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Defining Biomarkers天秤女和水瓶男
Biomarkers are measurable substances or characteristics in the hum an body that can be ud to m onitor the prence of a chemical in the body, biological respons, or adver health effects. The u of biom arkers will help us evaluate potential exposures to pesticides as well as predict effects that m ay result, allowing us to make decisions that are m ore protective of hum an health. Biomarkers are commonly grouped into biomarkers of exposure, effect, and susceptibility. This Web page describes the groups of biomarkers and provides examples.
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Biomarkers of Exposure
Biomarkers of exposure are ud to asss the amount of a chemical that is prent within the body. Many chemicals can be m easured in urine, blood, saliva, and, if they are fat soluble, in body fat and breast m ilk (e.g., DDT). Biomarkers of exposure provide information on
∙chemical exposures in individua ls,
∙changes in levels over tim e, and
∙variability am ong different populations.
They m ay also provide information on the relative importance of different exposure pathways and associated risk. It is important to note that the m easurement of a chemical in som eone’s body does not by itlf m ean that chemical has caud adver health effects.
Additionally, there are a number of us related to the interpretation of biomarkers of exposure. For example, the m easurement of 3-phenoxybenzioc acid (3-PBA) in urine is considered a non-specific biom arker of exposure becau 3-PBA is a common m etabolite of veral pyrethroid pesticides. Therefore, additional information is needed to resolve which pyrethroid was the parent chemical.
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Biomarkers of Exposure Categories
∙Chemical–The m ost specific exposure biomarker is direct m easurement of the chem ical of interest in the body. Typically, m easurement of the
chemical is made in an accessible biological matrix (e.g., blood, urine).
While some pesticides can be directly m easured in the body, it is generally
more common to m easure m etabolites of pesticides.
∙Metabolite– Many chem icals are rapidly m etabolized or difficult to m easure.
In the cas, a m ore stable breakdown product (m etabolite) of the
chemical m ay be m easured to estim ate exposure to the chemical. When a
metabolite m ay derive from a number of different chem icals (as in the
3-PBA example above), additional information is needed to resolve to
which chemical the person was expod.
∙Endogenous surrogate– In som e cas, a chemical or class of chem icals may result in an endogenous respon (respon within the body) that is
highly characteristic of that chemical or class. Measures of that respon
资助育人can be ud as a surrogate in lieu of direct m easurement of the chemical or
metabolite concentration when sufficient additional information is available.
Since there are m any factors that can influence endogenous respons,
this type of exposure biomarker is accom panied by m any uncertainties that
should be identified and discusd.
See examples in Table 1
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Biomarkers of Effect
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Biomarkers of effect are indicators of a change in biologic function in respon to a chemical exposure 1. Thus, they m ore directly relate to insight into the potential for adver health effects com pared with biomarkers of exposure.
One example of a biomarker of effect is blood cholinestera, which can becom e depresd following exposure to organophosphate and N-m ethyl carbamate pesticides. Measuring cholinestera levels can be a uful tool for m onitoring
agricultural workers and identifying workers that m ay potentially be overexpod to pesticides.
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Biomarkers of Effect Categories
∙Bioindicator– An ideal biomarker of effect has an explicitly known mechanism that links the marker and an adver outcom e. In most cas,
this is achieved by a sufficient understanding of the adver outcom e
pathway or m ode of action of the chemical, and the causal or correlative
relationship of biological events between the m arker and the adver
outcom e.
Bioindicators provide a high degree of confidence in predicting the
potential for adver effects in an individual or population bad on marker
levels. An understanding of the adver outcom e pathway also supports
development of a variety of bioindicators for different key events or
outcom es of interest (e.g., m arkers for precursor event s leading to a
clinically detectable adver outcom e to support early detection and
prevention).
When cellular or molecular initiating events can be identified as critical
steps in an adver outcom e pathway, bioindicators can be developed in
conjunction with high throughput screening assays to provide a rapid and
efficient m eans for early detection of adver outcom es in target
population. EPA rearchers are actively developing this class of
biomarkers of effects in support of Toxicity Testing in the 21st Century.
∙Undetermined conquence– This subgroup of biomarkers provides more limited and uncertain indication of the potential for adver effects,荷花五角
becau the events or deterministic linkages in an adver outcom e
pathway are less well known. An example would be markers of oxidative
stress where elevations have been associated with a variety of adver
outcom es, but the explicit relationships have yet to be defined. As the role
of oxidative stress in different dia process (and adver outcom e
pathways) becom es more clearly defined, there will be increasing certainty
in the u of oxidative stress biomarkers to predict the potential for
organism/population-level effects. Meanwhile, the biomarkers can be
ud in conjunction with other biomarkers in this or other subgroups to
improve the specificity and nsitivity of the overall t of m arkers for
development of an adver outcom e.
∙Exogenous surrogate– Som e chemicals have well known adver effects, which are accompanied by other effects that can be ud as surrogate
c0000005异常代码indicators of the m ain adver effect of interest. A common example is
paranitrophenol , a m etabolite of m ethyl parathion. Measurement in
humans of paranitrophenol in the urine has been ud as an exogenous
手机imei查询surrogate biomarker of exposure to m ethyl parathion, and as an indicator
of the potential for toxicity due to m ethyl parathion-induced
acetylcholinestera inhibition.
Exogenous surrogate biomarkers are suboptimal as effects m arkers
becau they do not directly capture the contribution of additional factors
(intrinsic and extrinsic) that m ay influence the incidence or verity of an
adver outcom e. Given the limitations, u of exogenous surrogates as
biomarkers is mostly limited to m easurement of tho effects that are
predominantly due to the chemical of interest (i.e., to reduce the num ber
of potentially confounding effects, and to decrea uncertainty associated
with the m easured surrogate biomarker).
See examples in Table 2
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Biomarkers of Susceptibility
Biomarkers of susceptibility are factors that m ay make certain individuals more nsitive to chem ical exposure. Biomarkers of susceptibility include:
∙genetic factors that m ay influence how the body interacts with a chemical ∙other biological factors related to nutritional status, health status, lifestyle, and life stage that m ay affect an individual’s susceptibility to chemical
exposure.
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Table 1: Examples of Biomarkers of Exposure from Different Categories
Table 2: Examples of Biomarkers of Effects from Different Categories
