Pesticides identifying metabolites

As with the FFDCA, the FIFRA requires pesticide firms to conduct batteries of extensive testing to identify and characterize a candidate pesticide s bioavailability, distribution, metabolites, routes of excretion in experimental animals, and any adverse or toxic effects that the substance may cause, so that the safety of the pesticide can be assessed. In addition, in cases of pesticides intended to have food uses, extensive field trials must be conducted to characterize residues of the pesticide or metabolites thereof remaining on or in raw agricultural commodities. 

In the case of pesticides which are not ChE inhibitors, exposure is measured by the analysis of blood and/or urine for the active ingredient or its metabolites. Baseline levels of pesticides and/or metabolites are not usually determined, with the exception of methyl bromide. In this case, a blood sample is taken to check for bromide ion before fumigators use the pesticide. Blood and urine tests are run only in the case of spills or other accidents to assist in identifying the cause of poisoning or to monitor workers in a workplace. Paraquat, chlorinated hydrocarbons, mercury, p-nitrophenol, and dinitrophenol are examples of pesticides or metabolites of pesticides that have been found in the urine of exposed workers. 

Because of the prowess of the analytical chemist, it is now possible to find residues of the chlorinated hydrocarbon insecticides in the environment at concentrations of a few parts per trillion. He is not so adept at finding nanogram quantities of some of the other classes of compounds for many pesticides, the metabolites are not identified, so he doesn t know what to look for. There is little question, however, that many of the compounds that now escape detection are present in the environment, and it is only a matter of time until the analytical chemist finds them. 

It has already been stated that no one method can identify an unknown residue with absolute certainty (22) and in this context four parameters have been suggested from which the confirmation of identity of a residue can be inferred with reasonable assurance (23), Two of these parameters are the EC-CLC retention time (on a given stationary phase) before and after chemical reactions. The pesticides or metabolites concerned are converted before injection to derivatives with diflFerent retention times from the parent compounds and also from other common pesticides that may be present. The other two parameters are R/ values (TLC or PC) or p-values (24) and insecticidal activity. 

The present approach for metabolism studies of pesticides and animal health drugs is to administer the compound to plants or animals in a manner that represents normal use conditions in the field. This approach prevents successful identification of metabolites and restrains what should be the proper way to identify metabolites. Little attempt is made to correlate metabolic results and toxicity. The chemist already knows that insoluble, unidentifiable residues will most likely occur from multiple dosing and that the problem of identifying metabolites and determining their toxicity is still present. 

In order to study the uptake and the metabolic fate of mephosfolan in fish reared in the rice paddy environment, fifteen Carasslus auratus (goldfish), a member of the carp family were introduced to mephosfolan-treated rice paddy tanks one week after the pesticide treatment. Fish were analyzed at periodic intervals. The radioactive residue levels found at various time intervals in the fish kept in the C-mephosfolan-treated rice paddy environment are presented in Table VII. All fish survived during the course of this study. The predominant metabolite in fish tissue was identified as thiocyanate ion. With this data and the data obtained from paddy water analyses, it is appropriate to evaluate... 

Environmental Defence recently released Toxic Nation A Report on Pollution in Canadians (Environmental Defence 2005). Samples were collected from 11 people for the presence of 88 chemicals, including heavy metals, PBDEs, PCBs, perfluorinated chemicals, organochlorine pesticides, organophosphorus-insecticide metabolites, and VOCs. The study objectives included determining whether pollutants were present at measurable concentrations in Canadians, identifying chemicals of concern, and creating public awareness of methods for avoiding exposure. 

Chicory (Cichorium intybus) is cultivated in cool regions such as Northern Europe. Recently, this vegetable has arisen out of claims that it is able to promote good health since no pesticides are used to cultivate chicory in the field, while the plant remains noticeably free from herbivore and microbial attack. The bitter substances, lactupicrin, 8-deoxylactucin and some phenolics had previously been shown to possess insect antifeedant properties in chicory (Rees and Harbome, 1985). Specifically, sesquiterpenoid lactones from chicory leaves, such as 8-deoxylactucin and lactupicrin (Figure 1), were identified as insect antifeedants against desert locust, Schistocerca gregaria. Similarly, we found some biologically active secondary metabolites in the... 

Concurrent with these biomethodological approaches to research has been the rapid advance of physicochemical methodology. These sophisticated techniques of detection have provided means for identifying and measuring infinitely small amounts of pesticides and other environmental toxicants and their metabolites, which may be involved in micro insults to cellular response in various species, including man. 

A9.5.2.3.9.4 If the BCF in terms of radiolabelled residues is documented to be > 1000, identification and quantification of degradation products, representing > 10% of total residues in fish tissues at steady-state, are for e.g. pesticides strongly reeommended in the OECD guideline No. 305 (1996). If no identifieation and quantifieation of metabolites are available, the assessment of bioeoneentration should be based on the measured radiolabelled BCF value. If, for highly bioaccumulative substanees (BCF > 500), only BCFs based on the parent compound and on radiolabelled measurements are available, the latter should thus be used in relation to classification. 

This overview will consider some of the advantages and limitations of using immunochemical techniques to identify and quantify environmentally important agents. A few illustrative examples will be taken from methods used to quantify nicotine and its metabolites. We are interested in nicotine because it is pharmacologically active and the agent responsible for addiction to tobacco products. Once, also, it was used widely as a pesticide. Its catabolism in mammals is complex some of the more common metabolites are shown in Figure 1 11,12). 

Fish have active Phase I and Phase II biotransformation pathways that can modify the disposition and toxicity of pesticides. Although more studies are characterizing in vivo metabolites of pesticides in fish, there is still a significant lack of knowledge about the ultimate fate of these compounds in the fish. In addition, very little is known about the specific enzymes responsible for the formation of specific metabolites of various pesticides. For example, although multiple CYP isoforms have been identified in fish, the substrate specificities with regard to pesticides are unknown and deserve further study. 

Gerhold et al. (9) developed research techniques to Identify the biochemical metabolite which conditioned resistance. They used the same plant materials that had been Included In Winner s genetic studies and Stark s research. All plants were grown from seed and were maintained without the use of pesticides. Included In their study was a resistant parent, a homozygous recessive susceptible parent, and their hybrid. In addition, they tested a susceptible parent which had one dominant locus for resistance. Basically their technique Involved the collection of exudate and subsequent analysis by gas- and high-performance-liquid chromatography, mass spectrometry, and nuclear magnetic resonance (NMR) spectroscopy. 

Furthermore as a result of industrial emissions the Teltow Canal sediments are highly polluted by the pesticides DDT and methoxychlor, accompanied by several metabolites (Schwarzbauer et al. 2001). Accordingly, numerous DDT-related compounds were identified in the hydrolysis extracts including DDE 6, DDMU 7, DDNU 8 and DDM 9. Highest concentrations were observed for DDA 10 and DBP IT, the more polar degradation products of DDT. 

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