The Organochlorine Insecticides - Organic Pollutants: An Ecotoxicological Perspective - page 110

TTX
saxitoxin

AV M
GABA

β-Scorpion
toxins

Benzodiazepines

Na + C -

α-Scorpion toxin

Veratridine
batrachotoxin
Pyrethroids
DDT

Barbiturates
Pyrethroids

TBPS, AV M
Lindane
Cyclodienes
To xaphene
Picrotoxinin

(a) (b)

fIgure 5.4 Sites of action of organochlorine insecticides: (a) sodium channel, (b) GABA
receptor. (From Eldefrawi and Eldefrawi 1990. With permission.)

on the channel, thereby altering its function. Normally, when an Na + current is gen-
erated, the signal is rapidly terminated by the closure of the sodium channel. In
DDT-poisoned nerves, the closure of the channel is delayed, an event that can cause
disruption of the regulation of action potential and can lead to repetitive discharge.
p,p ′-DDT can also act upon the K + channel, which is concerned with the repolariza-
tion of the axonal membrane after passage of the action potential.
Apart from the action upon Na + channels, p,p ′-DDT and its metabolites can have
certain other toxic effects. It has been reported that p,p ′-DDT can inhibit certain
ATPases (see EHC 83). In fish, the inhibition of ATPases can affect osmoregulation.
The ability of p,p ′-DDE to cause thinning of avian eggshells, even at very low con-
centrations in some species, has been a matter of considerable interest (see Ratcliffe
1967, 1993; Peakall 1993). The mechanism by which this is accomplished is still not
fully established. It seems clear that the basic problem is the failure of Ca 2+ transport
across the wall of the eggshell gland (Lundholm 1997). Levels of p,p ′-DDE that cause
eggshell thinning in birds do not cause any reduction in plasma calcium levels. They
do, however, bring an increase in concentration in the mucosa and a reduction in con-
centration in the lumen, which contains the developing egg. Thus, there appears to be
a failure of the transport system into the lumen. It has been demonstrated that p,p ′-
DDE can inhibit the Ca 2+ ATPase of the avian shell gland (Lundholm 1987); this has
been proposed as a mechanism for the severe eggshell thinning caused by this com-
pound in certain species of birds, including the American kestrel ( Falco sparverius ),
sparrow hawk ( Accipiter nisus ), peregrine falcon ( Falco peregrinus ), and Gannet
( Sula bassana ; Wiemeyer and Porter 1970; Peakall 1993). However, there is also
evidence that p,p ′-DDE can affect prostaglandin levels in the eggshell gland, and this
may be a contributory factor in eggshell thinning (Lundholm 1997). Dietary levels
as low as 3 ppm have been shown to cause shell thinning in the American kestrel
(Peakall et al. 1973; Wiemeyer and Porter 1970). The implications of this finding will
be discussed in Section 5.2.5.
Finally, there is evidence that constituents of technical DDT can have a feminiz-
ing effect on avian embryos (for further discussion, see Chapter 15, Section 15.6). Of