Organophosphorus and Carbamate Insecticides

When OCs were phased out, the less persistent insecticides that replaced them were thought to be more environment friendly. However, some of the insecticides that were used as replacements also presented problems because of very high acute toxicity. The insecticides to be discussed in this chapter illustrate well the ecotoxi-cological problems that can be associated with compounds that have low persistence but high neurotoxicity. 

The rapid growth in the use of OPs and the proliferation of new active ingredients and formulations was not without its problems. Some OPs proved to be too hazardous to operators because of very high acute toxicity. A few were found to cause delayed neurotoxicity, a condition not caused by ChE inhibition (e.g., mipafox, lepto-phos). There was also the problem of the development of resistance, for example, by 

Organic Pollutants An Ecotoxicological Perspective, Second Edition 

In the following account, OPs will be discussed before considering carbamates. 

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Rodgers KE, Leung N, Imamura T, et al. 1986. Rapid in vitro screening assay for immunotoxic effects of organophosphorus and carbamate insecticides on the generation of cytotoxic T lymphocyte responses. Pestic Biochem Physiol 26 292-301. 

T. Noguer, B. Leca, G. Jeanty, and J.L. Marty, Biosensors based on enzyme inhibition detection of organophosphorus and carbamate insecticides and dithiocarbamate fungicides. Field Anal. Chem. Tech. 3, 171-178 (1999). 

Boublik, T., Fried, V., Hala, E. (1984) The Vapor Pressure of Pure Substances, 2nd revised Edition, Elsevier, Amsterdam, The Netherlands. Bowman, B. T., Sans, W. W. (1983) Determination of octanol-water partitioning coefficient (KqW) of 61 organophosphorus and carbamate insecticides and their relationship to respective water solubility (S) values. J. Environ. Sci. Health B18, 667-683. Bradley, R. S., Cleasby, T. G. (1953) The vapour pressure and lattice energy of some aromatic ring compounds. J. Chem. Soc. 1953, 1690-1692. 

Chlordane interacts with other chemicals to produce additive or more-than-additive toxicity. For example, chlordane increased hepatotoxic effects of carbon tetrachloride in the rat (USEPA 1980 WHO 1984), and in combination with dimethylnitrosamine acts more than additively in producing liver neoplasms in mice (Williams and Numoto 1984). Chlordane in combination with either endrin, methoxychlor, or aldrin is additive or more-than-additive in toxicity to mice (Klaassen et al. 1986). Protein deficiency doubles the acute toxicity of chlordane to rats (WHO 1984). In contrast, chlordane exerts a protective effect against several organophosphorus and carbamate insecticides (WHO 1984), protects mouse embryos against influenza virus infection, and mouse newborns against oxazolone delayed hypersensitivity response (Barnett et al. 1985). More research seems warranted on interactions of chlordane with other agricultural chemicals. 

Some organochlorine, organophosphorus, and carbamate insecticides used after World War II (since 1945) were found to have various problems of adverse effects on mammals and environmental behavior and influences. The use of many industrial chemicals has been prohibited because those contained as impurities in minute quantities produced critical toxic substances by transformation and repeated chemical reactions in their environment. 

The establishment of a common mechanism of mammalian toxicity for the pyrethroids is not a straight forward process, as it was for the organophosphorus and carbamate insecticides, due to the occurrence of multiple potential target sites and the varied action of pyrethroids at these sites as reviewed above. In view of... 

Fukuto TR (1990) Mechanism of action of organophosphorus and carbamate insecticides. Environ Health Perspect 87 245-254... 

Bowman BT, Sans WW. 1983. Determination of octanol-water partitioning coefficients (Kow) of 61 organophosphorus and carbamate insecticides and their relationship to respective water solubility (S) values. J Environ Sci Health [B] 13 667-633. 

Felsot, A. and Dahm, P.A. Sorption of organophosphorus and carbamate insecticides by soil, J. Agric. Food Chem., 27 (3) 557-563, 1979. 

There are hundreds of organophosphorus and carbamate insecticides in agricultural and household use. Two important examples are malathion, an organophosphorus compound, and carbaryl, a carbamate, both shown in Figure 15.20. Malathion kills a variety of insects, such as aphids, leafhoppers, beetles, and spider mites. Carbaryl, like many other carbamates, is relatively selective in the types of insects it kills. 

Bowman, B. T., and W. W. Sans, Determination of Octanol-Water Partitioning Coefficients (KOW) of 61 Organophosphorus and Carbamate Insecticides and Their Relationship to Respective Water Solubility (5) Values. J. Environ. Sci. Health, 1983 B18(6), 667-683. 

A. Modes of Toxic Action. This includes the consideration, at the fundamental level of organ, cell and molecular function, of all events leading to toxicity in vivo uptake, distribution, metabolism, mode of action, and excretion. The term mechanism of toxic action is now more generally used to describe an important molecular event in the cascade of events leading from exposure to toxicity, such as the inhibition of acetylcholinesterase in the toxicity of organophosphorus and carbamate insecticides. Important aspects include the following ... 

Figure 11.5 Hydrolysis of acetylcholine by the enzyme acetylcholinesterase and its inhibition by toxicants such as organophosphorus and carbamate insecticides.

Organophosphorus and carbamate insecticides LC-MS with thermospray or electro spray interface sub ppb [26]... 

Kanazawa, J. (1975) Uptake and excretion of organophosphorus and carbamate insecticides by fresh water, Motsugo (Pseudorasbora parva). Bull. Environ. Contam. Toxicol. 14, 346-352. 

N-Dealkylation This is a common reaction in the metabolism of xenobiotics, including organophosphorus and carbamate insecticides. The reaction is believed to proceed by an unstable a-hydroxy intermediate that spontaneously releases an aldehyde in the case of the primary alkyl group. For example, the carbamate insecticide propoxur is N-demethylated to 2-isopropoxyphenyl carbamate via 2-iso-propoxyphenyl N-hydroxymethyl carbamate. Microsomal N-dealkylation results in detoxification (Figure 8.5). 

Acetylcholinesterase. Altered acetylcholinesterase less sensitive to organophosphorus and carbamate insecticides has been observed in a wide variety of insects and mites (51). Acetylcholinesterase inhibiting insecticides phosphorylate or carbamylate the serine residue in the active site of the enzyme preventing vital catalysis of acetylcholine. Resistance due to reduced sensitivity to inhibition of this target enzyme has been found in house fly, mosquitoes, green rice leafhopper, and both phytophagous and predacious species of mites. 

Enzyme inhibitors may or may not be very selective, and their effects depend on the importance of the enzyme in different organisms. Plants lack a nervous system and acetylcholinesterase does not play an important role in other processes, whereas essential amino acids are not produced in animals. Glyphosate and other inhibitors of amino acid synthesis are therefore much less toxic in animals than in plants, and the opposite is true for the organophosphorus and carbamate insecticides. 

Organophosphorus and carbamate insecticides are the two classes of anticholinesterase insecticides. All anticholinesterases inhibit nervous tissue acetylcholinesterase, the enzyme that deactivates the neurotransmitter acetylcholine (Ecobichon 1996). Poisoning causes accumulation of acetylcholine in the synaptic cleft, resulting in continuous electrical stimulation (Chambers 1992 Costa 1988). Described best by Chambers (1992), the mechanism of acute symptoms of poisoning occurs through three pathways ... 

Beginning in the mid to late 1960 s the biodegradable organophosphorus and carbamate insecticides began to replace the chlorinated hydrocarbons as the rootworm control chemicals of choice. Dlazinon, oxydisulfoton, and phorate were the first, and were quickly followed by bufencarb, trimethacarb, fonofos, and fensulfothion. In the mid to late 1970 s the introduction of new chemicals continued as ethoprop, carbofuran, chlorpyrifos and terbufos came into use. 

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