Exposure profile

Pre-employment medical for selection and establishment of base levels Working conditions in specific areas Employees routine medicals, exposure profiles Biological monitoring where appropriate... 

The toxic effects model translates the exposure profiles into casualty probabilities for the personnel, assuming a probabilistic dose-effect relationship. The casualty levels and spectra can be obtained for various type of health effects, e.g. eye effects, inhalation, percutane, subdivided in two levels (incapacitating and lethal), and various protection levels, e.g. no protection, suit only, mask only, mask and suit, and collective protection. Table 1 gives a typical result for one scenario. In case no protection is used, 63% of the population dies due to inhalation of sarin and 25% dies due to percutaneous exposure. Clearly, when both mask and suit are worn, the casualty levels are dropping drastically. 

Most of the assessment of toxicology and safety of therapeutics is focused on the patients who are to benefit from the new medicine. However, there are two other groups of individuals (each of which has different exposure profiles) that one must be concerned about the healthcare providers (nurses, pharmacists and physicians) who provide and/or administer the drugs and the individuals involved in manufacturing them. The concerns here are in the realm of occupational toxicology. 

M. M. et al. Brain and plasma exposure profiling in early drug discovery using cassette administration and fast liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 2004, 34, 359-368. 

Figure 10.8 Predictability of systemic exposure profile using a PBPK approach and Biopharmaceutics Drug Disposition Classification System (adapted from Wu and Benet [24]).

Bogers M, Appelman LM, Feron VJ, et al. 1987. Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats. J AppI Toxicol 7 185-191. 

Plummer JL, de la Hall P, Isley AH, et al. 1990. Influence of enzyme induction and exposure profile on liver injury due to chlorinated hydrocarbon inhalation. Pharmacol Toxicol 67 329-335. 

In exposure characterization, credible and relevant data are analyzed to describe the source(s) of stressors, the distribution of stressors in the environment, and the contact or co-occurrence of stressors with ecological receptors. An exposure profile is developed that identifies receptors and exposure pathways, describes the intensity and spatial and temporal extent of exposure, describes the impact of variability and uncertainty on exposure estimates, and presents a conclusion about the likelihood that exposure will occur. 

A population-linked database was developed to assess exposure to the herbicides atrazine and simazine in the drinking water of community water systems (CWS) fed by groundwater and surface water sources in 32 major-use states. These states represent about 99% of the annual atrazine and simazine use in the United States. Herbicide concentration and population data from 1993 through 2000 were paired for each water system and then aggregated to construct state and multistate exposure profiles. 

Figure 29.2 Atrazine CWS exposure profile for three water sources and associated percentage of assessed population. Bar width is proportional to the percent of the population in the 32 major-use states exposed in each water source category.

Both Models 107 for benzene and 108 for multiple chemicals are based on the Benzene Exposure Assessment Model (BEAM) (Behar et al 1993) to generate benzene or chemical inhalation exposure profiles for different human subgroups. For an estimation of dermal dose, Model 109 is a simple film-thickness -based model like DERMAL (Versar, Inc., 1995). Model 110 estimates multiple pathways exposure (i.e. inhalation and dermal doses) to multiple chemicals from the use of consumer products. 

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