Dose-Time Relationship

The most important factor is the dose-time relationship. The amount of a substance that enters or contacts a person is called a dose. An important consideration in evaluating a dose is body weight. Dose is the quantity of a chemical substance that a surface, plant, or animal is exposed to. Time means how often one is exposed to or the duration of exposure to a chemical substance. In simple terms, the dose-time relationship provides information on how much of the test substance is involved and how often the exposure to the test substance occurs. This relationship gives rise to two different types of toxicity of a chemical substance—namely, acute toxicity and chronic toxicity. 

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Have mixed-function oxidase degradation rates that are significantly modified by sex, age, diet, water temperature, dose-time relationships, and other variables. 

Several factors effecting the metabolic index have been examined. Dose-time relationships have been investigated in... 

Effects of Toxic Extracts. We have shown that the crude ESAP of 6. toxicus had an LD n of 4.96 mg/kg mouse. Recently, Tachibana T yiJtTTTzed a dose time relationship to estimate the LD50 of... 

The most important factor is the dose-time relationship. The dose-time relationship forms the basis for distinguishing between two types of toxicity acute and chronic. Acute toxicity of a chemical refers to its ability to inflict systemic damage as a result (in most cases) of a one-time exposure to relative large amounts of the chemical. In most cases, the exposure is sudden and results in an emergency situation. 

Organophosphates illustrate several points. First, repeated exposure can be a problem not only because of accumulation of the substance (as can occur with other substances such as aspirin) but also because of accumulation of the effect, if it is irreversible. Therefore the dose-time relationship is important as weU as the dose-response relationship. Secondly, understanding the mechanism allows effective detection and treatment thirdly, other factors such as decomposition and exposure to other chemicals can have a large impact on toxicity and finally the dose is crucial, and it would seem, at least from the information available at present, that OPs can be used safely if they are used sparingly and carefully. 

This entry presents a discussion of the principles of respiratory toxicology including (1) an historical perspective, (2) approaches used to evaluate respiratory responses to inhaled chemicals, (3) classification of airborne chemicals, (4) concepts of dose-time relationships, (5) factors influencing toxicity of airborne substances, (6) the basic biology of the respiratory system with emphasis on those structures and functions that are involved in toxicological responses, (7) biomarkers of pulmonary effects, (8) toxicological response associated with inhaled chemicals, and (9) assessing the human risk of airborne chemicals. 

The physical state of a pollutant is obviously important a particulate coUector cannot remove vapor. Pollutant concentration and carrier gas quantity ate necessary to estimate coUector si2e and requited efficiency and knowledge of a poUutant s chemistry may suggest alternative approaches to treatment. Emission standards may set coUection efficiency, but specific regulations do not exist for many trace emissions. In such cases emission targets must be set by dose—exposure time relationships obtained from effects on vegetation, animals, and humans. With such information, a Ust of possible treatment methods can be made (see Table 1). 

Natural and synthetic chemicals affect every phase of our daily Hves ia both good and noxious manners. The noxious effects of certain substances have been appreciated siace the time of the ancient Greeks. However, it was not until the sixteenth century that certain principles of toxicology became formulated as a result of the thoughts of Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus (1493—1541). Among a variety of other achievements, he embodied the basis for contemporary appreciation of dose—response relationships ia his often paraphrased dictum "Only the dose makes a poison."... 

A potential pitfall with stop-time experiments comes with temporal instability of responses. When a steady-state sustained response is observed with time, then a linear portion of the production of reporter can be found (see Figure 5.15b). However, if there is desensitization or any other process that makes the temporal responsiveness of the system change the area under the curve will not assume the linear character seen with sustained equilibrium reactions. For example, Figure 5.16 shows a case where the production of cyclic AMP with time is transient. Under these circumstances, the area under the curve does not assume linearity. Moreover, if the desensitization is linked to the strength of signal (i.e., becomes more prominent at higher stimulations) the dose-response relationship may be lost. Figure 5.16 shows a stop-time reaction dose-response curve to a temporally stable system and a temporally unstable system where the desensitization is linked to the... 

Drug elimination may not be first order at high doses due to saturation of the capacity of the elimination processes. When this occurs, a reduction in the slope of the elimination curve is observed since elimination is governed by the relationship Vmax/(Km- -[conc]), where Vmax is the maximal rate of elimination, Km is the concentration at which the process runs at half maximal speed, and [cone] is the concentration of the drug. However, once the concentration falls below saturating levels first-order kinetics prevail. Once the saturating levels of drugs fall to ones eliminated via first-order kinetics, the half time can be measured from the linear portion of the In pt versus time relationship. Most elimination processes can be estimated by a one compartment model. This compartment can... 

A retrospective case-control study conducted in humans compared spontaneous abortion rates among women who had been exposed occupationally or nonoccupationally to trichloroethylene and other solvents to rates among women without solvent exposure (Windham et al. 1991). The authors observed approximately three times the risk of spontaneous abortion with exposure to trichloroethylene. This risk increased further when women with less than a half hour of exposure to trichloroethylene each week were excluded from the analysis. However, a consistent dose-response relationship was not observed, and most of the women were exposed to a variety of solvents, not just trichloroethylene. 

As has been emphasized so many times in the preceding chapters, these various manifestations of toxicity all display dose-response characteristics, where by response we refer to the incidence or severity of specific adverse health effects. As we demonstrated in earlier chapters, toxic responses increase in incidence, in severity, and sometimes in both, as dose increases. Moreover, just below the range of doses over which adverse effects can be observed, there is usually evidence for a threshold dose, what we have called the no-observed adverse effect level (NOAEL). The threshold dose must be exceeded before adverse effects become observable (Chapter 3). Deriving from the literature on toxic hazards, descriptions of the dose-response relationships for those hazards comprise the dose-response assessment step of the four-step process. 

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