Generic physiologically based kinetic modelling for farm animals: Part I. Data collection of physiological parameters in swine, cattle and sheep

Abstract Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and application of these models requires data for physiological, anatomical and chemical specific parameters. Here, we present the results of a structured data collection of anatomical and physiological parameters in three key farm animal species (swine, cattle and sheep). We performed an extensive literature search and meta-analyses to quantify intra-species variability and associated uncertainty of the parameters. Parameters were collected for organ weights and blood flows in all available breeds from 110 scientific publications, of which 29, 48 and 33 for cattle, sheep, and swine, respectively. Organ weights were available in literature for all three species. Blood flow parameter values were available for all organs in sheep but were scarcer in swine and cattle. Furthermore, the parameter values showed a large intra-species variation. Overall, the parameter values and associated variability provide reference values which can be used as input for generic PBK models in these species

Predicting concentrations of human pharmaceuticals throughout the river systems of Europe

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An open source physiologically based kinetic model for the chicken (Gallus gallus domesticus): Calibration and validation for the prediction residues in tissues and eggs.

Xenobiotics from anthropogenic and natural origin enter animal feed and human food as regulated compounds, environmental contaminants or as part of components of the diet. After dietary exposure, a chemical is absorbed and distributed systematically to a range of organs and tissues, metabolised, and excreted. Physiologically based kinetic (PBK) models have been developed to estimate internal concentrations from external doses. In this study, a generic multi-compartment PBK model was developed for chicken. The PBK model was implemented for seven compounds (with log Kow range −1.37–6.2) to quantitatively link external dose and internal dose for risk assessment of chemicals. Global sensitivity analysis was performed for a hydrophilic and a lipophilic compound to identify the most sensitive parameters in the PBK model. Model predictions were compared to measured data according to dataset-specific exposure scenarios. Globally, 71% of the model predictions were within a 3-fold change of the measured data for chicken and only 7% of the PBK predictions were outside a 10-fold change. While most model input parameters still rely on in vivo experiments, in vitro data were also used as model input to predict internal concentration of the coccidiostat monensin. Future developments of generic PBK models in chicken and other species of relevance to animal health risk assessment are discussed. Keywords: Risk assessment, Chicken, Physiologically based kinetic model, In vitro to in vivo extrapolation, Global sensitivity analysi

Physiologically based kinetic models for farm animals: Critical review of published models and future perspectives for their use in chemical risk assessment

Abstract Physiologically based kinetic (PBK) models in the 10 most common species of farm animals were identified through an extensive literature search. This resulted in 39 PBK models, mostly for pharmaceuticals. The models were critically assessed using the WHO criteria for model evaluation, i.e. 1) purpose, 2) structure and mathematical representation, 3) computer implementation, 4) parameterisation, 5) performance, and 6) documentation. Overall, most models were calibrated and validated with published data (92% and 67% respectively) but only a fraction of model codes were published along with the manuscript (28%) and local sensitivity analysis was performed without considering global sensitivity analysis. Hence, the reliability of these PBK models is hard to assess and their potential for use in chemical risk assessment is limited. In a risk assessment context, future PBK models for farm animals should include a more generic and flexible model structure, use input parameters independent on calibration and include assessment tools to assess model performance. Development and application of PBK models for farm animal species would furthermore benefit from the setup of structured databases providing data on physiological and chemical-specific parameters as well as enzyme expression and activities to support the development of species-specific QIVIVE models

The Lifelines Cohort Study:a data source available for studying informal caregivers’ experiences and the outcomes of informal caregiving

Background Informal care is taking an increasingly important role in our health care system, and an improvement in our understanding of caregiving experiences and outcomes has become more relevant. The Lifelines informal care add-on study (Lifelines ICAS) was initiated within the Lifelines Cohort Study to cover the large heterogeneity in the caregiver population and to investigate the complex interplay among the characteristics of the caregiver, care recipient, and care situation and positive and negative caregiver outcomes. In this paper, we discuss the study design and data collection procedures of Lifelines ICAS, provide a detailed overview of its measures, and describe the caregiver study population. Methods Lifelines participants who participated in the 2nd Lifelines follow-up questionnaire were asked whether they provided informal care. Subsequently, they were invited to participate in Lifelines ICAS. Descriptive statistics were used to describe all informal caregivers in the 2nd Lifelines follow-up questionnaire and to describe the subsample of informal caregivers participating in Lifelines ICAS. Results A total of 11,651 Lifelines participants were self-identified as an informal caregiver and provided basic information about their care situation. A subsample of 965 informal caregivers participated in Lifelines ICAS and completed a comprehensive questionnaire about their care situation. In this subsample, the average age of caregivers was 53 years (SD 9.8), 75% were female, and 56% cared for a parent (in-law). Care recipients were on average 68 years old (SD 23.5), and 64% were female. Discussion Considering that informal caregivers are a huge resource for our health care system, Lifelines ICAS enables the study of differences among caregivers, care recipients, and care situations, as well as the study of common characteristics and features across caregiver groups. Notably, data from the Lifelines Cohort Study and Lifelines ICAS are available to all researchers on a fee-for-service basis, and Lifelines ICAS data may be enhanced by one or more follow-up measurements or linkages with other data sources

The importance of over-the-counter-sales and product format in the environmental exposure assessment of active pharmaceutical ingredients

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The influence of uncertainty and location-specific conditions on the environmental prioritisation of human pharmaceuticals in Europe

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