A physiologically-based pharmacokinetic (PBPK) model represents the structural components of the body with physiologically relevant compartments connected via blood flow rates described by mathematical equations to determine drug disposition. PBPK models are used in the pharmaceutical sector for drug development, precision medicine, and the chemical industry to predict safe levels of exposure during the registration of chemical substances. However, one area of application where PBPK models have been scarcely used is forensic science. In this review, we give an overview of PBPK models successfully developed for several illicit drugs and environmental chemicals that could be applied for forensic interpretation, highlighting the gaps, uncertainties, and limitations.

Nanotoxicology is the study of the toxicity of nanoparticles (NPs). Nanotoxicological studies are meant to define the extent to which nanomaterials pose threats to human health and negatively impact the environment. Nanoparticle toxicity, or nanotoxicity, mainly arises due to their specific characteristics like large surface-area-to-volume ratio and other physicochemical properties, which can lead to different biological activity compared with their bulk counterparts. In the past few decades, there has been huge advancement in utilizing nanotechnology in many fields, including biomedical sciences, due to NPs’ novel and unique properties, which make them biologically more reactive. The most important biomedical applications of nanomaterials are in disease diagnosis, drug design, drug delivery, regenerative medicine, and treatment. The biomedical applications of nanomaterials in disease diagnosis, treatment, and monitoring to control biological functions have been referred to as “nanomedicine” (Moghimi et al., 2005). This magnifies the need for and importance of nanomaterials as drug molecules for many pathological conditions, but the potentially unpredictable and 236unwanted consequences after exposure to the nanomedicine have yet to be evaluated. Exposure of NPs adversely affects the normal physiology of humans as well as animals by disrupting biomolecules at the cellular level by invading the cells, possibly by interrupting the normal structure of tissues and organs; this is known as nanotoxicity. The toxicity depends upon physicochemical properties of NPs, especially the size of particles, shape, surface area and charge, chemical composition, and their stability. The underlying mechanism of nanotoxicity is under extensive research (Figure 20.1), but it is known that cytotoxicity and gene activation related to oxidative stress are a result of reactive oxygen species (ROS) generated upon exposure to NPs at the cellular and molecular level (Jebali, and Kazemi, 2013). Figure 20.1 Possible mechanisms of toxicity due to NP exposure.

Many chemicals are detected in the environment at very low levels, they were viewed as being incapable of causing harm. Their risks to human health and associated environment are now emerging. But effects of their multiple interactions at cellular and molecular levels is unknown. We have investigated the effects of treatment of wild type and PPARα knockout mice on fatty acid contents in different organs. Mice were treated with low concentrations of multiple persistent environmental chemicals: atrazine, dieldrin, endrin, endosulfan and anthracene (1–100ng/L) in drinking water for six weeks and brain, liver, kidney, heart and spleen were collected, processed for fatty acid/lipid contents determination by GC/MS. The percentage changes in the levels of the fatty acid following treatment were calculated for wild type (WT) and PPARα −/− (KO). The changes (WT and KO) were compared to find the effects of treatment and the genetic (PPARα) influence on the regulation of fatty acid levels. Our results show differential presence of fatty acids: hexadecanoic acid, hexadecanoic acid methyl ester, hexadecanamide, 9‐octadecanemaide, pentadecanoic acid, octadecanoid acid, arachidonic acid, and cholesterol in the different organs as well as their differential regulation in the WT and KO. Results are summarized in Tables 1 and 2. Briefly, treatment increased 9‐octadecanemaide by 145% (WT) and 38% (KO) in the heart, reduced in the kidney 17% (WT), 29% (KO); hexadecanoic acid, octadecanoic acid was increased 0% (WT) but by 178% and 110% respectively (KO) (kidney), octadecanoic acid went up by 334% (KO) with not change in WT, hexadecanamide increased by 92% in KO Liver with 5% in WT. Generally, more perturbations in the regulation of the levels of fatty acid species in the KO than in the WT. These results indicate that multiple persistent environmental chemicals at low concentrations have limited effects on fatty acid dynamics in the WT but enhanced possible dysregulations in the PPARAα−/− mice. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .