Whole Organism Effects

Commercialized bisacylhydrazine insecticides manifest their toxicity to susceptible insects almost exclusively via ingestion, and have very low contact toxicity only when used at ten-fold higher doses than required for oral toxicity. The effects of bisacylhydrazines have been studied in several susceptible insects belonging to 

2 Basis for Selective Insect Toxicity of Bisacy I hydrazine Insecticides 

However, the data to date indicate that lepidopteran ecdysone receptor affinities for methoxyfenozide and chromafenozide are most likely the primary drivers for their selective toxicity for lepidopteran larvae. 

While the very high affinities of tebufenozide, methoxyfenozide and chromafenozide for lepidopteran ecdysone receptors help explain the basis for their selective lepidopteran toxicity, the same does not apply to the fourth BAH insecticide, halofenozide, which is toxic to both lepidopteran and coleopteran larvae. Halofe-nozide has significantly reduced affinity for ecdysone receptors from the two insect orders. It seems that the relatively weak affinity of halofenozide to the ecdysone receptor of the target susceptible insect may be compensated by its increased metabolic stability in the same insect. 

The reader is referred to more in-depth reviews and specific bibliography on the BAH insecticides by Dhadialla et al. [4, 5]. A brief and important description of the spectrum of activity of the four insecticides is given below. 

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Smit, M.G.D., Bechmann, R.K., Hendriks, A.J., Skadsheim, A., Larsen, B.K., Baussant, T, Bamber, S. and Sanni, S. (2009). Relating biomarkers to whole organism effects using species sensitivity distributions a pilot study for marine species exposed to oil. Environmental Toxicology and Chemistry, Vol. 28, No. 5, pp. 1104-1109. 

Zinc deficiency effects have been produced experimentally in freshwater sponges at <0.65 pg Zn/L (Francis and Harrison 1988), in rainbow trout fed diets containing <15 mg Zn/kg FW (Spry et al. 1988), in certain species of marine algae at <0.7 pg Zn/L (Vymazal 1986), and in certain species of marine invertebrates at <6.5 pg Zn/L (Clapper et al. 1985a, 1985b) or <34 mg Zn/kg DW whole organism (White and Rainbow 1985). Zinc deficiency in natural aquatic ecosystems has not yet been credibly documented. 

In view of these complexities, environmental studies that seek to verify proposed cause-effect relationships between contamination and response need to be carefully designed to avoid bias and misunderstanding. Most environmental assessments adopt a multi-tiered approach to testing, in which combinations of biological responses (biomarkers) are measured in tissue samples, body fluids or at the whole organism level to indicate exposure to or adverse effects of contamination.8. Auffret and colleagues60 surveyed Pacific oysters from the Atlantic coast of Brittany after the Erika oil spill between... 

The results of in vitro exposures to different classes of chemicals can be useful when assessing the direct effects of chemicals on certain immunological endpoints, differences in susceptibility among species (at the cellular level), and differences in susceptibility within a species but between different immune functions. However, such an approach on its own cannot take into account such factors at the whole-organism level including exposure, absorption, metabolism and excretion, the built-in redundancy of the immune system, as well as host resistance. 

Objectives Optimize biological activity of drugs Find new active lead compounds Characteristics Response in isolated systems Effects are specific and well defined Specific mechanism of action Receptor is known in most cases Techniques Hansch Approach Multivariate Analysis Computerized molecular modeling Estimate rates of fate processes Analyze Processes Whole organism response Net effects (mortality growth, etc.) Specific nonspecific mechanisms Receptor unknown in most cases Hansch Approach Multivariate Analysis Molecular modeling not applied... 

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