Toxicology of Insecticides — Introductory Considerations

TIMOTHY C MARRS

Edentox Associates, Pinehurst, Four Elms Road, Edenbridge, Kent, UK and UK National Poisons Information Service (Birmingham Centre), City Hospital, Birmingham, UK. Email: timothymarrs05@aol.com

1.1 Introduction

Insecticides are a group of substances with heterogeneous toxicity, whose desired activity is the killing of unwanted insects. Closely allied are acaricides or miticides, terms used for substances that kill mites. Indeed, many acaricides are also insecticides. Many insecticides have mammalian toxicity that is related to their toxicity to the target organism, especially those insecticides that target the insect nervous system. Notable exceptions to this are insecticides that target systems present in insects but not mammals, such as the juvenile hormone analogues and chitin-synthesis inhibitors. Even those insecticides that target systems present in both insects and mammals may have target organism specificity conferred by physical or metabolic differences between insects and mammals.

To be weighed against their mammalian toxicity are the facts that insects and are important sources of agricultural loss of food and other crops such as cotton and can give rise to damage to buildings, where construction is of wood. A very important role of insecticides in public health is vector control. Many insects carry diseases such as malaria, yellow fever, Lyme disease, dengue and sleeping sickness, all of which cause considerable mortality and/or morbidity. Probably the most serious of these is malaria, where the use of insecticides is a very important part of disease control.

As with many uses of chemicals, the key to a successful insecticide is selective toxicity against target insects and away from non-target insects and mammals. An ideal insecticide will interfere with a biological system in the insect that has no counterpart in non-target species: this is the advantage of the juvenile hormone analogue and chitin-synthesis inhibiting insecticides. In the case of agricultural insecticides, the insecticide should be toxic to insects, but less toxic to plants, to humans and to other non-target organisms. In the case of insecticides targeting the insect neurological system, insecticides often exploit the relative accessibility of the insect nervous system to xenobiotics, when compared to humans, or different distribution of neurotransmission systems, together with the lack of a nervous system in plants.

In recent years, there has been some concern as to the possibility of deleterious effects from exposure to multiple pesticides, inter alia insecticide exposure, either as residues in food and water or at the workplace, home or environment, or indeed a combination of these pathways; this is further discussed below. Another recent development is the use of microbial insecticides: these are discussed in Chapter 10.

1.2 Classification

The insecticides can be classified in several ways, for example into those of natural or synthetic origin (see Table 1.1). This division, while perhaps useful for organic farmers, tell us little about toxicology. Insecticides of natural origin — e.g. pyrethrum, nicotine, rotenone (Derris), the 'mectins — have little in common from the point of view of mammalian toxicology and, of course, the synthetic insecticides can be divided into many groups, depending on their mode of action and/or structure. Indeed some natural insecticides (e.g. pyrethrum) have more in common with synthetic insecticides (the synthetic pyrethroids) than they do with other natural insecticides.

Another way of classifying insecticides is by chemical structure (Table 1.2). This classification is of much more use to toxicologists, partly because it provides some guide to effects in mammals. However, it is important to remember that this classification is not a complete guide to mammalian toxicology. The organophosphate esters are commonly anticholinesterase insecticides (exceptionally, pyrazophos is a fungicide), but other organic compounds of phosphorus have different actions both in target and non-target species e.g. glyphosate, which is a herbicide. Similarly, most carbamate insecticides are N-methyl carbamates: other carbamates have fungicidal and herbicidal action and are not cholinesterase inhibitors.

The most useful classification for toxicologists is probably by mode of action in the target species and a recent classification on that basis has been proposed by the Insecticide Resistance Action Committee, although it should be noted that the mode of action in target species is not always completely known. Nevertheless, in many cases where the mode of action in target insects is known, it may provide some guide to the toxicological action in mammals. Thus, many insecticides act on the insect nervous system and their effects in mammals are often related to this. Action on the insect nervous system may be on enzymes involved in neurotransmission (anticholinesterases — see Chapter 4) or directly on receptors (nicotine and the neonicotinoids [see Chapter 6] and fipronil [see Chapters 9 and 12]). Other neuronal structures may be targeted: the avermectins stimulate the release and binding of γ-aminobutyric acid (GABA), a neurotransmitter, at nerve endings (see Chapter 8). Organochlorines such as DDT have a more general action on sodium channels in neurons (see Chapter 3), and pyrethrins and synthetic pyrethroids also act on sodium channels by keeping them open (see Chapter 5). The reason for the utility of this classification is that the mammalian toxicology of these potentially neurotoxic insecticides is in large part related to the neurotoxicity in target organisms. With insecticides that target the insect nervous system, specificity towards insects and away from mammals may be achieved by exploiting the greater accessibility of the insect nervous system, metabolic differences between insects and mammals, or differences in distribution of receptors and other components of neurotransmission systems....