PACEMweb: a tool for aggregate consumer exposure assessment.

Background: To ascertain the safe use of chemicals that are used in multiple consumer products, the aggregate human exposure, arising from combined use of multiple consumer products needs to be assessed.

Objective: In this work the Probabilistic Aggregate Consumer Exposure Model (PACEM) is presented and discussed. PACEM is implemented in the publicly available web tool, PACEMweb, for aggregate consumer exposure assessment.

A congener-specific modelling approach for the transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin-like polychlorinated biphenyls from feed to eggs of laying hens.

Calibration of a kinetic model for the transfer of PCDD/Fs and dl-PCBs from feed to the hen's body and eggs was thus far restricted to the total TEQ concentration, i.e. the summed concentrations of PCDD/Fs and dl-PCBs expressed in terms of equivalents of 2,3,7,8-TCDD.

Challenges in Predicting the Change in the Cumulative Exposure of New Tobacco and Related Products Based on Emissions and Toxicity Dose-Response Data.

Many novel tobacco products have been developed in recent years. Although many may emit lower levels of several toxicants, their risk in the long term remains unclear. We previously published a method for the exposure assessment of mixtures that can be used to compare the changes in cumulative exposure to carcinogens among tobacco products.

Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring.

Background: In human biomonitoring, blood is often used as a matrix to measure exposure to per- and polyfluoroalkyl substances (PFAS). Because the toxicokinetics of a substance (determining the steady-state blood concentration) may affect the toxic potency, the difference in toxicokinetics among PFAS has to be accounted for when blood concentrations are used in mixture risk assessment.

Objectives: This research focuses on deriving relative potency factors (RPFs) at the blood serum level.

Quantitative chemical risk assessment for mixtures: Application to alkylphenol mixtures and phthalate mixtures in tap and bottled water.

The occurrence and hazard risks of mixtures of Contaminants of Emerging Concern (CECs) in drinking water (DW) lead to serious consideration regarding the possible impacts on public health. Consequently, there is ongoing research, development and empowerment of risk assessment procedures to get more toxicological insight. For instance, alkylphenols and phthalates have been frequently reported to be present both in bottled and tap water, affecting different human endpoints.

Combined Exposure to Multiple Mycotoxins: An Example of Using a Tiered Approach in a Mixture Risk Assessment.

Humans are exposed to mycotoxins on a regular basis. Exposure to a mixture of mycotoxins may, therefore, result in a combination of adverse effects, or trigger the same effects. This should be accounted for when assessing the combined risk of multiple mycotoxins.

Pulmonary toxicity and gene expression changes after short-term inhalation exposure to surface-modified copper oxide nanoparticles.

Copper oxide nanoparticles (CuO NPs) have previously been shown to cause dose-dependent pulmonary toxicity following inhalation. Here, CuO NPs (10 nm), coated with polyethylenimine (PEI) or ascorbate (ASC) resulting in positively or negatively charged NPs, respectively, were evaluated. Rats were exposed nose-only to similar exposure dose levels of ASC or PEI coated CuO NPs for 5 consecutive days.

Development of a quantitative chemical risk assessment (QCRA) procedure for contaminants of emerging concern in drinking water supply.

The uncertainties on the occurrence, fate and hazard of Contaminants of Emerging Concern (CECs) increasingly challenge drinking water (DW) utilities whether additional measures should be taken to reduce the health risk. This has led to the development and evaluation of risk-based approaches by the scientific community. DW guideline values are commonly derived based on deterministic chemical risk assessment (CRA).

Culture Conditions Affect Chemical-Induced Developmental Toxicity : The Case of Folic Acid, Methionine and Methotrexate in the Neural Embryonic Stem Cell Test.

tests are increasingly applied in chemical hazard assessment. Basic culture conditions may affect the outcome of tests and should be optimised to reduce false predictions. The neural embryonic stem cell test (ESTn) can predict early neurodevelopmental effects of chemicals, as it mimics the differentiation of stem cells towards the neuroectodermal lineage.

Probabilistic approach for assessing cancer risk due to benzo[a]pyrene in barbecued meat: Informing advice for population groups.

Background: Consumption of meat prepared by barbecuing is associated with risk of cancer due to formation of carcinogenic compounds including benzo[a]pyrene (BaP). Assessment of a population's risk of disease and people's individual probability of disease given specific consumer attributes may direct food safety strategies to where impact on public health is largest. The aim of this study was to propose a model that estimates the risk of cancer caused by exposure to BaP from barbecued meat in Denmark, and to estimate the probability of developing cancer in subgroups of the population given different barbecuing frequencies.

Modelling the long-term feed-to-fillet transfer of leuco crystal violet and leuco malachite green in Atlantic salmon (Salmo salar).

Leuco crystal violet (LCV) and leuco malachite green (LMG) are the main metabolites of two dyes that are forbidden for use in food production, but can be present at low background concentration in novel Atlantic salmon feed ingredients such as processed animal proteins (animal by-product [ABP]). In this study, the potential transfer of dietary LCV or LMG to the fillet of farmed Atlantic salmon was investigated. The uptake and elimination rate kinetics were determined in seawater-adapted Atlantic salmon (initial weight 587 ± 148 g) fed two levels of either LCV- or LMG-enriched diets (~500 and 4000 µg kg, respectively) for 40 days, followed by a 90-day depuration period with feeding on control diets (<0.

APROBA-Plus: A probabilistic tool to evaluate and express uncertainty in hazard characterization and exposure assessment of substances.

To facilitate the application of probabilistic risk assessment, the WHO released the APROBA tool. This tool applies lognormal uncertainty distributions to the different aspects of the hazard characterization, resulting in a probabilistic health-based guidance value. The current paper describes an extension, APROBA-Plus, which combines the output from the probabilistic hazard characterization with the probabilistic exposure to rapidly characterize risk and its uncertainty.

Organ burden and pulmonary toxicity of nano-sized copper (II) oxide particles after short-term inhalation exposure.

Introduction: Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. Releases into the air may occur and, therefore, the inhalation route is of specific interest. Here we tested copper oxide nanoparticles (CuO NPs) after repeated inhalation as hazard data for this material and exposure route is currently lacking for risk assessment.

The probabilistic aggregate consumer exposure model (PACEM): validation and comparison to a lower-tier assessment for the cyclic siloxane D5.

Current practice of chemical risk assessment for consumer product ingredients still rarely exercises the aggregation of multi-source exposure. However, focusing on a single dominant source/pathway combination may lead to a significant underestimation of the risk for substances present in numerous consumer products, which often are used simultaneously. Moreover, in most cases complex multi-route exposure scenarios also need to be accounted for.

Exploring the uncertainties in cancer risk assessment using the integrated probabilistic risk assessment (IPRA) approach.

Current methods for cancer risk assessment result in single values, without any quantitative information on the uncertainties in these values. Therefore, single risk values could easily be overinterpreted. In this study, we discuss a full probabilistic cancer risk assessment approach in which all the generally recognized uncertainties in both exposure and hazard assessment are quantitatively characterized and probabilistically evaluated, resulting in a confidence interval for the final risk estimate.

Comparative hazard identification of nano- and micro-sized cerium oxide particles based on 28-day inhalation studies in rats.

There are many uncertainties regarding the hazard of nanosized particles compared to the bulk material of the parent chemical. Here, the authors assess the comparative hazard of two nanoscale (NM-211 and NM-212) and one microscale (NM-213) cerium oxide materials in 28-day inhalation toxicity studies in rats (according to Organisation for Economic Co-operation and Development technical guidelines). All three materials gave rise to a dose-dependent pulmonary inflammation and lung cell damage but without gross pathological changes immediately after exposure.

Presence and risks of nanosilica in food products.

This study uniquely describes all steps of the risk assessment process for the use of one specific nanomaterial (nanosilica) in food products. The aim was to identify gaps in essential knowledge and the difficulties and uncertainties associated with each of these steps. Several food products with added silica (E551) were analyzed for the presence, particle size and concentration of nanosilica particles, using experimental analytical data, and the intake of nanosilica via food was estimated.

Comparison of two models for the estimation of usual intake addressing zero consumption and non-normality.

Various models exist for estimating the usual intake distribution from dietary intake data. In this paper, we compare two of these models, the Iowa State University Foods (ISUF) model and the betabinomial-normal (BBN) model and apply them to three different datasets. Intake data are obtained by aggregating over multiple food products and are often non-normal.

Deriving a data-based interspecies assessment factor using the NOAEL and the benchmark dose approach.

In deriving human health-based exposure limits from animal data, differences in sensitivity to a compound between animals and humans must be taken into account. These interspecies differences can be caused by differences in toxicokinetics and or toxicodynamics. Apart from that, species differ in body size, and this is usually accounted for by scaling doses to body weight (i.

A comparison of ratio distributions based on the NOAEL and the benchmark approach for subchronic-to-chronic extrapolation.

One approach to derive a data-based assessment factor (AF) for subchronic-to-chronic extrapolation is to determine ratios between the NOAEL(subchronic) and NOAEL(chronic) for the same compounds. Instead of using ratios of NOAELs, the distribution can also be estimated by ratios of subchronic and chronic Benchmark Doses (or Critical Effect Doses, CEDs, for continuous data). In this study 314 dose-response datasets on body weights and liver weights of mice and rats were selected providing dose-response information after both subchronic and chronic exposure.