Factors determining dietary intakes of heterocyclic amines in cooked foods.

The identification of heterocyclic amines (HCAs) in cooked foods has focused attention on the potential health effects from their consumption in the diet. Recent studies have estimated daily dietary intakes of HCAs that vary 10-fold and implicated different cooked meats as the prime source of HCAs in the diet. These varied estimates can be attributed to the different dietary assessment methods used in these studies, as well as the different levels of HCAs ascribed to the most commonly consumed cooked meats. Epidemiological studies utilizing information on dietary practice and food intake have found higher risks for several cancers among individuals consuming the highest levels of HCAs. These studies have highlighted the importance of using information on cooking methods in addition to food intake to accurately estimate dietary exposure to HCAs.

Risk management for plausibly hormetic environmental carcinogens: the case of radon.

Risk management typically involves efforts to reduce human exposures by establishing regulations that limit the concentration of the substance in environmental media. In cases where a substance is widely used in commerce or is naturally occurring in the environment, compliance costs can be substantial because of nationwide requirements to add expensive control technologies. Uncertainties in a dose-response function further impact risk management decisions because they may correspond to large differences in health benefit per unit exposure reduction. These problems are highlighted in the case of plausibly hormetic environmental carcinogens, for which a linear-no-threshold (LNT) dose-response model has been the traditional regulatory default assumption. In this case, model uncertainty is pivotal, and risk management is consequently inherently controversial. However, marginal cost functions that arise for plausibly hormetic carcinogens are expected to possess a common analytic feature that may be particularly useful for this type of risk management problem. Specifically, marginal cost functions in this context are expected to have roots reflecting contaminant concentration values above which regulatory goals may be optimally placed subject to cost constraints. Here we illustrate this heuristic feature in the case of residential radon, using both a LNT model and a biologically plausible hormetic model to predict associated risks of lung cancer mortality.

Comparison of multi-media transport and transformation models: regional fugacity model vs. CalTOX.

Two multimedia environmental transport and transformation computer models are summarized and compared. The regional fugacity model published by Mackay and Paterson (1991), termed Fug3ONT, is a four compartment steady-state model designed to simulate the relative distribution of nonionic organic chemicals in a multimedia system. CalTOX is a seven compartment multimedia total exposure model for hazardous waste sites. Both models are based on the principles of fugacity. CalTOX, however, separates the soil into three layers (surface, root, and vadose) and uses a different approach to estimate the diffusive mass transfer rate in soil. These differences result in lower estimates of the steady-state contaminant concentrations of six environmentally relevant chemicals in the root soil of CalTOX as compared to the bulk soil of Fug3ONT. The difference is greatest for compounds with low mobility in soil such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Benzo(a)pyrene where estimates from CalTOX and Fug3ONT differ by more than 3 orders of magnitude. Otherwise, the models provide similar estimates for the distribution of the six chemicals among the air, water, sediment and surface soil.

Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research.

Heterocyclic amines (HAs) are formed as pyrolysis products during the cooking of meats/fish. These substances are potent mutagens in the Ames/Salmonella assay and are also carcinogens in laboratory animals. In order to assess the magnitude of the cancer risk posed by their presence in the US diet, we estimated the average intakes of HAs, based on analyses of the concentrations of HAs in cooked foods and data from a dietary survey of the US population and quantified the cancer potencies of the individual compounds using dose-response data from animal bioassays. Measured concentrations of HAs in cooked foods were taken from a major review of the open literature. Only those concentrations that were associated with normal cooking conditions were chosen for use in estimating dietary intakes. The average consumption of HA-bearing foods was determined by analyzing statistically the intakes of 3563 individuals who provided 3 day dietary records in a USDA sponsored random survey of the US population during 1989. Dietary intakes of the five principal HAs in descending order were 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) > 2-amino-9H-pyrido[2,3-b]indole (A alpha C) > 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) > 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) > 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The carcinogenic potencies, in contrast, were almost the reverse order: IQ > DiMeIQx > MeIQx > PhIP > A alpha C. An upper-bound estimate of the incremental cancer risk is 1.1 x 10(-4), using cancer potencies based on a body surface area basis. Nearly half (46%) of the incremental risk was due to ingestion of PhIP. Consumption of meat and fish products contributed the most (approximately 80%) to total risk.

Metabolically consistent breathing rates for use in dose assessments.

Assessments of doses resulting from exposures to airborne gases and particles are based almost exclusively on inhalation rates that are inconsistent with the quantities of oxygen needed to metabolize dietary intakes of fats, carbohydrates, and protein. This inconsistency leads to erroneous estimates of inhalation exposures and can distort the relative importance of inhalation and ingestion-based exposures to environmental contaminants that are present in foods, air, and water. As a means of dealing with this problem, a new methodology for estimating breathing rates is presented that is based on the oxygen uptake associated with energy expenditures and a ventilatory equivalent that relates minute volume to oxygen uptake. Three alternative energy-based approaches for estimating daily inhalation rates are examined: (1) average daily intakes of food energy from dietary surveys, adjusted for under reporting of foods; (2) average daily energy expenditure calculated from ratios of total daily expenditure to basal metabolism; and (3) daily energy expenditures determined from a time-activity survey. Under the first two approaches, inhalation rates for adult females in different age cohorts ranged from 9.7 to 11 m3 d-1, whereas for adult males the range was 13 to 17 m3 d-1. Inhalation rates for adults determined from activity patterns were higher (i.e., 13 to 18 m3 d-1), however, those rates were shown to be quite sensitive to the energy expenditures used to represent light and sedentary activities. In contrast to the above estimates, the ICRP 23 reference values for adult females and males are 21 and 23 m3 d-1 (Snyder et al. 1975). Finally, the paper provides a technique for determining the short-term breathing rates of individuals based on their basal metabolic rate and level of physical activity.

Deriving allowable daily intakes for systemic toxicants lacking chronic toxicity data.

The lack of human toxicological data for most chemical compounds makes it difficult to quickly assess health risks associated with exposure to contaminants at hazardous waste sites. It would therefore be advantageous to have a technique for estimating acceptable daily intakes (ADIs) of potentially toxic substances based on more widely available animal toxicity data. This article focuses on the use of LD50 data to derive provisional ADIs, and it suggests multiplying oral LD50 values (expressed in mg/kg of body wt) by a factor in the range of 5 X 10(-6) to 1 X 10(-5) day-1 to convert them to such ADIs. It is emphasized that these interim ADI values are no substitute for toxicity testing, but that such testing would most likely result in higher ADI estimates.

Screening the potential risks of toxic substances using a multimedia compartment model: estimation of human exposure.

Managing environmental health risks requires the assessment of environmental fate, exposure, and health risk of an ever-increasing list of contaminants. The magnitude of this list precludes an experimental evaluation of each contaminant. For this reason, computer models are being used more frequently to simulate the transport and transformation of chemicals based on physical and chemical properties. This paper describes a multimedia compartment model that we have developed for screening toxic substances. This model, referred to as GEOTOX, uses a combination of physical, chemical, and landscape properties to establish the partitioning, reaction, and interphase-transport characteristics of a chemical. These properties are used to estimate concentrations in the air, soil, water, and food of a representative or generic environment. We use these concentrations in exposure-pathway models to calculate the quantities absorbed by humans; then dose-response data are used to estimate health risks. The capability of GEOTOX as a screening tool is illustrated in a sample ranking of three chemicals (i.e., 2,4,6-trinitrotoluene, hexahydro-1,3,5-trinitro-1,3,5-triazine, and benzene) being continuously added to the upper-soil compartment. We find that ranking based on both toxic potency and environmental fate can enhance the risk-management process when compared to ranking based on toxic potency alone.