The Concept of Threshold

The early concept was that these were values which must not be exceeded in other words, they were truly maximum values. As the understanding of limits and the development of the philosophy for such limits grew, it was realized that short-term exposures to somewhat higher concentrations could be permitted without undue harm if the total exposure during the day was sufficiently below the maximum limit. This led to the development of the concept of Threshold Limit Values (TLV s) by the ACGIH. 

However, the Subcommittee on Ozone and Other Photochemical Oxidants did not discuss—and does not necessarily endorse—the adoption of fixed federal standards as the prime approach to pollution control. The subcommittee also did not attempt to determine the concentration at which the standard should be set, except to recognize the difficulty of arriving at such a number. There was, howeve/, general skepticism concerning the applicability of the concept of threshold concentration (the concentration below which there are no biologic effects). 

The concept of thresholds in toxicology and risk assessment has been discussed in an article by Slob (1999). According to Slob, a dose-threshold may be defined in different ways ... 

Rose et al. (1979) discuss the concept of threshold, the upper limit of normal background fluctuations. Values above background are considered anomalous. This approach is directly applicable to contamination studies since a contaminated soil is an anomalous soil. The simplest way of identifying threshold concentrations is by collecting samples from apparently uncontaminated areas (eg, those remote from urban or industrial influences). After analysis the geometric means and deviations are calculated. The threshold is then the value lying two or more standard deviations from... 

Especially in models of transient cerebral ischemia, apoptotic cell death has been observed after 3-7 days post insult in selected brain regions in which basal energy metabolism has been preserved (Chen et al. 1997 Du et al. 1996). In the meantime, molecular switches have been identified that gate different populations of neurons with regard to the type of cell death they eventually undergo (Nicotera 2003). However, there is little doubt that in animal stroke the vast majority of cells would die from necrosis or, alternatively, secondary energy failure even in the presence of a pro-apop-totic genetic balance. The concept of thresholds of cerebral blood flow (CBF) for various functions of brain parenchyma (see below) explains why the infarct core suffers from pan-necrosis whereas the peri-infarct border in which function is suppressed, but structure initially preserved (the so-called ischemic penumbra), may show apoptotic cell death or a combination of both. 

Brown, C.C. Mathematical aspects of dose response studies in carcinogenesis The concept of thresholds. Oncology, 1976,... 

For mixtures of components that are determined to act through a similar (common) mode of action, the likelihood of toxicity associated with a mixture is determined by adding the normalized doses of the components, where the concept of threshold is applied to the mixture rather than to the individual components as is done in response addition. The assumption for dose addition is that components are essentially toxicological clones of one another such that the relative proportions of each in a mixture are treated as dilutions of one another [1,4,5]. Toxicity data for the components must be sufficient to support their grouping according to a common mode or mechanism of toxicity. 

Toxicological databases and the concept of thresholds of toxicological concern as used by the JECFA for the safety evaluation of flavouring agents - A. G. Renwick - Toxicology Letters 149(1-... 

The concept of threshold is used to assess the toxicity of noncarcinogenic chemical substances. The dose-effect relationship is generally characterized by a threshold below... 

Horowitz, G. et al.. The concept of threshold voltage in organic field-effect transistors, Adv. Mater. 10, 923, 1998. 

The concept of thresholds , always applied in a given medium (water, dilute alcohol solution, white wine or red wine), is used to indicate the characteristics of various aromatic substances ... 

For nongenotoxic chemicals, risk assessment is based on the concept of threshold doses, below which no adverse effect results from exposure. From human or experimental animal data, one tries to establish the no observable adverse effect level (NOAEL) and the lowest observed adverse effect level (LOAEL). In order to establish safe levels of exposure to potentially toxic agents, the NOAEL is divided by a safety factor (often named uncertainty factor). When the risk assessment is based on data from experimental animals, a default safety factor of 100 is usually applied. The safety factor constitutes a factor of 10 for potential differences in susceptibility between animals and man, and another factor of 10 for interindividual differences among humans. The factors are combinations of differences in toxicokinetics and toxicodynamics, both in animals and man. If true factors are known, the size of the safety factor may be changed accordingly. When risk assessment is based on human data, a safety factor of 10 is applied in most cases, for instance, for food additives. However, for natural toxins in food, smaller factors are usually applied. This is a risk management decision, often based on information on the absence of adverse health effects at intake levels close to the estimated LOAELs. 

While thresholds are accepted for acute toxicity measmements, there is some controversy around the concept of thresholds for chronic toxicity measurements, especially for carcinogenicity detection. Many scientists believe there is no safe level for carcinogens but other scientists believe there are thresholds for carcinogens just as there are for acute effects. We will present below the complications in applying this threshold concept to chronic toxicants. Another phrase to describe this threshold is the No Observed Adverse Effect Level , or NOAEL. A closer examination of this simple concept reveals many underlying complexities. 

Discuss the concept of threshold in chemical toxicity. How is the no observed adverse effect level (NOAEL) determined What is the relationship of the NOAEL to the threshold of toxicity ... 

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