The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others.
Socrates' death has almost always been attributed to his ...drinking an extract of poison hemlock,
despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains.
Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato.
Seen in this way, the death of Socrates can be accepted as a limited case report of
poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.
From at least the fifteenth to late nineteenth centuries, peasants in the Austrian province of Styria ate up to several hundred milligrams of arsenic trioxide or sulfide daily or weekly for periods ...up to a number of years. Taking these doses of arsenic was believed to increase muscular power and enhance the beauty and sexual attractiveness of peasant girls. There do not appear to be contemporaneous records of the known consequences of chronic arsenic exposure. The historical records of arsenic eating there are reviewed and appear to be valid. The benefits are subjective judgements by arsenic eaters. The lack of objective reports of the anticipated external and internal clinical and pathological effects of arsenic poisoning depends on a smaller number of clinical accounts and autopsy reports and the general medical literature of those times, so it is weaker, but it is consistent.INTRODUCTIONFrom at least the fifteenth to late nineteenth centuries, peasants in the Austrian province of Styria ate up to several hundred milligrams of arsenic trioxide or sulfide daily or weekly for periods up to a number of years. Taking these doses of arsenic was believed to increase muscular power and enhance the beauty and sexual attractiveness of peasant girls. There do not appear to be contemporaneous records of the known consequences of chronic arsenic exposure. The historical records of arsenic eating there are reviewed and appear to be valid. The benefits are subjective judgements by arsenic eaters. The lack of objective reports of the anticipated external and internal clinical and pathological effects of arsenic poisoning depends on a smaller number of clinical accounts and autopsy reports and the general medical literature of those times, so it is weaker, but it is consistent.Why the arsenic eaters did not show the well-known consequences of prolonged exposure to high doses of arsenic is not known. Possible explanations include increases in detoxifying metabolism in the consumers due to induced genomic changes and selection in people and in the gut microbiome, as shown in other populations. Whether these effects would suffice to protect people against their high doses of arsenic has not been explored.CAN THE CLAIMED BENEFITS OF ARSENIC EATING AND THE APPARENT ABSENCE OF HARMFUL TOXIC EFFECTS BE TRUE?Why the arsenic eaters did not show the well-known consequences of prolonged exposure to high doses of arsenic is not known. Possible explanations include increases in detoxifying metabolism in the consumers due to induced genomic changes and selection in people and in the gut microbiome, as shown in other populations. Whether these effects would suffice to protect people against their high doses of arsenic has not been explored.Although the nature and mechanisms of arsenic toxicity have been extensively described, much still remains to be discovered.CONCLUSIONAlthough the nature and mechanisms of arsenic toxicity have been extensively described, much still remains to be discovered.
This special issue of Regulatory Toxicology and Pharmacology contains 9 scientific papers from Philip Morris International about the laboratory and 1 about early clinical investigation of a novel ...‘Tobacco Heating System’. The studies have employed conventional and a wide range of newer ‘omics and bioinformatics techniques to seek and explore potential toxic actions of the inhalable vapour it generates. The methods of study and display of results employed are considered to be a valuable guide and model for wider application in other toxicological investigations because they are directed more to proximal causes of effects than to the cruder distal end points revealed by conventional, empirical procedures. As such they should be regarded as a paradigm for the applicability and accuracy of the testing and prediction of toxic risks.
•New toxicological procedures.•Risk prediction.•Markertobacco heating system.
The Minipig in Biomedical Research is a comprehensive resource for research scientists on the potential and use of the minipig in basic and applied biomedical research, and the development of drugs ...and chemicals. Written by acknowledged experts in the field, and drawing on the authors' global contacts and experience with regulatory authorities and
Methoxyflurane is an inhaled analgesic administered via a disposable inhaler which has been used in Australia for over 40 years for the management of pain associated with trauma and for medical ...procedures in children and adults. Now available in 16 countries worldwide, it is licensed in Europe for moderate to severe pain associated with trauma in conscious adults, although additional applications are being made to widen the range of approved indications. Considering these ongoing developments, we reviewed the available evidence on clinical usage and safety of inhaled analgesic methoxyflurane in trauma pain and in medical procedures in both adults and children. Published data on methoxyflurane in trauma and procedural pain show it to be effective, well tolerated, and highly rated by patients, providing rapid onset of analgesia. Methoxyflurane has a well-established safety profile; adverse events are usually brief and self-limiting, and no clinically significant effects on vital signs or consciousness levels have been reported. Nephrotoxicity previously associated with methoxyflurane at high anesthetic doses is not reported with low analgesic doses. Although two large retrospective comparative studies in the prehospital setting showed inhaled analgesic methoxyflurane to be less effective than intravenous morphine and intranasal fentanyl, this should be balanced against the administration, supervision times, and safety profile of these agents. Given the limitations of currently available analgesic agents in the prehospital and emergency department settings, the ease of use and portability of methoxyflurane combined with its rapid onset of effective pain relief and favorable safety profile make it a useful nonopioid option for pain management. Except for the STOP! study, which formed the basis for approval in trauma pain in Europe, and a few smaller randomized controlled trials (RCTs), much of the available data are observational or retrospective, and further RCTs are currently underway to provide more robust data.
The Mirasol PRT System (Gambro BCT, Lakewood, CO) for platelets and plasma uses riboflavin and UV light to reduce pathogens and inactivate white blood cells in donated blood products. An extensive ...toxicology program, developed in accordance with International Organisation for Standardisation (ISO) 10993 guidelines, was performed for the Mirasol PRT system. Test and control articles for most of the reported studies were treated (test) or untreated (control) blood products. For some studies, pure lumichrome (the major photoproduct of riboflavin) or photolyzed riboflavin solution was used. Systemic toxicity was evaluated with in vivo animal studies in the acute and subchronic settings. Developmental toxicity was evaluated with an in vivo animal study. Genotoxicity and neoantigenicity were evaluated with in vitro and in vivo tests. Hemocompatibility and cytotoxicity were assessed with standard, in vitro assays. The pharmacokinteics, excretion, and tissue distribution of14 C-riboflavin and its photoproducts was evaluated with an in vivo animal study. The possible presence of leachable or extractable compounds (from the disposable set) was evaluated with novel assays for measuring these compounds in blood. No treatment-related toxicity was observed in any of the studies.
In 1820, Frederick Accum published a book, best known by its biblical subtitle ‘Death in the Pot', showing the widespread fraudulent and dangerous adulteration of common foods and drinks bought in ...London. Despite its brief popularity, there was no effective legislation in Britain until 1875 after more extensive analytical surveys by Hassall and Letheby in 1855 and a parliamentary enquiry had confirmed the frauds and risks to public health. There were similar surveys and legal action against food adulteration in France and Germany towards the end of the 19th century. In the USA, campaigning by Harvey Wiley and others revealed the same risks and frauds and led to the Pure Foods and Drugs Act in 1906 and formation of the FDA. We should have celebrated Accum’s bicentennial in 2020 to recognise his achievement and to remind us of the continuing dangers of food adulteration today.
The terrifying dog in the Hound of the Baskervilles is described as having 'blazing eyes' and a 'luminous muzzle', appearances attributed by Watson and Holmes to the application of phosphorus. Review ...of the toxicity and flammability of white phosphorus make this improbable. It is suggested that Conan Doyle's description was probably influenced by knowledge of the recent and much publicized discovery of luminescence due to the radioactivity of uranium salts.
The International Agency for Research on Cancer (IARC) has recently proposed employing “ten key characteristics of human carcinogens” (TKCs) to determine the potential of agents for harmful effects. ...The TKCs seem likely to confuse the unsatisfactory correlation from testing regimes that have ignored the differences evident when cellular changes are compared in short and long-lived species, with their very different stem cell and somatic cell phylogenies. The proposed characteristics are so broad that their use will lead to an increase in the current unacceptably high rate of false positives. It could be an informative experiment to take well-established approved therapeutics with well-known human safety profiles and test them against this new TKC paradigm. Cancers are initiated and driven by heritable and transient changes in gene expression, expand clonally, and progress via additional associated acquired mutations and epigenetic alterations that provide cells with an evolutionary advantage. The genotoxicity testing protocols currently employed and required by regulation, emphasize testing for the mutational potential of the test agent. Two-year, chronic rodent cancer bioassays are intended to test for the entire spectrum of carcinogenic transformation. The use of cytotoxic doses causing increased, sustained cell proliferation that facilitates accumulated genetic damage leads to a high false-positive rate of tumor induction. Current cancer hazard assessment protocols and weight-of-the-evidence analysis of agent-specific cancer risk align poorly with the pathogenesis of human carcinoma and so need modernization and improvement in ways suggested here.
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