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ESRA19-0271 Intrathecal administration of hyperbaric prilocaine is a source of systemic O-toluidine
Background and aimsHyperbaric 2% prilocaine (HP) is increasingly used for spinal anesthesia. It is the only local anesthetic metabolized to o-toluidine, a human bladder carcinogen. Massive increase of o-toluidine hemoglobin adducts (HAoT), a marker of o-toluidine carcinogenic pathway, was described following subcutaneous injection. In the present study we aimed to assess a single intrathecal dose of HP as a source of HAoT and urinary o-toluidine (UoT).MethodsAfter ethical committee approval and informed written consent, 10 patients undergoing surgery received 50 mg of HP intrathecally. Blood and urine samples were collected before injection and up to 24 hours later.UoT and HAoT were measured by tandem mass-spectrometry after gas-chromatographic separation. Values are expressed as mean ± standard deviation. Pair Students t-test was used for the significance tests.ResultsIntrathecal administration of 50 mg of HP leads to a massive increase of HAoT (0.11±0.02 to 11.59±1.89 ng/g Hb after 24h, p<0.0001, figure 1). Peak of UoT was observed after 8h (0.1±0.1 to 351.6±352.7 µg/L, p<0.001) and declined to 80.0±66.8 µg/L after 24h (figure 2).Abstract ESRA19-0271 Figure 1Abstract ESRA19-0271 Figure 2ConclusionsIntrathecal administration of HP leads to a relevant systemic burden of carcinogenic o-toluidine. Therefore, the carcinogenic risk of HP administration should be the object of ethical considerations and further clinical investigations.
Journal Article
The fluorspar mines of Newfoundland : their history and the epidemic of radiation lung cancer
John Martin tells the history of Newfoundland's fluorspar mines from their founding to the last shipment of fluorspar in 1990 and declaration of bankruptcy a year later. He focuses on the health hazards experienced by the miners, and how the mining companies, workers, governments, and health services came to terms with the unfolding human tragedy. He also covers such matters as the improvement of methods for dust quantification and radiation surveillance in the mines, battles for compensation, and the influence of the St Lawrence case on the development of labour law in the province.
Book
Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract
Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.
Triclosan (TCS), an antimicrobial agent commonly found in consumer products, has been reported to exacerbates colitis in animal models. Here, using in vitro and in vivo approaches, the authors show that gut bacterial enzymes can drive the metabolic activation and gut toxicity of TCS, highlighting an important role of intestinal microbial factors in the complex etiology of colitis.
Journal Article
Key Characteristics of Carcinogens as a Basis for Organizing Data on Mechanisms of Carcinogenesis
A recent review by the International Agency for Research on Cancer (IARC) updated the assessments of the > 100 agents classified as Group 1, carcinogenic to humans (IARC Monographs Volume 100, parts A-F). This exercise was complicated by the absence of a broadly accepted, systematic method for evaluating mechanistic data to support conclusions regarding human hazard from exposure to carcinogens.
IARC therefore convened two workshops in which an international Working Group of experts identified 10 key characteristics, one or more of which are commonly exhibited by established human carcinogens.
These characteristics provide the basis for an objective approach to identifying and organizing results from pertinent mechanistic studies. The 10 characteristics are the abilities of an agent to 1) act as an electrophile either directly or after metabolic activation; 2) be genotoxic; 3) alter DNA repair or cause genomic instability; 4) induce epigenetic alterations; 5) induce oxidative stress; 6) induce chronic inflammation; 7) be immunosuppressive; 8) modulate receptor-mediated effects; 9) cause immortalization; and 10) alter cell proliferation, cell death, or nutrient supply.
We describe the use of the 10 key characteristics to conduct a systematic literature search focused on relevant end points and construct a graphical representation of the identified mechanistic information. Next, we use benzene and polychlorinated biphenyls as examples to illustrate how this approach may work in practice. The approach described is similar in many respects to those currently being implemented by the U.S. EPA's Integrated Risk Information System Program and the U.S. National Toxicology Program.
Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert P, Hecht SS, Bucher JR, Stewart BW, Baan R, Cogliano VJ, Straif K. 2016. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect 124:713-721; http://dx.doi.org/10.1289/ehp.1509912.
Journal Article
Increased cancer burden among pesticide applicators and others due to pesticide exposure
A growing number of well-designed epidemiological and molecular studies provide substantial evidence that the pesticides used in agricultural, commercial, and home and garden applications are associated with excess cancer risk. This risk is associated both with those applying the pesticide and, under some conditions, those who are simply bystanders to the application. In this article, the epidemiological, molecular biology, and toxicological evidence emerging from recent literature assessing the link between specific pesticides and several cancers including prostate cancer, non-Hodgkin lymphoma, leukemia, multiple myeloma, and breast cancer are integrated. Although the review is not exhaustive in its scope or depth, the literature does strongly suggest that the public health problem is real. If we are to avoid the introduction of harmful chemicals into the environment in the future, the integrated efforts of molecular biology, pesticide toxicology, and epidemiology are needed to help identify the human carcinogens and thereby improve our understanding of human carcinogenicity and reduce cancer risk. [PUBLICATION ABSTRACT]
Journal Article
This simple trick can reduce meat carcinogens by 88
To help counteract the carcinogenic compounds that form when you cook meat at high temperatures, such as when you grill it, you just have to marinate it. Ask a Doctor columnist Dr. Trisha Pasricha explains.
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SUBSTANCJE CHEMICZNE I PROCESY TECHNOLOGICZNE O DZIAŁANIU RAKOTWÓRCZYM LUB MUTAGENNYM W ŚRODOWISKU PRACY W POLSCE W LATACH 2013–2017
Pr. 2020; 71(2):187-203 Slowa kluczowe: narazenie zawodowe, rejestr, srodowisko pracy, czynniki rakotw rcze, czynniki mutagenne, rozklad przestrzenny ABSTRACT Background: The aim of this paper was to present data on occupational exposure to carcinogens and mutagens in Poland in 20132017, based on information sent to the Central Register of Data on Exposure to Carcinogenic or Mutagenic Chemical Substances, Mixtures, Agents or Technological Processes, kept by the Nofer Institute of Occupational Medicine, L dz, Poland. The data were shown in various configurations and presented in the form of spatial distribution of the exposure to and occurrence of selected occupational carcinogens and mutagens. The most common chemical agents in the reference years were formaldehyde, particular polycyclic aromatic hydrocarbons (PAH), benzene and chromium(VI) compounds. Med Pr. 2020;71(2):187-203 Key words: occupational exposure, register, work environment, carcinogens, mutagens, spatial distribution WSTEP Zachorowalnosc i umieralnosc na nowotwory zlosliwe w Polsce stopniowo rosna od kilkudziesieciu lat.
Journal Article