Measure of exposure

FKI073 Relation between different measures of Exposure-Induced Shifts in Ductile-Srittle Transition temDeratures-Validalion of surveillance oractice mitiaation methods Dr E. G. Taylor Magnox Electric Pic... 

Elliot JW, Walker KC, Penick AE, et al. 1960. A sensitive procedure for urinary p-nitrophenol determination as a measure of exposure to parathion. J Agric Food Chem 8 111-113. 

Shafik TM, Sullivan HC, Enos HR. 1973b. Multiresidue procedure for halo- and nitrophenols. Measurement of exposure to biodegradable pesticides yielding these compounds as metabolites. J Agr Food Chem 21 295-297. 

Some biomarkers only provide a measure of exposure others also provide a measure of toxic effect. Biomarkers of the latter kind are of particular interest and importance and will be referred to as mechanistic biomarkers in the present text. Some mechanistic biomarker assays directly measure effects at the site of action as described in Section 2.4 (see Chapter 4, Table 4.2, for examples). Inhibition of acetylcholinesterase is one example. Others measure secondary effects on the operation of nerves or the endocrine system (examples given in Table 4.2 and Chapters 15 and 16). 

The use of the methods for monitoring metabolites of trichloroethylene in blood and urine is, however, rather limited since the levels of TCA in urine have been found to vary widely, even among individuals with equal exposure (Vesterberg and Astrand 1976). Moreover, exposure to other chlorinated hydrocarbons such as tetrachloroethane, tetrachloroethylene, and 1,1,1-trichloroethane would also be reflected in an increase in urinary excretion of TCA. In addition, there may be sex differences regarding the excretion of trichloroethylene metabolites in urine since one experiment shows that men secrete more trichloroethanol than women (Inoue et al. 1989). The use of the level of trichloroethylene adduction to blood proteins as a quantitative measure of exposure is also possible, although obtaining accurate results may be complicated by the fact that several metabolites of trichloroethylene may also form adducts (Stevens et al. 1992). 

Measurement of exposure can be made by determining levels of toxic chemicals in human serum or tissue if the chemicals of concern persist in tissue or if the exposure is recent. For most situations, neither of these conditions is met. As a result, most assessments of exposure depend primarily on chemical measurements in environmental media coupled with semi-quantitative assessments of environmental pathways. However, when measurements in human tissue are possible, valuable exposure information can be obtained, subject to the same limitations cited above for environmental measurement methodology. Interpretation of tissue concentration data is dependent on knowledge of the absorption, excretion, metabolism, and tissue specificity characteristics for the chemical under study. The toxic hazard posed by a particular chemical will depend critically upon the concentration achieved at particular target organ sites. This, in turn, depends upon rates of absorption, transport, and metabolic alteration. Metabolic alterations can involve either partial inactivation of toxic material or conversion to chemicals with increased or differing toxic properties. 

Field techniques for performing worker exposure/re-entry research direct measurement of exposure... 

A third enzyme may have limited potential as a measure of exposure. Neurotoxic esterase, also known as neuropathy target esterase (NTE), is inhibited by certain organophosphate esters. When brain NTE is inhibited above 70% for acute or possibly as low as 50% for repeated exposures, there is a consensus that delayed neuropathy is likely. NTE also is found in lymphocytes and platelets (Lotti et al. 1984). The... 

Excretion of hydrogen sulfide was documented after dermal exposure in rabbits. Trunk fiir of rabbits was clipped and left intact or abraded for exposure to hydrogen sulfide gas (unknown concentrations) for 1.5-2 hours the animals then breathed clean air (Laug and Draize 1942). Evidence for the excretion of hydrogen sulfide by the rabbits was a sulfide reaction of the expired air with lead acetate paper (Laug and Draize 1942). Sulfides in the expired air were noted in one rabbit with intact skin after 7 minutes of exposure. This study was limited by the lack of measurement of exposure concentrations and the small number of animals used. 

Renal function in workers exposed to lead has also been examined in relation to bone lead, since this measurement of exposure provides a better assessment of cumulative dose of lead to the kidneys than... 

Lifetime of peroxynitrite versus hydrogen peroxide. Peroxynitrite decomposes rapidly at physiological pH with a half-life of less than a second in phosphate buffer. In biological media, the half-life is even shorter. A better comparison is to use the area under each curve as a measure of exposure. 

No measurement of exposure to diethyl sulfate was available for the industrial processes investigated in the epidemiological studies. It is therefore difficult to assess the contribution of diethyl sulfate to the increased cancer risks. Furthennore, exposure to mists and vapours from strong inorganic acids, primarily sulfuric acid (see lARC, 1992b), may play a role in increasing these risks.]... 

The training program also includes a provision for timely feedback of new measurements of exposure levels, with additional control information where needed. 

If proper safeguards are to be maintained economically, it is essential to define the extent of the hazard and identify the problem areas. Research is needed to determine the sites and duration of exposure and to measure the amounts of residues and their rates of dissipation. Such measurements can be made with precision. The problem is to use knowledge gained in a particular situation to provide guidelines or models which can be applied more generally to field operations. Such extrapolations are controversial and they may also be dangerous if they are in error. The symposium includes descriptions of techniques for measurement of exposure, and some contributors indicate the controversial aspects of solutions that have been proposed. 

Durham, W. F. and Wolfe, H. R. Measurement of Exposure of Workers to Pesticides, Bull, of World Health Organization, 1962, 26, 75. 

Dow Study. In a review of direct and indirect measurements of exposure in applicators, Leng (3) reported an unpublished early study by Dow in which 2, t,5-T exposure was measured in eight field personnel and two observers. Direct measurements of exposure were based on analyses of air samples and of patches simulating skin exposure. Indirect measurements of actual dose received were based on analyses of blood samples and 2 i-hour urine collections from these individuals. 

The measurement of DNA adducts is an indirect indication of genotoxic (carcinogenic) potential, and DNA adducts in the urine are an indication, obtained by a noninvasive technique, of recent exposure. Protein adducts give an integrated measure of exposure because they accumulate over the life span of the protein and, at the same time, indicate possible organ toxicity. 

The last step in the problem formulation phase is the development of an analysis plan or proposal that identifies measures to evaluate each risk hypothesis and that describes the assessment design, data needs, assumptions, extrapolations, and specific methods for conducting the analysis. There are three categories of measures that can be selected. Measures of effect (also called measurement end points) are measures used to evaluate the response of the assessment end point when exposed to a stressor. Measures of exposure are measures of how exposure may be occurring, including how a stressor moves through the environment and how it may co-occur with the assessment end point. Measures of ecosystem and receptor characteristics include ecosystem characteristics that influence the behavior and location of assessment end points, the distribution of a stressor, and life history characteristics of the assessment end point that may affect exposure or response to the stressor. These diverse measures increase in importance as the complexity of the assessment increases. 

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