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In order to evaluate the potentially harmful effects of diesel engine emissions, inhalation exposure studies were carried out using a variety of animal species and strains, and measuring a wide range of toxicological parameters. Exhaust was provided by a 6 cylinder Nissan diesel engine operated 20 hours/day, 7 days/week, during a 2 month preliminary trial and 8 hours/day, 7 days/week during a 2 year, 4 month long-term study. The exhaust was diluted to produce a concentration of 6 mg/m3 particulate matter during the preliminary study and during the first year of the long term study and 12 mg/m3 thereafter. Exposure to diesel emissions did not result in detectable genotoxic effects as measured by increases in sister chromatid exchange (SCE), micronucleus testing and metaphase analysis in Chinese hamster and mouse bone marrow cells or in the morphology of cat sperm. SCE in lung cells from Syrian hamsters, however, was increased at the higher exposure level. The incidence of heritable mutations was not increased in mice. An increase in lung tumor incidence was detected in female Senear mice exposed from conception, but not in males, or in either male or female strain A mice exposed from 6 weeks of age. Voluntary activity was decreased in rats during exposure and learning ability was impaired in adult animals exposed during the early postnatal period. Susceptibility to an infectious challenge was increased in diesel exposed mice. Clearance of particles from the lung was found to be minimal even after 90 days recovery in clean air. Pulmonary function alterations in diesel exposed cats suggested the presence of a lesion restricting the air flow. The integrity of the lung as measured by leakage of 131I labeled protein into the alveoli did not seem to be impaired, but increased collagen synthesis suggested that fibrosis may develop with long-term exposure. The preliminary inhalation study resulted in the induction of xenobiotic metabolizing enzymes in the liver. In later studies, however, enzyme induction was found only in male mice injected with large doses of diesel particulate extract.

A problem in evaluating the hazard represented by an environmental toxicant is that exposures can occur via multiple media such as water, land, and air. Lead is one of the toxicants of concern that has been associated with adverse effects on heme metabolism, serum vitamin D levels, and the mental and physical development of infants and children exposed at very low environmental levels. Effects of lead on development are particularly disturbing in that the consequences of early delays or deficits in physical or mental development may have long-term consequences over the lifetime of affected individuals. Experimental and epidemiologic studies have indicated that blood lead levels in the range of 10-15 micrograms/dl, or possibly lower, are likely to produce subclinical toxicity. Since a discernible threshold has not been demonstrated, it is prudent to preclude development of a Reference Dose (RfD) for lead. As an alternate, the U.S. Environmental Protection Agency (U.S. EPA) has developed the uptake/biokinetic lead model that provides a means for evaluating the relative contribution of various media to establishing blood lead levels in children. This approach will allow for the identification of site- and situation-specific abatement strategies based on projected blood lead levels in vulnerable human populations exposed to lead in air, diet, water, soil/dust, and paint; thus making it possible to evaluate regulatory decisions concerning each medium on blood levels and potential health effects.

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Approaches usually available for the assessment of exposures that occur via water, land and/or air are limited by their ability to integrate multiroute scenarios. Additionally, there are indications that these exposures can differentially affect specific subgroups, each having unique sensitivities to chemical insults. Lead is one of the major toxic contaminants of concern found at approximately 47% of the Superfund National Priority List (NPL) Sites. Low level exposure to lead has been shown to produce adverse effects on heme metabolism, serum vitamin D levels, mental and physical development of infants and children, and blood pressure in adults. Experimental and epidemiologic studies have indicated that blood lead levels in the range of 10–15 μg/dl, or possibly lower, are likely to produce subclinical toxicity. Since a threshold has not been established it is prudent to assume that, for regulatory purposes, a threshold for lead toxicity does not exist. As an alternate to the traditional reference dose approach, the U.S. EPA has developed the Uptake/Biokinetic Lead Model that provides a means for evaluating the relative contribution of various media to establishing blood lead levels. The model is flexible and versatile and predicts mean blood lead levels and population distributions associated with multimedia exposure in children. This allows for the identification of site- and situation-specific abatement strategies based on projected blood lead levels in vulnerable human populations. This paper will present examples of NPL site exposure scenarios for lead and how the UBK lead model may be used for characterization of potential health risks as a result of these exposure scenarios.