Application Note 35

Human Biomonitoring: Attogram Level Sensitivity and Consequences for Analytical Standards Purity

Donald G. Patterson Jr., PhD

President, EnviroSolutions Consulting, Inc., Auburn, GA 30011 USA

Internal Versus External Dose in Human Exposure Assessment

The objectives of human exposure assessment to environmental chemicals are to quantify the magnitude, duration, frequency, and routes of exposure, and to characterize and enumerate the exposed population. There are several ways to do human exposure assessment. The first is the external dose measurement process followed by modeling to predict the individual internal dose. This method usually involves the collection of questionnaire data and a measurement or estimation of concentrations of the chemical(s) in various environmental media such as air, water, soil, dust, food, consumer products, etc. This is followed by assumptions of media contact or intake routes that yield a level of applied dose. Predicting levels of toxicants in people using environmental media monitoring is very difficult and involves many assumptions such as: individual lung, intestine and skin absorption coefficients; genetic factors; personal habits; lifestyle factors; nutritional status; and many others. 

A second approach to human exposure assessment is the biomonitoring approach which provides exposure estimates that are more directly related to concentrations of the active agent(s) at the target site or organ. Biomonitoring is an assessment of the internal dose by measuring a toxicant (or its metabolite or protein adduct) in human blood, urine, milk, saliva, adipose tissue, or other tissues. The biomonitoring approach provides a direct measure of exposure that integrates exposures from multiple pathways and sources. This approach decreases the uncertainty inherent in exposure assessment by the external dose method and provides a more biologically relevant measure of true exposure. Instead of predicting levels in people, this approach measures levels of toxicants in people and markedly decreases uncertainty in assessing human risk (Sexton et al. 2004). An example of the usefulness of the internal dose measurement versus the external dose process is shown in Figure 1. 

The US Air Force conducted a 20-year prospective study examining the health, mortality and reproductive outcomes in US Air Force veterans of Operation Ranch Hand (RH), the unit responsible for the aerial spraying of herbicides, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated Agent Orange, in Vietnam from 1962 to 1971 (Pavuk et al. 2007). Prior to beginning the study, the Air Force measured the levels of 2,3,7,8-TCDD in the serum (Patterson et al. 1987) of RH veterans and compared the levels to the external dose exposure index that had been developed for the Health Study. Figure 1 shows that the exposure index was poorly correlated with the internal dose TCDD measurements. Based on these results, the Air Force decided to use the internal dose TCDD serum measure­ments as the exposure index for the Health Study (Michalek 1989). 

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