Toxicity pesticide metabolites

A possible example of this thesis is the crystalline insect toxin found in Bacillus thuringiensis spores and discussed here by Dr. Anderson. Although neither the bacillus nor its spores exhibit useful antibiotic activity against other microorganisms, the very specific toxicity to insects has become of major commercial interest. The enormous number and variety of fungal species available for further examination must lead inevitably to one or more which produces pesticidal metabolites. 

When the products formed by metabolic processes are toxico-logically insignificant and, when this is a known fact, the findings may be valuable in assessing pesticide risk. Contrarily, a number of pesticides yield metabolites known to be highly toxic and these materials may be taken into account in the risk assessment process. Too many times, however, the isolation and identification of pesticide metabolites tell us very little about risks that may be associated with the use of a particular chemical because the information can not be related to in vivo toxicological significance. 

While strong evidence is lacking and difficult to obtain, many if not all of the aforementioned halogenated metabolites are likely produced as defensive environmental adaptations. Just as chlorine substitution increases the potency of commercial pesticides, the toxicity of simple terpenes is greatly increased by virtue of added bromine substituents. Those marine organisms that produce substances of this nature cleeirly benefit by enhanced survival against potential predators. 

Innumerable factors, such as crop pattern, food habits, processing conditions, species variations, and multiple uses of pesticides and toxic metabolites, complicate the determination however, human data on a pesticide, whether from volunteer studies or from other investigation,s of human exposures in the workplace or environment, can be extremely valuable in placing the animal data in context and, when available, should always be evaluated even when they are not u,sed to derive ADls. 

Figure 12.63 provides another example of the diversity of metabolic processes to which pesticides are subjected after application. In the case of the carbamate insecticide carbaryl, the predominant processes are oxidation and hydrolysis, which maybe followed by conjugation of primary metabolites with glutathione. The character of metabolic transformations is closely related to the pesticide selectivity (toxicity) to target and non-target organisms. 

The full extent of the toxicity of pesticides to aquatic life is not known. Although chronic toxicity testing is required for new substances, little is known about the long-term effects of older pesticides. Also, very little is known about the toxicity and occurrence of the products formed when pesticides break down (metabolites) or the many non-pesticidal additives (co-formulants and adjuvants) used in pesticide formulations. However, the future is looking brighter. New modelling techniques, EQS development, and the involvement of the NRA in the pesticide registration process, coupled with the development of newer, less persistent pesticides with lower dose rates, all should help to reduce the risk of pesticide pollution. 

Some of these compounds could be considered as dietary additives, but various other terms, including pesticides, can also be used. They can have beneficial effects on the environment and this aspect will be discussed later. The ionophore monensin, which is an alicyclic polyether (Figure 1), is a secondary metabolite of Streptomyces and aids the prevention of coccidiosis in poultry. Monensin is used as a growth promoter in cattle and also to decrease methane production, but it is toxic to equine animals. " Its ability to act as an ionophore is dependent on its cyclic chelating effect on metal ions. ° The hormones bovine somatotropin (BST) and porcine somatotropin (PST), both of which are polypeptides, occur naturally in lactating cattle and pigs, respectively, but can also be produced synthetically using recombinant DNA methods and administered to such animals in order to increase milk yields and lean meat production. "... 

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

Toxic Pollutants (Concentrations Shown in jxg/L) Pesticides and metabolites Aldrin 37 2 4-11 7... 

All pesticides introduced into the natural environment undergo transformations. Sometimes the metabolites produced are more toxic than the original substance. 

Just like mammals, birds have a delayed reaction to lipotropHc pesticides such as OCPs and their metabolites. These toxic substances dissolve and accumulate in the fatty tissues of well-fed birds, and are comparably harmless in this form. However, once the bird starts using the stored fat (at the end of a long flight or when laying eggs), the substances are carried through the bloodstream to the brain, liver, or yolk of the egg, and poison all the systems [1]. In particular, well-fed raptors have lower DDE concentrations in their liver (0.5 mg/kg) than less well-fed (3.5 mg/kg) and emaciated birds (7.3 mg/kg) [6]. 

Table 4.15. Comparative toxicity of pesticides and their metabolites (for rats) [80]...

Chemicals degraded by WRF include pesticides such as organochlorines DDT and its very toxic metabolite DDE [8, 9] and organophosphate pesticides such as chlorpyrifos, fonofos and terbufos [10] polychlorinated biphenyls (PCBs) of different degrees of chlorine substitution [11-13], some even to mineralization [14, 15] diverse polycyclic aromatic hydrocarbons (PAHs) in liquid media and from contaminated soils or in complex mixtures such as creosote [16-18] components of munition wastes including TNT and its metabolites DNT [19-23], nitroglycerin [24] and RDX [25]. 

Microbial activity can also be stimulated by mineral colloids through their ability to sorb metabolites that would otherwise have an adverse effect on microbial growth (Filip et al. 1972 Filip and Hattori 1984) This may be due to the toxicity of metabolites, and their feed back repression and, encouraging competitors. Predictably, montmorillonite (CEC —100 cmol kg-1 and specific surface of 800 m g 1) is more effective than kaolinite and finely ground quarts. Other substances, such as antibiotics and pesticides that are toxic to some microorganisms, can also be adsorbed by the surfaces of mineral colloids (Theng and Orchard 1995 Dec et al. 2002). 

Organic isocyanates (R-N=C=0) are xenobiotics used extensively in the manufacture of paints, pesticides, and polyurethanes. The reactivity of the isocyanate group can also underlie the toxic reactions observed in patients that have been exposed to organic isocyanate monomers. Furthermore, the isocyanates formed in the body can be metabolites of various other xenobiotics, such as ... 

Barr, Dana B., et al. (2004). Concentrations of dialkyl phosphate metabolites of organophosphorus pesticides in the U.S. population. Environmental Health Perspectives 112(2) 186-200. Greenlee, A. R., T. M. Ellis, and R. L. Berg. (2004). Low-dose agrochemicals and lawn-care pesticides induce developmental toxicity in murine preimplantation embryos. Environmental Health Perspectives 112(6) 703-709. 

Somasundaram, L.. Coats, J.R., Racke. K.D., and Stahr, H.M. Application of the Microtox system to assess the toxicity of pesticides and their hydrolysis metabolites. Bull Environ. Contam. Toxicol, 44(2) 254-259,1990. 

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