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Environmental Inhaled Agents and Their Relation to Lung Cancer
Published in Jacob Loke, Pathophysiology and Treatment of Inhalation Injuries, 2020
These are volatile electrophilic reactants used in industry in the synthesis and preparation of bactericides, fungicides, ion-exchange resins, and polymers (Harris, 1983). Two forms are important: chloromethyl methyl ether and the more potent bis-(chloromethyl)ether. Their carcinogenicity has been described in laboratory animals (Drew et al., 1975), and exposed workers have shown an increased risk of lung cancer (Nelson, 1976; Weiss et al., 1979; McCallum et al., 1983), which was related more to the degree than to the duration of exposure.
The Pathogenesis of Nasal Neoplasia Induced by Alkylating and Aldehyde Compounds
Published in D. V. M. Gerd Reznik, Sherman F. Stinson, Nasal Tumors in Animals and Man, 2017
A. R. Sellakumar, R. Albert, M. Kuschner
Among the chlorinated ethers, bis(chloromethyl)ether (BCME) represents the most interesting compound, based on its once widespread industrial use, extreme reactivity, and its implication as a carcinogen following skin, subcutaneous, and epidemiological studies.11 A lifetime study was initiated originally with 70 male Sprague-Dawley rats at a level of 0.1 ppm of BCME. Inhalation studies showed tumors in the olfactory and nasal epithelium.12 By the time they had received 80 expsoures, 50% of the group had died. Of those remaining, 20 were removed from the exposure regimen and held for lifetime observation while the remainder continued to receive exposures. Further details of this study are given elsewhere.12 In other studies with BCME, a total of 200 rats were exposed to levels of 0.1 ppm BCME for either 10, 20, 40, 60, or 100 exposures and then held for lifetime observation. The data from the 20 animals removed from the chronic study above at 30 exposures were included here in the calculation of dose response curves and tumor incidences.
Synthesis, in vitro screening and molecular docking of isoquinolinium-5-carbaldoximes as acetylcholinesterase and butyrylcholinesterase reactivators
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
David Malinak, Rafael Dolezal, Vendula Hepnarova, Miroslava Hozova, Rudolf Andrys, Petr Bzonek, Veronika Racakova, Jan Korabecny, Lukas Gorecki, Eva Mezeiova, Miroslav Psotka, Daniel Jun, Kamil Kuca, Kamil Musilek
Further, the group of unsymmetrical isoquinoline-isonicotinamide bisquaternary salts was synthesized by SN2 reaction of aldoxime 15 with monoquaternary isonicotinamide salts 27–29. The reaction was carried out in DMF at 73 °C, and final products 30–32 were obtained in 53–77% yield (Scheme 3). Monoquaternary salts 27–29 were prepared according to the procedure described by Chennamaneni et al.19. In this work, symmetrical bisisoquinolinium salt containing dimethylene ether chain was also synthesized by reacting aldoxime 15 with bis(chloromethyl)ether in DMF as a solvent. The product 33 was obtained in 45% yield (Scheme 3). Based on HPLC with UV detection (λ = 254 nm), the non-calibrated purity of all products was ≥95%.
The 2-year rodent bioassay in drug and chemical carcinogenesis testing: Sensitivity, according to the framework of carcinogenic action
Published in Toxicology Mechanisms and Methods, 2020
Jose D. Suarez-Torres, Fausto A. Jimenez-Orozco, Carlos E. Ciangherotti
Even carcinogenesis solely at contact sites was accounted as carcinogenic action (i.e. the nasal cavity for inhaled acetaldehyde, or the skin for dermally applied bis[chloromethyl] ether). Because (a) current guidelines do not recommend injection as an exposure route for the RCB (U.S. EPA 1998; U.S. FDA 2006a; OECD 2012) (except for some pharmaceuticals), and (b) parenteral carcinogenicity not necessarily indicates carcinogenicity through non-parenteral exposures, efforts were made to ascertain a representative SEN on this issue.