Evaluating the impact of anatomical and physiological variability on human equivalent doses using PBPK models.

Addressing human anatomical and physiological variability is a crucial component of human health risk assessment of chemicals. Experts have recommended probabilistic chemical risk assessment paradigms in which distributional adjustment factors are used to account for various sources of uncertainty and variability, including variability in the pharmacokinetic behavior of a given substance in different humans. In practice, convenient assumptions about the distribution forms of adjustment factors and human equivalent doses (HEDs) are often used. Parameters such as tissue volumes and blood flows are likewise often assumed to be lognormally or normally distributed without evaluating empirical data for consistency with these forms. In this work, we performed dosimetric extrapolations using physiologically based pharmacokinetic (PBPK) models for dichloromethane (DCM) and chloroform that incorporate uncertainty and variability to determine if the HEDs associated with such extrapolations are approximately lognormal and how they depend on the underlying distribution shapes chosen to represent model parameters. We accounted for uncertainty and variability in PBPK model parameters by randomly drawing their values from a variety of distribution types. We then performed reverse dosimetry to calculate HEDs based on animal points of departure for each set of sampled parameters. Corresponding samples of HEDs were tested to determine the impact of input parameter distributions on their central tendencies, extreme percentiles, and degree of conformance to lognormality. This work demonstrates that the measurable attributes of human variability should be considered more carefully and that generalized assumptions about parameter distribution shapes may lead to inaccurate estimates of extreme percentiles of HEDs.

Population model for the decline of Homalodisca vitripennis (Hemiptera: Cicadellidae) over a ten-year period.

The glassy-winged sharpshooter, Homalodisca vitripennis (Germar), is an invasive pest which presents a major economic threat to grape industries in California, because it spreads a disease-causing bacterium, Xylella fastidiosa. In this note we develop a time and temperature dependent mathematical model to analyze aggregate population data for H. vitripennis from a 10-year study consisting of biweekly monitoring of H. vitripennis populations on unsprayed citrus, during which H. vitripennis decreased significantly. This model was fitted to the aggregate H. vitripennis time series data using iterative reweighted weighted least squares (IRWLS) with assumed probability distributions for certain parameter values. Results indicate that the H. vitripennis model fits the phenological and temperature data reasonably well, but the observed population decrease may possibly be attributed to factors other than the abiotic effect of temperature. A key factor responsible for this decline but not analyzed here could be biotic, for example, potentially parasitism of H. vitripennis eggs by Cosmocomoidea ashmeadi. A biological control program targeting H. vitripennis utilizing the mymarid egg parasitoid Cosmocomoidea (formerly Gonatocerus) ashmeadi (Girault) is described.