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Ammunitions containing toxic chemical warfare agents (CWAs) that were seized from Germany at the end of World War II were disposed mainly by sea-dumping in the Skagerrak Strait and the Baltic Sea. In an area located 25 nautical miles south-east of Arendal, Norway, several ships carrying cargo of chemical munitions were scuttled. Previous investigations have revealed that CWAs are leaking from containers and munitions into surrounding sediments in the area, raising concerns of bioaccumulation of these chemicals in marine biota. In this study, Hagfish (Myxine glutinosa) was used as a model animal to investigate uptake of phenylarsenic CWAs by marine biota caught from the dumping area outside Arendal. Two laboratories analysed hagfish samples for primary degradation products of the phenylarsenic chemicals Clark I/II, namely diphenylarsinic acid and triphenylarsine oxide which have been previously found in sediment samples from the same area. The investigation showed that studied chemicals, originating from leaking munitions, are bioaccumulating in hagfish. These results support earlier findings of bioaccumulation of CWA-related phenylarsenic chemicals in different marine biota species living in the vicinity of dumping areas with increasing concern on environmental impacts caused by marine munitions. In addition, a novel biotransformation product of Clark I/II, methyldiphenylarsine oxide (MDPAO) was detected in studied fish samples for the first time. Based on findings reported in this study, biotransformation products of phenylarsenic CWAs should be considered as target chemicals in future evaluations of CWA exposure in marine biota. As the information on bioaccumulation and biological effects of CWAs in marine species are narrow, results gained in this study are essential for risk assessment related to marine munitions, as well as for future monitoring campaigns., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

During the World Wars large quantities of phenylarsenic chemical warfare agents (CWAs) were dumped in the Baltic Sea. Many transformation products of these chemicals have been identified, but the pathways that produce the found chemicals has not been investigated. Here we studied the biotic and abiotic transformation of phenylarsenic CWAs under oxic and anoxic conditions and investigated how the sediment bacterial communities are affected by CWA exposure. By chemical analysis we were able to identify seventeen CWA-related phenylarsenicals, four of which (methylphenylarsinic acid (MPAA), phenylthioarsinic acid (PTAA), phenyldithioarsinic acid (PDTAA) and diphenyldithioarsinic acid (DPDTAA)) have not been reported for marine sediments before. For the first time PTAA was verified from environmental samples. We also observed equilibrium reactions between the found transformation products, which may explain the occurrence of the chemicals. 16S rRNA-analysis showed that bacterial communities in sediments are affected by exposure to phenylarsenic CWAs. We observed increases in the amounts of arsenic-resistant and sulphur-metabolising bacteria. Different transformation products were found in biotic and abiotic samples, which suggests that bacteria participate in the transformation of phenylarsenic CWAs. We propose that methylated phenylarsenicals are produced in microbial metabolism and that chemical reactions with microbially produced sulphur species form sulphur-containing transformation products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent studies have found primary degradation products of phenylarsenic chemical warfare agents (CWAs) accumulating in fish tissues, while the potential effects of these dumped phenylarsenic CWAs, such as Clark I and II, in the Baltic Sea biota are poorly understood. In this study, the metabolism and cytotoxicity of diphenylarsinic acid (DPA), a primary degradation product of phenylarsenic CWA, was studied by incubating rainbow trout cell line RTL-W1 cells in media with 100 mg/L DPA. Previously undescribed metabolites were identified by ultra-high performance liquid chromatography-high resolution mass spectrometry (UPHLCHRMS). Moreover, the cytotoxicity of diphenylarsine glutathione conjugate (DPA-SG), the major metabolite of DPA, was studied. Cytotoxicity of the compounds was evaluated using the Neutral Red retention test (NRR), showing an IC 50 value of 278 mg/L for DPA and 1.30 mg/L for DPA-SG, indicating that the glutathione (GSH) conjugate of DPA is more than two orders of magnitude toxic than DPA itself, suggesting that toxic properties of DPA are increased after conjugation with intracellular GSH leading enhanced toxicity after uptake. Results gained in this study give more detailed information for elucidating biological effects of dumped chemical munitions in marine environment. Moreover, the results help in assessing the environmental and health risks posed by marine munition continued presence and deterioration in the sea bottom., (Copyright © 2021. Published by Elsevier B.V.)

Sea dumping of chemical warfare (CW) took place worldwide during the 20th century. Submerged CW included metal bombs and casings that have been exposed for 50-100 years of corrosion and are now known to be leaking. Therefore, the arsenic-based chemical warfare agents (CWAs), pose a potential threat to the marine ecosystems. The aim of this research was to support a need for real-data measurements for accurate risk assessments and categorization of threats originating from submerged CWAs. This has been achieved by providing a broad insight into arsenic-based CWAs acute toxicity in aquatic ecosystems. Standard tests were performed to provide a solid foundation for acute aquatic toxicity threshold estimations of CWA: Lewisite, Adamsite, Clark I, phenyldichloroarsine (PDCA), CWA-related compounds: TPA, arsenic trichloride and four arsenic-based CWA degradation products. Despite their low solubility, during the 48 h exposure, all CWA caused highly negative effects on Daphnia magna. PDCA was very toxic with 48 h D. magna LC50 at 0.36 μg × L -1 and Lewisite with EC50 at 3.2 μg × L -1 . Concentrations at which no immobilization effects were observed were slightly above the analytical Limits of Detection (LOD) and Quantification (LOQ). More water-soluble CWA degradation products showed no effects at concentrations up to 100 mg × L -1 ., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Recently, sea-dumped chemical weapons (CWs) containing toxic chemical warfare agents (CWAs) have raised international attention. It is well known that CWAs are leaking from corroded munitions causing a risk to the surrounding marine environment, while the impact on marine biota is still unknown. In this study, cod (Gadus morhua) was used as a model species to study the possible bioaccumulation of phenylarsenic CWAs and their negative effects at multiple levels of biological organization on fish living in the vicinity of a major CWs dumpsite in the Bornholm Basin in the Baltic Sea. In total, 14% of the cod muscle samples collected close to the main dumpsite contained trace levels of phenylarsenic CWAs. However, most of the biomarkers measured did not show clear differences between this area compared with a lesser contaminated reference area. On the other hand, significant changes in some biomarkers were observed in individuals containing trace levels of CWA-related chemicals. The results gained in this study have significant importance for environmental risk assessment and for evaluating the risk of CWA contamination for human seafood consumers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

After World War II, thousands of tons of highly toxic chemical warfare agents (CWA) were deposited in the Baltic Sea, the main dumping site locating in the Bornholm Basin. In the present study, Baltic mussels (Mytilus trossulus) were transplanted in the area in cages at two hotspot sites and a reference site at the depths of 35 and 65 m for 2.5 months to study bioaccumulation and biological effects of CWA possibly leaking from the corroding warfare materials. No traces of degradation products of the measured phenylarsenic CWA could be detected in the tissues of mussels. Nevertheless, several biochemical and histochemical biomarkers, geno- and cytotoxicity indicators, and bioenergetic parameters showed significant responses. The Integrated Biomarker Index calculated from the single biomarkers also showed a higher total response at the two hotspot areas compared to the reference site. Although no direct evidence could be obtained confirming the responses being caused specifically by exposure to CWA, the field exposure experiment showed unambiguously that organisms in this sea area are confronting environmental stress affecting negatively their health and this is likely related to chemical contamination, which is possibly connected to the sea-dumped CWA., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Organofluorosilicon based 18 F-radiolabeling is an efficient method for incorporating fluorine-18 into 18 F-radiopharmaceuticals for positron emission tomography (PET) by 19 F/ 18 F isotopic exchange (IE). The first PET radiopharmaceutical, 18 F-SiFA lin -TATE, radiolabeled with a silicon-based [ 18 F]fluoride acceptor (SiFA), namely, a para-substituted di- tert -butyl[ 18 F]fluorosilylbenzene, has entered clinical trials, and is paving the way for other potential [ 18 F]SiFA-labeled radiopharmaceuticals for diagnostic use. In this study, we report the in vitro metabolism of an oxime-linked SiFA tetrazine (SiFA-Tz), a new PET-radiotracer candidate, recently evaluated for pretargeted PET imaging and macromolecule labeling. Metabolism of SiFA-Tz was studied in mouse liver microsomes (MLM) for elucidating its major biotransformation pathways. Nontargeted screening by ultrahigh performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS) was utilized for detection of unknown metabolites. The oxime bond between the SiFA and Tz groups forms two geometric ( E / Z ) isomers, which underwent the same biotransformations, but unexpectedly with different kinetics. In total, nine proposed metabolites of SiFA-Tz from phase I and II reactions were detected, five of which were defluorinated in MLMs, elucidating the metabolic pathway leading to previously reported defluorination of [ 18 F]SiFA-Tz in vivo . Based on the HRMS studies a biotransformation pathway is proposed: hydroxylation (+O) to tert -butyl group adjacent to the silicon, followed by oxidative defluorination (+OH/-F) cleaving the fluorine off the silicon. Interestingly, eight proposed metabolites of a reduced dihydrotetrazine analogue, SiFA-H 2 Tz, from phase I and II reactions were additionally detected. To the best of our knowledge, this is the first reported comprehensive investigation of enzyme mediated metabolic pathway of tetrazines and para-substituted di- tert -butylfluorosilylbenzene fluoride acceptors, providing novel structural information on the biotransformation and fragmentation patterns of radiotracers bearing these structural motifs. By investigating the metabolism preceding defluorination, structurally optimized new SiFA compounds can be designed for expanding the portfolio of efficient 19 F/ 18 F isotopic exchange labeling probes for PET imaging.

Large quantities of chemical warfare agents (CWAs), such as phenylarsenic chemicals, were disposed by sea-dumping after World War II. Nowadays, the release of these toxic chemicals from munitions poses a potential threat to living organisms. This study investigates the fate of these chemicals in fish by exposing selected CWA-related phenylarsenic chemicals and their oxidation products to cod (Gadus morhua) liver S9 fraction in vitro. Clark I (DA), Adamsite (DM) and their corresponding oxidation products as well as triphenylarsine oxide (TPA[ox]) and phenylarsonic acid (PDCA[ox]) were used as chemicals in in vitro experiments. Glutathione (GSH) conjugates of DA, DM and PDCA-related chemicals were found to be the most dominant metabolites, and methylated metabolites were detected as well, suggesting that these compounds are metabolised in the presence of cod liver enzymes. TPA[ox] was the only compound tested that did not form a GSH conjugate or methylated metabolite, indicating a different biotransformation pathway for this compound. Furthermore, hydroxylated metabolites were detected for each tested chemical. Due to their reactive nature, GSH conjugates may be difficult to detect in fish samples from CWA dumpsites. In contrast, both methylated and hydroxylated metabolites of phenylarsenic chemicals are promising target chemicals for the detection of CWA-related contamination in fish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previously unknown phenylarsenic chemicals that originated from chemical warfare agents (CWAs) have been detected and identified in sediment samples collected from the vicinity of chemical munition dumpsites. Nontargeted screening by ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) was used for detection of 14 unknown CWA-related phenylarsenic chemicals. Methylated forms of Clark I/II, Adamsite, and phenyldichloroarsine were detected in all analyzed sediment samples, and their identification was based on synthesized chemicals. In addition, other previously unknown CWA-related phenylarsenic chemicals were detected, and their structures were elucidated using MS/HRMS technique. On the basis of relative isotope ratios of protonated molecules and measures of exact masses of formed fragment ions, it could be concluded that some of these unknown chemicals contained a sulfur atom attached to an arsenic atom. In addition to that, some of the samples contained chemicals that had formed via addition of an OH group to the aromatic ring. However, it is not possible to say how these chemicals are formed, but the most plausible cause is activities of marine microbes in the sediment. To our knowledge, these chemicals have not been detected from sediment samples previously. Sensitive analytical methods are needed for these novel chemicals to assess the total CWA burden in marine sediments, and this information is essential for the risk assessment.

Baltic blue mussels (Mytilus trossulus) were implemented to assess potential toxicity, health impairments and bioaccumulation of dumped chemical warfare agents on marine benthic organisms. Mussels were collected from a pristine cultivation side and exposed under laboratory conditions to different mixtures of chemical warfare agents (CWAs) related phenyl arsenic compounds, Clark I and Adamsite as well as chloroacetophenone. Using a multi-biomarker approach, mussels were assessed thereafter for effects at different organisational levels ranging from geno-to cytotoxic effects, differences in enzyme kinetics and immunological responses. In an integrated approach, chemical analysis of water and tissue of the test organisms was performed in parallel. The results show clearly that exposed mussels bioaccumulate the oxidized forms of chemical warfare agents Clark I, Adamsite (DAox and DMox) and, to a certain extent, also chloroacetophenone into their tissues. Adverse effects in the test organisms at subcellular and functional level, including cytotoxic, immunotoxic and oxidative stress effects were visible. These acute effects occurred even at the lowest test concentration., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A new method has been developed to determine oxidation products of three chemical warfare agent (CWA) related phenylarsenic compounds from marine biota samples by a liquid chromatography-heated electrospray ionization/tandem mass spectrometry (LC-HESI/MS/MS). The target chemicals were oxidation products of Adamsite (DM[ox]), Clark I (DPA[ox]), and triphenylarsine (TPA[ox]). Method was validated within the concentration range of 1-5, 0.2-5, and 0.2-5 ng/g for DM[ox], DPA[ox], and TPA[ox], respectively. The method was linear, precise and accurate. Limits of quantification (LOQ) were 2.0, 1.3, and 2.1 ng/g for DM[ox], DPA[ox], and TPA[ox], respectively. A total of ten fish samples and one lobster sample collected from near Swedish coast, Måseskär dumpsite were analyzed. Trace concentrations below LOQ values were detected in three samples and the elemental composition of oxidized form of Clark I and/or II was confirmed by LC-HESI/HRMS. To our knowledge, this is the first study that provides the presence of CWA related chemicals in marine biota samples.