Threshold effects, definition

The adverse reproductive effects are considered as being threshold effects, i.e., effects for which there are expected to be a threshold of substance concentration below which the effects will not be manifested. For the hazard and risk assessment, it is important to identify those dose levels at which adverse reproductive effects are observed, and the dose level at which adverse reproductive effects are not observed, i.e., to derive a NOAEL for reproductive toxicity. Crucial in the derivation of the NOAEL and/or LOAEL, is the definition of adverse effects (Section 4.2.2). In the derivation of the NOAEL and/or LOAEL, a number of factors need to be considered these issues are addressed in detail in Sections 4.2.3 and 4.2.4. An alternative approach to the derivation of the... 

It is well established that mitochondrial function defects are not severe until the proportion of mutant mtDNA reaches a high level, which forms the basis of the concept of the threshold effect. In skeletal muscle, the level of the A3243G mutation is related to the severity of strokelike episodes, epilepsy, and dementia in patients with MELAS syndrome (C6, H14, PI). Similarly, the level of the A8344G mutation is correlated with the degree of cerebellar ataxia and myoclonus in patients with MERRF syndrome (C6). Thus, molecular genetic analysis of mtDNA mutations in muscle biopsies usually provides more definitive diagnosis of... 

The results are shown in Fig. 3.5. According to Fig. 3.5b, mechanochemical yield per unit of consumed energy appeared to be a constant only starting from some threshold power per 1 g of the mixture under treatment. This threshold is about 5 W/g. The existence of threshold effect in solids is connected with fragile-viscous transition the latter occurs only when a definite level of energy input to a solid is exceeded. 

It is of interest to gauge performance of additives against the Ryznar Index for the water. Fig. 14.7 shows the effect of the threshold additive acetodiphosphonic acid and the crystal modifier polymaleic acid at different Ryznar indices. As would be expected from the definition of the Ryznar Index, the scaling is increased as the index is reduced when there is no additive present. In the presence of the threshold agent the rate of scaling is also reduced but below a Ryznar Index of about 4.5, the threshold effect is exceeded and the scaling rate rapidly rises. 

As outlined in Section III.A, knowledge of the molecular wavefunction implies knowledge of the electron distribution. By setting a threshold value for this function, the molecular boundaries can be established, and the path is open to a definition of molecular shape. A quicker, but quite effective, approach to this entity is taken by assuming that each atom in a molecule contributes an electron sphere, and that the overall shape of a molecular object results from interpenetration of these spheres. The necessary radii can be obtained by working backwards from the results of MO calculations21, or from some kind of empirical fitting22. 

Endpoint/Concentration/Rationale Because the exposures did not result in effects consistent with the definition of an AEGL-3, the concentration vs percent hemoglobin formation data presented by the authors was graphed and projected to a methemoglobin level of 70-80%, which was considered the threshold for lethality in humans. This value was approximately 250 ppm. An 8-h exposure to 250 ppm was chosen as the basis for the AEGL-3 calculations. 

The most notable data deficiency is the absence of a well-defined exposure response relationship for monomethylhydrazine toxicity related to AEGL-2 effects. This deficiency precluded a definitive determination of the thresholds... 

Critical research needs include definition of thresholds for adverse health effects and how these thresholds vary with exposure concentration and duration. Such data would be valuable for affirming AEGL values. Additionally, the mode of dimethylhydrazine toxicity is not fully understood and, therefore, research providing insight into the underlying mechanism(s) of dimethylhydrazine toxicity would reduce current uncertainties in quantitative health risk issues. 

The AEGL-1 values were based on concentrations at 0.5 ppm and 0.1 ppm, which were the thresholds for mild headaches in healthy individuals at exposure durations of 1 and 6 h, respectively (Stewart et al. 1974). This effect can be considered the threshold for mild discomfort (only one subject was affected at each exposure), which falls within the definition of an AEGL-1. The 0.5-ppm concentration was used to derive the 30-min and 1-h AEGL-1 values, and the 0.1-ppm concentration was used for the 4- and 8-h values. Because the time and concentration values were based on the most susceptible subject, these concentrations were adjusted by an uncertainty factor (UF) of 3 to account for potential differences in human sensitivity and scaled to the appropriate time periods using the C xt=k relationship. A UF of 3 was considered sufficient as no susceptible populations were identified (the headache effect is the same as that experienced by patients medicated with nitro... 

Risk assessment of chemicals does not, in practice, estimate the incidence and severity of the adverse effects likely to occur in the human population or environmental compartment due to actual or predicted exposure to a substance — the definition of risk characterization in Article 2 of Directive 93/67/EEC. The assessment process hinges on being able to say that there is a threshold below which the chemical has no adverse effects, in other words on being able to derive a no-effect level. Recent debates, discussed later, challenge the idea that there normally is such a threshold. 

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