INSECTICIDES: THEIR ROUTE OF ENTRY, MECHANISM OF TRANSPORT AND MODE OF ACTION

(1) The assumption that the circulatory system of the insect is instrumental in transporting insecticides to their site of action appeared not to be based on good evidence. On the contrary, experiments specifically designed to test the hypothesis provided ample evidence to refute the idea. Salient points to disprove the haemolymph route of entry can be summed up as follows: (a) A topically applied dose of insecticide does not readily penetrate the insect and the minor fraction that does so is largely retained in the body wall. The small amount that actually passes into the blood is too small to cause symptoms of toxicity if injected into the haemocoel. (b) The amount of insecticide present in the haemolymph (and CNS) does not appear to have any bearing on toxicity - internally introduced insecticides are, in fact, basically very much less toxic than those externally applied. Where injected doses appear to be more toxic than equal amounts topically applied, this is due to the boosting effect of organic solvent carriers. Tests with parabiotically joined insects provide support for the view that haemolymph-borne insecticide is of no consequence. (c) The topographical proximity of the locus of external application with the site of action (the thoracic ganglia) seems to be important irrespective of the general direction of the blood flow, and this should not be so if the circulatory system was instrumental in the transport of insecticide. (d) The introduction into the haemocoel of material such as olive oil, which is an excellent absorbent for insecticides, does not affect the toxicity (speed of action) of externally applied compounds to a significant extent. It should have a pronounced effect if haemolymph-borne insecticide were an essential element in the process of poisoning. (e) As judged by speed of action, blocking of the blood circulation does not hamper the insecticide's movement to the site of action. (2) Only two other feasible routes remain. (a) The insecticide might reach the CNS via peripheral nerves and nerve cord, but the results of histochemical assays of cholinesterase inhibition in the insect's CNS make the idea improbable for organo-phosphates. The nerve route is also incompatible with the observation that a wax barrier blocked the movement in and over the body wall so as to delay the onset of symptoms of toxicity, as such a barrier would not hinder movement into lateral nerves near the locus of application. (6) The only other feasible alternative, i.e. entry by means of lateral transport via the integument of the body wall and tracheae, is supported by autoradiographic and other evidence which showed the insecticide to accumulate in the tracheal system. It is further supported by the fact that inter-tracheal introduction is faster acting than topical treatment, indicating that the tracheal system offers a very effective pathway to the internal organs. (3) Regarding the mechanism of entry, earlier reviews and text books maintain this to be associated exclusively with penetration into and through the integument by a physicochemical process. However, there is good evidence to show that an active process (requiring metabolic activity as the driving force) plays an essential part in lateral movement in the integument - the epidermis, being the only living tissue continuous throughout the general integument, must perform this function. (4) As to the mode of action, the new hypothesis expounded here implies a single mode based on the fact that insecticides cause the extrusion of fluid from the epidermis into the cuticle and beyond, fluid lost from the epidermal cell layer being replaced from haemolymph and internal tissues. The precise mechanism is not clear but could conceivably involve an as yet hypothetical local endocrine system designed to keep the water content in the integument within certain limits. It is suggested that water extrusion affects the integument's permeability to respiratory gases, resulting in a rate of respiration not commensurate with metabolic need, and that the insecticide's arrival in the trachea (tracheoles) of the CNS leads to excitation and knockdown. Death is thought most likely to be due to dehydration of the CNS and subsequent histological degeneration.