Exposure dose, calculation

Assessments of risks associated with the use of chlorpyrifos insecticide products for workers have been made. The assessments are based on the results of field studies conducted in citrus groves, a Christmas tree farm, cauliflower and tomato fields, and greenhouses that utilized both passive dosimetry and biomonitoring techniques to determine exposure. The biomonitoring results likely provide the best estimate of absorbed dose of chlorpyrifos, and these have been compared to the acute and chronic no observed effect levels (NOELs) for chlorpyrifos. Standard margin-of-exposure (MOE) calculations using the geometric mean of the data are performed however, probability (Student s f-test) and distributional (Monte Carlo simulation) analyses are deemed to provide more realistic evaluations of exposure and risk to the exposed population. 

The internal dose of propoxur was measured by assessing the total amount of 2-isopropoxyphenol (IPP) excreted in the urine, collected over a period of 24 hr from the start of exposure, and described in detail in previous studies (Brouwer et al., 1993 Meuling et al., 1991). Volunteer kinetics studies revealed a one-to-one relationship of absorbed propoxur and excreted IPP on a mole basis. Based on the results by Machemer et al. (1982), a pulmonary retention of 40% was used to calculate the relative contribution of the respiratory exposure to the internal exposure. To estimate the contribution of the dermal exposure, the calculated respiratory portion was subtracted from the total amount of IPP excreted in urine. 

More traditional approaches have calculated exposure doses from a particular medium via a specific route (ATSDR, 1992). Such exposure doses can then be compared with a reference value derived for the same substance via the same route of exposure. Usual assumptions are ingestion rates of 100 mg dust/day and 200 mg soil/day, child body weight of 15 kg, and continuous exposure scenarios. This approach assumes a threshold for the effects of lead and does not reflect the fullest possible use of the wealth of human data on PbB levels. 

The specific values of the physical and biological characteristics such as breathing patterns for occupational exposure and active and resting patterns for environmental exposure are given in the footnotes to the Tables. A few remarks should be made concerning the parameters used which affect the dose calculation significantly. 

A third possibility consists of comparing the theoretically calculated lung cancer rate based on risk coefficients derived from miners with the actual cancer occurrence among non-miners, derived from Rn-d exposure assessment in dwellings and using appropriate exposure-dose conversion factors (Steinhausler et al.. 1983 ... 

The chronic-duration oral MRL for disulfoton is 6xlo5 mg/kg/day, and the EPA chronic oral RfD) is 4x10" mg/kg/day (IRIS 1994). Both of these values are based on the same study (Hayes 1985) and the identical end point. Even though the MRL and the RfD are essentially the same, they have minor differences due to the manner in which the exposure doses were calculated. The LOAEL of 0.04... 

Mathematical modelling of the dose-response relationship is an alternative approach to quantify the estimated response within the experimental range. This approach can be used to determine the BMD or benchmark concentration (BMC) for inhalation exposure, which can be used in place of the LOAEL or NOAEL (Crump, 1984). The BMD (used here for either BMD or BMC) is defined as the lower confidence limit on a dose that produces a particular level of response (e.g., 1%, 5%, 10%) and has several advantages over the LOAEL or NOAEL (Kimmel Gaylor, 1988 Kimmel, 1990 USEPA, 1995 IPCS, 1999). For example, (1) the BMD approach uses all of the data in fitting a model instead of only data indicating the LOAEL or NOAEL (2) by fitting all of the data, the BMD approach takes into account the slope of the dose-response curve (3) the BMD takes into account variability in the data and (4) the BMD is not limited to one experimental dose. Calculation and use of the BMD approach are described in a US EPA... 

The use of a 0.22 micron Millipore filter in preliminary studies resulted in lowered mercury breakthrough on day 1 of use and probably on day 4 as well. With the use of filters, breakthrough levels smaller than 0.6 yCi/mCi were obtained during the 3 days of generator use. These levels result in a significantly lower radiation exposure dose than has been calculated for an unfiltered breakthrough of 1 yCi/mCi. On... 

Numerous mathematical models have been developed in attempts to estimate potential risks to humans from low-dose exposures to carcinogens. Each model incorporates numerous unverifiable assumptions. Low-dose calculations are highly model dependent, widely differing results are commonly obtained, and none of the models can be firmly justified on either statistical or biological grounds (22). Thus, the decision to use this approach and the choice of how to do the calculations are matters of judgment. Among the choices that the decision makers must consider are which model(s) to employ, which assumptions to incorporate, and which acceptable risk to allow. 

D to wheat. The resultant data were used to calculate exposure doses and urinary excretion relationships. 

In summary, conversion of biomonitoring data to exposure dose requires knowledge of chemical elimination rate and Vd and requires that conditions be approximately pseudosteady state. It may be useful to estimate dose from body burden however, this cannot be used to interpret an individual s biomonitoring result, because the elimination rate and Vd would not be known. Reasonable bounds on elimination rate and Vd could be used to calculate an upper end of daily dose that is still compatible with the biomonitoring results (for example, when both Vd and elimination rate are high). 

Case Example Pharmacokinetic Calculations to Interpret Phthalate Urinary Biomarker Data. The previous descriptions focused on blood or adipose biomarker concentrations that were converted to body burden to yield estimates of daily dose based on chemical half-life. A modified form of that is conversion of urinary biomarker data to daily exposure dose via simple model calculations as described for phthalates. 

In summary, the PFOA risk assessment is a good example of biomonitoring-led risk assessment. There is no attempt to calculate exposure dose with pathway analysis, because the sources of human PFOA exposure are too uncertain. Instead, the biomonitoring data served as the sole source of human exposure information. Those data could be interpreted in a risk-assessment framework with the aid of PK mod-... 

Pharmacokinetic calculations yielded estimates of chlorpyrifos intake of 0.05-1 pg/kg per day in the general population. The model estimates compare favorably with pathway analysis estimates of aggregate chlorpyrifos exposure from numerous dose routes, including indoor inhalation, dermal contact, and food ingestion (Shurdut et al. 1998 Pang et al. 2002). The calculated exposure doses ranged from 0.02 to 1 pg/kg per day. Further... 

The integrated dose to a tissue over a 14-hour period (6-hour exposure, 8 hours following exposure) was calculated for benzene metabolites in Fischer 344 rats and B6C3Fj mice that were exposed to 50 ppm of radiolabeled (3H) benzene (Sabourin et al. 1988). The major metabolic products in rats were detoxification products that were marked by phenyl conjugates. In contrast, mice had substantial quantities of the markers for toxification pathways (muconic acid, hydroquinone glucuronide, and... 

The most accmate estimates of population exposme due to radioactive contamination of marine water can be performed through direct dose calculations via different exposure paths. Evaluation calculations can be done in compliance with the Methodic Guides "Estimate of the impacts of radiation-hazardous operations performed by nuclear shipbuilding enterprises on the environment and population " [5]. 

An analysis of the calculation results shows that, if using the conservative approach (time of NS waterborne storage prior to dismantlement 5 years, that of storage after dismantlement 0 years), imder the taken assmnptions effective exposure doses would be approximately the same for all professional groups equaling 20 pSv/year. The main contribution to the exposure dose would be due to inhalation intake of radionuclides with marine aerosols. 

Calculations show that maximum annual effective population exposure dose at the boundary of Sanitary Protection Area (500 meters from radioactive release point) will be 37 mSv under the hypothetical accident related to spontaneous nuclear reaction. It will not be the necessity to evacuate the population in accordance to Radiation Safety Standards (NRB -99). Collective radiation doses for population will not exceed the annual dose of this region received from natural radiation background. 

The models and methods used for purposes of estimating potential residential exposure (and absorbed dose) continue to be refined and validated as new monitoring studies become available. The goal is to simulate actual exposure conditions as closely as possible. The following sections present an example of a simplistic screening-level exposure assessment calculation for a consumer product, followed by a discussion of how more refined, probability-based or uncertainty analysis methods can be used. Screening-level methods typically include conservative bias in the form of default assumptions that are used in the absence of directly relevant and robust exposure monitoring data and other information. These methods can be used to predict potential exposure. However, it... 

Doses calculated in animals are converted to equivalent doses in humans on the basis of comparative physiological considerations (c.g., ventilatory parameters and regional lung surface areas). Additionally, if the exposure period was discontinuous, it is adjusted to reflect continuous e.xposure. 

The exact fetal radiation dose must be calculated for every case of exposure, based on information on file at each hospital. As a rule of thumb, until accurate dose calculations can be performed, you may make the following assumptions ... 

Several times each year, I receive phone calls or e-mail from women who have been advised to terminate their pregnancy after receiving only a few X-rays, some of which do not even image the uterus. Many medical personnel continue to fear that all fetal radiation exposure is harmful, and they inappropriately recommend therapeutic abortion. Before making this recommendation, medical personnel must perform a fetal dose calculation or ask a knowledgeable medical physicist or health physicist to perform these calculations. No recommendation to terminate a pregnancy should be made until these calculations have been performed and evaluated by a competent medical physicist or health physicist. 

For data that serve as the basis for all components, relevance of the population, the route of exposure, dose/concentration and adequacy of numbers of sub-jects/samples must also be considered and the potential impact on the validity of the calculated ratio addressed. For example, for in vitro studies which inform primarily dynamic components [ADaf] and [HDaf]) the quality of the samples should be considered, and evidence provided that they are representative of the target population, e.g., viability, specific content, or activity of marker enzymes. 

Consider that the human exposure of a chemical X calculated via drinking water supply is 2 ppp, that is, 2mgl day . Suppose a 70kg man consumes 21 of drinking water per day then the estimated exposure dose would be 2 mg kg day x... 

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