PubMed Health⌕ Search

Biomedical subjects

C C Travis

Publications and source records attributed to C C Travis.

At least 37 records · Page 2Linked to original sources
PubMed1991

Benzo-a-pyrene: environmental partitioning and human exposure.

A multimedia transport model was used to evaluate the environmental partitioning of benzo-a-pyrene (BaP). Measured and predicted environmental concentrations were used to estimate the accumulation of BaP in the food chain and the subsequent extent of human exposure from inhalation and ingestion. Results show that BaP partitions mainly into soil (82%) and sediment (17%) and that the food chain is the dominant pathway of human exposure, accounting for about 97% of the total daily intake of BaP. Inhalation and consumption of contaminated water are only minor pathways of human exposure. The long-term average daily intake of BaP by the general population of the U.S. is estimated to be 2.2 micrograms (micrograms) per day. Cigarette smoking and indoor activities do not substantially increase human exposure to BaP relative to exposures to background levels of BaP present in the environment. Since the increased lifetime risk associated with human exposure to background levels of BaP is 3.5 x 10(-4), we conclude that ingestion of food items contaminated with BaP may pose a serious health threat to the U.S. population.

Animals↗
PubMed1991

Interspecies scaling of anesthetic potency.

Anesthetic potency data for 11 volatile anesthetics were correlated against body weight in multiple mammalian species, including man. The results indicate that the alveolar concentration necessary to produce anesthesia is approximately constant across species. Because alveolar ventilation rates scale with the 0.75 power of body weight, this implies that administered dose measured in mg/kg0.75/day produces the same anesthetic effect in all species. This analysis provides further support for the use of a mg/kg0.75/day interspecies scaling metric for acute toxic effects.

Anesthetics↗
PubMed1991

Interspecies extrapolation in risk analysis.

This report provides an overview of one of the fundamental problems in cancer risk assessment: extrapolation of observed experimental results between animal species and man. Lacking detailed information on interspecific differences, researchers assume that experimental results can be extrapolated between species using the first power of body weight or using surface area scaling (body weight to 2/3 power). Neither of these extrapolation procedures will be exactly correct for all compounds. However, in the absence of species-specific data, body weight or surface area extrapolations are used with the explicit knowledge that they are only approximately correct. We recommend that when a scaling metric for a specific compound is known, the scaling metric should be used in a risk assessment. When there is no prior knowledge of a chemical's pharmacokinetics or mechanism of action (the usual case in risk assessment), we recommend that the 3/4 power of body weight be used as the most appropriate interspecies scaling metric. The methods and properties used in interspecies extrapolation include allometric scaling, scaling physiological parameters (organ volumes, volume rates, partition coefficients, and biological half-life), physiological time, and physiologically-based pharmacokinetics. The extrapolation of these physiological, biochemical, and metabolic parameters across species controls interspecific extrapolation of pharmacokinetics. We analyzed clearance and half-life data for several compounds in multiple species and determined that the 3/4 power scaling law provides a more accurate estimate of a compound's true scaling metric than does the surface area scaling metric or the first power of body weight scaling metric.

Animals↗
PubMed1990

Pharmacokinetics of benzene.

A physiologically based pharmacokinetic model was developed and used to describe the pharmacokinetics of benzene in three species: mice, rats, and humans. For each species, the body was divided into five anatomical compartments, consisting of liver, fat, bone marrow, and muscle, and organs such as brain, heart, kidney, and viscera, connected by the arterial and venous blood flow pathways. Metabolism of benzene followed Michaelis-Menten (nonlinear) kinetics in all species and occurred primarily in the liver compartment and, to a lesser extent, in the bone marrow. Comparison of model results with empirical data on inhalation, gavage, and intraperitoneal and subcutaneous injection in mice, rats, and humans, demonstrates the utility of a physiological pharmacokinetic model in describing the pharmacokinetics of benzene in three species across multiple routes of exposure.

Animals↗
PubMed1990

Interspecies extrapolation of pharmacokinetics.

The purpose of this paper is to use physiologically based pharmacokinetic models to demonstrate that if toxic response is a function of the time profile in physiological time of the concentration of the toxic moiety in the target tissue, then the appropriate interspecies scaling law for toxic compounds which are metabolically deactivated is mg kg-1 per unit of physiological time (mg kg-1 pt-1). At low dose rates this metric is approximately equivalent to mg kg-0.75 day-1. For reactive metabolites which are spontaneously deactivated, an approximate interspecies scaling law is mg kg-1 day-1.

Animals↗
PubMed1990

Small-scale field test of the genetically engineered lacZY marker.

Commercial genetic engineering is advancing into areas that require the small-scale introduction of genetically engineered microorganisms (GEMs) to better quantify variables that affect microorganism distribution and survival and to document potential long-term consequences. A recombinant DNA marker system, the lacZY marker, developed by the Monsanto Agricultural Co., enables the distribution and fate of marked fluorescent pseudomonad organisms to be monitored under actual field conditions. Critical evaluation of GEMs under field conditions is imperative if plant-beneficial effects are to be correlated with organism release. This paper evaluates the effectiveness of this marker system and its ability to facilitate the assessment of risks associated with deliberate environmental introductions of genetically engineered microorganisms. Results of prerelease contained growth chamber and field experiments demonstrated that: (1) the scientific risk assessment methodology adopted by Monsanto and approved by the U.S. Environmental Protection Agency was appropriate and comprehensive; (2) the deliberate introduction of a GEM did not pose unacceptable or unforeseen risks to human health or the environment; (3) the lacZY marker is an effective environmental tracking tool; and (4) regulatory oversight should reflect the expected risk and not be excessively burdensome for all GEMs.

DNA, Recombinant↗
PubMed1990

In vivo metabolic interactions of benzene and toluene.

The metabolic interactions of benzene and toluene co-exposure were investigated in male Fischer rats. A closed recirculated exposure system was used to obtain inhalation uptake curves for individual chemicals as well as for a mixture of the two compounds. Pharmacokinetic parameters for benzene and toluene individually were determined in previous experimental studies. These values were incorporated into a physiologically based pharmacokinetic model which simulated the inhalation uptake process for both chemicals simultaneously. An optimal fit to the uptake curves for simultaneous exposure was obtained by adjusting the metabolic interaction terms for each chemical. Mutual suppression of metabolism was apparent. Toluene more effectively inhibited benzene metabolism than the reverse. This simulation approach for analyzing gas uptake data provided a method to determine the metabolic interactions occurring upon inhalation exposure to two different chemicals. Such analyses will prove useful in improving predictive toxicokinetic models.

Animals↗
PubMed1990

Benzene: environmental partitioning and human exposure.

A multimedia transport model was used to evaluate the environmental partitioning of benzene. Measured and predicted environmental concentrations were used to estimate the accumulation of benzene in the food chain and the subsequent extent of human exposure from inhalation and ingestion. Results show that benzene partitions mainly into air (99.9%) and that inhalation is the dominant pathway of human exposure, accounting for more than 99% of the total daily intake of benzene. Ingestion of contaminated food items represents only a minor pathway of human exposure. The long-term average daily intake of benzene by the general population of the U.S. was estimated using three independent methods. Intake estimates based on measured personal air exposures, measured exhaled air concentrations, and a pharmacokinetically derived adipose tissue concentration (73, 63, and 72 micrograms/day, respectively) are in good agreement. Although inhalation is the primary route of human exposure to background levels of benzene in the environment, smoking was found to be the largest anthropogenic source of background human exposure to benzene.

Air↗
PubMed1990

Prediction of cancer potency using a battery of mutation and toxicity data.

Correlations between the carcinogenic potencies of 146 known mouse carcinogens and potency estimates determined from (i) Ames test results, (ii) a battery of mutation test results, and (iii) a battery of mutation and toxicity data are presented. The lowest correlation was found using Salmonella mutagenic potency (r = 0.37). The highest correlations were found using the battery of mutation and toxicity data to predict the potency of lung carcinogens (r = 0.94) and liver carcinogens (r = 0.91). The results suggest that short-term batteries which include tests for both mutagenicity and toxicity will be able to predict carcinogenic potency better than current batteries relying solely on mutagenicity tests.

Animals↗
PubMed1990

Tissue dosimetry for reactive metabolites.

In recent pharmacokinetically based risk assessments for methylene chloride, Andersen et al. argued that total reactive metabolite (TRM) divided liver weight was the proper measure of dose to target tissue, while the EPA argued that TRM divided by body weight to the two-thirds power was more appropriate. We demonstrate that the proper tissue metric for a reactive metabolite is dependent upon the mode of deactivation: metabolic or spontaneous. It is argued that the most appropriate measure of tissue dosimetry is: (1) TRM divided by the three-fourths power of body weight if the reactive metabolite is metabolically deactivated; or (2) TRM divided by body weight if the reactive metabolite is spontaneously deactivated.

Animals↗
PubMed1989

The superfund remedial action decision process: a review of fifty records of decision.

Although the Superfund remedial action decision process is a complex process involving a variety of technical, political, and public health issues, the primary goal of remedial action is the protection of public health. We performed an in-depth analysis of 50 post-SARA Records of Decision in order to characterize the role of risk assessment in the decision-making process and determine whether decisions are being made in an effective and environmentally protective manner. Our findings indicate that the majority of decisions to remediate Superfund sites are based on the existence of contamination per se and not on actual public health risk. Although hypothetical risk is an essential consideration, this gray area is not well-defined in the current decision-making process. The lack of assessment of the degree of risk reduction associated with the remedial alternatives evaluated and the lack of support indicating the effectiveness of the remedial alternatives selected also constitute major weaknesses in the majority of decisions. These inadequacies undermine rationales regarding the protectiveness and cost-effectiveness of the remedial alternatives selected. The fact that objectives beyond addressing public health risk are often unclear in the decision-making process also weakens rationales for cost-effectiveness.

Environmental Pollution↗
PubMed1989

Dose-modification factor for accumulated dose to cell nucleus due to protein-bound 3H.

The purpose of this work was to estimate the dose-modification factor for accumulated dose in the cell nucleus due to protein-bound 3H in animal organs. The animal tissues were modeled to make a simplified theoretical estimation of the extent of dose modification due to the differential distribution of proteins between the cell nucleus and the extranuclear region. The results of theoretical calculation were applied to the case of mouse organs for which various cytological factors were determined experimentally. It was found that the dose-modifying factor (f) for mouse organs was between about 0.8 and 1.5, indicating that dose modification due to protein localization is of minor importance for the dosimetry of internally retained 3H.

Animals↗
PubMed1989

A perspective on dioxin emissions from municipal solid waste incinerators.

This paper discusses the following key issues concerning human exposure to dioxins and furans emitted from typical, modern MSW incinerators: (1) Are MSW incinerators the major source of PCDD/PCDF input into the environment? (2) Are environmental concentrations around MSW incinerators substantially elevated relative to background levels? And (3) are MSW incinerators the major source of human exposure to PCDDs and PCDFs? Current scientific evidence indicates that (1) combustion sources in general (including steel mills, copper smelting plants, motor vehicles, pulp and paper mills, and MSW incinerators) are major sources of PCDD/PCDF input in the environment; (2) environmental concentrations of PCDDs and PCDFs around operating MSW incinerators are not substantially elevated; and (3) 99% of human exposure to PCDDs and PCDFs is from background contamination, even for individuals living near a modern MSW incinerator.

Air Pollutants↗
PubMed1989

Protein binding of benzene under ambient exposure conditions.

Based on examination of exposure monitoring studies, we speculate that under ambient conditions benzene binds appreciably to plasma proteins. The binding capacity, n*[beta], is estimated to be on the order of 10(-9) chi M (90.0 ng/L) and the association constant, Kas, on the order of 2 X 10(10) M-1 (.3 L/ng). These values indicate that protein binding of benzene is characterized by a very small capacity with a very large affinity. We predict that steady-state exposure to ambient benzene air concentrations in the range of 10 ppb to 1 ppb will result in 35 to 80 percent of benzene in blood being bound to plasma proteins.

Benzene↗
PubMed1988

Pharmacokinetics of tetrachloroethylene.

A physiological pharmacokinetic model is developed to describe the pharmacokinetics of tetrachloroethylene (PCE) in mice, rats, and humans. The body is divided into four tissue compartments (vessel-rich, muscle, slowly perfused fat, and liver) connected by the arterial and venous blood flow pathways. The physiological parameters of the model are blood flow rates, cardiac output, tissue volumes, ventilation rate, and tissue/air and blood/air partition coefficients. Metabolism is assumed to occur only in the liver compartment and is described by a combination of a linear metabolic component and a Michaelis-Menten component. The metabolic parameters for PCE were determined by fitting model predictions to species-specific empirical data. Comparison of model results with independent empirical data on inhalation and gavage exposures in mice, rats, and humans demonstrates that the physiological pharmacokinetic model can be used to determine the time course of PCE in these species. We show that human metabolic parameters can be predicted by scaling rat metabolic parameters as a function of body weight, whereas scaling of the metabolic parameters of mice overestimates human metabolism.

Animals↗