Estimation of seroconversion rates for infectious diseases: Effects of age and noise.

The presence of serum antibodies is a biomarker of past infection. Instead of seroclassification aimed at measuring seroprevalence a population sample of serum antibody levels may be used to estimate the incidence of seroconversion. This article expands an earlier study into seroincidence estimation, employing models of the seroresponse that include probability of escaping infection, as well as nonexponential decay kinetics and different sources of noise.

Detection of titanium particles in human liver and spleen and possible health implications.

Background: Titanium dioxide (TiO) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO particle consumption could not be excluded then.

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.

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.

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 (TiO NPs), based on currently available information.

Linking the seroresponse to infection to within-host heterogeneity in antibody production.

A recently published model for the serum antibody response to infection appeared well suited for use in statistical analyses of longitudinal serological data. The published model assumed exponential decay with fixed rates for pathogen and serum antibody kinetics, ignoring any within-host heterogeneity in the seroresponse. A bi-exponential model shows that there is rapid initial decay followed by a prolonged period of persistent low serum antibody concentrations.

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.

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.

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.

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.

Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure.

Introduction: Physiologically based pharmacokinetic (PBPK) models may be useful in emergency risk assessment, after acute exposure to chemicals, such as dichloromethane (DCM). We evaluated the applicability of three PBPK models for human risk assessment following a single exposure to DCM: one model is specifically developed for DCM (Bos) and the two others are semi-generic ones (Mumtaz and Jongeneelen).

Materials And Methods: We assessed the accuracy of the models' predictions by simulating exposure data from a previous healthy volunteer study, in which six subjects had been exposed to DCM for 1h.

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.

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.

Toxicokinetic model assessment on the dechlorination of dietary toxaphene CHB-62 into CHB-44 in Atlantic salmon (Salmo salar L.).

European Union legislation on the upper limits of toxaphene in feed and food include the congeners CHB-26, CHB-62 and CHB-50 and is set at 50 µg kg⁻¹ feed for the sum of these three congeners. However, due to their elevated presence in fish, the congeners CHB-40 and CHB-41, CHB-44, and CHB-42 should also be included according to the European Food Safety Authority (EFSA) in 2005. Earlier trials with model zebra fish have shown in vivo dechlorination of dietary CHB-62 to CHB-44 and, to a lesser degree, of CHB-50 to CHB-40.

Transfer of perfluorooctane sulfonic acid (PFOS) from contaminated feed to dairy milk.

Dietary intake is the predominant route for human exposure to perfluorooctane sulfonic acid (PFOS). Single pollution events may thus affect human exposure if polluted ground and water is used to produce animal feed or food. In this study, a physiologically based pharmacokinetic (PBPK-) model is derived that describes the uptake of PFOS from contaminated feed by cows and its subsequent elimination through the cows' milk.

Infectious disease transmission as a forensic problem: who infected whom?

Observations on infectious diseases often consist of a sample of cases, distinguished by symptoms, and other characteristics, such as onset dates, spatial locations, genetic sequence of the pathogen and/or physiological and clinical data. Cases are often clustered, in space and time, suggesting that they are connected. By defining kernel functions for pairwise analysis of cases, a matrix of transmission probabilities can be estimated.

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.

An improved model to predict physiologically based model parameters and their inter-individual variability from anthropometry.

We developed a population physiology model, physB, which provides a statistical description of the physiological characteristics in the human population, in terms of the physiological parameters that are needed in physiologically based pharmacokinetic modelling. The model predicts individual organ weights, blood flows and some respiratory parameters from anthropometric properties (body height and weight, age and gender). It draws on two existing models, PK-Pop and P(3)M, but various changes and improvements were made.

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.

Biomarker dynamics: estimating infection rates from serological data.

The marginal distribution of serum antibody titres in a cross-sectional population sample can be expressed as a function of the infection rate, taking into account heterogeneity in peak levels and decay rates. This marginal model allows estimation of incidences, as well as simple tests for homogeneity across age, gender or geographic strata, using likelihood ratio tests. An example is given using Campylobacter serum antibody 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.

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.

Toxicokinetics and carry-over model of α-hexabromocyclododecane (HBCD) from feed to consumption-sized Atlantic salmon (Salmo salar).

A two-compartmental model for the kinetics of carry-over of the brominated flame retardant α-hexabromocyclododecane (HBCD) from feed to the fillet of farmed harvest-sized Atlantic salmon (Salmo salar L.) was developed. The model is based on a fat compartment for storage of the lipophilic α-HBCD and a central compartment comprising all other tissues.

The kinetics of the tissue distribution of silver nanoparticles of different sizes.

Blood kinetics and tissue distribution of 20, 80 and 110 nm silver nanoparticles were investigated in rats up to 16 days after intravenous administration once daily for 5 consecutive days. Following both single and repeated injection, silver nanoparticles disappeared rapidly from the blood and distributed to all organs evaluated (liver, lungs, spleen, brain, heart, kidneys and testes) regardless of size. The 20 nm particles distributed mainly to liver, followed by kidneys and spleen, whereas the larger particles distributed mainly to spleen followed by liver and lung.

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.