Search Results (7)

Per- and polyfluoroalkyl substances (PFAS) have been found worldwide in water, soil, plants, and animals, including humans. A primary route of exposure for humans and animals to PFAS is through the diet and drinking water. Perfluorooctane sulfonate (PFOS), a long-chain PFAS with a relatively long half-life, has been associated with adverse health effects in humans and laboratory animals. There are few toxicokinetic studies on PFOS in domestic livestock raised for human food consumption, which are critical for assessing human food safety. This work aimed to develop a simple daily accumulation model (DAM) for predicting PFOS residues in edible beef cattle muscle. A one-compartment toxicokinetic model in a spreadsheet format was developed using simple calculations to account for daily PFAS into and out of the animal. The DAM was used to simulate two case studies to predict resultant PFOS residues in edible beef cattle tissues. The results demonstrated that the model can reasonably predict PFOS concentrations in beef cattle muscle in a real-world scenario. The DAM was then used to simulate dietary PFOS exposure in beef cattle throughout a typical lifespan in order to derive a generic bioaccumulation factor. The DAM is expected to work well for other PFAS in beef cattle, PFAS in other livestock species raised for meat, and other chemical contaminants with relatively long half-lives. Full article

Toxicokinetic or pharmacokinetic models, physiologically based or not, offer a unique avenue to understand the transport of toxins or pharmaceuticals in living organisms. The availability of analytical solutions to such models offers the means to engage in a plethora of applications. In the present work, we provide the framework to solve analytically such models using the matrix exponential, and we then apply this method to derive an explicit solution to four-to-five-compartment physiologically based toxicokinetic (PBTK) models considering a single- and an infinite-exponential expression for the amount of mass released from an implantable device. We also offer the conditions that need to be met for analytical solutions to be obtained when the kinetic rates are time-dependent functions. Our analysis compares the computation time between analytical and numerical solutions and characterizes the dependency of the maximum substance mass value and the time it occurs in the various tissue compartments from the material surface diffusion characteristics. Our analytical solutions, which have several advantages over the solutions obtained using numerical solvers, can be incorporated into in silico tools and provide valuable information for human health risk assessment. Full article

The in vitro biotransformation of phenol at 11 °C was studied using pre-spawn adult rainbow (Oncorhynchus mykiss) (RBT), brook (Salvelinus fontinalis) (BKT), and lake trout (Salvelinus namaycush) (LKT) hepatic microsomal preparations. The incubations were optimized for time, cofactor concentration, pH, and microsomal protein concentration. Formation of Phase I ring-hydroxylation and Phase II glucuronidation metabolites was quantified using HPLC with dual-channel electrochemical and UV detection. The biotransformation of phenol over a range of substrate concentrations (1 to 180 mM) was quantified, and the Michaelis–Menten kinetics constants, Km and Vmax, for the formation of hydroquinone (HQ), catechol (CAT), and phenylglucuronide (PG) were calculated. Species differences were noted in the Km values for Phase I enzyme production of HQ and CAT, with the following rank order of apparent enzyme affinity for substrate: RBT > BKT = LKT. However, no apparent differences in the Km for Phase II metabolism of phenol to PG were detected. Conversely, while there were no apparent differences in Vmax between species for HQ or CAT formation, the apparent maximum capacity for PG formation was significantly less in LKT than that observed for RBT and BKT. These experiments provide a means to quantify metabolic activation and deactivation of xenobiotics in fish, to compare activation and deactivation reactions across species, and to act as a guide for future predictions of new chemical biotransformation pathways and rates in fish. These experiments provided the necessary rate and capacity (Km and Vmax) inputs that are required to parameterize a fish physiologically based toxicokinetic (PB-TK) model for a reactive chemical that is readily biotransformed, such as phenol. In the future, an extensive database of these rate and capacity parameters on important fish species for selected chemical structures will be needed to allow the effective use of predictive models for reactive, biotransformation chemicals in aquatic toxicology and environmental risk assessment. Full article

Physiologically based pharmacokinetic/toxicokinetic (PBPK/PBTK) models are designed to elucidate the mechanism of chemical compound action in organisms based on the physiological, biochemical, anatomical, and thermodynamic properties of organisms. After nearly a century of research and practice, good results have been achieved in the fields of medicine, environmental science, and ecology. However, there is currently a lack of a more systematic review of progress in the main research directions of PBPK models, especially a more comprehensive understanding of the application in aquatic environmental research. In this review, a total of 3974 articles related to PBPK models from 1996 to 24 March 2024 were collected. Then, the main research areas of the PBPK model were categorized based on the keyword co-occurrence maps and cluster maps obtained by CiteSpace. The results showed that research related to medicine is the main application area of PBPK. Four major research directions included in the medical field were “drug assessment”, “cross-species prediction”, “drug–drug interactions”, and “pediatrics and pregnancy drug development”, in which “drug assessment” accounted for 55% of the total publication volume. In addition, bibliometric analyses indicated a rapid growth trend in the application in the field of environmental research, especially in predicting the residual levels in organisms and revealing the relationship between internal and external exposure. Despite facing the limitation of insufficient species-specific parameters, the PBPK model is still an effective tool for improving the understanding of chemical–biological effectiveness and will provide a theoretical basis for accurately assessing potential risks to ecosystems and human health. The combination with the quantitative structure–activity relationship model, Bayesian method, and machine learning technology are potential solutions to the previous research gaps. Full article

Toxicokinetics plays a crucial role in the health risk assessments of xenobiotics. Classical compartmental models are limited in their ability to determine chemical concentrations in specific organs or tissues, particularly target organs or tissues, and their limited interspecific and exposure route extrapolation hinders satisfactory health risk assessment. In contrast, physiologically based toxicokinetic (PBTK) models quantitatively describe the absorption, distribution, metabolism, and excretion of chemicals across various exposure routes and doses in organisms, establishing correlations with toxic effects. Consequently, PBTK models serve as potent tools for extrapolation and provide a theoretical foundation for health risk assessment and management. This review outlines the construction and application of PBTK models in health risk assessment while analyzing their limitations and future perspectives. Full article

Toxicokinetic (TK) models have been used for decades to estimate concentrations of per-and polyfluoroalkyl substances (PFAS) in serum. However, model complexity has varied across studies depending on the application and the state of the science. This scoping effort seeks to systematically map the current landscape of PFAS TK models by categorizing different trends and similarities across model type, PFAS, and use scenario. A literature review using Web of Science and SWIFT-Review was used to identify TK models used for PFAS. The assessment covered publications from 2005–2020. PFOA, the PFAS for which most models were designed, was included in 69 of the 92 papers, followed by PFOS with 60, PFHxS with 22, and PFNA with 15. Only 4 of the 92 papers did not include analysis of PFOA, PFOS, PFNA, or PFHxS. Within the corpus, 50 papers contained a one-compartment model, 17 two-compartment models were found, and 33 used physiologically based pharmacokinetic (PBTK) models. The scoping assessment suggests that scientific interest has centered around two chemicals—PFOA and PFOS—and most analyses use one-compartment models in human exposure scenarios. Full article

Organophosphate esters (OPEs) are widely used and harmful to organisms and human health. Dust ingestion is an important exposure route for OPEs to humans. In this study, by integrating ToxCast high-throughput in vitro assays with in vitro to in vivo extrapolation (IVIVE) via physiologically based Toxicokinetic (PBTK) modeling, we assessed the hepatocyte-based health risk for humans around the world due to exposure to two typical OPEs (TPHP and TDCPP) through the dust ingestion exposure route. Results showed that the health guidance value of TPHP and TCDPP obtained in this study was lower than the value obtained through animal experiments. In addition, probabilistic risk assessment results indicate that populations worldwide are at low risk of exposure to TPHP and TDCPP through dust ingestion due to low estimated daily intakes (EDIs) which are much lower than the reference dose (RfDs) published by the US EPA, except in some regional cases. Most margin of exposure (MOE) ranges of TDCPP for children are less than 100, which indicates a moderately high risk. Researchers should be concerned about exposure to TDCPP in this area. The method proposed in this study is expected to be applied to the health risk assessment of other chemicals. Full article