Factors affecting toxicity thresholds

Occlusion of the skin, seen with application of water-impermeable drug vehicles or patches, alters the rate and extent of toxicant absorption. As the skin hydrates, a threshold is reached where transdermal flux dramatically increases (approximately 80% relative humidity). When the skin becomes fully hydrated under occlusive conditions, flux can be dramatically increased. This occlusive effect must be accounted for when extrapolating toxicology studies conducted under occlusive conditions to field scenarios where the ambient environmental conditions are present. Hydration may also markedly affect the pH of the skin, which varies between 4.2 and 7.3. Therefore, dose alone is often not a sufficient metric to describe topical doses when the method of application and surface area become controlling factors. Dose must be expressed as mg/cm2 of exposed skin. 

Terrestrial wildlife movements are such that site-specific tools are more efficiently used to refine exposure estimate. In this case, site-specific exposure estimates are used and compared with safe thresholds for toxicity, termed toxicity reference values (TRVs). Toxicity reference values for wildlife have been developed for energetic compounds. This chapter presents a brief overview of the processes used to establish these tools for ERA for explosives and related soil contaminants that are frequently of potential ecological concern at the affected military sites. This chapter also provides recommendations for use of these values in the ERA process. Investigations addressing the importance and extent of habitat disturbance as a component of the ERA process on explosives-contaminated ranges are reviewed in Chapter 11. General bioaccumulation principles and applications of the bioaccumulation factor and bioconcentration factor (BAF and BCF, respectively) concepts that are often employed in the ERA process to determine bioaccumulation potential of MC for terrestrial receptors are reviewed in Chapter 10. 

Thresholds exist for when and how insects respond to these chemical actions. These thresholds are governed by intrinsic factors related to the mode of action of the chemical and the insects susceptibility, as well as by extrinsic factors that modify those effects. Among the extrinsic factors, the physical environment, humidity, air movement, and temperature can affect the volatility of the active ingredient. The dose-dependent order in which thresholds are exceeded determines whether the primary mode of chemical action is repellent, irritant, or toxicant. Some pyrethroids can produce excitorepellency with possible mortality as a result of the exposure. Other pyrethroids with sufficiently high vapor phase concentration, for example, metofluthrin and transfluthrin, can result in a spatial repellent (barrier) effect regardless of knockdown and mortality of insects. 

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