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In the early 1890s at Trinil, Eugène Dubois found a hominin skullcap (Trinil 2) and femur (Trinil 3, Femur I), situated at the same level ca. 10-15 m apart. He interpreted them as representing one species, Pithecanthropus erectus (now Homo erectus) which he inferred to be a transitional form between apes and humans. Ever since, this interpretation has been questioned-as the skullcap looked archaic and the femur surprisingly modern. From the 1950s onward, chemical and morphological analyses rekindled the debate. Concurrently, (bio)stratigraphic arguments gained importance, raising the stakes by extrapolating the consequences of potential mixing of hominin remains to the homogeneity of the complete Trinil fossil assemblage. However, conclusive evidence on the provenance and age of the hominin fossils remains absent. New Trinil fieldwork yielded unmanned aerial vehicle imagery, digital elevation models, and stratigraphic observations that have been integrated here with an analysis of the historical excavation documentation. Using a geographic information system and sightline analysis, the position of the historical excavation pits and the hominin fossils therein were reconstructed, and the historical stratigraphy was connected to that of new sections and test pits. This study documents five strata situated at low water level at the excavation site. Cutting into a lahar breccia are two similarly oriented, but asynchronous pre-terrace fluvial channels whose highly fossiliferous infills are identified as the primary targets of the historical excavations (Bone-Bearing Channel 1, 830-773 ka; Bone-Bearing Channel 2, 560-380 ka), providing evidence for a mixed faunal assemblage and yielding most of the hominin fossils. These channels were incised by younger terrace-related fluvial channels (terminal Middle or Late Pleistocene) that directly intersect the historical excavations and the reconstructed discovery location of Femur I, thereby providing an explanation for the relatively modern morphology of this 'bone of contention'. The paleoanthropological implications are discussed in light of the current framework of human evolution in Southeast Asia., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Estragole is a naturally occurring food-borne genotoxic compound found in a variety of food sources, including spices and herbs. This results in human exposure to estragole via the regular diet. The objective of this study was to quantify the dose-dependent estragole-DNA adduct formation in rat liver and the urinary excretion of 1'-hydroxyestragole glucuronide in order to validate our recently developed physiologically based biodynamic (PBBD) model. Groups of male outbred Sprague Dawley rats (n = 10, per group) were administered estragole once by oral gavage at dose levels of 0 (vehicle control), 5, 30, 75, 150, and 300mg estragole/kg bw and sacrificed after 48h. Liver, kidney and lungs were analysed for DNA adducts by LC-MS/MS. Results obtained revealed a dose-dependent increase in DNA adduct formation in the liver. In lungs and kidneys DNA adducts were detected at lower levels than in the liver confirming the occurrence of DNA adducts preferably in the target organ, the liver. The results obtained showed that the PBBD model predictions for both urinary excretion of 1'-hydroxyestragole glucuronide and the guanosine adduct formation in the liver were comparable within less than an order of magnitude to the values actually observed in vivo. The PBBD model was refined using liver zonation to investigate whether its predictive potential could be further improved. The results obtained provide the first data set available on estragole-DNA adduct formation in rats and confirm their occurrence in metabolically active tissues, i.e. liver, lung and kidney, while the significantly higher levels found in liver are in accordance with the liver as the target organ for carcinogenicity. This opens the way towards future modelling of dose-dependent estragole liver DNA adduct formation in human.

In this review many examples are given of the complexities involved in using some biomarkers in relation to assessing the effects of dietary exposure, when there is frequently a need to determine changes following long-term low level exposure to dietary components. These range from understanding why the biomarker might be valuable and how best it can be measured, to the pitfalls which can occur in the interpretation of data. Analytical technique is considered in relation to folate and selenium, and flavonoid and carotenoid species are used to illustrate how the metabolism of a compound may alter the validity or adequacy of a marker. Vitamin A is discussed in relation to the difficulties which can arise when there are several biomarkers that may be available to assess exposure to one nutrient. Vitamin B12 is discussed in relation to the dietary choices made by individuals. Possible interactions and the role of measuring total antioxidant capacity is considered in some detail. In contrast to most nutrients, there is a marked lack of biomarkers of either exposure or effect for most non-nutrients. The role of biological effect monitoring is considered for dietary contaminants, fumonisins and polyhalogenated aromatic hydrocarbons. Aflatoxins are discussed to exemplify food contaminants for which the biomarker approach has been extensively studied. Finally some compounds which are deliberately added to foods and some which appear as processing contaminants are each considered briefly in relation to the requirement for a biomarker of exposure to be developed.