These are the conclusions, Bill.
Kind regards,

Ghislain De Roeck,
Belgium.


3. CONCLUSION AND PERSPECTIVES
Insecticides can induce more or less serious effects on neural functions
that can lead to an impairment of behaviour and physiological functions. The
mechanisms by which insecticides elicit their effects are not restricted to
the exclusive interaction between the active substance and the molecular
target responsible for the insecticidal action. The effects of a given
insecticide involve multiple molecular targets of different affinities for
the molecule that can be recruited at different exposure levels and that may
induce various effects, some of which are opposite or can induce a feedback
action. Time appears as an important factor in insecticide toxicity. The
final action of the insecticides is strongly dependent on the circadian
hythms, the time following exposure, the age or the developmental stage of
the bees and the season. The route and the mode of exposure (acute,
subchronic or chronic) play a particularly determining role in the nature
and the intensity of the effects induced, and are often involved in
differential effects elicited by a given substance. 
Metabolic processes modulate the intrinsic toxicity and may lead to
metabolites that exhibit toxicity levels higher or lower than that of the
parent compound and may elicit completely different effects. However, the
simultaneous presence of several pesticides in a site or in food leads to
interactions between substances that can drastically change the nature and
the importance of the effects observed with one insecticide alone. Thus,
investigations on pesticide combinations should take a more prevalent place
in honey bee toxicology in the future. Because of the large number of
pesticides, combinations to be studied will need to be prioritised. This
could be based on the spatio-temporal occurrence of active substances.
The potential means to decrease the side effects of pesticides in the
beneficial organisms, particularly the honey bees and pollinators, are of
great concern. Different approaches involving highly repellent pesticides or
genetic selection of pesticide-resistant bees have been proposed in the
past. However, they were not considered fully satisfactory because of the
unwanted impacts they can have on honey bees.
Repellent substances with a long life span may elicit a drastic decrease in
nectar and pollen gathering that could be damaging for both the honey bee
colony and the beekeepers, and may prevent the proper pollination of crops.
However, recent studies suggest that the combination of repellent and
insecticide molecules can act synergistically on the insect pest (Pennetier
et al. 2009). This type of action could be used advantageously to decrease
the field dosages of pesticides, but it needs further investigation to
assess the risk to the bees. The development of pesticide-resistant bees
raises questions on foodsafety and genetic stability of colonies. It could
be argued that pesticide-resistant bees could exhibit a higher survival rate
after poisoning that enables them to harvest larger quantities of
contaminated pollen or nectar. This could have harmful consequences for the
human consumers of honey and pollen, and for honey bee colonies if the brood
and the juveniles are more sensitive to pesticides than adult workers. Up to
now, no pesticide-resistant bee populations have been reported. This is
mainly due to the absence of strong selection pressure because the queen bee
is not directly exposed to pesticides. Considering the variety and the
complexity of the modes of action of the pesticides, it would not be
possible to select bees that exhibit a multiple resistance due to biological
targets that are less sensitive to pesticides. Multiple resistance based on
an enhanced detoxification capacity should be more relevant but could create
problems with pesticides having toxic metabolites such as organophosphates
and neonicotinoids. However, in all cases of resistance, the problem of
stabilising the resistant bee populations cannot
be solved if the origin of queens and males in the apiary is not strictly
controlled. A promising approach to preventing side effects of pesticides
on beneficial organism has been derived from improved knowledge of the mode
of action of pesticides in targeted pests and honey bees.
Information on the mode of action can be used to develop substances that act
selectively on pests. New substances might be designed to act preferentially
on target subtypes of pests sensitive to insecticides such as neonicotinoids
of phenylpyrazoles (Courjaret et al. 2003; Dupuis et al. 2010;
Lavialle-Defaix et al. 2011; Bordereau-Dubois et al. 2012). 
A little explored way to act more selectively on pests consists in the
designing of substances than act synergistically on the signalling pathways
involved in the action of insecticides (Courjaret and Lapied 2001; Brandon
et al. 2002; Es-Salah et al. 2008; Grünewald and Wersing 2008). This
could improve the targeting of pesticides on pests and help to reduce the
field dosages for decreasing the environmental impacts and the
hazard to honey bees.

             ***********************************************
The BEE-L mailing list is powered by L-Soft's renowned
LISTSERV(R) list management software.  For more information, go to:
http://www.lsoft.com/LISTSERV-powered.html

Guidelines for posting to BEE-L can be found at:
http://honeybeeworld.com/bee-l/guidelines.htm