Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. MATERIALS AND METHODS: We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. RESULTS: Pre-chelation blood lead concentrations ranged between 99 and 150 µg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. CONCLUSIONS: Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.

CONTEXT: No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning. OBJECTIVE: Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model. MATERIAL AND METHODS: This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies. RESULTS: The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability. CONCLUSIONS: A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.

Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations.

Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (<100 nm). It is applied in food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO2 NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO2 NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO2, particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO2 (NPs) in animals are recommended to refine this assessment.

Carry-over of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in dairy cows fed smoke contaminated maize silage or sugar beet pulp.

Fires and improper drying may result in contamination of feed with PCDD/Fs and PCBs. To predict the impact of elevated feed levels, it is important to understand the carry-over to edible products from food producing animals. Therefore, a carry-over study was performed with maize silage contaminated by a fire with PVC materials, and with sugar beet pulp contaminated by drying with coal, containing particles from a plastic roof. Levels of PCDD/Fs and dl-PCBs in the maize silage were 0.93 and 0.25 ng TEQ kg(-1), those in beet pulp 1.90 and 0.15 ng TEQ kg(-1) (both on 88% dry matter (DM)). Dairy cows (3 per treatment) received either 16.8 kg DM per day of maize silage or 5.6 kg DM per day of sugar beet pellets for a 33-d period, followed by clean feed for 33 days. This resulted in a rapid increase of PCDD/F levels in milk within the first 10 days with levels at day 33 of respectively 2.6 and 1.7 pg TEQ g(-1) fat for maize silage and beet pulp. Levels of dl-PCBs at day 33 were lower, 1.0 and 0.5 pg TEQ g(-1) fat. In the case of the maize silage, the carry-over rates (CORs) at the end of the exposure were calculated to be 25% and 32% for the PCDD/F- and dl-PCB-TEQ, respectively. For the dried beet pulp the CORs were 18% and 35%. This study shows that the carry-over of PCDD/Fs and dl-PCBs formed during drying processes or fires can be substantial.

Implementation of toxicokinetics in toxicity studies--Toxicokinetics of 4-methylanisole and its metabolites in juvenile and adult rats.

The current risk assessment of compounds is generally based on external exposure and effect relationships. External doses are often not representative for internal exposure concentrations. The aim of this study was to show how the implementation of toxicokinetics in a scheduled toxicity study contributes to improved data interpretation without additional use of animals and to the three goals of the 3R principles for animal testing. Toxicokinetic analyses were implemented in a rat developmental immunotoxicity study with 4-methylanisole without interfering with the outcome of the study and without the use of additional animals. 4-Methylanisole and its metabolites were analysed in plasma of adult rats and in pups at postnatal day 10. 4-Methylanisole has a short half-life in adult animals and the plasma concentrations increased more than proportional with increasing dose. The metabolic profile appeared to be different at low dose as compared to high dose. This information on the dose-proportionality of the internal exposure is crucial for the interpretation of the toxicity data and helps to identify the toxic agent and the appropriate dose metric. The metabolism was similar in adult and juvenile animals. Large inter-individual variability in adult animals, as observed for 4-methylanisole, may hamper dose-response analyses of the results. In addition, 4-metylanisole was excreted via milk, but concentrations in the juvenile animals appeared to be 20- to 100-fold lower than via direct gavage exposure. The toxicokinetic parameters support the data interpretation, among others by providing better insight into internal exposures. Subsequently, it will help to prevent testing of irrelevant exposure scenarios and exposure concentrations. Overall, implementation of kinetics with limited effort provides useful information to support the interpretation of toxicological data and can contribute to reduction and refinement of animal testing.

Concentrations of dimethylaniline and other metabolites in milk and tissues of dairy cows treated with lidocaine.

Lidocaine is a topical anaesthetic drug used in dairy cows for laparotomy (caesarean section, abomasal displacement). Because there are no registered drugs for this indication, it can be applied under the so-called Cascade rules (off-label use), with the restriction that the off-label withdrawal periods of 7 days for milk and 28 days for meat are taken into account. In animals, lidocaine is rapidly metabolised into various metabolites, one being 2,6-dimethylaniline (DMA) which is reported to possess carcinogenic and mutagenic properties and detected also in milk. To investigate whether the off-label withdrawal periods are long enough to exclude the presence of lidocaine and DMA, and potential other metabolites, in edible products, a study was performed with eight dairy cows treated with lidocaine by injection in the abdominal muscles. At various time points blood samples, milk and urine were collected. Four animals were slaughtered 3.5 h after treatment, the other four after 48.5 h. The injection site, meat, liver and kidney were analysed for levels of lidocaine, DMA, monoethylglycinexylidide (MEGX) and 3-OH-lidocaine. It was shown that DMA is an important metabolite in dairy cows and can be detected in both meat and milk. In addition, also MEGX, 3-OH-lidocaine and three other metabolites were identified and to some extent quantified. These metabolites were 4-OH-lidocaine, lidocaine-N-oxide and 4-hydroxy-DMA. The latter compound was the most important metabolite in urine. However, levels in milk and meat decreased rapidly after the application. Overall, it can be concluded that the off-label withdrawal times of 7 and 28 days for milk and meat, respectively, guarantee the absence of detectable levels of lidocaine and metabolites.

Carryover of cadmium from feed in growing pigs.

Growing male pigs were exposed to cadmium (Cd) at levels around 1 and 10 mg kg(-1) feed for up to 12 weeks, administered as CdCl2 or Cd-cysteine (CdCys). Pigs exposed to 10 mg kg(-1) showed decreased growth during the last 3 weeks. Liver and kidney concentrations of Cd continuously increased over the entire 12-week exposure, exceeding the European Union limits of 1.0 mg kg(-1) (kidney) and 0.5 mg kg(-1) (liver) within 3 weeks at the feed level of 10 mg kg(-1). A switch to clean feed after 3 weeks for 5 or 9 weeks resulted in steadily decreased levels in kidney and liver, which could be completely attributed to organ growth. At the lower feed level, the level in kidney exceeded the limit almost twofold after 12 weeks, but not after 3 weeks. Liver levels remained below the limit. Metallothionein (MT) levels in livers showed a steady decrease in both untreated and treated animals over time. In kidney such a decrease was only observed in control animals, whereas in the highest-dosed animals the MT concentrations steadily increased. The observed carryover of Cd from feed to liver and kidney was modelled by means of a simple transfer model relating levels in feed via MT levels to accumulation of Cd. Using this model, it was shown that the exposure period of growing pigs to feed containing the European Union limit of 0.5 mg kg(-1) feed should be less than 12 weeks in order to prevent Cd levels in the kidneys to exceed the European Union limit.

Novel insights into the risk assessment of the nanomaterial synthetic amorphous silica, additive E551, in food.

This study presents novel insights in the risk assessment of synthetic amorphous silica (SAS) in food. SAS is a nanostructured material consisting of aggregates and agglomerates of primary particles in the nanorange (<100 nm). Depending on the production process, SAS exists in four main forms, and each form comprises various types with different physicochemical characteristics. SAS is widely used in foods as additive E551. The novel insights from other studies relate to low gastrointestinal absorption of SAS that decreases with increasing dose, and the potential for accumulation in tissues with daily consumption. To accommodate these insights, we focused our risk assessment on internal exposure in the target organ (liver). Based on blood and tissue concentrations in time of two different SAS types that were orally and intravenously administered, a kinetic model is developed to estimate the silicon concentration in liver in (1) humans for average-to-worst-case dietary exposure at steady state and (2) rats and mice in key toxicity studies. The estimated liver concentration in humans is at a similar level as the measured or estimated liver concentrations in animal studies in which adverse effects were found. Hence, this assessment suggests that SAS in food may pose a health risk. Yet, for this risk assessment, we had to make assumptions and deal with several sources of uncertainty that make it difficult to draw firm conclusions. Recommendations to fill in the remaining data gaps are discussed. More insight in the health risk of SAS in food is warranted considering the wide applications and these findings.

Biokinetics of chlorpromazine in primary rat and human hepatocytes and human HepaRG cells after repeated exposure.

Since drug induced liver injury is difficult to predict in animal models, more representative tests are needed to better evaluate these effects in humans. Existing in vitro systems hold great potential to detect hepatotoxicity of pharmaceuticals. In this study, the in vitro biokinetics of the model hepatotoxicant chlorpromazine (CPZ) were evaluated in three different liver cell systems after repeated exposure in order to incorporate repeated-dose testing into an in vitro assay. Primary rat and human hepatocytes, cultured in sandwich configuration and the human HepaRG cell line were treated daily with CPZ for 14 days. Samples were taken from medium, cells and well plastic at specific time points after the first and last exposure. The samples were analysed by HPLC-UV to determine the amount of CPZ in these samples. Based on cytotoxicity assays, the three models were tested at 1-2 µM CPZ, while the primary rat hepatocytes and the HepaRG cell line were in addition exposed to a higher concentration of 15-20 µM. Overall, the mass balance of CPZ decreased in the course of 24 h, indicating the metabolism of the compound within the cells. The largest decrease in parent compound was seen in the primary cultures; in the HepaRG cell cultures the mass balance only decreased to 50%. CPZ accumulated in the cells during the 14-day repeated exposure. Possible explanations for the accumulation of CPZ are a decrease in metabolism over time, inhibition of efflux transporters or binding to phospholipids. The biokinetics of CPZ differed between the three liver cell models and were influenced by specific cell properties as well as culture conditions. These results support the conclusion that in vitro biokinetics data are necessary to better interpret chemical-induced cytotoxicity data.

Fish consumption during child bearing age: a quantitative risk-benefit analysis on neurodevelopment.

The fish ingredient N3-docosahexaenoic acid 22:6 n-3 (DHA) stimulates brain development. On the other hand methylmercury (MeHg) in fish disturbs the developing central nervous system. In this Context the IQ score in children is considered as an aggregate measure of in utero brain development. To determine the effect of DHA exposure on prenatal neurodevelopment the maternal DHA intake during pregnancy was compared with its epidemiologically observed effect on the IQ score of children. For MeHg the maternal intake was converted into its accumulation in the maternal body. The maternal body burden then was compared with its epidemiologically observed relationship with the IQ score. Taking the MeHg and DHA content of 33 fish species the net effect of these compounds on the IQ score was quantified. For most fish species the adverse effect of MeHg on the IQ score exceeded the beneficial effect of DHA. In the case of long-living predators a negative effect up to 10 points on the IQ score was found. The results of this study indicate that food interventions aiming at the beneficial effects of fish consumption should focus on fish species with a high DHA content, while avoiding fish species with a high MeHg content.

Benefit-risk assessment of plant sterols in margarine: a QALIBRA case study.

This paper presents the benefit-risk assessment of adding plant sterols to margarine as an illustration of the QALIBRA method and software. With the QALIBRA tool health effects, risks as well as benefits are expressed in a common metric (DALY) which allows quantitative balancing of benefits and risks of food intake. The QALIBRA software can handle uncertainties in a probabilistic simulation. This simple case study illustrates the data need and assumptions that go into a quantitative benefit-risk assessment. The assessment shows that the benefits of plant sterols added to margarine outweigh the risks, if any.

Transport of chlorpromazine in the Caco-2 cell permeability assay: a kinetic study.

The intestinal transport of compounds can be measured in vitro with Caco-2 cell monolayers. We took a closer look at the exposure and fate of a chemical in the Caco-2 cell assay, including the effect of protein binding. Transport of chlorpromazine (CPZ) was measured in the absorptive and secretory direction, with and without albumin basolaterally. Samples were taken from medium, cells, and well plastic. For the secretory transport experiments with albumin, the free CPZ concentration at the start of the experiment was measured by negligible depletion-solid phase microextraction (nd-SPME). Recovery of CPZ from the medium was low, especially in the absorptive transport direction. CPZ was found in the cells (≤20%) and bound to the well plastic (≤25%), and 94% of CPZ was bound to albumin. An initial lag phase was observed, which was likely caused by partitioning of CPZ between the donor concentration and the Caco-2 cells; after 20 min, transport of CPZ to the receiver compartment was linear. The low recovery and the test compound found both inside the Caco-2 cells and bound to the well plastic complicate the calculation of the fraction transported and render reliable estimates of permeability constants impossible. For a chemical like chlorpromazine, which is hydrophobic in its neutral form, but in general also for more lipophilic compounds, the Caco-2 cell assay might not be straightforward, and a more detailed study into the fate and exposure of the test compound might be needed to arrive at meaningful data for transport and permeability.

Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans.

BACKGROUND: To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL) cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods. METHODS AND RESULTS: The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL) cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose. CONCLUSION: We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (re)absorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory) mechanisms.

Disposition of smoked cannabis with high Δ(9)-tetrahydrocannabinol content: a kinetic model.

INTRODUCTION: No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose. We aimed to develop a kinetic model providing estimates of the THC serum concentrations after smoking cannabis cigarettes containing high THC doses (up to 69mg THC). METHODS: Twenty-four male non-daily cannabis users smoked cannabis cigarettes containing 29.3mg, 49.1mg, and 69.4mg THC. Blood samples were collected over a period of 0-8h and serum THC concentrations were measured. A two-compartment open model was fitted on the individual observed data. RESULTS: Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were Cmax=175ng/mL, Tmax=14min, and AUC0-8h=8150ng×min/mL for the 69.4mg THC dose. Median model results show an almost linear dose response relation for Cmax/Dose=2.8×10(-6)/mL and AUC0-8h/Dose=136×10(-6)min/mL. However, for increasing dose level, there was a clear decreasing trend: Cmax/Dose=3.4, 2.6 and 2.5×10(-6)/mL and AUC0-8h/Dose=157, 133 and 117×10(-6)min/mL for the 29.3, 49.1 and 69.4mg dose, respectively. Within the restriction of 8h of observation, the apparent terminal half life of THC was 150min. CONCLUSION: The model offers insight into the pharmacokinetics of THC in recreational cannabis users smoking cannabis containing high doses of THC mixed with tobacco. The model is an objective method for providing serum THC concentrations up to 8h after smoking cannabis with a high THC content (up to 23%).

Effect of administration route on the biodistribution and shedding of replication-deficient HAdV-5: a qualitative modelling approach.

Gene therapy is a rapidly developing field in which recombinant nucleic acid sequences are introduced to individuals. Its therapeutic, prophylactic or diagnostic effect relates directly to the sequence it contains or to the product of genetic expression of this sequence. Recombinant adenoviral vectors (in particular HAdV-5 vectors) are frequently used in gene therapy. Knowledge on biodistribution and shedding is crucial in the risk assessment for the patient and the patient's environment. This review presents a critical overview on biodistribution and shedding data of non-replicating viral vector HAdV-5, related to the used administration route. Based on these data, a qualitative model for the biodistribution and shedding of HAdV-5 based viral vectors is presented. Biodistribution and shedding depend on the route of administration. Some routes lead to local biodistribution and no shedding or one shedding route only. Other routes lead to systemic biodistribution and to shedding via several excreta. Shedding via semen and transport across the blood-brain barrier is not expected for HAdV-5. The presented qualitative model can help researchers and risk assessors to determine the possible distribution in the body and the risk of shedding via the different excretion routes. Furthermore, it can help regulators to predict the different shedding routes after a certain administration route and thus in deciding which studies are warranted or which safety precautions are needed after administration to patients.

Effect of administration route on the biodistribution and shedding of replication-deficient AAV2: a qualitative modelling approach.

Gene therapy is a rapidly developing field in which recombinant nucleic acid sequences are introduced to individuals to regulate, repair, replace, add or delete a genetic sequence. Recombinant adeno-associated viral (AAV) vectors, especially AAV2, are frequently used in gene therapy. Knowledge on the biodistribution and potential shedding of AAV2 is crucial to evaluate the risks of infection with the viral vector for the patient and the environment. Literature was analysed for biodistribution and shedding data for AAV2. Preclinical and clinical studies were included with a focus on the influence of the administration route on spreading. Based on biodistribution and shedding data, a qualitative model for the biodistribution and shedding of AAV2 related to the administration route is presented. It is concluded that biodistribution and shedding of AAV2 depends on the route of administration. Some routes lead to local biodistribution and thus to no shedding or shedding via one route only. Other routes lead to systemic biodistribution and to shedding via several excretion routes. The qualitative model presented can help to determine the possible biodistribution in the body and the risk of shedding via the different excretion routes. In addition, it can help to predict the different shedding routes after a certain administration route of AAV2 and thus in deciding which studies are warranted or which safety precautions are needed after administration to patients.

Dose addition and the isobole method as approaches for predicting the cumulative effect of non-interacting chemicals: a critical evaluation.

The prediction of the effect of cumulative exposure to similarly acting chemicals is commonly done by dose addition, such as in the relative potency factor approach. This can only be done under the assumption of zero interaction between the chemicals. The related, but not equivalent, isobole method is the most common criterion to judge whether interactions between similarly acting chemicals have taken place in a mixture experiment. Many who apply this latter method assume that it is applicable to any combination of substances, regardless of the shape of the dose-response curves of the individual substances or their underlying mechanism of action. Proponents commonly refer to the work of Berenbaum, who claimed to have proven the general applicability of the isobole method based on zero interaction. In this article, we argue that his argumentation is not generally valid. We further demonstrate that the isobole method, just like dose addition, has limited applicability. Using a physiologically based mathematical model, we provide a theoretical example of a combination of chemicals with zero interaction where the isobole method would result in the decision that they do interact. We discuss the implications for research focusing on detecting or defining interactions, and for the prediction of effects from combined exposures assuming zero interaction.

Toxicodynamic analysis of the combined cholinesterase inhibition by paraoxon and methamidophos in human whole blood.

Theoretical work has shown that the isobole method is not generally valid as a method for testing the absence or presence of interaction (in the biochemical sense) between chemicals. The present study illustrates how interaction can be tested by fitting a toxicodynamic model to the results of a mixture experiment. The inhibition of cholinesterases (ChE) in human whole blood by various dose combinations of paraoxon and methamidophos was measured in vitro. A toxicodynamic model describing the processes related to both OPs in inhibiting AChE activity was developed, and fit to the observed activities. This model, not containing any interaction between the two OPs, described the results from the mixture experiment well, and it was concluded that the OPs did not interact in the whole blood samples. While this approach of toxicodynamic modeling is the most appropriate method for predicting combined effects, it is not rapidly applicable. Therefore, we illustrate how toxicodynamic modeling can be used to explore under which conditions dose addition would give an acceptable approximation of the combined effects from various chemicals. In the specific case of paraoxon and methamidophos in whole blood samples, it was found that dose addition gave a reasonably accurate prediction of the combined effects, despite considerable difference in some of their rate constants, and mildly non-parallel dose-response curves. Other possibilities of validating dose-addition using toxicodynamic modeling are briefly discussed.

Toxicodynamic analysis of the inhibition of isolated human acetylcholinesterase by combinations of methamidophos and methomyl in vitro.

The applicability of dose addition to combinations of OP-esters and carbamates has been questioned based on theoretical considerations, but these have not been well supported by experimental findings. In the present study, the inhibition of AChE by combinations of methamidophos (an OP-ester) and methomyl (a carbamate) was examined in vitro. AChE inhibition was measured by the Ellman assay. We addressed the question of interaction between the OP-ester and carbamate by a toxicodynamic (TD) model reflecting the mechanism of action of the individual chemicals, without incorporating any interactions between them. The model was extended by including the experimental actions in the Ellman assay to correct for the difference in reactivation rates between phosphorylated and carbamylated AChE, which caused a bias in the observations from the assay. This zero-interactive TD model described the observations well, indicating that the OP-ester and carbamate did not interact. The applicability of dose addition was further explored by applying dose addition to the predicted inhibition by the TD model. Despite the differences in dynamics between methamidophos and methomyl, their dose-response curves were close to parallel, and dose addition gave a reasonably accurate prediction of the combined effects.

Facilitated transport of polychlorinated biphenyls and polybrominated diphenyl ethers by dissolved organic matter.

The exchange rate of hydrophobic organic chemicals between the aqueous phase and a sorbent (e.g., soil, organism, passive sampler) is relevant for distribution processes between environmental compartments, including organisms. Dissolved phases such as humic acids, proteins, and surfactants can affect the transfer of such chemicals between the aqueous and sorbent phases by sorption and desorption processes. In this study, the desorption of polychlorinated biphenyls and polybrominated diphenyl ethers from a polymer phase to an aqueous medium was monitored at different humic acid concentrations. The rate of release of the chemical by the polymer phase demonstrates thatthe chemical sorbed to dissolved humic acid contributed significantly to the total mass transfer when the affinity for the humic acid was sufficiently high. This illustrates that environmentally relevant humic acid concentrations can facilitate transport of hydrophobic organic chemicals. The consequences of these facilitated transport mechanisms for uptake into passive samplers are discussed, in particular in situations where equilibration is very slow or when exposure varies in time or space.