Environmental Neurotoxicology (1992) / Chapter Skim
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3. Biologic Markers in Neurotoxicology
3. Biologic Markers in Neurotoxicology
Pages 43-52
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From page 43... ...
Current interest in the biologic markers of the nervous system stems from a desire to identify the early stages of system impairment and damage and to understand the dynamics of exposure and the basic mechanisms of response to toxic exposure. There is growing interest in the use of biologic markers in clinical medicine, epidemiology, toxicology, and related biomedical fields to study the human necrologic effects of exposures to environmental toxicants (NRC, 1989a,b)
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From page 44... ...
Thus, the choice of a marker and its interpretation depend on the purpose of its use, and its intended use depends on characteristics peculiar to a particular exogenous agent, to an individual organism, or to a particular target organ or tissue (see Table 3-1~. If the goal is prevention, the major emphasis will be on monitoring markers that TABLE 3-1 Examples of Characteristics of Exogenous Agents, Organisms, or Targets That Influence Choice of Biologic Marker Agent-specific characteristics Physiochemical properties Interactions Routes of exposure Duration of exposure Exposure concentration Pattern of exposure Metabolism Activation Detoxification Organism-specific characteristics Species Age Sex Physiologic state Pharmacokinetic characteristics Genetic factors Lifestyle factors Organ- or tissue-specific characteristics Blood flow Membrane permeability Transport Receptors Function Homeostasis Structure Physiologic state Source: NRC (1989b)
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From page 45... ...
· — Am~nerg~c Norepinephrine Serotonin Dopamine Peptidergic Vasoactive intestinal peptide Substance P Enkephalin Cell biologic responses Second messengers Cyclic nucleotide Phosphorylation Calcium-dependent transmitter release Voltage-dependent NA+ or Ca2+ uptake toxic substance. Organisms might be particularly susceptible to a toxic substance for several reasons, including a genetic predisposition, existing disease, unique metabolic characteristics, or even the consequences of increased stress (see discussion on markers of susceptibility)
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From page 46... ...
Other environmental factors, such as temperature, can affect exposure by changing amounts of water consumption and thus of waterborne pollutants ingested. Diet alters intestinal motility and gastric emptying time, as well as the transport of specific substances across barriers in the gastrointestinal system.
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From page 47... ...
Metabolism critically affects biologically effective doses of many compounds; the tissue distribution of metabolizing enzymes is an important determinant of effective dose. Many nervous system toxicants act by interfering with neurotransmitter-receptor interactions.
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From page 48... ...
. An intrinsic characteristic or preexisting disease state that increases the internal dose or the biologically effective dose or that amplifies the effect at the target tissue can be a biologic marker of increased susceptibility (NIEHS, 1985; Omenn, 1986~.
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From page 49... ...
, then potential biologic markers for predicting eventual disease can be explored, and early indicators of the disease might be identified for use in human studies (e.g., peripheral neuropathy3. A major goal of research with biologic markers is to develop markers that reliably indicate an early stage in the development of a disease process in humans when effective intervention is still possible.
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From page 50... ...
Markers that indicate the delivery of an internal dose or a biologically effective dose or the induction of a disease process can be useful In hazard identification i.e., in the qualitative step by which an environmental agent is causally associated with an adverse effect. Biologic markers can also be used to determine dose-response relationships, especially at the low doses relevant to exposure to many environmental chemicals.
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From page 51... ...
It is important to note that, because of the metabolism and the pharmacodynamics of chemical toxicants, there is a continuing need for the development of better and more accurate markers of internal dose that can be used to estimate biologically effective doses. That refinement of dose-response modeling is fundamental to risk assessment.
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From page 52... ...
The ENVIRONMENTAL NEUROTOXICOLOGY role of biologic markers is to measure the steps of disease processes at as many different points as is feasible and to aid the development of means to stop and reverse the processes.
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