Insecticide, case involving

Accessibility of the deposit to the insects by contact is the chief feature of the small vial method, but fumigant action cannot be eliminated entirely. In the case of DDT this has been found to be unimportant, for flies kept in the vials out of contact with the surface are not affected. But with 7-hexachlorocyclohexane or parathion there is a noticeable toxic effect. If the vials are stood upright, laid on the side, or hung upside down, there is a decrease in the mortality produced in the order given. The position on the side has been adopted because it avoids extremes and because practical use of an insecticide often involves limited but not accentuated ventilation. 

Blisard KS, Kornfeld M, McFeeley PJ, et al. 1986. The investigation of alleged insecticide toxicity A case involving chlordane exposure, multiple sclerosis, and peripheral neuropathy. J Forensic Sci 31 1499-1504. 

Observed differences between strains of rats and mice, as described below, may be the result of gene polymorphisms. In cases involving insecticide selection pressure, resistant populations may arise as a result of direct mutations of insecticide-metabolizing enzymes and/or insecticide target sites that are passed on to succeeding generations. 

In some cases, increased toxicity of insecticides can be attributed to materials that enhance cuticular penetration of the insecticides without involving inhibition of metabolic detoxification. For example, Sun and Johnson (1972) found that carbaryl was more toxic to houseflies when topically applied in kerosene than in acetone. These authors classified this type of synergism as quasi-synergism. 

Not only has PBO continued to be used as an insecticide synergist but, in addition, it has become a diagnostic tool for two important aspects of insecticide toxicology to determine if in vivo metabolism of an insecticide is oxidative and to determine if cases of insecticide resistance involve oxidative metabolism by P450. 

The two main federal agencies involved in the protection of human health and the environment are the Environmental Protection Agency (EPA) and the Occupational Safety and Health Administration (OSHA). EPA s principal concern is the protection of the environment, in most cases, the area outside of an industrial faciUty. There are 10 regional offices that carry out the regulatory functions of the agency (Table 1). Primary laws covered by EPA are the Clean Air Act Amendments (CAAA), the Clean Water Act (CWA), Resource Conservation and Recovery Act (RCRA), Comprehensive Environmental Response, Compensation, and LiabiUty Act (CERCLA), Toxic Substances Control Act (TSCA), and Eederal Insecticide, Eungicide, and Rodenticide Act (FIFRA). 

There have also been reports of neoplasms in native bottomfeeding fish with a suggestion that carcinogenic hydrocarbons from motor boat exhausts, rotenone and insecticides such as DDT may be involved as causative agents (59.). Similarly (an) unidentified carcinogen(s) are suspected in the case of adematous polyps of gastric mucosa of fish, reported recently (60). The diet of these fish was free of aflatoxins. 

More general cases are encountered in the metabolism of a variety of ha-log enated hydrocarbon solvents and insecticides [58]. Examples include the dehydrochlorination of 1,1,2,2-tetrachloroethane to trichloroethylene in the mouse, and of DDT (l,l,l-trichloro-2,2-bis(4-chlorophenyl)ethane) to DDE (l,l-dichloro-2,2-bis(4-chlorophenyl)ethene) [58][77]. Glutathione transferases may be involved in some of these reactions. 

Two incidents involving thermal decomposition of an unspecified phosphorus ester insecticide which imintentionally became heated to 150-160°C are described. In one case the overheating arose from a relatively slow exotherm occurring at 90-100°C, and in the second, material at 55°C was heated instead of being cooled... 

Insecticide Action. The mode of action involved in the toxic effect of oils on hatched forms is no better understood than in the case of ovicides. Several theories which have been advanced are siunmarized by Shepard 19) as follows ... 

The most common adsorption systems consist of silica gel or alumina adsorbents in association with an organic solvent system. The adsorbent can exert a considerable influence on the separation of compounds. Alumina and silica gel, for example, have significantly different properties and can result in quite different separations. Activation of the adsorbent also influences sample retention. The presence of water on the adsorbent decreases the adsorbent activity due to blockage of active sites. If large quantities of water are present, a partition system may be set up which may extensively change the retention times due to the different chromatographic principle involved. Table 2.1 compares results obtained for the separation of the insecticide carbaryl (Sevin) and its hydrolysis product 1-naphthol on alumina and silica gel. Comparisons between activation and deactivation are made. The results show that separation of the two components is reversed with the two adsorbents examined. In most cases, activation of the plates caused the/ f values to increase relative... 

Irreversible inhibition, which is much more important toxicologically, can arise from various causes. In most cases the formation of covalent or other stable bonds or the disruption of the enzyme structure is involved. In these cases the effect cannot be readily reversed in vitro by either dialysis or dilution. The formation of stable inhibitory complexes may involve the prior formation of a reactive intermediate that then interacts with the enzyme. An excellent example of this type of inhibition is the effect of the insecticide synergist piperonyl butoxide (Figure 9.6) on hepatic microsomal monooxygenase activity. This methylenedioxyphenyl compound can form a stable inhibitory complex that blocks CO binding to P450 and also prevents substrate oxidation. This complex results from the formation of a reactive intermediate, which is shown by the fact that the type of inhibition changes from competitive to irreversible as metabolism, in the... 

One of the classic cases is the potentiation of the insecticide malathion by another insecticide, EPN, the LD50 of the mixture being dramatically lower than that of either compound alone. This potentiation can also be seen between malathion and certain contaminants that are formed during synthesis, such as isomalathion. For this reason quality control during manufacture is essential. This example of potentiation involves inhibition, by EPN or isomalathion, of the carboxylesterase responsible for the detoxication of malathion in mammals. 

The inhibition by other organophosphate compounds of the carboxylesterase which hydrolyzes malathion is a further example of xenobiotic interaction resulting from irreversible inhibition because, in this case, the enzyme is phosphorylated by the inhibitor. A second type of inhibition involving organophosphorus insecticides involves those containing the P=S moiety. During CYP activation to the esterase-inhibiting oxon, reactive sulfur is released that inhibits CYP isoforms by an irreversible interaction with the heme iron. As a result, these chemicals are inhibitors of the metabolism of other xenobiotics, such as carbaryl and fipronil, and are potent inhibitors of the metabolism of steroid hormones such as testosterone and estradiol. 

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