toxicity - pesticides, herbicides and insecticides - Blackherbals.com

Continued from page 86 – Natural Pesticides from Plantschemical modification can increase persistence.After promising biological activity is discovered,extraction of larger amounts of the compound for moreextensive bioassays can be considered. Also, analoguesof the compound should be made by chemicalalteration of the compound and/or chemical synthesis.Structural manipulation could lead to improvement ofactivity, toxicological properties, altered environmentaleffects, or discovery of an active compound that can beeconomically synthesized. This has been the case withseveral natural compounds that have been used as atemplate for commercial pesticides (e.g., pyrethroids).Before a decision is made to produce a naturalpesticide for commercial use, the most cost-effectivemeans of production must be found. Although this is acrucial question in considering the development of anypesticide, it is even more complex and critical withnatural products. Historically, preparations of crudenatural product mixtures have been used as pesticides.However, the potential problems in clearing a complexmixture of many biologically active compounds for useby the public may be prohibitive in today's regulatoryclimate. Thus, the question that will most probably beconsidered is whether the pure compound will beproduced by biosynthesis and purification or bytraditional chemical synthesis.Before considering any other factors, there are twoadvantages to the pesticide industry to industrialsynthesis. They have invested heavily in personnel andfacilities for this approach. Changing this approachmay be difficult for personnel trained in disciplinesgeared to use it. Secondly, in addition to the patent foruse, patents for chemical synthesis often further protectthe investment that a company makes in developmentof a pesticide.However, many natural products are so complex thatthe cost of chemical synthesis would be prohibitive.Even so, more economically synthesized analogueswith adequate or even superior biological activity maytip the balance toward industrial synthesis. If notbiosynthesis must be considered. There are a growingnumber of biosynthetic options.The simplest method is to extract the compound fromfield-grown plants. To optimize production, the speciesand the variety of that species that produce the highestlevels of the compound must be selected and grownunder conditions that will optimize their biosyntheticcapacity to produce the compound. Geneticallymanipulating the producing plants by classical orbiotechnological methods could also increase productionof some secondary products. For instance, low doses ofdiphenyl ether herbicides can cause massive increases inphytoalexins in a variety of crop species.Another alternative is to produce the compound in tissue orcell culture. With these methods, cell lines that producehigher levels of the compound can be rapidly selected.However, genetic stability of such traits has been aproblem in cell culture production of secondary products.Cells that produce and accumulate massive amounts ofpossibly autotoxic secondary compounds are obviously at ametabolic disadvantage and are thus selected against undermany cell or tissue culture conditions. A technique, such asan immobilized cell column that continuously removessecondary products can increase production by decreasingfeedback inhibition of synthesis, reducing autotoxicity, andpossibly increasing generic stability. Other culture methodsthat optimize production can also be utilized. For instance,supplying inexpensively synthesized metabolic precursorscan greatly enhance biosynthesis of many secondaryproducts. Also, plant growth regulators, elicitors, andmetabolic blockers can be used to increase production.Genetic engineering and biotechnology may allow for theproduction of plant-derived secondary products by genetransfer to microorganisms and production byfermentation. This concept is attractive because of theexisting fermentation technology for production ofsecondary products. However, it may be prohibitivelydifficult for complex secondary products in which severalgenes control the conversion of several complexintermediates to the desired product.Genetic engineering might also be used to insert thegenetic information for production of plant-producedpesticides from one plant species to another species to beprotected from pests. However, such transgenicmanipulation of the complex metabolism of a higher plantmight be extremely difficult. A simpler alternative mightbe to infect plant-colonizing microbes with the desiredgenetic machinery to produce the natural pesticide, as hasbeen done with bacterial-produced insecticides.THE FUTUREPlants contain a virtually untapped reservoir of pesticidesthat can be used directly or as templates for syntheticpesticides. Numerous factors have increased the interest ofthe pesticide industry and the pesticide market in thissource of natural products as pesticides. These includediminishing returns with traditional pesticide discoverymethods, increased environmental and toxicologicalconcerns with synthetic pesticides, and the high level ofreliance of modern agriculture on pesticides. Despite theContinnued on page 8887-- Traditional African Clinic July 2013