effects of
predation or competition are absent. Constant and benign
environmental conditions alleviate other sources of physio-
logical stress, allowing test organisms to devote more energy
to compensate toxic effects [30,31], Under these circum-
stances, a disparity between a direct biochemical measure of
toxicity and whole-organism responses is predictable, and
may even be maximized because of availability of abundant
resources for compensation.
The potential for development of tolerance to carbamate
and organophosphate insecticides emphasizes that there are
situations in which AChE inhibition is not a useful measure
of toxic effects. Another instance is when the observed ad-
verse effect results from nonspecific toxic effects [32]. Inhi-
bition of brain AChE is an example of a specific toxic effect
of carbamate and organophosphate insecticides. However,
at extraordinary levels of exposure, toxicants with a specific
mode of action may have nonspecific toxic effects, and the
organism may die before the specific effect is manifested. For
example, Gibson et al. [33] reported that fish that became
moribund after a 30-min exposure to 750 p.g/L parathion
showed only 25070 AChE inhibition, whereas those exposed
to 20 p.g/L for 13 h showed 57% inhibition. Protective mech-
anisms like the blood-brain barrier may retard transfer of
AChE inhibitors to the brain, and responses resulting from
relatively short-duration exposure may be manifestations of
nonspecific toxic effects in other organs like liver or hepa-
topancreas where bioactivation of pesticides occurs, or in re-
spiratory tissues.
The mode of action of most toxicants in fish is unknown,
and physiological or biochemical effects must be inferred
from standard test end points. Chemicals that inhibit AChE
provide a unique opportunity for research because their mode
of action is understood. We showed that in vivo AChE in-
hibition is a more sensitive indicator of exposure to carba-
ryl or malathion than growth or survival in 32-d ELS tests,
and attributed the differences to development of tolerance
and greater sensitivity of biochemical processes compared
to whole-organism responses. Mehr1e and Mayer [26] sug-
gested that toxicant-induced physiological and biochemical
responses be unequivocally correlated with whole-organism
responses like survival, growth, reproduction, and fish health,
Simple relations between within- and whole-organism re-
sponses may be confounded, or at least complicated, by

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