Indicators of exposure

The biological determinant is an indicator of exposure to the chemical, but the quantitative interpretation of the measurement is ambiguous. These determinants should be used as a screening test if a quantitative test is not practical or as a confirmatory test if the quantitative test is not specific and the origin of the determinant is in question. 

A recent method to screen the urine for alkyl phosphates as an indicator of exposure to organophosphate insecticides shows that the method can be used to determine environmental exposure to a specific organophosphate pesticide. The method was found to be sensitive, identifying low levels of exposure to insecticides in the environment by quantitation of urinary phosphates (Davies and Peterson 1997). The test is limited in that it is only useful for assessing recent exposure, due to the short half-life of the organophosphate pesticides. 

Fairbrother A, Bennett RS, Bennett JK. 1989. Sequential sampling of plasma cholinesterase in mallards (Anasplatyrh5Uichos) as an indicator of exposure to cholinesterase inhibitors. Environ Toxicol Chem 8 117-122. 

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Cf The biological determinant is an indicator of exposure to the chemical but the quantitative interpretation of the measurement is ambiguous. 

As with urine, saliva (spumm) is easy to collect. The levels of protein and lipids in saliva or spumm are low (compared to blood samples). These matrices are viscous, which is why extraction efficiency of xenobioties amoimts to only 5 to 9%. By acidifying the samples, extraction efficiencies are improved as the samples are clarified, and proteinaceous material and cellular debris are precipitated and removed. Some xenobioties and their metabohtes are expressed in hair. Hair is an ideal matrix for extraction of analytes to nonpolar phases, especially when the parent xenobioties are extensively metabolized and often nondetectable in other tissues (parent molecules of xenobioties are usually less polar than metabolites). Hair is a popular target for forensic purposes and to monitor drug compliance and abuse. Human milk may be an indicator of exposure of a newborn to compounds to which the mother has been previously exposed. The main components of human milk are water (88%), proteins (3%), lipids (3%), and carbohydrates in the form of lactose (6%). At present, increasing attention is devoted to the determination of xenobioties in breath. This matrix, however, contains only volatile substances, whose analysis is not related to PLC applications. 

Exposure. Few studies were found regarding the measurement of diisopropyl methylphosphonate or its metabolites as indicators of exposure. IMPA in urine or plasma has been suggested as a biomarker of acute exposure. It would be useful to more fully explore urinary excretion of IMPA to determine dose relationships and its utility as a bioindicator of diisopropyl methylphosphonate exposure. 

Kangas J, Savolainen H. 1987. Urinary thiosulphate as an indicator of exposure to hydrogen sulphide vapour. Clin Chim Acta 164(1) 7-10. 

Organophosphate insecticides also inhibit RBC-ACHE and PCHE. Inhibition of ACHE in erythrocytes is assumed to mirror inhibition of ACHE in the nervous system, which is the receptor of the toxic action, to some extent. Therefore, measurements of RBC-ACHE and PCHE are used for biological monitoring of exposure to OP insecticides (Maroni, 1986). Inhibitions of RBC-ACHE and PCHE activities are correlated with intensity and duration of exposure, although at different levels for each OP compound. Blood ACHE, being the same molecular target as that responsible for acute toxicity in the nervous system, is a true indicator of effect, while PCHE can only be used as an indicator of exposure. 

Even though all OP insecticides have a common mechanism of action, differences occur among individual compounds. OP insecticides can be grouped into direct and indirect ACHE inhibitors. Direct inhibitors are effective without any metabolic modification, while indirect inhibitors require biotransformation to be effective. Moreover, some OP pesticides inhibit ACHE more than PCHE, while others do the opposite. For example, malathion, diazinon, and dichlorvos are earlier inhibitors of PCHE than of ACHE. In these cases, PCHE is a more sensitive indicator of exposure, even though it is not correlated with symptoms or signs of toxicity. 

Pastorelli, R., Allevi, R., Romagnano, S., Meli, G., Fanelli, R., and Airoldi, R. (1995) Gas chromatography-mass spectrometry determination of ethylenthiourea hemoglobin adducts a possible indicator of exposure to ethylene-fczs-dithiocarbam-ate pesticides, Archives of Toxicology, 69(5) 306-311. 

The purpose of this chapter is not to discuss the merits, or lack thereof, of using plasma cholinesterase inhibition as an adverse effect in quantitative risk assessments for chlorpyrifos or other organophosphate pesticides. A number of regulatory agencies consider the inhibition of plasma cholinesterase to be an indicator of exposure, not of toxicity. The U.S. Environmental Protection Agency, at this point, continues to use this effect as the basis for calculating the reference doses for chlorpyrifos, and it is thus used here for assessing risks. 

In adults, a study of 75 autopsies of persons who had resided in a soft-water, leached soil region of North Carolina found a positive correlation between lead level in the aorta and death from heart-related disease (Voors et al. 1982). The association persisted after adjustment for the effect of age. A similar correlation was found between cadmium levels in the liver and death from heart-related disease. (Aortic lead and liver cadmium levels were considered to be suitable indices of exposure.) The effects of the two metals appeared to be additive. Potential confounding variables other than age were not included in the analysis. The investigators stated that fatty liver (indicative of alcohol consumption) and cigarette smoking did not account for the correlations between lead, cadmium and heart-disease death. 

A study of 137 lead-exposed workers found that of various indices of exposure, time integrated index of PbB was the best predictor of variation in serum P2 1 -globulin, serum -globulin, and urinary albumin... 

Concentrations of lead in blood, urine, serum, and cerebrospinal fluid have been used as indicators of exposure to lead. Measurement of lead in blood is the most common method of assessing exposure. 

Alessio L. 1988. Relationships between "chelatable lead" and the indicators of exposure and effect in current and past occupational life. Sci Total Environ 71 293-299. 

Dose- related increases in thiocyanate were observed, indicating that cyanide is liberated with the metabolism of acrylonitrile. In a study with human volunteers under controlled conditions, 2-cyanoethylmercapturic acid (CMA) was monitored in urine as an indication of exposure. On average, 22% of the absorbed acrylonitrile was metabolized to CMA however, considerable individual variability was observed. The CMA excretion ranged from 13% to 39% of the absorbed dose (Jakubowski et al. 1987). 

Studies using radioactivity-labeled acrylonitrile indicate that acrylonitrile or its metabolites form covalent adducts with cellular macromolecules in most tissues. Studies to develop chemical or immunological methods for measuring these adducts would be especially valuable in detecting and perhaps even quantifying human exposure to acrylonitrile. Adverse health effects demonstrated following exposure to acrylonitrile, particularly acute exposures, were characteristic of cyanide toxicity. Because these effects are also indicative of exposure to many other toxicants, additional methods are needed for more specific biomarkers of effects of acrylonitrile exposure. 

Blair, P.C., M.B.Thompson, R.E.Morrissey, M.P.Moorman, R.A.Sloane, and B.A. Fowler. 1990a. Comparative toxicity of arsine gas in B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters system organ studies and comparison of clinical indices of exposure. Fundam. Appl. Toxicol. 14 776-787. 

Varies according to the type of incapacitating agent. Care must be taken in that many signs and symptoms associated with exposure to incapacitating agents are also associated with anxiety or physical trauma. Potential indications of exposure include apprehension,... 

Anke, M., B. Groppel, E. Riedel, and H.J. Schneider. 1980a. Plant and animal tissues as indicators of exposure to nickel. Pages 65-68 in S.S. Brown andF.W. Sunderman, Jr. (eds.). Nickel Toxicology. Academic Press, NY. 

Holladay, S.D. and Luster, M.I. Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants, Environ. Health Perspect., 104 Suppl. 4, 809, 1996. 

Certain LMW agents will cause OA via a poorly defined mechanism. Only about 20% of workers with OA to toluene diisocyanate (TDI) have IgE detectable to TDI indicating that IgE antibody may be more an indicator of exposure rather than a mediator of the disease [10], Similar data exist for workers with asthma caused by plicatic acid from western red cedar [11], The inability to detect IgE antibody in the majority of these workers may be based in technical issues such as the nature of the chemical-protein... 

The concentration of chemical and/or metabolites in the blood (or plasma/serum) integrated over time. This is typically considered the best indicator of exposure. 

The method compares the predicted environmental concentrations (PECs), as indices of exposure, with predicted no effect concentrations (PNECs), as indices of... 

Exposure. Measurement of endrin and its metabolites can be useful indicators of exposure. Since endrin is cleared from the blood rapidly, such measurements are suitable only for recent exposures. Additional studies are needed to determine the usefulness of metabolites in urine as biomarkers of exposure in humans. A quantitative relationship between the urinary concentration of anti-12-hydroxyendrin and the dose of endrin should be clarified. 

Baldwin MK, Hutson DH. 1980. Analysis of human urine for a metabolite of endrin by chemical oxidation and gas-liquid chromatography as an indicator of exposure to endrin. Analyst 105 60-65. 

There are medical tests to determine whether you have been exposed to chlordecone and/or its breakdown product, chlordecone alcohol. Levels of chlordecone and/or chlordecone alcohol can be measured in blood, saliva, feces, or bile. Chlordecone levels in blood are the best indicator of exposure to chlordecone. Since chlordecone remains in the blood for a long time, the test is useful for a long time after exposure has stopped. Chlordecone can be detected in saliva only within the first 24 hours after exposure therefore, this test has limited use. Blood levels of chlordecone are a good reflection of total body content of chlordecone. However, the test is an unsatisfactory indicator of the amount of chlordecone to which you have been exposed because you cannot be sure how much chlordecone left your body between the time you were exposed and the time the test is performed. These tests cannot predict how your health may be affected after exposure. The tests are not done in routine medical examinations, but doctors can collect body fluid samples and send them to a university medical center or a medical laboratory for analysis. Refer to Chapters 2 and 6 for more information. 

Blood is a better indicator of exposure to chlordecone than is saliva (Borzelleca and Skalsky 1980 Skalsky et al. 1980). Chlordecone has been detected in saliva of humans only in trace amounts and in rats at concentrations three to four times lower than in blood (Guzelian et al. 1981 Skalsky et al. 1980). Peak chlordecone concentrations occurred within the first 24 hours of exposure therefore, the period of utility of saliva as a biomarker is limited. The movement of chlordecone from the blood into the saliva is one of passive diffusion and is not concentration dependent (Borzelleca and Skalsky 1980 Skalsky et al. 1980). Thus, blood is a better biological material than saliva for monitoring exposure. 

These can be measured and are reliable indicators of exposure to chlordecone. 

Oishi 1990) however, the data are very limited. More information on the accuracy, precision, and sensitivity of these methods is needed to evaluate the value of using the levels of di-ra-octylphthalate and its metabolites (particularly in urine) as indicators of exposure. The lack of data for these methods makes it difficult to assess whether these methods are sufficiently sensitive to measure levels at which health effects might occur, as well as background levels in the population. 

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