Cadmium accumulation by invertebrates living at the sediment-water interface

Benthic animals can take up trace metals both from the sediment compartment in which they burrow and from the water column compartment above their burrows (we define both compartments as containing water and particles). If criteria for the protection of benthic animals are based on metal concentrations in one of these two compartments, then it should first be demonstrated that the majority of the metal taken up by these animals comes from the given compartment. To determine whether benthic animals take up the majority of their cadmium (Cd) from the sediment compartment, we created a Cd gradient in lake sediment and compared Cd accumulation by the invertebrates colonizing these sediments with Cd concentrations in the sediment compartment. On the basis of this relationship and using a bioaccumulation model, we estimate that indigenous benthic invertebrates take up the majority of their Cd from the water column compartment. The results of our experiment are similar to those from a previous study conducted on a different benthic community in a larger lake. Taxa common to both lakes obtained similar proportions of their Cd from the water column compartment, suggesting that Cd accumulation by the same species will be constant across lakes of differing size and chemistry. Our results strengthen the argument that the protection of benthic communities from metal pollution should consider metal in both the water column and sediment compartments. In this regard, the AVS model, which considers only sedimentary metals, was more effective in predicting Cd concentrations in pore waters than those in most animal taxa. We suggest that measurements of vertical chemical heterogeneity in sediments and of animal behavior would aid in predicting the bioaccumulation and effects of sedimentary pollutants.     

The near field/far field model with constant application of chemical mass and exponentially decreasing emission of the mass applied

The near field/far field (NF/FF) model is a contaminant dispersion construct that permits making airborne contaminant exposure estimates for an individual located close to an emission source. In the present analysis, chemical emission involves a constant mass rate of chemical application to surfaces, denoted I (mg/min), and an exponentially decreasing rate of emission of the chemical from the surfaces with rate constant α (min^?1). The time-dependent emission rate function is: G(t), mg/min = I ? I exp(? αt), where time t is in minutes. The exact time-dependent equations for the contaminant concentration in the NF and the FF are presented. These equations are used to revise a previous analysis of a study in which a penetrant liquid containing benzene was applied to parts on a work table in a test room. The previous analysis assumed that the benzene was applied as a bolus at the start of a 15-min use period, whereas the present analysis assumes the same total benzene mass was applied at a uniform rate over the 15-min use period, but with the same evaporation rate constant α. The new G(t) function leads to a lower 15-min time weighted average NF benzene concentration that better matches the experimental data. It is also shown that the exact equation for the NF concentration is well approximated by combining two well-mixed single-zone equations. The approximation method is mathematically simpler and obviates the need to derive the exact NF equation.     

The concept of compartmentalisation

The rationale for establishing trade 'regions' and 'zones' is based on principles of epidemiological science and risk analysis that assess and manage animal disease risks so that the safety of trade can be ensured. However, the boundaries of geographical regions and zones may readily be breached through numerous epidemiological pathways. The concept of a 'compartment' extends the application of a 'risk boundary' beyond that of a geographical interface and considers all epidemiological factors that can contribute to the creation of an effective boundary. The fundamental requirement for application of either concept (regions/zones or compartments) is that the population considered for trade is maintained within management or geographical boundaries which allow clear epidemiological differentiation to be made between those animals and surrounding populations of higher risk. Seven factors are presented that an exporting country might use to guide the identification and documentation of a compartment. Additionally, the steps that would be undertaken to implement trade based on the compartmentalisation concept are discussed.     

Physiological modelling of organic compounds

In pharmacokinetic modelling the body is represented as a set of compartments. The characteristics of these compartments are defined either by fitting predetermined mathematical equations to the data ('data-based compartments') or by defining compartments based on the actual biological structure of the animal ('physiologically based compartments'). Physiological models of chemical disposition are developed using these physiologically based compartments. These models then consist of sets of organs or types of tissue compartments whose characteristics are based as far as possible on the anatomy and physiology of the test species. Individual organs or types of tissue are defined with respect to their blood flow, volume, kinetic constants for metabolism, storage capacity for the compound involved, protein binding and other relevant characteristics. Linking these compartments together in a proper anatomical arrangement yields the physiological model for compound disposition. This paper provides an overview of the basics for constructing physiological models for organic compounds, focusing on the structure of individual compartments in these models and the data required for model development. Some past applications of physiological models are reviewed and speculation offered on future developments in this field.     

Conceptual model for assessment of dermal exposure

Dermal exposure, primarily to pesticides, has been measured for almost half a century. Compared with exposure by inhalation, limited progress has been made towards standardisation of methods of measurement and development of biologically relevant exposure measures. It is suggested that the absence of a consistent terminology and a theoretical model has been an important cause of this lack of progress. Therefore, a consistent terminology based on a multicompartment model for assessment of dermal exposure is proposed that describes the transport of contaminant mass from the source of the hazardous substance to the surface of the skin. Six compartments and two barriers together with eight mass transport processes are described. With the model structure, examples are given of what some existing methods actually measure and where there are limited, or no, methods for measuring the relevant mass in a compartment or transport of mass. The importance of measuring the concentration of contaminant and not mass per area in the skin contaminant layer is stressed, as it is the concentration difference between the skin contamination layer and the perfused tissue that drives uptake. Methods for measuring uptake are currently not available. Measurement of mass, concentration, and the transport processes must be based on a theoretical model. Standardisation of methods of measurement of dermal exposure is strongly recommended.

 

     

Indoor air exposure to volatile compounds emitted by paints: experiment and model

To describe the evaporation of organic solvents from paints and the resulting indoor concentrations, a mathematical model and an indoor paint experiment are presented. The model describes painting in terms of an increasing area of paint during application and two compartments of paint once applied. Evaporation of organic solvents is driven by the vapor pressure of the organic solvent. The experiment revealed concentrations of n-alkanes in indoor air, during painting, and 3 days thereafter. To compare experimental results to model predictions, model parameters were measured at the start of the experiment. Diffusional exchange between paint compartments and fraction of paint applied to the upper compartment were set by expert judgment. Model predictions and experimental results were in agreement, although the timing of the concentration peak appeared difficult to predict.     

A stochastic differential equation for exposure yields a beta distribution

This paper presents a stochastic differential equation for exposure based on a modified version of the standard dilution ventilation equation. An equilibrium solution is obtained with the assumption that variability in the rate of change of concentration is proportional to the product of concentration and one minus concentration. Appropriate definitions for concentration are used to ensure a physically consistent model. The probability distribution for exposure that results is the standard beta distribution. This model is supported by several exposure data sets, which fit the beta distribution well. Issues regarding parameter estimation for the beta distribution, and application of the model are presented. Recommendations are made for simultaneously collecting contaminant generation rate information, ventilation rates, and time-dependent breathing-zone tracer concentrations, in addition to the exposure data.     

Comparison of the ICRP and MIRD models for Fe metabolism in man

A task group of the Medical Internal Radiation Dose (MIRD) Committee has recently published a model of Fe metabolism in man. This model was developed to calculate doses from radioiron injected for medical diagnostic purposes. It is a compartment model with recirculating Fe exchanging between plasma and extracellular fluids, tissue storage compartments, bone marrow and red blood cells (RBC). It is a first order model with the exception of Fe in the RBC compartment, which is assumed to retain Fe for 120 days, at which time the Fe returns to the extracellular fluid compartment. By contrast, the International Commission on Radiological Protection (ICRP) model is a "once through" first order compartment model, with the compartments represented by organs (spleen, liver and other soft tissue) rather than physiological compartments as in the MIRD model. Both of these models have been implemented in the computer code GENMOD which contains the ICRP recommended lung and gastrointestinal tract models and which is used at the Chalk River Nuclear Laboratories to calculate doses, excretion rates, derived investigation levels, etc. The results of calculations using these models have been compared to see if the much less sophisticated ICRP model was adequate for radiation protection purposes. It was found that the effective dose per unit intake of radioiron was higher for the MIRD model and urinary excretion rates following an exposure were considerably different. It is concluded that the ICRP model should not be used in dosimetry calculations, or for comparing monitoring results to model calculations.     

A logical starting point for developing priorities for lizard and snake ecotoxicology: a review of available data

Reptiles, specifically lizards and snakes, usually are excluded from environmental contamination studies and ecological risk assessments. This brief summary of available lizard and snake environmental contaminant data is presented to assist in the development of priorities for lizard and snake ecotoxicology. Most contaminant studies were not conducted recently, list animals found dead or dying after pesticide application, report residue concentrations after pesticide exposure, compare contaminant concentrations in animals from different areas, compare residue concentrations found in different tissues and organs, or compare changes in concentrations over time. The biological significance of the contaminant concentrations is rarely studied. A few recent studies, especially those conducted on modern pesticides, link the contaminant effects with exposure concentrations. Nondestructive sampling techniques for determining organic and inorganic contaminant concentrations in lizards and snakes recently have been developed. Studies that relate exposure, concentration, and effects of all types of environmental contaminants on lizards and snakes are needed. Because most lizards eat insects, studies on the exposure, effects, and accumulation of insecticides in lizards, and their predators, should be a top priority. Because all snakes are upper-trophic-level carnivores, studies on the accumulation and effects of contaminants that are known to bioaccumulate or biomagnify up the food chain should be the top priority.     

Innate host selection in Anopheles vestitipennis from southern Mexico

We assessed the degree of host specificity of the purported anthropophilic and zoophilic populations of Anopheles vestitipennis. A series of experiments were conducted in an experimental hut with 3 compartments lined with nylon netting. A central release compartment and 2 side compartments were each baited with equivalent surface area of human and animal baits. Wild An. vestitipennis collected on each host, as well as corresponding F1 mosquitoes, were released in the central compartment. Overall, 22% (166/748) of all mosquitoes collected on humans were recaptured in the human compartment, whereas 23% of mosquitoes originally collected on animals were recaptured in this compartment. Experiments with F1 females resulted in 59% human selection rates, a 2.6 times increase compared with wild anthropophilic females, while a 1.2 times decrease in human selection rates (from 24% to 20%) was observed in F1 of wild zoophilic females. Host selection experiments in the Lacandón Forest revealed the same trend. These findings suggested that the complex mode of inheritance that resulted in female mosquitoes showing a stronger tendency to return to their preferred host was obscured by the nature of the method of collection, i.e., wild parental females selecting a host either innately or opportunistically, the majority of which were likely innately attracted. This was revealed by F1 females, of which, when given the choice to select a host, a higher proportion opted for the preferred one. The results presented here are in accordance with other studies that identified a subpopulation of An. vestitipennis in southern Mexico with higher anthropophily.     

Application of in vitro biotransformation data and pharmacokinetic modeling to risk assessment

The adverse biological effects of toxic substances are dependent upon the exposure concentration and the duration of exposure. Pharmacokinetic models can quantitatively relate the external concentration of a toxicant in the environment to the internal dose of the toxicant in the target tissues of an exposed organism. The exposure concentration of a toxic substance is usually not the same as the concentration of the active form of the toxicant that reaches the target tissues following absorption, distribution, and biotransformation of the parent toxicant. Biotransformation modulates the biological activity of chemicals through bioactivation and detoxication pathways. Many toxicants require biotransformation to exert their adverse biological effects. Considerable species differences in biotransformation and other pharmacokinetic processes can make extrapolation of toxicity data from laboratory animals to humans problematic. Additionally, interindividual differences in biotransformation among human populations with diverse genetics and lifestyles can lead to considerable variability in the bioactivation of toxic chemicals. Compartmental pharmacokinetic models of animals and humans are needed to understand the quantitative relationships between chemical exposure and target tissue dose as well as animal to human differences and interindividual differences in human populations. The data-based compartmental pharmacokinetic models widely used in clinical pharmacology have little utility for human health risk assessment because they cannot extrapolate across dose route or species. Physiologically based pharmacokinetic (PBPK) models allow such extrapolations because they are based on anatomy, physiology, and biochemistry. In PBPK models, the compartments represent organs or groups of organs and the flows between compartments are actual blood flows. The concentration of a toxicant in a target tissue is a function of the solubility of the toxicant in blood and tissues (partition coefficients), blood flow into the tissue, metabolism of the toxicant in the tissue, and blood flow out of the tissue. The appropriate degree of biochemical detail can be added to the PBPK models as needed. Comparison of model simulations with experimental data provides a means of hypothesis testing and model refinement. In vitro biotransformation data from studies with isolated liver cells or subcellular fractions from animals or humans can be extrapolated to the intact organism based upon protein content or cell number. In vitro biotransformation studies with human liver preparations can provide quantitative data on human interindividual differences in chemical bioactivation. These in vitro data must be integrated into physiological models to understand the true impact of interindividual differences in chemical biotransformation on the target organ bioactivation of chemical contaminants in air and drinking water.     

The biological half-time of heavy metals

Summary Concentrations of Cd (475 samples), Pb (271), and total Hg (166) were determined in the organs and tissues during autopsies of inhabitants of the Tokyo metropolitan area who had experienced no known exposure to an abnormally high level of heavy metals and had died sudden deaths by accident. The results of this study do not differ greatly from those of other reports. Based on the intraorganic accumulation of the heavy metals according to age when they were not experimentally administered, the biological half-time (BHT) was estimated using a mathematical model with differential equations. It was hypothesized that the input of heavy metals into organs is proportional to the amount of food intake according to age (assuming little or no chronological change of heavy metals concentrations in food over several decades), and that the output is proportional to the intraorganic accumulation. The resulting BHT was very long, 10 to 100 times that computed in a number of studies from observation of the attenuation curve for a relatively short period after the experimental adminstration of heavy metals to humans or animals.The author devised a model consisting of two series compartments in one organ: the superficial, where heavy metals enter directly and are weakly bound with protein, and the profound, where they enter only via the superficial compartment to be strongly bound with the constituents. It was elucidated theoretically that the short BHT obtained by heavy metal administration is associated only with the superficial compartment of the organ, and that the long BHT obtained without experimental administration of heavy metals is due to the detour circuit from the superficial to the profound compartments. The ratio of the short BHT to the long BHT is the proportion of the content of a heavy metal in the superficial compartment to the total content in the whole organ. In order to prove the existence of the two compartments, superficial and profound, and to compute their ratios, further studies should be performed. The attenuation curve of the concentration, or of the amount after a single administration of a heavy metal, consists of the rapid component (first) and the slow component (second). The latter has been generally used for computation of BHTs. The slowest component is frequently present several years after the first two. There is a fair chance that the BHT based on the slowest component agrees with the BHT found in the present study.     

Uptake and depuration of paralytic shellfish toxins in the green-lipped mussel, Perna viridis: a dynamic model

Uptake and depuration of paralytic shellfish toxins in the green-lipped mussel, Perna viridis, were investigated by exposing the mussels to dinoflagellates (Alexandrium tamarense, ACTI01) under laboratory conditions for 8 d, then depurating them in clean seawater for 14 d. First-order linear differential equations were set up for five tissue compartments: Viscera, gill, hepatopancreas, adductor muscle, and foot. The solutions to these equations were used to fit the experimental data. We then estimated the parameters governing the model, which depend on the elimination rate from each compartment and the transfer coefficient between compartments. An assumption of the model is that the gills transport the dinoflagellates directly to the mouth and then to the viscera, where the ingested cells are broken down, releasing the toxins. The toxins absorbed are transferred to other tissues. During the uptake phase, the transfer coefficients from viscera to gill, hepatopancreas, adductor muscle, and foot were 0.03, 0.24, 0.01, and 0.004 per day, respectively. During the depuration phase, the transfer coefficients were 0.01, 0, 0.01, and 0.003 per day, respectively. In terms of the anatomical distribution of N-sulfocarbamoyl-11-hydroxysulfate (C2) toxins in various tissues, viscera and hepatopancreas contained the highest percentages (47-74% and 8-41%, respectively). Together, these two tissue compartments accounted for 71 to 96% of all C2 toxins present. The biokinetic model allows a quantitative prediction of C2 toxins in whole ussel as well as individual tissue compartments based on the density estimates and toxin load of dinoflagellate cells in the surrounding waters over time.     

Plasma carnitine compartment and red blood cell carnitine compartment of healthy adults

Carnitine is needed for a variety of important physiological functions in energy metabolism. Assessment of the carnitine status of an individual is compromised by limited data on the number of metabolic compartments of carnitine and their interrelationship, if any. Possible compartmentalization of carnitine in the blood of healthy adults was investigated because blood is one of the more readily available samples for the assessment of carnitine status. The data suggest that blood carnitine is partitioned into a plasma carnitine compartment and a red blood cell carnitine compartment, compartments that are separate and distinct metabolic compartments.     

Assessment of interrelationships among levels of intake and production, organ size and fasting heat production in growing animals

Although the concept of metabolic body size (kg0.75) has gained widespread use in the field of energy metabolism, its application to the growing animal has been questioned. Fasting heat production, or maintenance, rather than being a constant function of body size, has been shown to vary because of breed, sex, condition, physiological state, production level, nutrition level and environmental conditions. Data are presented to show that fasting heat production and maintenance vary with nutritional level or rate of growth in animals postweaning. Variation in these energy expenditures are related to variation in weight of metabolically active internal organs. Weights of liver and gut and fasting heat production are shown to be functions of body size and level of production. More information is needed to ascertain the primary components of energy expenditures in animals and to quantitatively relate these components to animal energy metabolism.     

Models for nearly every occasion: Part IV – Two-box decreasing emission models

New two-box “well-mixed room” decreasing emission (DE) models are introduced for scenarios that involve local controls, such as some form of local exhaust or local exhaust with filtered return. In addition, these models allow for the recirculation of a filtered (or cleaned) portion of the general room ventilation.

?For each control device scenario, a steady state and transient near and far field model is presented. The transient equations predict the concentration at time t after the application of the substance. The steady state equations can be use to predict the steady, unvarying “average concentration per application” whenever there are continuous applications of a substance and sufficient time has elapsed. The steady state equations can also be used to calculate the TWA for a task (or a series of tasks) whenever the beginning and end concentrations for the task (or task series) are expected to be zero (or near zero). The transient equations should be used to predict TWA exposures whenever these criteria cannot be met, or it is necessary to predict short-term exposures or peak concentrations.

?A structured calibration procedure, based on a mass balance approach, is proposed for each model. Depending upon the model, one or more calibration measurements are collected. Rearranged versions of the steady state equations are used to calculate estimates of the mass applied during each application, the near field flowrate, and (depending upon the model) the various efficiencies (e.g., local exhaust capture efficiency and the recirculation filtration efficiency). The emission rate constant must be determined using either a published approximation algorithm or experimentally.     

A microcomputer algorithm for solving first-order compartmental models involving recycling

A general algorithm for solving first-order compartmental models including recycling systems has been developed and its implementation on a microcomputer is described. Matrix algebra is used to obtain for any compartmental model an analytical solution, which is expressed as the exponential of a matrix of rate constants. A special technique is used in the algorithm to enable this exponential to be evaluated with a rapidly converging series. Truncation errors incurred in this process are estimated automatically. Thus, in an extreme case, where these errors may be significant, the appropriate action can be taken. Given a particular model, the user enters the model parameters into a rate matrix according to a simple rule. The algorithm then uses this matrix to solve the model, and thus no specialized mathematical knowledge is needed. The algorithm is given in a short BASIC program (60 lines) listed in an appendix. No additional software is required. By running this program on a standard microcomputer, the user can solve models of any complexity: those up to 15 compartments in seconds and those up to 30 compartments within a minute. The algorithm is thus ideally suited to solve kinetic models describing the transport of radionuclides in the environment or the translocation of elements in biological systems such as the metabolic models recommended by the International Commission on Radiological Protection (ICRP). Given the initial amount of material in each compartment at time t = 0, together with its radioactive decay constant, the algorithm gives both the amount in each compartment at any future time t and the number of disintegrations that will have occurred in each compartment up to time t. The computer program, shown in an appendix, could easily be used to calculate disintegrations over any time interval of interest, or to predict the quantities or fractions of an intake expected to be present in any in vivo or excretion compartments of interest. Thus, the algorithm can be useful in both the design and conduct of bioassay and internal dose assessment procedures.