Minimum-observed-adverse-effect-level

Feron et al., studied the effects of mixtures administered at the no observed adverse effect level (NOAEL) and the minimum observed adverse effect level (MOAEL). Evidence of an increased hazard was found when combinations of chemicals were administered at the NOAEL of each of the components, despite the fact that exposures to the individual chemicals had no adverse effects. When mixtures were administered at the MOAEL levels of the individual components, some severe adverse effects were noted. 18 ... 

MOEL Minimum observed effect level. This is the lowest concentration at which adverse effects are note. This level is often presented as minimum observed adverse effect level (MOAEL)... 

In the effects assessment step the relationship between the level of exposure and the incidence, nature, and severity of an (adverse) effect following the exposure is determined. For most types of effects, it is assumed that there is a minimum dose or concentration below which adverse effects will not occur the no effect level or threshold. To determine the threshold, different doses are tested, for most chemical hazards usually in laboratory animals. In toxicology, the highest tested dose without adverse effects is called the no observed adverse effect level (NOAEL). Based on the NOAEL established in an experimental study, a human limit value can be calculated, taking into account uncertainties and differences in experimental design and circumstances. Uncertainties and differences are accounted for by uncertainty factors (e.g., for interspecies differences, intraspecies variability, and exposure duration). For some types of substances, it is assumed that every level of exposure can result in adverse effects, in which case no threshold would exist. This, for instance, is assumed to apply for genotoxic carcinogens. 

Fig. 3.21 The safe dose range of vitamins is found at the minimum of this curve. Doses smaller than the RDA involve a risk of deficiency, whereas does larger than the NOAEL (no observed adverse effect level) may result in side effects or toxic symptoms. (Authors own work)...

Endocrine In patients receiving the minimum dose of amiodarone, thyroid abnormalities were observed at a rate between 14% and 18%. The effects on the thyroid gland are variable. Amiodarone may cause abnormal thyroid function detected only by laboratory test as well as clinically manifested thyroid dysfunction. The mechanism of this adverse effect is complex. Amiodarone inhibits the action of deiodinase and decreases peripheral conversion of thyroid hormones. Moreover, it decreases their renal elimination and inhibits their entry to peripheral tissues. The level of T4 increases by 40% within 1-4 months of amiodarone therapy. The deiodinase activity inhibition can be noticed after 3 months of treatment. It leads to an increase in the level of thyroid stimulating hormones. Amiodarone and its metabolite have a direct cytotoxic effect on thyroid follicular cells, which results in destructive thyroiditis. Amiodarone-induced thyroid damage can lead either to hypo- or hyperthyroidism. The latter can be of two types. Type 1 usually occurs in patients with prior thyroid damage. In this type, iodine excess causes excessive synthesis of thyroid hormones whereas in type 2 the inflammatory process is followed by destruction. A destructive thyroiditis leads to the release of hormones from damaged thyroid follicular cells. This mechanism occurs in patients with no history of thyroid disorders [15]. 

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