Infants are sensitive to negative effects caused by food contaminants such as mycotoxins. To date, analytical methods assessing mycotoxin mixture exposure in infant stool are absent. Herein, we present a novel multi-mycotoxin LC-MS/MS assay capable of detecting 30+ analytes including the regulated mycotoxin classes (aflatoxins, trichothecenes, ochratoxins, zearalenone, citrinin), emerging Alternaria and Fusarium toxins, and several key metabolites. Sample preparation consisted of a ‘dilute, filter, and shoot’ approach. The method was in-house validated and demonstrated that 25 analytes fulfilled all required criteria despite the high diversity of chemical structures included. Extraction recoveries for most of the analytes were in the range of 65–114% with standard deviations below 30% and limits of detection between 0.03 and 11.3 ng/g dry weight. To prove the methods’ applicability, 22 human stool samples from premature Austrian infants (n = 12) and 12-month-old Nigerian infants (n = 10) were analyzed. The majority of the Nigerian samples were contaminated with alternariol monomethyl ether (8/10) and fumonisin B1 (8/10), while fumonisin B2 and citrinin were quantified in some samples. No mycotoxins were detected in any of the Austrian samples. The method can be used for sensitive human biomonitoring (HBM) purposes and to support exposure and, potentially, risk assessment of mycotoxins. Moreover, it allows for investigating potential associations between toxicant exposure and the infants’ developing gut microbiome. Graphical abstract

Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possible models for studying maternal–fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 63 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Introduction Gold nanoparticles (AuNPs) have the potential to be used in various biomedical applications, partly due to the inertness and stability of gold. Upon intravenous injection, the NPs interact with the mononuclear phagocyte system, first with monocytes in the blood and then with macrophages in tissue. The NP–macrophage interaction will likely affect the stability of the AuNPs, but this is seldom analyzed. This study aimed to elucidate the role of macrophages in the biodissolution of AuNPs and underlying mechanisms. Methods With an in vitro dissolution assay, we used inductively coupled plasma mass spectrometry to quantitatively compare the dissolution of 5 and 20 nm AuNPs coated with citrate or PEG in cell medium alone or in the presence of THP1-derived macrophages at 24 hours. In addition, we analyzed the cell dose, compared extra- and intracellular dissolution, and explored the possible role of reactive nitrogen species. Results The results showed a higher cellular dose of the citrate-coated AuNPs, but dissolution was mainly evident for those sized 5 nm, irrespective of coating. The macrophages clearly assisted the dissolution, which was approximately fivefold higher in the presence of macrophages. The dissolution, however, appeared to take place mainly extracellularly. Acellular experiments demonstrated that peroxynitrite can initiate oxidation of gold, but a ligand is required to keep the gold ions in solution. Conclusion This study suggests extracellular dissolution of AuNPs in the presence of macrophages, likely with the contribution of the release of reactive nitrogen species, and provides new insight into the fate of AuNPs in the body.